Physiology

Study Designs in Medical Research

Dr. John Domantay| April 20-21, 2015

Study Designs in Medical Research 2. CROSS-SECTIONAL – Go by all of the following names:

• Classification of Study Design o Surveys- administered or participated in
• Observational Studies: o Epidemiologic Studies –involve surveys
• Case Series o Prevalence Studies –about the prevalence of a
• Cross-sectional Studies disease in a community
• Case Control Studies
• Cohort Studies
• Experimental Studies or Clinical Trials
• Meta-analysis & review papers

 Knowing how a study is designed is important for

understanding the concepts that can be drawn from it.
 It gives us an idea on how the study was conducted and what
to expect from it.
 Now is the age of evidence-based medicine. Evidence= found in
literature or research journals.
 You should be able to understand research in medicine. It starts
by knowing the research design.

Studies are divided into:

I. Observational Studies
- one or more groups of patients are observed (no intervention done)
- different variables/characteristics are recorded for analysis

II. Experiments − Descriptive of the timeline (done in one point in time or almost
- Involve an intervention (an investigator-controlled in an instant)
maneuver/manipulated maneuver) − Important concept: Analyze data collected on a group of
subjects at one point in time. Does not involve a follow-up
- Effect on the study of subjects period to the future or looking back to the past. It is something
done at the present.
*Both observational and experimental studies may involve animals or − determine “What is happening?” right now
objects (more common in experimental studies) − Exposure (Independent Variable) vs. Outcome (Dependent
*it can only be called an experiment depending on how the study is Variable)
designed. Ex.
*Most studies in medicine involve people but we can’t do away with o You want to determine if there is an association with
experimental animals cigarette smoking (exposure) and lung cancer
(outcome)
I. Observational Studies have 4 main types: differ in their time Steps:
1. Determine if he has lung cancer
relationship
2. Ask if he smokes and smoking habits
1. Case Series *collect the data at the same time
2. Cross- sectional o Hyperlipidemia (exposure) and CAD (outcome)
3. Case Control (not an experiment; observational) 1. Assess CAD with ECG and other tests
4. Cohort 2. Establish hyperlipidemia- measure cholesterol,
HDL, LDL extracted from blood
1.CASE SERIES – simplest − Subjects are selected and the information is obtained in a short
− A report that is a descriptive account of interesting period of time
characteristics observed in a group of patients
− also called prevalence studies because they focus in one point in
− mostly done in hospitals or clinics time and one of the outcomes of a cross sectional studies is the
− data from patients chart prevalence of a certain disease in a community.
o Patients with disease  obtain data from chart Ex. Prevalence of lung cancer and CAD in a certain group of
(demographic and clinical)  incorporate into a journal people
article
− ex. Pts with DHF who are admitted in a certain or group of − Surveys & polls are generally cross-sectional studies. However, they
hospitals  observe certain characteristic (age, sex, social can also be part of a cohort or case control study
demographic data like educational attainment, ethnicity, − Ex.
socioeconomic status, signs and symptoms, diagnostics, o Diagnosing or staging a disease
treatment) o Establishing norms/reference ranges
− includes description of the manifestations of the group of o Evaluating different methods of doing the same thing (ex.
patients.
Diagnosing a certain disease via laboratory tests-measure
− they generally involve patients seen over a relatively short-time
− no comparison group/control subjects (only a group of people specificity, sensitivity, validity, and reliability)
who suffer from the same disease) o Surveys
− A precursor to other studies
3. CASE CONTROL STUDIES − study might outlive the researcher because the waiting period is
- Not experimental a long period of time
− Begin with the absence / presence of an outcome then look backward − asks the question, “what will happen?”
in time to detect possible risk factors or causes. − direction is forward in time
Ex. determine association b/n cigarette smoking & lung cancer − all subjects are followed over a certain period to observe the effect
(outcome) of the risk factor or exposure. They are followed-up in time
- Begin with 2 groups: Ex. Cigarette smoking and Lung Cancer
 Those with the disease (cases) ex. Lung cancer - Onset of study is also w/ the outcome (people w/ and w/o
the lung cancer)
 Those who do not have the disease/outcome (controls)
- Study begins with two groups: exposed- smokers and
- Look backward in time to detect possible risk factors or causes unexposed- non-smokers
- Determine who are exposed or unexposed in both groups - Determine their smoking status from previous records
 Exposed- smokers (should not ask them about their smoking habits in the past
 Unexposed- non-smokers
because it will become a case control study)
 Risk factor/ exposure- cigarette smoking
- They are followed-up in time. Wait for the outcome to
− begins with the outcome − cases and controls appear. For lung cancer you might wait until “kingdom
 cases are individuals with disease or outcome o controls are come”. You should be careful in designing a research design.
individuals w/o disease or outcome
− the history or previous events of both cases & controls are analyzed − Sometimes called prospective studies
via questionnaire or interview about the past. − A typical cohort study is the Framingham Study of Cardiovascular
 Done to detect presence/absence of pre-disposing disease
-determine risk factors of cardiovascular disease
characteristics or risk factors
− studies that asses medical outcome are reported in Medical
− The nature of the inquiry is backward in time / retrospective (ask literature (all followed-up over several years)
about events in the past) o Functional status –followed-up in time
− investigators sometimes use matching (like age and sex), if such
o Quality of Life - questionnaire o Patient Satisfaction
characteristics are important
Ex. If the case is child, the corresponding control should also o Cost-effectiveness & cost-benefit analysis
be a child) − A Historical Cohort Study uses information collected in the past
− Answers the question, “what happened?” & kept in records or files if they exist
 The onset of the study begins with the outcome
 Not similar to case study
 You can’t interview. Evidences are files and records.
 Save time because you won’t have a long follow-up
period.
− also called retrospective cohort because the exposure was
determined from records that were collected in the past or
events being evaluated occurred before the onset of the study.
- The events being evaluated happened before the onset of the
study

Observation studies differ in their time relationships

4. COHORT STUDIES
− is a group of people who have something in common
− originally used in military which means “group of soldiers”
− in medicine, the subject in a cohort study are selected by some Answer the question: “What is happening?”
defining characteristic suspected of being a precursor to or risk  cross sectional
factor for a disease or health effect
− study begins with the exposure/independent variable (Opposite “What happened?”
of case control wherein the study begins with the outcome) Case control
Ex. Cigarette Smoking and Lung Cancer
“What will happen?”
Exposure: cigarette smoking
Cohort
2 groups : Smokers and Non-Smokers
- Follow them up overtime and wait for them to develop the Historical Cohort – makes use of exposure data in past but also
outcome (lung cancer) moves forward
II. EXPERIMENTAL OR CLINICAL TRIALS - Not as simple as taking the mean and the sum, there are
• Involve an intervention (an investigator-controlled maneuver) o complicated statistics to consider such as the sample size
Manipulation of the exposure / independent variable - Statistical results are combined together
o Drugs, intervention, treatment etc. - Almost similar to a review (qualitative) but includes a
• Effect on the study subjects quantitative assessment and summary of the findings
• Experimental studies in medicine that involve humans are called - Assumes that you have reviewed all of the literature available
clinical trials on the topic
• Experimental- some form of intervention and this is tested on trial - This method is appropriate when studies have small numbers of
• Their purpose is to draw conclusions about a particular procedure subjects, or different conclusion
or treatment
• Subjects meting entry criteria  control and experimental with
outcome and without outcome
• Both observational and experimental studies may involve animals or
objects

RANDOMIZED CONTROLLED TRIALS/RCT

- have far greater validity in medicine than uncontrolled studies
- we have participants who meet the intervention trial
a. receive intervention group/ experimental
b. no intervention group/ control
- The one that receives the experimental procedure is the
experimental / intervention group
 The one that receives the placebo or standard procedure is the
control group
 In medicine, it is unethical to withhold the treatment for the control
group (reason for giving standard procedure and not placebo)
 Both groups should be treated alike in all ways except in the
intervention
 Any differences between the groups later on will be due to the
procedure and not to other factors

a. Double blind clinical / randomized trial

- Neither the subject nor investigator knows what group the subject
is in:
 Usually with a third party, (independent group) who
knows who is in which group
 Important to eliminate bias on the part of the investigator
 Usually it is the standard
b.Single blind trial - when only the subject is unaware
- Sometimes inevitable (cases like surgical procedures where the
surgeon cannot be blind)
c. Another issue is how to assign patients to the experimental and
control groups
Group of patients  Randomization/ Random Assignment  Control or
Experimental group o Best method of assignment is randomization

d. The randomized controlled trial (RCT) is the epitome of all

research designs
 It provides the strongest evidence for concluding causation /
cause and effect
 Gold standard
e. Other experimental designs:
 Nonrandomized trials
 Trials with self-controls
 Trials with external controls
 Uncontrolled studies

META ANALYSIS AND REVIEW PAPERS

- Meta Analysis uses published information from other studies
a. Study of studies (gather studies or journals)
b. Results of studies are combined in order to permit an overall
conclusion – “Forest Plot”
c. Quantitative – with numerical results
Physiology
Advantages and Disadvantages of Different Research Designs
Dr. John Domantay| April 21, 2015

A. CLINICAL TRIALS  There is a hierarchy

ADVANTAGES: o Hypothesis from either case series or cross sectional
o The RCT is the gold standard or reference in medicine as far as o Case control
causation is concerned o Cohort
o It provides the greatest justification or evidence for concluding o Clinical Trial – epitome
causality  Generally the quickest and least expensive studies to undertake
o It is subject to the least number of problems or biases
 Selection bias – randomization DISADVANTAGES:
 Information bias – blinding − They have the largest number of possible biases or errors
 It is the best type of study to use to establish efficacy of a • Selection bias
treatment or procedure o One of the greatest problems is the selection of an
appropriate control group
DISADVANTAGES: • Information bias
− Obstacles to using them include their great expense and long • You will have to ask the subjects about events in the past
duration
D. CROSS-SECTIONAL STUDIES
*RCT not done probably due to ethical issues, then use the next
ADVANTAGES:
best thing: Cohort studies
 Determining prevalence of a disease in a population
B. COHORT STUDIES  Evaluating diagnostic procedures
ADVANTAGES:  They are relatively quick and inexpensive to complete
 Cohort studies are the designs of choice for studying:
 Causes of a condition – eg. Framingham study DISADVANTAGES:
 Course of a disease − Provide only a “snapshot in time” of the disease or process.
 Risk factors – eg. Framingham study − A common problem with survey research is obtaining sufficiently
large response rate – might be low (can’t retrieve the forms)
 Causation generally cannot be proved with cohort studies o Many people asked to participate in a survey decline
 Observational o Solution: select samples that may have high response rate
 Do not involve interventions − Conclusions are based on a subset of people who may not be
 Provide the correct time sequence to provide strong evidence for representative of the entire population
possible cause and effect o You cannot generalize to a larger
 Cause  Effect – There is follow up period population
 Temporal relationship – Time sequence − Issue: the way questions are posed to participants.
 Investigators can control many sources of bias related to patient o Need skills and proper ways on writing questions/items
selection and recorded measurement − Responses may not truly represent the participants’ feelings or
 Selection bias – patient selection opinions o Inherent to questionnaire
o Solution: correct phrasing of questions & increase respondents’
 Information bias – recorded measurements
interest
DISADVANTAGES:
E. CASE SERIES
− The length of time depends on problem being studied
2 ADVANTAGES:
 Diseases that develop over a long period of time (Eg. Cancer)
 Easy to write
 Conditions that result from long term exposure to an agent (Eg.
AIDS from HIV, prions)  Observations useful in designing other studies and when there is a
− Extended time periods make such studies costly new disease
 Follow up = expenses  Can lead to more complex design
− Other events in the intervening period may have an effect on  Hierarchy: Cross sectional → Case-control → Cohort → golden
outcome standard =Randomized Clinical Trial
− Cohort studies are especially vulnerable to problems associated
with patient follow up DISADVANTAGES:
• Patient attrition − Susceptible to biases
 “dropped out”  Subject selection - In the hospital, diseases encountered usually
 Lost to follow up, death etc. manifest in severe conditions already which doesn’t represent the
• Patient migration - migrated to another place and couldn’t whole scenario.
report to you due to the distance  Characteristics observed - Not all information in the patient’s chart
are accurate.
C. CASE-CONTROL STUDIES
ADVANTAGES: NOTE: Case series studies should be viewed as hypothesis-generating
 Appropriate for studying rare diseases or events (genetic diseases) and not as conclusive but still basis for higher study designs
 Appropriate for examining conditions that develop over a long
period of time Note Takers:
 Appropriate for investigating a preliminary hypothesis (educated Nikka P. Apostol
guess about the association between the exposure and outcome) Tate A. Galletes
 QUIZ

Identification
1. It provides the greatest justification for concluding
causality.
2. It is the design of choice for studying course of a
disease.
3. Applicable for studying rare diseases or events
4. It is best for determining the prevalence of a
disease in a population
5. It is susceptible to bias
6. Use to generate hypothesis
7. Corresponds to dependent variable
8. Corresponds to independent variable
9. This method is appropriate when studies have small
number of subjects or different conclusions.
10. The best method of assigning patient to
experimental and control groups.

T/F
1. Case studies are also known as epidemiologic
studies
2. Cross sectional studies answer the question
“What is happening?”
3. Cohort studies look backward in time to detect
possible risk factors or causes.
4. Experimental studies in medicine that involve
humans are called clinical trial. Answers: Identification
5. Placebo used in controlled trials are the standard 1. Randomize controlled trial
drugs used in treating the disease involved in the 2. Cohort studies
3. Case- control study
study. 4. Cross sectional study
6. The two types of bias are: information bias and 5. Case series studies
6. Case series study
selection bias. 7. Outcome
7. Meta- analysis is the same as Review of literature 8. Exposure
8. Case series studies answer the question “what 9. Meta – analysis
10. Randomization or Random assignment
will happen?”
9. Case series studies do not include control
subjects.
10. Case control study is an experimental study. Answers: T/F
1. F – cross sectional studies.
2. T
3. F- case control studies
4. T
5. T
6. T
7. F – meta analysis includes quantitative assessment
and summary of the findings.
8. F- Cohort studies
9. T
10. F- observational study
 METHODS OF 1P CROSS-SECTIONAL STUDIES (Part 1)
RESEARCH (2ND SEM)
Dr. John Anthony Domantay | January 20, 2016

CROSS-SECTIONAL STUDIES
Survey
Cross-sectional studies are used in investigation the etiology of
disease
• Not the best to use, but still used
• example: Increased serum cholesterol (exposure) ECG
evidence of CHD (disease/outcome)

HOW: We survey a population, and for each participant:

• Determine the serum cholesterol level by blood test
• Perform an ECG for evidence of CHD

In a Cross-sectional study, both of these are determined

simultaneously for each subject
• Exposure: independent variable
• Disease outcome: dependent variable

It is as if we were viewing a snapshot or a photo of the population at

LIMITATIONS
a certain point in time
• See different aspects of the population o Prevalent cases may not be
representative of all cases of
CHD in the population
In a Cross-sectional study, we have sliced through the population
The cases of disease that we identify are prevalent cases • Exclude those who died
before the study was
• They existed at the time of the study
carried out
• Aka PREVALENCE STUDY
• Those who were
treated/cured
(from gordi’s) General DESIGN of a cross-sectional or prevalence
study • Decrease the actual
prevalence
o The associated might be with
survival after CHD rather than
the risk of developing CHD

It is often not possible to establish a temporal relationship

- Temporal: timing - we cannot know
which came first
• EXPOSURE
• DISEASE OUTCOME
• The association cannot reflect a causal relationship:
o The findings can be viewed In a 2x2 table - Casual Relationship - cause and effect
DISEASE NO DISEASE
It is only suggestive of a possible risk factor for disease
EXPOSED A: ↑ cholesterol, B :↑ cholesterol, • We rely on cohort and case-control studies to establish
(+) CAD (-) CAD etiologic relationships

NOT EXPOSED C: ↓ cholesterol, D: ↓ cholesterol,

(+) CAD (-) CAD Reference:
o Epidemiology 5th ed.Leon Gordis
o Batch 2017 OT
There are two approaches to interpreting the findings (figure in
gordi’s) Notetaker:
 Determine the prevalence of disease in exposed compared NegiePOGI (k.fine!)
to non-exposed disease a / a + b vs. c / c + d
 Determine the prevalence of exposure in diseased and Proofreader:
non-diseased a / a + c vs. b / b + d chaim|herr|2016
- more like case control, in practice this is the one seen
more.
• Cross sectional studies are analyzed (at present) as if they
were case control studies
- Compute for odds ratio (OR), which is a characteristic
of case control
METHODS OF RESEARCH (2P) Problem Solving: Case Control Studies
PRELIM EXAM Dr. John Anthony Domantay & Block Reporters | February 10, 2016
of the topic based on the topic guide given

How is a case-control study designed? Cite a specific

example.

DESIGN OF A CASE-CONTROL STUDY

A hypothetical example of a case-control study is seen

in Table 10-2. We are conducting a case-control study of whether
smoking is related to coronary heart disease (CHD). We start with
200 people with CHD (cases) and compare them to 400 people
- To examine the possible relation of an exposure to a without CHD (controls). If there is a relationship between smoking
certain disease, we identify a group of individuals with and CHD, we would anticipate that a greater proportion of the
that disease (called cases) and, for purposes of CHD cases than of the controls would have been smokers
comparison, a group of people without that disease (exposed). Let us say we find that of the 200 CHD cases, 112 were
(called controls). smokers and 88 were nonsmokers.
- We determine what proportion of the cases were Of the 400 controls, 176 were smokers and 224 were nonsmokers.
exposed and what proportion were not. We also Thus 56% of CHD cases were smokers compared to 44% of the
controls. This calculation is only a first step. Parenthetically, it is
determine what proportion of the controls were exposed
of interest to note that if we use only the data from a case-control
and what proportion were not. study, we cannot estimate the prevalence of the disease.
In this example we had 200 cases and 400 controls, but
this does not imply that the prevalence is 33%, or (200/200 + 400).
The decision as to the number of controls to select per case in a
case-control study is in the hands of the investigator, and does not
reflect the prevalence of disease in the population. In this
example, the investigator could have selected 200 cases and 200
controls (1 control per case), or 200 cases and 800 controls (4
controls per case). Because the proportion of the entire study
population that consists of cases is determined by the ratio of
controls per case, and this proportion is determined by the
investigator, it clearly does not reflect the true prevalence of the
disease in the population in which the study is carried out.

Table 10-1 presents a hypothetical schema of how a

case-control study is conducted. We begin by selecting cases
(with the disease) and controls (without the disease), and then
measure past exposure by interview and by review of medical or
employee records or of results of chemical or biologic assays of
blood, urine, or tissues.
If exposure is dichotomous, that is, exposure has
either occurred (yes) or not occurred (no), breakdown into four
groups is possible: There are a cases who were exposed and c Table 10-3 presents the results of a case-control study of
cases who were not exposed. the use of artificial sweeteners and bladder cancer. This study
Similarly, there are b controls who were exposed and included 3,000 cases with bladder cancer and 5,776 controls
d controls who were not exposed. Thus the total number of cases without bladder cancer. Why the unusual number of controls?
is (a + c) and the total number of controls is (b + d). If exposure The most likely explanation is that the investigation
is associated with disease, we would expect the proportion of planned for two controls per case (6,000 controls), and that some
the cases who were exposed, (a/a + c), to be greater than the of the controls did not participate. Of the 3,000 cases, 1,293 had
proportion of the controls who were exposed, (b/b + d). used artificial sweeteners (43.1%), and of the 5,776 controls, 2,455
had used artificial sweeteners (42.5%).
The proportions are very close, and the investigators in
this study did not confirm the findings that had been reported in
animal studies, which had caused considerable controversy and
had major policy implications for government regulation.
 Any risk factors that are identified may be unique to a
certain hospital and the results may not be generalizable
to all patients with the disease

If hospitalized cases are to be used, it

is desirable to
Select the cases from several
hospitals in the community.

If the hospital from which the cases are drawn is a

tertiary care facility, which selectively admits severely ill patients,
any risk factors identified in the study may be risk factors only in
persons with severe forms of the disease.
In any event, it is essential that in case-control studies,
just as in randomized trials, the criteria for eligibility be carefully
specified in writing before the study is begun.
Table 10-4 presents data from their study of 1,357 males
with lung cancer and 1,357 controls according to the average number
of cigarettes smoked per day in the 10 years preceding the present Incident cases vs. Prevalent
illness.
We see that there are fewer heavy smokers among the
Cases
controls and very few nonsmokers among the lung cancer cases, a
finding strongly suggestive of an association between smoking and
lung cancer.
In contrast to the previous example, exposure in this study is
not just dichotomized (exposed or not exposed), but the exposure data
are further stratified in terms of dose, as measured by the number of
cigarettes smoked per day. Because many of the environmental
exposures about which we are concerned today are not all-or-nothing It is generally preferable to use incident cases of the
exposures, the possibility of doing a study and analysis that takes into disease in case-control studies of disease etiology
account the dose of the exposure is very important.

The reason is that any risk factors we may identify in

How can SELECTION bias be minimized in case-control
a study using prevalent cases may be related more to survival
studies in terms of: with the disease than to the development of the disease
a) Selection and sources of cases (incidence).
b) Selection and sources of controls For example, most people who develop the disease
die soon after diagnosis, they will be underrepresented in a
SELECTION AND SOURCES OF CASES study that uses prevalent cases, and such a study is more likely
to include longer-term survivors.
In a case control study, cases can be selected from a This would constitute a highly non representative
variety of sources group of cases, and any risk factors identified with this non
representative group may not be a general characteristic of all
Patients in patients with the disease, but only of survivors.
physicians’ Community
Hospital patients
practices / Clinic registries

(2P) Problem Solving: Case Control Studies

patients
Even if we include only incident cases in a case-
Community registries – for example cancer, data on how control study, we will exclude any patients who
many had cancer, this can serve as a valuable source of cases for such may have died before the diagnosis was made.
studies

*There is no easy solution to this

Several problems must be kept in mind in selecting cases problem or to certain other problems
for a case-control study. in case selection, but it is important
that we keep these issues in mind
when we finally interpret the data
Criteria for Use of Incident & and derive conclusions from the
eligibility Prevalent cases study.

2
 SELECTION AND SOURCES OF CONTROLS However, referral patterns at the same hospital may differ
Controls may be selected from: for various clinical services, and such an assumption may be
questionable.
School rosters, Service - In using hospital controls, If we wish to choose specific
Non-hospitalized Hospitalized
lists, & Insurance diagnostic groups, on what basis do we select those
person patients company lists groups, and on what basis do we exclude others?
- The problem would be even if it is desirable to choose the
Neighbourhood Spouse or sibling hospitalized controls, which is somehow unrelated to the
Best friend control case being studied, such controls are unlikely to be
controls control;
representative of the general reference population

Non-hospitalized - a probability sample of the total population As a result, it will not be clear whether it is the cases or the
might be selected, but as a practical matter, this is rarely controls that differ from the general population
possible.
Neighbourhood - interviewers are instructed to identify the
home of a case as a starting point, and from there walk past a Example: Prevalence of cigarette smoking is known to be
higher in hospitalized patients than in community
specified number of houses in a specified direction and seek the
residents; many of the diagnoses for which people are
first household that contains an eligible control. admitted to the hospital are smoking related.
Best friend - a person who has been selected as a case is asked
for the name of a best friend who may be more likely to
participate in the study knowing that his or her best friend is
Emphysema
also participating. CASE: LUNG
patients
Spouse or sibling control - provide some control over genetic CANCER Smoking &
=
differences between cases and controls CONTROL: Emphysema
high number
EMPHYSEMA
of smokers
Hospital inpatients are often selected as controls
because of the extent to which they are a “captive
population”
Analyze the study data separately for different diagnostic
They represent a sample subgroups that constitute the control group
of an ill-defined
They differ from people
reference population *Emphysema patients, would include a high number of
in the community.
that generally cannot be smokers. Consequently, any relationship of smoking to lung cancer
characterized. would not be easy to detect in this study, because we would have
selected as controls a group of persons in which there is a greater-
Hospital inpatients are also clearly identified; it should
than-expected prevalence of smoking.
therefore be relatively more economical to carry out a study using
We might therefore want to exclude from our control group
such controls.
those persons who have other smoking-related diagnoses, such as
coronary heart disease, bladder cancer, pancreatic cancer, and
However they represent a sample of an ill-defined emphysema.
reference population that generally cannot be characterized. Such exclusions might yield a control group with a lower-
Moreover, hospital patients differ from people in the than-expected prevalence of smoking and the exclusion process
community. becomes complex.

In using hospital controls, One alternative is to not exclude any groups from

(2P) Problem Solving: Case Control Studies

selection as controls in the design of the study, but to analyse
the study data separately for different diagnostic subgroups
To use a sample of all Whether to select a that constitute the control group
other patients admitted specific “other
to the hospital diagnosis.”
KEY POINTS:
Given that we generally cannot characterize the reference • Ask whether the level of exposure observed in the
population from which hospitalized cases come, there is a conceptual controls is really the level expected in the population
attractiveness to comparing hospitalized cases to hospitalized in which the study was carried out or
controls from the same institution, who presumably would tend to • The controls may have a particularly high or low level
come from the same reference population
of exposure that might not be representative of the
level in the population in which the study was
carried out.

3
 How can INFORMATION bias be minimized in case-control RECALL BIAS
studies in terms of:  more serious potential problem in case-control
a.) Limitations in recall studies
b.) Recall bias

LIMITATIONS IN RECALL
- Much of the information relating to exposure in case-
control studies often involves collecting data from
subjects by interviews.
- Because virtually all human beings are limited to varying
degrees in their ability to recall information, limitations in
recall are an important issue in such studies. A related
issue that is somewhat different from limitations in recall
is that persons being interviewed may simply not have the
information being requested.

Study carried out by Lilienfeld and Graham published in 1958

- Interest centered on the observation that cancer of the cervix Case-control study and interview mothers of
was highly unusual in two groups of women: Jewish women children with congenital malformations (cases) and mothers
and nuns. IMPORTANT risk factor for cervical cancer could be of children without malformations (controls). A mother who
sexual intercourse with an uncircumcised man. has had a child with a birth defect often tries to identify
- Authors were skeptical about the validity of the responses some unusual event that occurred during her pregnancy
- To address this question they asked a group of men whether with that child. She wants to know whether the
or not they had been circumcised. abnormality was caused by something she did. Why did it
happen?
Such a mother may even recall an event, such as a
mild respiratory infection, that a mother of a child without a
birth defect may not even notice or may have forgotten
entirely.

Nevertheless, the potential problem cannot be disregarded,

and the possibility for such bias must always be kept in mind.

How should the following issues regarding case-control

studies be addressed?
a.) Matching
b.) Use of multiple controls

MATCHING
The men were then examined by a physician. - Process of selecting the controls so that they are similar
As seen in Table 10-8, of the 56 men who stated they to the cases in certain characteristics.
were circumcised, 19, or 33.9%, were found to be uncircumcised. - Major concern: Cases and Controls may differ in
Of the 136 men who stated they were not circumcised, 47, or characteristics or exposures other than the one that has
34.6%, were found to be circumcised. These data demonstrate that been targeted for study.

(2P) Problem Solving: Case Control Studies

the findings from studies using interview data may not always be *Certain characteristics like: age, sex, race,
clear-cut
socioeconomic status and occupation.
Table 10-9 more recent data (self-reported vs actual
status). These data suggest that men have improved in their
knowledge and reporting of their circumcision status, or the
- If more cases than controls are found to have been
differences observed may be due to the studies having been exposed, the researcher can be left with the “QUESTION”
conducted in different countries. There may also have been if the observed associations are due to the differences
methodological differences, which could have accounted for the between the cases and controls other than the Exposure
different results between the two studies or Factor being studied. (Because the cases and controls
were not matched with the same characteristics in the
- If a limitation of recall regarding exposure affects all subjects first place).
in a study to the same extent, regardless of whether they are
cases or controls, a misclassification of exposure status may
result.

4
- Are the observed association due to the differences USE OF MULTIPLE CONTROLS
between the cases and controls in factors other than the • The investigator can determine how many controls will be
exposure being studied? For example, if most of the used per case in a case-control study.
CASES are of low income and most of the CONTROLS are • Multiple controls for each case are frequently used.
of high income, we would not know whether the factor • Controls may either be:
determining the development of disease is due to the a.) Controls of the same type
factor being studied or due to the socioeconomic status b.) Controls of different types
which is not the factor being studied. So to avoid these
confusions, we employ matching which can be of two Controls of the same type
types.  Used to increase the power of the study
 A noticeable increase in power is gained only up to a ratio
Types of Matching of 1 case to 4 controls
A. Group Matching / frequency matching
Example: Cases: 25 % are married  Controls: 25% are married “So why are controls of the same type used?”
- The proportion of controls with a certain characteristic is - Because there is a limited number of potential cases
identical to the proportion of cases with the same available for study and the number of cases cannot be
characteristic. increased without:
- Requires that all of the cases be selected first. o Extending study time to enroll more cases,
o Collaborative multicentre study. The option
B. Individual Matching / Matched pairs oftenly chosen is just to increase the number of
- For each case selected in the study, a control is selected controls per case.
who is similar to the case in terms of the specific variables
of concern. Controls of different types
- Meaning, each case is individually matched to a control. • Valuable for exploring alternate hypotheses and for taking
- Often used in case control studies that use hospital into account possible potential biases such as recall bias.
controls • The investigator should ideally decide which comparison
- This type of matching is more convenient in case control will be considered the “gold standard of truth” before
studies that use hospital controls. embarking on the actual study.

Problems with Matching This is an example of a study using control of different

Practical Problems types. Gold’s study of brain tumors in children.
- Attempt to match according to too many characteristics
- Difficult to find a suitable control

Conceptual Problems
- Once we have matched controls to cases according to a
given characteristic, we cannot study that characteristic.
- Do not match on any variable that we may wish to explore Let us consider the question: “Did mothers of children with brain
in our study. tumors have more prenatal radiation exposure than control
So if we conduct a case control study, we must be mothers?”
*Some possible results are:
reminded that should not match on any variable that we may
wish to explore in our study.

(2P) Problem Solving: Case Control Studies

“Unplanned Matching”
- This may happen when neighbourhood controls or best
friend controls are used

“Overmatching”
- Match only on variables that we are convinced are risk
factors for the disease, which we are therefore NOT
If such a result is obtained, one could conclude that:
interested in investigating.
- Radiation is a carcinogen that is not site specific meaning that
*In case control studies, unplanned matching can happen in
prenatal radiation is a risk factor both for brain tumors and for other
cases of using neighbourhood and best friend controls because cancers.
one or several characteristics may be the same for the case and OR
the control and in effect, we can’t study those characteristics - Findings could have resulted from recall bias where mothers of
anymore. children with any type of cancer recall prenatal radiation exposure
*There is also what we term as “overmatching”, if we match better than mothers of normal children.
variables other than these, in a planned or inadvertent
manner, overmatching happens.
5
 Identify cases from:
a) Disease registries
b) Hospital records
c) Other sources

Versus Cohort studies for a “rare” disease where:

a.) An extremely large study population may be needed to
observe a sufficient number of individuals who develop
the disease
b.) Involves many years of follow-up depending on the
Another set of findings here would generate another set of
conclusions. In here we can see that the a larger proportion of mothers interval between exposure and development of disease
with children having brain tumor had prenatal radiation as compared c.) Logistical difficulty and expense to maintain follow-up
to mothers with children having other cancer types and mothers with over time.
normal children. This then would suggest that:
Prenatal radiation is a specific carcinogen for the brain and ------------------------------------------
that there is a reduced likelihood of recall bias because it would be
implausible that mothers of children with brain tumors would recall
prenatal radiation better than mothers of children with other cancers. Notetaker:
DEL ROSARIO, Dennis Myles R.
When is a case-control study warranted?
Proofreader:
Case Control Study chaim|herr|2016
• Useful as a first step when searching for a cause of an
adverse health outcome.

Carry out a cohort study

In the case control study

- we compare people with the disease (cases) and people
without the disease (controls).

(2P) Problem Solving: Case Control Studies

- So in this respective group of people, we can explore their
exposure to a certain factor and see if it is related to the
development of a disease.
- If the exposure is related to the disease, then we expect
that the proportion of people exposed would be higher
in people with the disease as compared to the people
without the disease where we can see that there is a
higher proportion of unexposure.
- When such a relationship is documented, the next step is
to conduct a cohort study.
- Because case control studies are less expensive and can
be carried out more quickly than cohort studies, they are
the first step in determining whether an exposure is linked
to an increased risk of disease.
- Valuable when the disease being investigated is rare.

6
 RESEARCH II (1M) Cohort Studies
MIDTERM EXAM Dr. John Anthony Domantay & Batch 2018 Presenters | March 16, 2016

Design of a Cohort Study Incidence of exposed: 84/3000

o Incidence per 1000 per year in exposed: 28.0
o Incidence of unexposed: 87/ 5000
o Incidence per 1000 per year in unexposed: ___

We can determine whether a temporal relationship exists

o Identify new (incident) cases as they occur
o Important if considering exposure as a cause
o Cause and effect: cause should always come
first
o The study begins with the exposure
o The investigator selects 2 groups: Selection of Study population
o group of exposed individuals o Outcome in an exposed groups and in a non-exposed
o group of non-exposed individuals group are compared
o NOTE: May include more than two groups
(Depending upon complexity of the cohort o There are 2 ways to generate such groups:
study) 1st Approach:
o Follow up to compare the incidence of disease
o If a positive association exists between the exposure
and the disease:
Incidence in the exposed group > Incidence in the
non- exposed group

 We can create a study population by selecting

groups for inclusion in the study, on the
basis of whether or not, they were exposed.
As illustrated, we start by selecting groups who are
exposed and not exposed then this is followed up by
identifying who in each group have the disease.
o exposed group and a non-exposed group OT:
o The (a + b) exposed persons the disease  Select the group on whether or not they were exposed
develops in a but not in b  the disease  Gather individual with and without exposure
among the exposed is (a/ a+b) o Ex: Occupational Exposure – those who
o The (c + d) non-exposed persons in the work with a certain chemical
study, the disease develops in c but not in d
 incidence of the disease among the non- 2nd Approach:
exposed is (c/c+d).

OT:
Hypothetical cohort study:
o Smoking and coronary heart study
 Exposure: smoking
 Outcome: Coronary heart disease
Then follow to see Totals
whether  We can select a defined population first before
CHD CHD any of its members becomes exposed or
develops does before their exposures are identified. This
not defined population can be selected on the basis of
develop some factor not related to exposure for example
First Smoke 84 2916 3000 their community of residence. After which, histories
selection are taken, or blood test or other assays are performed on
Do not 87 4913 5000 this entire define population. Using the results of
smoke the histories or tests, then can separate the
population into exposed and non-exposed
 groups. A good example for this is the Framingham Study Types of Cohort Studies
of cardiovascular disease which is the most important o Prospective cohort study
and best known cohort study. • Concurrent cohort study or longitudinal study
o Retrospective cohort study
OT: • Non-concurrent cohort or historical cohort
 Select the defined population before their exposure are study
identified
 Ideal way
 Selection of groups are not randomly assigned
o To differentiate from Randomized control
trial (RCT)
o The population is selected on the basis of a factor
not related to exposure
o Ex: Residence
o Take histories or perform tests on entire
population
o Separate into exposed and non-exposed
o This approach was done in the Framingham study
o Community/town in Massachusetts (1940) In a nutshell, in Retrospective Cohort Study, all the events -
 Followed up over time who will exposure, latent period, and subsequent outcome (ex.
develop cardiovascular disease development of disease) have already occurred in the PAST. We
 Maintained by Boston University merely collect the data now, and establish the risk of
o Cohort studies often require a long follow-up period developing a disease if exposed to a particular risk factor. On
o Length of follow up is greater with this the other hand, Prospective Cohort Study is conducted by
approach starting with two groups at the current point, and following up
in FUTURE for occurrence of disease, if any.

• The designs for both the prospective cohort study

and the retrospective or historical cohort study are
identical: we are comparing exposed and
A defined population was selected on the basis of nonexposed populations.
location of residence which is Framingham,
Massachusetts, or other factors such as their age ranging The only difference between them is calendar time.
from 30 to 62 years old. These bases are not related to
the exposures in question. The population was OT:
then observed over time to determine which o A major problem is that the study population must
individuals developed or already had the be followed up for a long period
“exposures” of interest such smoking, obesity, elevated o Ex: selection of the defined population:
BP, elevated cholesterol, low levels of physical activity and 2008
other factors. Later on, it was determined which ones  Determination of exposed and
developed the cardiovascular disease. non-exposed: 10 years
 NO RESULTS YET
 The second approach offers an important  Follow-up period who develop
1M Cohort Studies

advantage and who will not develop the

disease: 10 years
o Hypothetical study: Relationship of smoking to lung
cancer
o Defined population: Elementary pupils
2
 o Determination of Exposed and non-  If the patient is not “inspired” he will not
exposed: Latent period come back
o This type of study is called a PROSPECTIVE COHORT  You have to give incentives/ reward
STUDY  Ex: transportation fund/ money; some form
o AKA: Concurrent Cohort Study or of treatment
Longitudinal Study
o What are the problems with this approach c. Loss to follow up
 Funding is generally limited to 3-5 o Similarly, loss to follow-up can also cause serious
years problems. For example, if some of the people with
 Risk that study subjects with the disease are lost to follow-up, and those lost to
outlive the investigator/ researcher follow-up differ from those not lost to follow-up, the
o There is an alternative approach calculated incidence rates in the exposed and non-
o AKA: RETROSPECTIVE COHORT STUDY exposed groups can be difficult to interpret.
 AKA: Historical Cohort Study or
Non- concurrent prospective study 2. Information bias
 Assume present time is 2008 o A significant bias can be introduced if the quality
 Same study: lung cancer and and extent of information obtained is different
smoking for exposed and non-exposed persons.
 With and without lung cancer  Likely to occur in historical cohort studies
o Look back in time for evidences  Information obtained from past records
of smoking (survey of smoking o Ex: Patient’s chart
habits) o The person’s judgment whether the disease has
 Old roster of school children developed in each subject may be biased by the
 Difference from a case control following:
study  Knows whether that subject was exposed
 Begin with a disease: In case  Aware of the hypothesis being tested
control, there is an interview: o Strong preconceptions of the epidemiologists
there is recall bias and statisticians may unintentionally introduce
o There is no existing evidence in their biases into:
cohort  Data analyses
 Main feature  Interpretation of the study findings
 Exposure ascertained from past  There should be an independent body/
records someone else to analyse the data,
 Outcome ascertained at the time especially if it was a very big study
the study is begun  According to OT, it is called “Analytic Bias”

Combined Prospective and Retrospective Cohort Study

When is a cohort study warranted?
• It is also possible to conduct a study that is a
combination of prospective cohort and retrospective A cohort study is indicated when good evidence suggests an
cohort designs. association of a disease with a certain exposure or
• With this approach, exposure is ascertained from exposures.
objective records in the past (as in a historical cohort
study), and follow-up and measurement of outcome To carry out a cohort study, one must have some idea of
continue into the future. which exposures are suspected as possible causes of a disease
and are worth investigating. Because of this, a cohort study is
Potential biases in cohort studies indicated when good evidence suggests an association of a
Potential biases in cohort studies can be divided into two disease with a certain exposure or exposures.
major categories:
1. Selection bias This “good evidence” can be obtained from either clinical
a. Nonparticipation observations or case-control or other types of studies.
b. Nonresponse
OT: OT:
o Non-participation and non-response can complicate
1M Cohort Studies

o What would we expect if exposure is associated

interpretation of findings with disease?
o There is a very long follow-up period o If exposure is associated with disease we
 Ask the individual to report to the research would expect:
center, hospital, or university every do often
3
  (There is a meaning to the sizes of
the boxes)
 Exposed people
 Develop disease
o Bigger box
 Do not develop disease
o Smaller box
 Not exposed people
 Develop disease
o Smaller boxy
 Do not develop disease
o Bigger box
o A cohort study is indicated when evidence suggests
an association
o From
 Clinical observation
 Case-control studies
 Other studies
o You should not choose a cohort study 1st.
 Case series
 Cross sectional
 Case control
o Cohort studies are easier to conduct when the
interval between exposure and disease is short
o Minimize losses to follow up (attrition/
losses to follow up)
o Cohort studies are easier to conduct when the
interval between exposure and disease is short
o Examples: Popular among obstetricians
 Rubella infection in pregnancy
 Congenital malformation
o Oncologists: Use case control
o Several consideration can make the cohort design
impractical
o Lack of strong evidence of a risk factor
o Inability to identify a cohort of exposed and
non-exposed person
o Lack of appropriate past records or sources
of data
o Disease occurs at very low rates
o Very large cohorts must be enrolled to
ensure enough cases develop

Note taker: Jyn Desire Oillas

Proofreader: chaim|herr|2016
1M Cohort Studies

4
 RESEARCH II (2M) Randomized Control Trial/ Randomized Clinical Trial
MIDTERM EXAM Dr. John Anthony Domantay & Batch 2018 Presenters | March 30, 2016

1. What is a randomized trial? Describe the basic design of a 2. How should participants for a randomized trial be
randomized trial. Cite a specific example. selected?

RANDOMIZED TRIAL/RANDOMIZED CLINICAL TRIAL SELECTION OF SUBJECTS

 Ideal design for evaluating the effectiveness and side - The criteria for determining who will or will not be included
effects of new forms of interventions. in the study must be PRECISE
 Determine the value of available preventive or • Precise inclusion and exclusion criteria
therapeutic measures • Spelled out in writing with great precision
 Major applicability to studies outside the clinical • No subjective decision-making
setting, such as community-based trials • Must, in principle, be replicable by others.
PURPOSES
• Evaluating new drugs 3. How should participants in Randomized Trials be
• Evaluating new treatment of disease allocated to different group in the study?
• Testing of new health and medical care technology - The best approach for such trials is Randomization
• Assessing new programs for screening and early
detection
• Assessing new ways of organizing and delivering Table of
health services Random Computer
(ex. OpenEpi)
BASIC DESIGN Numbers

How is
Randomiza on
done?

I. Table of Random Numbers

Example:
We need 2 groups:
ODD Group- receives Drug A
Even Group- receives Drug B
Point out the Starting Point
Note the Direction
Starting point is the FIRST PATIENT
*We begin with a defined population that is randomized to
NOTE THAT THE PATIENT ASSIGNMENT – is not
receive either new treatment or current treatment, and we
PREDICTABLE (no pattern)
follow the subjects in each group to see how many are
improved in the new treatment group compared with how
many are improved in the current treatment group. If the new
treatment is associated with a better outcome, we would
expect to find better outcome in more of the new treatment
group than the current treatment group.
*We may choose to compare two groups receiving different
therapies, or we may compare more than two groups.
Although, at times, a new treatment may be compared with
no treatment, often a decision is made not to use an
untreated group. Often, we would compare a newly
developed therapy with a currently recommended regimen
(Termed as the “standard of care”/ currently accepted
treatment)
*Divided into rows and Columns- REASON?? For Easy
Readability
How to use this?
1. We close our Eyes and we put a finger anywhere in
the table 
 2. Write down the column and row of starting point IN PROGNOSTIC PROFILE AT ENTRY
THIS CASE IT IS “4” in Row 02 Column 08– The ■ If we know he risk factors for a bad outcome, we want to
Starting Point depicts the Treatment of the FIRST verify that randomization has provided reasonable
PATIENT similarity between the two groups in terms of these risk
3. Then note the direction of from the starting point in factors
this case it’s RIGHTWARD - ■ Data for prognostic factors should be obtained at the
time of subject entry into the study
The first number which is 4 is EVEN, so first patient receives ■ Example:
DRUG A, ■ If exposure (environment, social habits, etc.)
The second number is 3 w/c is ODD, so he receives Drug B, is a significant factor, we should ensure that
the next is 8 which is EVEN so he must receive DRUG A randomization has resulted in groups that
The next patient is represented by 3 which is ODD so Drug B are comparable for the exposure.
The next is 8 so give Drug A
Then is 6 which is EVEN, give Drug A MASKING (BLINDING)
■ First, we would like the subjects not to know which
II. Random Numbers using A Computer group they are assigned to
 Using OpenEpi ■ This is important when the outcome is a subjective
 Microsoft Excel measure
■ Enthusiasm and certain psychological factors on the
4. When collecting data from the participants, how would part of the patient may operate to elicit a positive
the following issues be addressed? response even if the therapy had none.
• Assigned treatment vs. Received treatment ■ To eliminate psychological factors, subjects are
• Measurement of the outcome masked
• Prognostic profile at entry ■ Placebo: an inert substance that looks, tastes, and
• Masking (Blinding) smells like the active agent.
• Non-compliance ■ But, this does not guarantee that the patients are
masked, as in the case when the patients try to
ASSIGNED TREATMENT VS. RECEIVED TREATMENT determine whether they are taking the placebo or
■ First, we must know to which treatment group the the active drug.
patient was assigned ■ Does it make any difference that the patients know?
■ Next, we must know which therapy the patient actually Yes (state a situation)
received ■ Therefore, we must be very concerned about the lack
■ This is important to know, in cases when the of masking or blinding of the subjects and its
patient assigned to receive the treatment did not potential effects on the results of the study,
comply particularly when we are dealing with subjective
■ Conversely, it is important to know in cases when a endpoints.
patient, not assigned to receive the treatment, takes the ■ The use of a placebo is also important for studying
treatment on his or her own, even unknowingly. the rates of side effects and reactions
■ There is the need for comparable measurements in all ■ The placebo plays a major role in identifying both
study groups, particularly for the measurement of the the real benefits of an agent and its side effects.
outcome ■ In addition to blinding the subjects, we also want to
■ Measurements include: mask (or blind) the observers or data collectors in
(1) improvement (the desired effect) regard to which group a patient is in. The masking of
(2) any size effect that may appear both participants and study personnel is called
■ This presents the need for explicitly stated criteria for all “double blinding”
outcomes to be measured in a study ■ Each of us comes with a certain number of
■ Once explicitly stated, we must be certain that they are subconscious or conscious biases and
2M Randomized Control / Clinical Trial

measured comparably in all study groups. preconceptions.

■ This is especially important, for example, in cases where
the study outcome is that of a new drug being compared NON-COMPLIANCE
to a currently available therapy. ■ Non-compliance may be Overt or Covert
■ Masking (Blinding), can prevent much of this problem, ■ People may overtly articulate their refusal to comply or
but because blinding is not always possible, attention may stop participating in the study
must be given to ensuring comparability of measurement ■ People may just stop taking the agent assigned without
and of date quality I all of the study groups admitting this to the investigator or the study staff
■ These non-compliers are also called Drop-outs
■ Whenever possible, checks on potential non-compliance
should be built into the study
2
■ Drop-ins: patients in one group may inadvertently take Problem 3.) Enrollment as a participant in a study has
the agent assigned to the other group been marketed to potential volunteers on the basis that
■ The net effect of non-compliance on the study results only though participation will a participant has a chance
will be to reduce any observed differences, because the of being treated with the newest available treatments
treatment group will include some who did not receive
the therapy, and the no-treatment group may include Solution 3.) It is critical that the persons conducting the
some who received the treatment. Thus, the groups will trial avoid being overly zealous in promising the
be less different in terms of therapy than they would participants benefits that have not yet been conclusively
have had there been no non-compliance, so that even if demonstrated to be associated with the therapy being
there is a difference in the effects of the treatments, it tested.
will appear much smaller.
■ People who do not comply or who do not participate in Problem 4.) Retaining volunteers for the full duration of
studies differ from those who do comply and who do the study; losses to follow-up and other forms of non-
participate. compliance (Participants may lose interest in the study
■ Therefore, in conducting a study to evaluate a therapy or over time, or find participation too inconvenient over the
other intervention, we cannot offer the agent to a long term.
population and compare the effects in those who take
the agent to the effects in those who refuse or do not, Solution 4.) Investigators must develop an appreciation
because the two groups are basically different in terms of of why participants often drop out of studies and develop
many demographic, social, psychological, and cultural appropriate measures to prevent losses to follow-up.
variables that may have important roles in determining
outcome. These are all forms of Selection bias 6. How could the results of randomized trials be reported?
■ Randomization, or some other approach that reduces
selection bias, is essential in valid clinical trial. - Efficacy of an agent being tested can be expressed in
terms of the rates of developing disease
5. What problems may be encountered in the recruitment of o Efficacy = (the rate in those who received
study participants, and how can these problems be the placebo) - (rate in those who received
addressed? the vaccine)/rate in those who received the
• Enrollment as a participant in a study has been placebo
marketed to potential volunteers  The risk of death or of developing a disease or
• Avoid being overly zealous in promising the complication in each group can be calculated along
participants benefits that have not yet been with the Reduction in risk (efficacy). This formula
conclusively demonstrated tells us the extent of the reduction in disease by use
of the vaccine. Calculated per person-years (unit)
Problem 1.) Failure to recruit a sufficient number of  Efficacy- how well a treatment works under ideal
volunteers can leave a well-designed trial without a conditions
sufficient number of participants to yield statistically valid  Effectiveness- how well a treatment works in real life
results; Trials may be significantly delayed by limited situations
recruitment; and costs of completing such trials may be  Randomized trials most often evaluate efficacy of a
increased treatment
o Calculate the ratio of the risk in the 2
Solution 1.) Within the limits of a randomized trial, treatment groups (Relative Risk)
participants must be fully informed of the risks and what o Comparing the survival curves for each of
arrangements must be made for their compensation if the groups and determine whether they
untoward effects should occur. differ
o Calculate the number of needed to harm
Problem 2.) Payment of cash incentives to prospective (NNH) to cause one additional person to be
2M Randomized Control / Clinical Trial

volunteers will often risk subtle or overt coercion; biases harmed

and distortion of the study result may occur, particularly o Estimate the number of patients who
if large incentives are paid would need to be treated (NNT) to prevent
one adverse outcome
Solution 2.) Appropriate arrangements must be made to - NNT = 1/(Rate in untreated group) – (rate in treated
cover participants’ expenses such as transportation, group)
accommodations if needed, and the participants’ time, - This approach can be used in studies of various
particularly if participation is associated with loss of interventions including both treatment and
income prevention

3
 7. How can the results of a Randomized Trial be generalized • Randomized trials may lead the physician or
beyond the study population? researcher to lose sight of individual differences and
Through External and Internal Validity preferences.
EXTERNAL VALIDITY • In a non-randomized world, would a given patient
• aka Generability respond in the same way that a randomized patient
- the ability to apply the results obtained in the study might respond in a trial?
population to a broader population
• To be able to generalize from the study findings to all 9. What ethical consideration should be observed when
patients with the disease in the community conducting randomized trials?
• Must characterize those who did not participate in the How can we knowingly withhold a drug from patients,
study and identify characteristics of the study patients particularly those with serious and life threatening diseases?
that might differ from those who were not included in • Randomization: ethical only when we do not know
the study whether drug A is better than drug B
• Often it is not clear at what point we “know” that
drug A is better than drug B
• When do we have adequate evidence to support the
conclusion that drug A is better than drug B?
Is it ethical to use a placebo?
- the issue of whether it is ethical to withhold a
treatment that has been shown to be effective
Is it ethical not to randomize?
• When we are considering drugs, preventive
measures, or systems of health care delivery that
apply to large numbers of people, the mandate may
be to carry out a randomized trial to resolve the
INTERNAL VALIDITY questions of benefit and harm not to continue to
- Randomization has been properly done and the subject people to unnecessary toxic effects and raise
study is free of other biases and is without any of the false hopes
major methodological problems Another important question is whether truly informed
consent can be obtained
RANDOMIZED TRIAL • Patient may be incapable of giving consent
- Gold standard of study designs • The family may be so shocked by the diagnosis that
has just been received its implications that they have
8. What are the implications of the results of a randomized great difficulty in dealing with the notion of
trial for physicians treating individual patients? randomization and agreement to be randomized
• Parents are so distressed that one may question
whether they are capable of giving truly informed
consent
• *Many protocols for multicentered clinical trials
require that patients be entered into the study
immediately after the diagnosis
Under what circumstances should a trial be stopped earlier
than originally planned?
• Arise because either:
• harmful effects or beneficial effects of the
agent become apparent early,
• before the full sample has been enrolled
• before subjects have been studied for the
2M Randomized Control / Clinical Trial

full follow-up period

__________________________________________________

• Most randomized trials do not provide information

the physician would need to characterize an Notetaker: Pagod.
individual patient to predict what responses her
patient might have to the therapies available. Proofreader: chaim|herr|2016
• Participants in randomized trials are usually not
representative of the general population.

4
METHODS OF (1M) SAMPLING AND SAMPLE SIZE
RESEARCH Dr. John Anthony Domantay | October 1, 2015

Outline: METHODS OF SAMPLING

 Populations and samples - The best way to ensure that a sample will lead to valid
 Reasons for sampling inferences is to use probability samples.
 Methods for sampling - General Methods: Probability vs. Non probability
 Using and interpreting random samples
Blue: Audio Black: OT/Slides
PROBABILITY SAMPLES
PURPOSE OF RESEARCH
- Probability of being included in the sample is known
- Is to infer, or generalize from a sample to a
for each subject.
population.
- There are four commonly used probability sampling
- This process of inference is accomplished by using
methods in medicine:
statistical methods based on probability. o Simple random sampling
o Systematic Random sampling
o Stratified Random sampling
POPULATION o Cluster Random sampling
- is a large set of items that have something in
1. SIMPLE RANDOM SAMPLING
common.
- Every subject has an equal probability of being
- In medicine and other health fields, it generally refer
selected for the study.
to PATIENT and other living organisms
- The usual way: lottery, fish bowl technique
- can also be used to denote collection of inanimate
- The recommended way to select random sample is to
objects:
use a table of random numbers – found at the back
o Autopsy,
of statistic text books.
o Hospital Charges/ Bills,
- A computer generated list of random numbers may
o Birth Certificate
also be used. (BEST SIMPLE RANDOM SAMPLING METHOD)
- ** OpenEpi app
SAMPLE
- Example: A list of ID numbers, called a sampling
- is a fraction or subset of the population selected so
frame must be available
as to be representative of the larger population.
- As much as possible, it should be like/close to
2. SYSTEMATIC RANDOM SAMPLING
population in terms of its characteristics
- Systematic random sample is one in which every
“kth” item is selected
The term population is frequently misused to describe a
- K – means the interval
sample. EX: “…the population of patients in the study...”
- K is determined by dividing the number of items in the
- The term SAMPLE rather than population.
sampling frame be the desired sample size
- should not be used when a cyclic repetition is
REASONS TO STUDY SAMPLES & NOT POPULATION
inherent in the sampling frame
 Samples can be studied more quickly than populations
 Study of a sample is less expensive than studying an
3. STRATIFIED RANDOM SAMPLING
entire population
- the population is first divided into relevant strata
 Study of an entire population (census) is impossible in
(subgroups)
most situations
- A random sample is then selected from each stratum.
 Sample results are often more accurate than results (using table of random number, computer generated, lottery etc.)
based on a population - Commonly used strata in medicine include:
 Probability methods can be used to estimate the error in o Age group (commonly according to decade)
the resulting statistics (e.g. Pulse Asia, SWS survey etc.) o Gender
 Samples can be selected to reduce heterogeneity o Severity or stage of disease (mild, moderate, severe)
o Duration of disease (acute vs. chronic)
**HETEROGENEITY - Characteristics used to stratify should be related to
- implies different people comprising the population the measurement of interest.
**In medicine, even if we are dealing with certain disease or just one
disease, the manifestations of a disease are not always the same or 4. CLUSTER RANDOM SAMPLING
the characteristics of the people suffering from a certain disease, are
- Is a two stage process:
not always the same.
For example Pneumonia, there is a mild in severity, moderate or one
o Population is divided into clusters/groups
which is severe. So if you want to eliminate that, then you can just zero o A subset of the cluster is randomly selected
in on the mild, moderate or severe cases. You reduce the - Cluster are commonly based on geographic areas or
heterogeneity. If you are interested in severe cases only of a certain districts
disease, you will go to the hospital not in the community. - This approach is used more often in epidemiologic
research than in clinical studies.
 - In multicenter clinical trials, the institutions selected
to participate in the study constitute the clusters.
o Patients from each institutions can be
selected using another random sampling
procedure
- The method of choice for obtaining adequate number
of patient – specially rare diseases

NON PROBABILITY SAMPLING

- Convenience samples
- Quota samples
**May reflect SELECTION BIAS

PRINCIPLES IN USING AND INTERPRETING RANDOM

SAMPLES
- In actual clinical studies, patients are not always
randomly selected from the population
- The clinical researcher often uses all patients at hand
who meet the entry criteria for the study.
- This critical procedure is used especially when
studies involve uncommon conditions.
- The target population is the population to which the
investigator wishes to generalize
- The sampled populations is the population from
which the sample was actually drawn.

Notetaker:
chaim|herr|2015

AND SAMPLE SIZE 

METHODS OF RESEARCH: SAMPLING

2
METHODS OF (1M) SAMPLING AND SAMPLE SIZE Part 2
RESEARCH Dr. John Anthony A. Domantay | October 8, 2015

Italicized Texts– Audio o Equivalent of IRB in our institution is Research

OUTLINE:
Ethics Committee (REC)
- Introduction
- Studies with one mean
- Studies with one proportion ‒ Granting agencies require this information as well
- Studies about means in two groups o Ex. Philippine Council for Health Research and
- Studies about proportions in two groups
Development (PCHRD) – branch of DOST
FINDING THE APPROPRIATE SAMPLE SIZE FOR RESEARCH
- Researchers must learn how large a sample is needed HOW TO DETERMINE SAMPLE SIZE:
before beginning their research - A variety of formulas can determine what size sample is
o Often this is missed out in research proposal needed
because researchers don’t know how to - Many prefer to use a computer program to calculate sample
determine the sample size size
- They may not be able to determine significance when it - ONE MEAN, ONE PROPORTION
occurs: HYPOTHESIS TESTING
Studies with One Mean (One Group);
Studies with One Proportion
- Cross sectional study (Descriptive study) or Survey study

Using OpenEPI
 Click on Sample Size then Proportion
 Enter new data
 Fill up:

Table: For Hypothesis Testing

2 Types of Hypothesis:
1. Null Hypothesis (Ho) – No significant difference
2. Alternative Hypothesis – with significant
difference

Statistical tests are meant to test the NULL Hypothesis. *Confidence limits – aka Level of Significance
Null hypothesis would either be TRUE or FALSE. *Values above are default values
- If TRUE = NOT significant  Click Calculate
- If FALSE = Significant
Studies About Means in Two Groups;
Possible Actions: Studies About Proportions in Two Groups
- Fail to Reject Ho - Depend on what you are studying, whether a MEAN or a
- Reject Ho PROPORTION
 A relationship exists between sample size and being able
Examples for the use of the table: to conclude the results
1. If you FAIL TO REJECT Ho and in reality it is TRUE,  As the SAMPLE SIZE INCREASES, the POWER to detect an
then you have made a CORRECT decision. actual difference also INCREASES
2. If you FAIL TO REJECT Ho but in reality it is FALSE, you o POWER – ability to detect an actual difference if it
have made an ERROR (Type II or β error). really exists. (Preferably HIGH)
 Probably due to LOW POWER.
 LOW POWER can occur if sample size is too STUDIES ABOUT MEANS IN TWO GROUPS
small The researchers need to answer 4 QUESTIONS:
1. What level of significance (α level or P value)
‒ Readers of research reports also need to know what related to the Null Hypothesis is wanted?
sample size was needed in a study. - Default level of significance/confidence: 5%
o Important in evaluating whether the results of 2. How great should the chances be of detecting an
the study are valid or not. actual difference; that is, what is the desired level
‒ Institutional Review Boards (IRB) require sample size of power (equal to 1 – β)?
estimates before approving a study - Default Power: 80%
 3. How large should the difference between the mean STUDIES ABOUT PROPORTIONS IN 2 GROUPS
in one group and the mean in the other group be - How Many? Prevalence
for the difference to have clinical importance? The researcher needs to answer 4 questions:
- It has to be clinically significant 1. What is the level of significance related to the null
- Example: Is there a clinical significance between a hypothesis is warranted?
difference of 90 and 91 mmHg DBP? Maybe none. AGAIN: - Default level of significance: 5%
**Answers to this question may be found in - Confidence interval: 95%
Review of Related Literature (RRL) 2. What should be the chance of detecting an actual
4. What is a good estimate of the standard difference, that is, what is the desired power to be
deviations? associated with the alternative hypothesis?
To simplify this process, we assume that the AGAIN: - Default power: 80%
standard deviations in the two populations are equal 3. How large should the difference be between the
2 options for getting Standard Deviation: two proportions for it to be clinically significant?
i. Based on Related Literature - Depend on the researcher or Related Literature
ii. Conduct PRE-TEST 4. What is the good estimate of the standard
deviation in the population?
**These 4 questions should be answered before you can determine a Null hypothesis assumes that the Proportions are
sample size** Equal and the PROPORTION ITSELF determines the
estimated standard deviation.
Example:
Investigators wished to have large enough sample of patients to be Example:
able to detect a mean difference of 2 or more. Assume they were Investigators wanted to estimate the sample size needed to detect a
willing to accept a type 1 error of 0.05 and wanted to be able to significant difference if the proportions were 0.85 and 0.55. They are
detect a true difference with 80% probability. willing to accept a type I error of 0.05 and they wanted a 90%
probability of detecting a true difference.
Based on Clinical experience they estimated the standard deviation
as 6. Using OpenEpi: Sample Size for Cross Sectional/Cohort and
Randomized Clinical Trials
Using OpenEPI: Sample Size Comparing 2 Means  Click on Sample Size then Cohort/RCT
 Click on Sample Size then Mean Difference  Enter new data
 Enter new data  Fill up:
 Fill up:

METHODS OF RESEARCH: Survey Research 

 Click Calculate
 Click Calculate
RESULT:

- Different Sample Sizes shown depending on the

author.
- Select the largest number to be safe.
Note taker: Faith L Malecdan
Proofreader: chaim|herr|2015

2
METHODS OF (2M) SURVEY RESEARCH
RESEARCH Dr. John Anthony Domantay & Presenters: Herrera, Castro, Martin, Dometita

Scenario: You want to conduct a survey as part of a research study. OPEN-ENDED CLOSED-ENDED
Purpose Actual words or quotes Most common answers
1. What important steps should be undertaken before Respondents Capable of providing answers Willing to answer only if
deciding on the survey method to use? in their words easy and quick; may
write illegibly
Asking the question Choices are unknown Choices can be
- Formulation of a clear research question and specific
anticipated
objectives. Analyzing results Content analysis; time- Counting or scoring
o Guide the design of a survey questionnaire. consuming
o The need to know the answer. Reporting results Individual or grouped Statistical data
o A crucial step is to review the literature. responses

- Investigation of survey topics with focus groups Examples:

Open- ended questions
o Survey topics may need to be investigated with focus
• What habits do you believe increase a person’s chance of having a
groups in order to know the specific issues that are stroke?
important to study. **lack statistical significance
o It may be difficult to specify the precise issues that Closed- ended questions
should be addressed in a survey and focus groups • Which of the following do you believe increase the chance of
may help refine the issues. having a stroke?
o focus group - composed of 7-10 members (Check all that apply.)
o conduct a focus group discussion before a survey, if  Smoking
 Being overweight
the questions to be asked are still unclear
 Stress
o done, in order to generate the specific questions or  Drinking alcohol
the specific statements that the respondents will react
to
2. What survey methods may be used? What should be SCALE OF MEASUREMENT
taken into consideration when deciding on the o The precision with which a characteristic is measured.
survey method to use? o Determines the statistical methods for analysing the data.
o Most surveys use self- administered questionnaires: in
person, mail, email Different forms of Measurement:
o Or interviews: in person, over the telephone 1. NOMINAL - categories are in words and there is no
particular order
Advantages and disadvantages of different survey methods - ex. Favorite color, gender
Self Self- Phone Interview in 2. ORDINAL - categories are in words with particular order
Administered administered in interview Person
Mail/Email Person
o ex. excellent, very good, good fair, poor
3. NUMERICAL – interval & ratio
Cost ++ + - -
o responses are in numbers
Time ++ + - - o ex. Age in years
Standardization + + +/- +/-
Depth/ detail - - + ++ NOMINAL
o used to classify things into categories
Response rate - ++ + ++
o weakest form of measurement
Missing responses - ++ ++ ++ EXAMPLE:
(+)ADVANTAGES; (-) DISADVANTAGES; (+/-) NEUTRAL What brand of laptop do you trust the most?
1 = Mansanas Electronis
3. How should questions be developed in terms of: 2 = Kubotan Electronics
3 = SOMY
4 = Toshebah
FORMAT
 Open- ended questions versus Close- ended questions
o Open-ended questions are exploratory in nature and ORDINAL
provide rich qualitative data. In essence, they provide o Allow classification/ranking.
the researcher with an opportunity to gain insight on o Ordinal scales also imply rank ordering
all the opinions on a topic they are not familiar with. o There is no difference between the importance of the
However, being qualitative in nature makes these choices
types of questions lack the statistical significance EXAMPLE:
needed for conclusive research. The support staff of the Technical Support Group is:
o Closed-ended questions are conclusive in nature as 1 - Extremely Helpful
they are designed to create data that is easily 2 - Very Helpful
quantifiable. 3 - Moderately Helpful
4 - Not Very Helpful
o Close ended is mostly utilized for survey, to minimize
5 - Not Helpful At All
the writing of the respondent
o Open ended is kept at minimum
INTERVAL
o show the order of things, but with equal intervals between
the points on the scale.

Ex:
RATIO
• The intervals between numbers are equal
• Ratio scales have an absolute zero

BALANCE OF CATEGORIES
 Questions using an ordinal response should provide as
many positive as negative

USE OF MUTUALLY EXCLUSIVE CATEGORIES

Ex:
How long do you spend Revised choices:
commuting each day (round  less than 15
trip): minutes
 less than 15 minutes  15 to 30 minutes
 15 to 30 minutes  more than 30
 30 minutes to one minutes but less
hour than an hour
 one hour or longer  one hour or
• A neutral option is also included to serve as a balance longer
between the two + and - options
 Use of questions in which the issue being addressed is
not understood by the subject, this may result because
the options are not mutually exclusive.
 Response categories should be mutually exclusive, or
independent. This means that none of the response
categories in a question should overlap or categories
must be distinct enough that no observations will fall
into more than one category.
 It should be clear to respondents where a response fits
and which response category should be selected.
Respondents should not have to puzzle over which
category their response fits in to and which category to

METHODS OF RESEARCH: (2M: SURVEY RESEARCH) 

choose. This also applies to questions where multiple
AVOIDANCE OF VAGUE QUALIFIERS responses are allowed so that respondents' answers can
o Adverbs like “usually” that can mean different to other be accurately interpreted as a discrete response.
people. Using such words makes it difficult to interpret the  Multiple choice response options should be mutually
participants’ responses because we cannot be sure how exclusive so that respondents can make clear choices.
they interpreted the qualifier. Ex:
o Response categories must be quantified rather than using Which option best describes
“always” “often” “never”. We can categorize the Revised choices:
your age group?
responses by using range. instead of using always we can  Under 18  Under 18
use 6-10 times.  18 – 25  18 – 24
o It must be quantified  25 – 35  25 – 34
o We can categorize the responses by using range  35 – 45  35 – 44
 45 – 55  45 – 54
 55 – 65  55 – 64
 65 or older  65 or older

2
POTENTIALLY OBJECTIONABLE QUESTIONS
- Some questions (esp in health research) are viewed as personal
and people hesitate to divulge information.
o income
o personal habits
o sexual activity
- These can be dealt by:
o Softening the manner in which the questions are asked –
don’t ask straightforward Qs; be creative
o Placing the question near the end of the questionnaire -
ask from the least sensitive to the most sensitive Qs
Example

Problem Revised
1. Have you ever shoplifted 1. Have you ever taken anything
something from a store? from a store without paying
for it?
YES
NO YES
NO
USING “DON’T KNOW”
- “Don’t know” or “Undecided” category
Problem Revised
- No established consensus
1. How many sex partners do 1. During the past 12 months,
- Opportunity for the respondent not to commit an answer
you have? with how many people did
VS.
you have sexual intercourse?
Forces respondents to indicate opinions they do not really hold
A. None
- Placement
B. 1-3 partners A. I have never had sexual
At the end/middle of questionnaire
C. 4-6 partners intercourse
D. More than 6 partners B. I have had sexual intercourse,
but not during the past 12 months • In your collegiate program, do they offer free access to
C. 1 person multimedia content such as instructional videos, e-books
D. 2 people and the like?
E. 3 people ___ Yes
F. 4 or more people ___ No
___ I don’t know

USE OF CHECK ALL-THAT-APPLY ITEMS RANK VS. RATING

- Items in which subjects can choose as many options as they
wish. - Writing questions:
- Used when survey questions ask about qualities of a product. o user friendly
- They do not force the subject to single out the best feature. o short and specific
Often used in health research (people, as they are complicated o simple and neutral
human beings, usually don’t just have 1 choice, but have several - Narrow the choices to avoid confusion.
choices.) - It is best not to have more than 7 to 10 choices
RANK

METHODS OF RESEARCH: (2M: SURVEY RESEARCH) 

 Position
 Value
 Worth
 Importance
 Level
- Question on rank
The best approach is to treat each option as a yes/no variable and Ex: Please indicate the order of importance of these
calculate the percentage of time each was selected. - might be
tedious, but this will make data analysis easier subjects to you by placing 1 beside the most
important, 2 beside the next most important and
so forth.
__ Genesis of Medicine
__ Family and Community Medicine
__ Physiology
__ Biochemistry
__ Neuroscience

3
RATING
 Quantity
 Quality
Ex:
On a scale from 0-10, where 0 means extremely dissatisfied and 10
means extremely satisfied, how satisfied are you with the nursing care
you received during your hospitalization?

Issue on whether Rank or Rating is not yet resolved. As much as

possible, AVOID RANKING because it is more difficult to analyze and might
get a lot of responses, while RATING/SCALE is easier to analyze.

USE OF SCALES
- Ordinal, Likert

ORDINAL SCALE

There is an option to list the categories vertically if each question

utilizes different options:

LIKERT SCALE - No consensus exists in the survey literature about the

number of categories to use.
- An EVEN number of categories, forces the respondent to
choose from two opposite options, even if he or she is
totally neutral.
4 options – strongly agree, agree, disagree, and strongly
- Ordinal psychometric measurement of attitudes beliefs disagree
and opinions
- In each question, a statement is presented in which a
respondent must indicate a degree of agreement or
disagreement in a multiple choice type format.

- Advantages: The preferred number of categories is usually ODD numbers;

o Most universal method for survey collection usually with either 5or7 categories. Has a middle or “neutral”
o Easily quantifiable option.
o Easily understood o There is an issue in removing the middle category, since
o Accommodates neutral answer tendency measures/central tendency must be avoided
o Quick, inexpensive, efficient (ODD.)
o Whereas the EVEN category will force the respondent more
to make a choice.
- Disadvantages:
- The choice of number of categories can have a major effect on
o Uni-dimensional (5-7 options of choice)
the conclusion made with the survey.
STANDARD is 5
o Each choice cannot possibly be equidistant, fails
to measure the true attitudes of respondents

METHODS OF RESEARCH: (2M: SURVEY RESEARCH) 

4. What should be observed regarding the LAYOUT of the
o Avoidance of extreme options although they are
most accurate questionnaire?
o ORIGINAL Likert uses “agree” and “disagree” GUIDELINES FOR QUESTONNAIRE LAYOUT
o In research it is use to measure the attitude of 1. Short surveys are preferable than longer surveys.
the respondents towards something: The shorter, the better
 positive/favorable 2. Well-designed questions place instructions where needed,
 negative/unfavorable even when it means repeating instructions at top of
continuation page.
Even if the instructions are too obvious
3. Avoid skipping or branching questions if possible.
Ex: if yes, skip numbers 3-5 and proceed to no.6
4. Most researchers opt to place easier questions first
(demographic data) and to list questions in logical order.
5. When scales are used, subjects are less confused when scale
direction is in consistent manner/ CONSISTENCY
There is an option to list the categories horizontally if each question
similar options: **More efficient in terms of space, especially if the
options are the same
4
5. How can the RELIABILITY of the questionnaire be established? MOST EFFCIENT FORM OF RELIABILITY:
Internal Consistency/ CRONBACH’S ALPHA
RELIABILITY: is how reproducible the findings would be if the same
measurement were repeatedly made on the same subject.
6. How can the VALIDITY of the questionnaire be established?

WAYS TO ENSURE RELIABILITY (SHOULD SELECT ONE) VALIDITY is a term for how well an instrument (or measurement
1) Test-retest reliability: procedure) measures what it purports to measure.
o An instrument’s capacity to provide the same
measurement on different occasion. Commonly used measures of validity:
o Questionnaire developers and testing agencies use
internal consistency reliability which measures between 1. Face validity
two scores ranging from 0-1.00; an acceptable level of - Refers to the degree to which a questionnaire or test
reliability is 0.80 or higher. appears to be measuring what it is supposed to measure.
o Appropriate to assess the reliability of knowledge - review of survey items by untrained judges
questions. - Ex. A questionnaire about domestic violence training
o Disadvantage: you have to give it twice over a period of
should have questions related to that issue.
weeks (same questionnaire given to a group of people
today, same questionnaire to be given 2 weeks later)
2. Content validity
2) Internal Consistency reliability/ CRONBACH’S ALPHA: - Indicates the degree to which the items on the
o Reliability of the items on the instrument or questionnaire instrument are representative of the knowledge being
indicating how strongly the items are related to one tested or the characteristic being investigated.
another; - Subjective measure of how appropriate the items seem
o Testing agencies sometimes use alternative forms of a test to a set of reviewers who have some knowledge of the
in which the items on the tests differ, but they measure subject matter
the same thing and have the same level of difficulty.
o In other words, to assess reliability of questions measured 3. Criterion validity
on an interval/ratio scale, internal consistency is - Refers to the instrument’s capacity to predict a
appropriate to use. characteristic that is associated with the characteristic.
o Advantage: administer questionnaire once - Established by comparing the measurement to a gold
o It is INTERNAL because there is a comparison of the odd standard, if one exists.
and even responses (responses from nos. 2,4,6,8,10 and - measure of how well one instrument stacks up against
from nos. 1,3,5,7,9) another instrument or predictor
o The principle is the ten items measure the same - Predictive: assess the ability of your instrument to
thing/average correlation of odd and even responses forecast future events, behavior, attitudes, or outcomes.

METHODS OF RESEARCH: (2M: SURVEY RESEARCH) 

3) Alternative forms reliability 4. Construct validity
o Is more of an issue with tests than with questionnaires. - consists of demonstrating that the instrument is related
o Disadvantage: 2 questionnaires are needed, which to other instruments that assess the same characteristic
measure the same thing and not related to instruments that assess other
characteristics
4) Intra- and Interrater reliability - established by using several instruments or tests on the
o Is referred to nominal measurement. If the measurement same group of individuals and investigating the pattern
is numerical, intra- and interobserver agreement is of relationships among the measurements
measured by the intraclass correlation coefficient. - most valuable and most difficult measure of validity
o The intraclass correlation is sensitive to both random error - measure of how meaningful the scale or instrument is
and statistical bias. when it is in practical use

5
TYPE CHARACTERISTICS HOW MEASURED ADVANCE NOTIFICATION
CONTENT Appropriateness of Subjective - Specialists recommend notifying the people who are to receive
content by experts the survey in advance of its administration.
FACE It looks on target by Subjective - PRENOTIFICATION may by be done by letter, telephone, or,
non-experts increasingly, by email.
CRITERION- Is associated with Correlation between - should include information:
CONCURRENT similar skills at scores on o who is doing the survey
present time instruments o what its purpose is
CRITERION- Predicts similar skills Correlation between o why the subject has been selected to receive the survey
PREDICTIVE in future scores on o how the results will be used
o whether responses will be anonymous
instruments
o when the questionnaire will be mailed (or emailed) or the
CONSTRUCT Theoretical measure Correlation with
interview scheduled
other measures
- Prenotification has been reported to increase response rate by 7–
8%.
7.How should the survey be administered, in terms of: COVER LETTERS AND RETURN ENVELOPS
- Cover letters should be short, relevant, on letterhead,
PILOT TESTING and signed.
o Carried out after the questionnaire is designed but before - Information on the letter includes the
it is printed or prepared for administration.  purpose of the survey
o may reveal that:  why the recipient’s response is important
o the reading level is not appropriate for the  How the data will be used- data will be strictly
intended subjects used for research and will remain anonymous
o some questions are unclear or are and confidential.
objectionable and need to be modified
o the instructions are unclear INCENTIVES
- a large sample is not required to pilot test an instrument
- Some researchers offer to share the results.
- it is more important to choose people who will provide
- To maintain anonymity, a separate postcard can be
feedback after completing the questionnaire
included for the recipient to return indicating a desire for a
- The best subjects will not be your friends or colleagues, copy of the results.
unless, of course, they are representative of the group
- More questionnaires are returned when a stamped
who will receive the survey.
envelope is included; this practice is reported to increase
response rates by 6–9%.
*If a large number of changes are required, it may be necessary to
- If a questionnaire is administered directly, such as to a
repeat the pilot test with another group of subjects.
group of physicians in a continuing-education course, it
is not necessary to include a cover letter.
RESPONSE RATE - Increase response rates more than any other single
- A high response rate increases the level of confidence in the action, except repeated follow-ups.
validity of the results and the likelihood that the results will be used.
- Monetary incentives, even modest ones of a few
- methods: dollars, are reported to increase responses by 16–30%
 Increase follow-up - 3-4 follow-ups at 2 week intervals
 Ethical consideration: No set amount of which is
 Effectiveness depends on the charisma or charm of ethical or unethical. Case to case basis. Incentive
the researcher or his ability to convince. should not be too much.
 Reminder postcards - 1-2 weeks after initial mailing
- Nonmonetary incentives increases response rates
 Telephone follow-up - With shortened questionnaire
containing only key questions by up to 8%.

METHODS OF RESEARCH: (2M: SURVEY RESEARCH) 

 Captive population - Students complete a questionnaire - Response rates are similar, regardless of whether
before they are given a grade. Someone waits at the door the incentive is sent with the questionnaire or as a
and collects the questionnaire. Ethical consideration: right reward after it is returned.
to refuse to answer the questionnaire. - Material incentives also increase response rates,
 Most commonly used but by only about half as much
 Other example: Large population of nurses or - Lotteries or chances to win tickets or prizes have
doctors. Health professionals are more aware
relatively little effect.
of the issues that exist in the health profession
and have some form of commitment to
contribute to the resolution of this issues. INCENTIVES RESPONSE RATE
 Surveys sent to authority - Authority disseminated to Monetary Increased response rates to 16-30%
subordinates (barangay captain, teacher, head of office) Non-monetary Increased response rates to 8%
 Mail survey
Material Incentives Increase response rates, but by only
about half as much
Lotteries or prizes Little effect

6
ANONYMITY AND CONFIDENTIALITY Summary of Issues Related to Administration of
Anonymity is the degree to which the identity of the message Questionnaires.
source is unkown and unspecified (Scott 2005, p243) ISSUES EFFECT ON SUCCESS OF SURVEY
- The cover letter should contain information on 1. Response Rates 50 – 85%
anonymity or confidentiality. 2. Follow-up Four to five every 2 weeks increases
- Depending on the purpose and sensitivity of the response rates significantly
questionnaire, it may be advisable to make the 3. Pilot Testing Critical to success of any survey
returns completely anonymous. 4. Cover Letter Provides purpose of survey and why
- The researcher can still keep track of who returns response is important
the questionnaire by asking the responder to mail a 5. Prenotification Increases response rates by 7–8%
separate postcard at the time he or she returns the 6. Return stamped Increases response rates by 6–9%
questionnaire. envelope
- Only the postcard and not the questionnaire itself 7. Providing incentives
contain any information that can be used to identify with survey
the respondent.  Monetary Increases response rates by 16–30%
- This practice permits the researcher to remove the
 Nonmonetary Increases response rates by 8%
responder’s name from the follow-up list, thereby
8. First-Class postage, Small increase
saving administrative costs and potentially annoying
stamps
the responder.
9. Color of questionnaire No known effect
Confidentiality of responses is a different issue.
10. Confidentiality Must be guaranteed; required by
- If questionnaires can be identified with a number or
Institutional Review Boards
code, it is easier to know who has returned the
questionnaire and streamlines the follow-up
In summary, there are so many things to take into consideration
process. when conducting a survey and constructing your own research
- Subjects always need to be assured that their instrument.
responses will be kept confidential.
- No individual’s response can be identified in any  Clinical trials have more issues
information reported or otherwise communicated.  Cohort study- will take 10 years
 Case control – has a lot of disadvantages
Legal Implication: With the increasing protection for human  So we are left with cross-sectional studies:
 When it comes to the research instrument, look for an
subjects, confidentiality is almost always required by
existing questionnaire. A questionnaire that already
institutional review boards (IRBs) as a prerequisite to exists in the literature whose validity and reliability is
approving the survey. established.
 Construct your own instrument as a last resort. When
 Anonymity- you can’t trace the questionnaire to the you have searched the literature and there is no existing
specific respondent questionnaire.
 Confidentiality- focused on the responses (will be kept a
secret ) Notetakers:
Labi, Imari Irish
 Is an informed consent needed for a survey? Proofreader: chaim|herr|2015
In general, YES!

METHODS OF RESEARCH: (2M: SURVEY RESEARCH) 

Use WHO template for informed consent.
 Other side of the issue: A formal informed consent is not
necessary for a survey. According to some ethics expert, the
filling up or the accomplishment of the questionnaire itself
is already evident that you consented.
 IN RESEARCH, MAS MABUTI PA ANG SOBRA KAYSA SA
KULANG (ALMOST IS NEVER ENOUGH haha )
 It is easier to correct the research proposal when told “this
is too much, you have to delete some parts of it” rather
than being told “It is not enough, you have to search the
literature again.”

7
 RESEARCH 3F Confounding Variable
Blue: Audio Black : slides
FINAL EXAMS Dr. John Anthony Domantay | May 12, 2016

be a third factor, let us say CIGARETTE SMOKING (confounder).

CONFOUNDING VARIABLE Why is it considered a confounder? Is smoking a risk factor for
What is Confounding? pancreatic CA? YES. Is smoking associated with coffee drinking?
YES. Many studies will show that coffee drinkers at the same time
also smoke V.V. so you see since smoking is associated with this
In many studies we observe an association and we are therefore smoking is a confounder. This journal, the aim is only to
tempted to derive a causal inference study two things the association between the Coffee drinking and
That many times we want to find out whether there is an cancer of the pancreas. But how come there are so many
association between the exposure and the outcome/disease. And variables that are being asked for? Like SMOKING, DIET, AGE,
when we do find an association, we are tempted to say that the SEX, SOCIOECONOMIC STATUS etc. why do we ask all of these?
exposure is the cause. That’s what we say causal inference. Because they are POTENTIAL CONFOUNDERS. Therefore ask all
the other risk factors of Pancreatic Cancer and all the association
However, the relationship may be causal with coffee drinking.
Often we say that the exposure is the cause of the disease but
this is not necessarily so. The relationship or the association may How do we address the problem of Confounding?
not be causal. That’s why my favorite term in research is Approaches in handling confounding
association, we do not say cause. We can say the most that the
EXPOSURE is ASSOCIATED with the outcome/disease because
this association may not be causal. Because what the cause may a. In designing and carrying out the study:
be something else and what we refer to as CONFOUNDING.  Individual Matching
 Group
Confounding is one of the most important problem in
epidemiologic studies and in health research. There are ways on how to address confounding? We might
What do we mean by confounding? In a study of encounter when we read the METHOD section of a journal.
whether factor A (exposure) is a cause of disease B Keyword is MATCHING. Related to CASE CONTROL STUDY. What
is matching? We match the cases and the control. For example.
(outcome), We say that a third factor (X) (confounder,
If the case is male the control should also be male. What
and maybe it is not the exposure that causes the disease variable is being matched there? SEX. SEX therefore is a possible
that but it might be something else) is a confounding if: confounder.

1. Factor X is a known risk factor for disease B a. In the analysis of data

2. Factor X is associated with factor A, but is not  Stratification
the result of Factor A  Statistical adjustment
-Multivariate statistics
Summarize: a variable is considered a confounder if it is a risk Ex: multiple linear regression
factor for the disease and it is associated with the exposure then
we call it a confounding variable.
Why so researchers use multiple linear regression? To eliminate
the confounders. That is what we call statistical adjustment. The
Example: Coffee drinking and cancer of the pancreas
analysis is adjusted for age, sex and educational attainment.
These 3 are confounding variables, they are not really the
interest of the study but they can confound or confuse and that is
what confounding means. That means that you are confused, it
can confuse the analysis of the study. Therefore they should be
controlled.

Example: age as a confounder

Exposure: Coffee drinking

Outcome/disease: cancer of pancreas
In your study, you found out that coffee drinking is associated
with pancreatic cancer. Does this mean that coffee drinking
causes pancreatic cancer? PROBABLY NOT because there might
The aim of the study is to determine if there is an association Let us say our cut off is 40, life begins at 40 so <40 vs. >/= 40.
between hair loss and coronary heart disease. In your initial Odds Ratio= 4.00 P<0.001
analysis, you classify them as bald or not bald. And if they have Interpret: is there an association between the age and the
coronary heart disease or not. And then in your initial analysis outcome? YES. Evidence. Is OR is >1 and the P value is <.05
you found out that there is an association between the two. So therefore it is significant, there is an association between age
let’s say the ODDS RATIO will be >1, let’s say the odds ratio is 2 and the outcome.
therefore the odds or the chances of CHD are 2x higher among
those who are bald as compared to those who are not bald. So so what else do we need to know to determine if age is a
can you say therefore that baldness causes CHD? Again probably confounder? Determine the association of AGE and the
not because we did not take into consideration the confounders. EXPOSURE. This table explains the association of AGE and
That is what we often overlook, that is why we need to consider BALDNESS
the confounders.

How to interpret odds ratio:

>1=Significant
1= No association
<1= Protective

Upon your reading you found out that AGE is a potential

confounder so is age associated with CHD? SYEMPRE. Is AGE
associated with BALDNESS? OF COURSE. That is why AGE is a
potential confounder.
Odds ratio: 0.111 P<0.001
Example in case control studies. Who are the Is there an association between AGE and BALDNESS? YES. OR=<1,
Cases=those with CHD <1 is protective. But there is still an association bet age and
Controls= Without CHD baldness.
Exposed=those who are bald
Unexposed=without baldness So there is an association bet age and the outcome and exposure.
Therefore age is a confounder. Thus the researchers will analyze
So what is the measure of association in a case control study? It’s the results separately for each age group. Analysis for the young,
the ODDS RATIO. <40 and the old >40. This is what we call STRATIFICATION. You
compute OR of both groups separately.

Odds ratio: 1.95

The odds of CHD is 1.95x greater among those who are bald than
those who are not bald. This sound absurd right so we need to
take into consideration the confounder. And the confounder is OR=1 for both groups. Interpretation of 1 is no association, thus
the AGE. So make another analysis. baldness does not cause CHD. So when we stratify the analysis
according to the confounder, it is clear that there is no
3F Confounding Variable

association between baldness and CHD. Because the result OR a

while ago is 1.95, so the result is confounded by or was confused
by the variable AGE. So ang totoo it is the AGE and not the
BALDNESS that causes CHD. Thus take this into consideration
when analyzing causations.

2
Another Example Example. Age is actually the risk factors that older people are at
risk so you would direct our preventive and therapeutic
measures towards the elderly if that is the case.

Confounding is not and error

Unlike bias. It is a natural phenomenon because people are
complicated. There are many variables in people. Age and sex
palang complication nay un.

LAST EXAM. LAST HAND OUT. LAST SUBJECT FOR THIS

SCHOOL YEAR.   

The main study wants to study the association of MI and total

cholesterol. And we want to see if obesity qualify as a
confounder. Obesity is related to both MI and Cholesterol.
Therefore obesity is a confounder.

So if we are going to stratify, we are going to have 2 separate

analysis according to obesity. Those that are obese and not
obese, and we take into consideration cholesterol and MI for the
two groups.

In summary, when we identify a confounder just like our variable

X we generally consider it as a problem because it is not our main
interest, our main interest is the exposure and the outcome, it is
a third variable and it is a problem.

To address the issue of confounding, for

Case control study= matching
3F Confounding Variable

Data analysis= stratification or statistical adjustment using multi

variate statistics.

Sometimes a confounding relationship is beneficial. 记录/Note Taker:

It permits us to identify people who are at high risk for a disease.
Sometimes it is not the exposure that is the risk factor but it is the
Lim, Joan Y.
confounder. It makes our research more interesting.
校正子/Proofreader:
It permits us to direct appropriate preventive and chaim|herr|2016
therapeutic measures
3
 (FINALS) PROBLEM-SOLVING ACTIVITY Summarizing Data and Presenting Data in Tables and Graphs
METHODS OF
RESEARCH Medisina 2018

-
SITUATION 1: You need to summarize numerical data with
3. MODE
numbers in the results section of your research paper.
o Value of the observations that occurs most frequently
MEASURES OF CENTRAL TENDENCY o Bimodal: two modes
1. MEAN o Multimodal: >2 modes
o Arithmetic average of the observations o Modal class: interval having the largest number of
o Formula: observation
4. GEOMETRIC MEAN
where o nth root of the product of the observations
𝑛
∑= sigma (to add) o GM = √(𝑥1 )(𝑥2 )(𝑥3 ) … (𝑥𝑛 )
x= individual observations o Used with data measured on a logarithmic scale
n= number of observations o Used with data measured on a logarithmic scale
o Steps in calculating mean: 𝒍𝒐𝒈 𝒙
i. log GM = Σ
1. Get the sum. 𝒏
2. Divide the sum by number of observations.
USING CENTRAL TENDENCY
Weighted Average
Two important factors
o Use when original observations are not
 Scale of measurement (ordinal or numerical)
available
 Shape of the distribution of observations
o No access to raw data, but need an estimate
• Symmetric distribution
When to use mean?
o Same shape on both sides
o  when numbers can be added
• Skewed distribution
o Used for numerical data. Not used for
o With outlying observations in one
ordinal data.
direction only (a few small values
o Note: Mean is sensitive to extreme values.
or a few large values)
o Very extreme data.
2. MEDIAN Guidelines
o Middle observation o Mean: for numerical data and for symmetric
o Steps in calculating median: distributions
1. Arrange observations from the smallest to o Median: for ordinal data or for numerical data
largest whose distribution is skewed
2. Find the middle value o Mode: for bimodal distributions, can also be used
• Odd number of observations= middle for ordinal data.
value o Geometric mean: for observations measured on a
• Even number of observations= mean of logarithmic scale
the two middle values
o When to use Median?
i.  ordinal observations MEASURES OF SPREAD (DISPERSION)
ii. Note: Median is LESS sensitive to extreme
values. 1. RANGE
o is defined as the difference between the
largest observation and the smallest
observation
2. STANDARD DEVIATION
o Most commonly used with medical and
health data, will measure the spread of
data about their mean.
3. COEFFICIENT OF VARIATION
o measures relative spread of data about
their mean
4. PERCENTILES
o indicate the percentage of a distribution
that is considered equal to or below that
number
 5. INTERQUARTILE RANGE Thank you for reviewing the calculations but
o is the measure of variation that makes use probably it's my fault I forgot to tell you that probably later
of percentiles; the difference between the on you don't have to mention the calculation anymore or the
25th and 75th percentiles formulas. I am just being practical because you are not going
to be statisticians but you should know how to analyze the
Note: Based on their definitions, we can conclude that
data that you have gathered in your research paper so you
STANDARD DEVIATION is the most important measure of
dispersion that is applicable to what the case wishes to
should know what measures of central tendency to use.
accomplish (We can disregard geometric mean because it is not
commonly used.)
STANDARD DEVIATION
 Formula: These are the things to consider:
1. Scale of measurement whether it is ordinal or numerical.
Whereas: 2. We have to consider the shape. It will lead us to the
• X – Item/ Subjects in the group
• X (barred)- mean
correct measure of central tendency.
• n- number of items/subjects Numerical-mean, if it is ordinal-median, for skewed? We will
use median because this is not affected by extreme values
The most important measure of dispersion that is applicable and if it is symmetric- mean.

METHODS OF RESEARCH: (FINALS) PROBLEM-SOLVING ACTIVITY Summarizing Data and Presenting Data in Tables and Graphs 
to what the case wishes to accomplish.
Negatively skewed
 Absolute Value of a number is its positive value and -most of the values are high; the tail is skewed to the
left.
is denoted by vertical bars “| |” on each side of the
number Positively skewed
 Bell-shaped Distribution -most of the values are low; the tail is skewed to the
right.
Symmetric
-normal curve.

In your research it will be tossed b/n the Mean and the

Median. Let us not leave out the measure of dispersion. The
central measures of the tendency should have a partner, the
measures of spread.

Standard deviation
 This graph will show us the bell shaped distribution 1. Used the value for further statistical testing.
made using standard deviation. The line in the center 2. It is the most useful in describing the spread.
will represent the mean. As items from a survey
deviate from the mean, their values in the graph If the SD is relatively low
move farther from the central mean. -the values are close to the mean
If the SD is relatively high
Why STANDARD DEVIATION is considered a very -the values are far from the mean.
important statistics?
o essential part of many statistical test, and SITUATION 2: You need to display numerical data in tables and
o Very useful in describing the spread of the graphs in the results section of your research paper.
observations about the mean value.
1. Frequency table
2. Histogram
Dean's Audio: 3. Box Plots
When you have gathered the data already, the first 4. Frequency polygon
thing you do is to summarize the data. We have learned in
our previous lessons that data are classified into three: FREQUENCY TABLE
Nominal, Ordinal, and Numerical. So what we are talking o Or frequency distributions
about now is: NUMERICAL. o Use to present information in scientific journals
If you are collecting NUMERICAL data, which you will o The scale of observations must first be divided into
collect in your Pharmacology research paper, what statistical classes, as in stem-and-leaf plots
should you use? What are they? Mean, Median, Mode. o Count the number of observation in each class
Granting you are talking about NUMERICAL data,
you will now use the measures of central tendency.

2
 Steps in Constructing a Frequency Table
1. Identify the largest and smallest observations
2. Obtain the RANGE
3. Determine the number of classes.

Guidelines determining the number of classes:

o Between 6 and 14 classes is generally adequate
to provide enough information without being
overly detailed.
o It should be large enough to demonstrate the
shape of the distribution but not so many that
minor fluctuations are noticeable
4. Obtain the width of the classes.
o WIDTH OF THE CLASSES =
RANGE OF OBSERVATION / NUMBER OF CLASSSES

Guidelines for determining class width: o Histograms usually present the measure of interest

METHODS OF RESEARCH: (FINALS) PROBLEM-SOLVING ACTIVITY Summarizing Data and Presenting Data in Tables and Graphs 
o Class Limits along the X-axis and the number or percentage of
o beginning and ending numbers observations along the Y-axis.
o must not overlap
To construct a histogram,
o Class widths should be equal since unequal class
o first step is to "bin" the range of values
widths present graphing problems and should be o divide the entire range of values into a series of
used only when large gaps occur in the data intervals
o Open-ended classes at the upper or lower end o Then count how many values fall into each interval.
of the range should be avoided because they do
not accurately communicate the range of the o The bins are usually specified as consecutive,
observations nonoverlapping intervals of a variable.
o Class limits should be chosen so that most of the o The bins (intervals) must be adjacent, and are usually
observations in the class are closer to the equal size.
o As the adjacent bins leave no gaps, the rectangles of a
midpoint of the class than to either end of the
histogram touch each other to indicate that the original
class. variable is continuous.
5. Tally the number of observation in each class.
HISTOGRAM VS BAR GRAPH
- Often this is neglected, which may lead to a bar
o STEM-AND-LEAF PLOT: the actual value of the chart being confused for a histogram.
observation is noted. o A histogram is used for continuous data, where the bins
o FREQUENCY TABLE: only the number of observations will represent ranges of data, and the areas of the rectangles
fall within the class are meaningful
o A bar chart is a plot of categorical variables and the
Note: If you are constructing a stem-and-leaf plot, the actual discontinuity should be indicated by having gaps
value of the observation is noted. If you are constructing a between the rectangles, from which only the length is
frequency table, you need use only the number of meaningful.
observations that fall within the class
BOX AND WHISKER PLOTS
HISTOGRAMS o Simply called as Box plot
o A diagram consisting of rectangles whose area is in o Use to display information when the objective is to
proportion to the percentage of observations within an illustrate certain locations in distribution
interval. o It is constructed from the information in a stem and leaf
o A histogram is a graphical representation of the plot.
distribution of numerical data. It is an estimate of the o In the stem/ leaf plot
probability distribution of a continuous variable o MIDPOINT (^) - number that divides the
(quantitative variable) and was first introduced by Karl distribution into halves
Pearson. o PLUS SIGN (+) - further divide each of the upper
o Communicates information about area. and lower limit halves of the distribution into
o This is the reason why the width of classes should be two equal parts
EQUAL. o This numbers are also called the first and third
quartiles/ hinges, respectively, of the
distribution
3
o Box and whisker plots are also effective when there is
more than one set of observations and the objective is to
compare them.

Steps in Constructing Box Plots

1. A box plot is constructed by 1st drawing a vertical scale
representing the data to be compared.
2. A box is then drawn, with the top of the box at the
third quartile. Dean's Audio:
3. The location of the midpoint of the distribution is - Second thing to do in Numerical data is to create
indicated with a horizontal line in the box. tables or graphs that will summarize and describe
4. Finally, straight lines, or “whiskers”, are drawn from the data.
the center of the top of the box to the largest - For the graphs, you should know how to do these in
observation and from the center of the bottom of the Microsoft Excel.
box to the smallest observation.
TAKE NOTE! In your Pharma research, let us use the simple
one (graphs), or a flat presentation.
FREQUENCY POLYGON

METHODS OF RESEARCH: (FINALS) PROBLEM-SOLVING ACTIVITY Summarizing Data and Presenting Data in Tables and Graphs 
Histogram vs. Bar graph
o Line graphs similar to histogram
Histogram- Numerical Data
o Line the graph creates resembles a half polygon
Bar Graph- Nominal Data
o Useful: comparison of two distributions on the same
graph
Notetakers:
Calara, Kevin & Balba, Kendralyn
Steps in Constructing Frequency Polygon
o First step: a stem-and-leaf-plot or frequency table is
generated
o Stem-and-leaf-plot is a plot where each MINI QUIZ:
data value is split into a "leaf" (usually the T/F:
1. Median is used for numerical data and for
last digit) and a "stem" (the other
symmetric distributions. (F - Mean)
digits). For example "32" is split into "3"
2. Mean is used for ordinal data or for
(stem) and "2" (leaf). The "stem" values are numerical data whose distribution is skewed
listed down, and the "leaf" values are listed (F – Median )
next to them. 3. If the SD is relatively low, the values are far
o Frequency table -> the data in this to the mean. (F - close)
frequency table are obtained by adding 4. Value of the observations that occurs most
each frequency to the sum of the previous frequently is Mode (T)
frequencies. 5. Standard deviation measure the spread of
data about their mean. (T)
o Find the midpoint of each class.
6. In a negatively skewed distribution, most of
o midpoints were computed by adding the
the values are low; the tail is skewed to the
upper and lower boundaries and dividing by left. (F – high)
2 which is repeatedly done until the last 7. A bar graph is used for continuous data,
class boundary. The midpoints are the ones where the bins represent ranges of data,
plotted to make the shape of our frequency and the areas of the rectangles are
polygon. meaningful (F - Histogram)
o Draw the x and y axis. 8. Histogram is used to display information
o Label the x axis with the midpoint of each when the objective is to illustrate certain
locations in distribution (F - box and
class, and use the suitable scale on the y axis
whisker plots)
for the frequencies.
9. Histogram is an estimate of the probability
o Use the midpoints for the x values and the distribution of a continuous variable (T)
frequencies as the y values, plot the points 10. Between 6 and 14 classes is generally
o Connect the adjacent points with line segments. adequate to provide enough information
Draw a line back to the x axis at the beginning and without being overly detailed (T)
end of the graph, at the same distance that the
Note: The frequency
previous polygon
and next and the
midpoint histogram
would are two
be located.
different ways to represent same data set. The choice of
which one to use is left to the discretion of the researcher.

4
 Situation 3: You need to summarize nominal and ordinal data RATES
with numbers in the results section of your research paper. - a multiplier (e.g. 1000, 10,000, or 100,000) is used and they
are computed over a specified period of time.
- the multiplier is called the base
When observations are measured on a nominal or ordinal 𝒂
𝒓𝒂𝒕𝒆 = × 𝒃𝒂𝒔𝒆
scale, they do not have numerical values and can only be 𝒂+𝒃
measured via the following:
E.g. Mortality Rates
1. PROPORTION no. of people who died during a given period of time
= 𝑥 𝑏𝑎𝑠𝑒
o the number, a, of observations with a given characteristic no of people who were at risk of dying at the same period
divided by the total number of observations, a + b, in a
given group  Our focus will be on Proportion and Percentage only.
𝒂
o Proportion =
𝒂+𝒃
o Expressed as decimal
Gender Situation 4: You need to display nominal and ordinal data in
tables and graphs in the results section of your research paper
Male Female Total

METHODS OF RESEARCH: (FINALS) PROBLEM-SOLVING ACTIVITY Summarizing Data and Presenting Data in Tables and Graphs 
Location o Methods to display nominal and ordinal data using
Barangay A 35 28 63 tables and graphs
Barangay B 94 143 237
2. SIMPLE METHOD
Barangay C 6 10 16 o list the categories in one column and frequency or
3.
4. percentage in the other

Example: E.g. Frequency of hematuria in patients with haemophilia

Proportion of dengue cases in City M
1. The proportion of male dengue patients in barangay A
35
Proportion of male dengue students in barangay A =
35+28
=0.55
2. The proportion of female dengue patients in barangay A
28
Proportion of female dengue students in barangay A =
28+35
=0.44
o Can also be termed as Frequency Distribution
5. o Focus on the Nominal variables (YES & NO), not on
the numbers (don’t confuse it as Numerical)
PERCENTAGE o In research, a 3rd column may be added showing the
o Simply the proportion multiplied by 100% PERCENTAGE (as stated in the definition of Simple
Method)
Example:
a. The percentage of male dengue patients in barangay A CONTINGENCY TABLE
Proportion of male dengue students in barangay A= 0.55 o used when 2 characteristics on a nominal scale is
percentage =0.55 x 100% = 55% examined and classified according to several factors
b. The percentage of female dengue patients in barangay A o Some may use the term ‘Cross tabulation’, but it is not
Proportion of female dengue students in barangay A= 0.44 the technical name of the table
percentage =0.44 x 100% = 44% o A table with 2 variables: E.g.
i. Sex
ii. Presence or absence of hematuria
RATIOS
o This is important because this will lead you to the next
o the number of observations in a group with a given
Inferential Statistical Test. For example, Chi-square
characteristic divided by the number of observations
should be used over T-test or ANOVA when provided
without the given characteristic
𝒂 with this kind of data.
𝒓𝒂𝒕𝒊𝒐:
𝒃
E.g.: The number of foreign students enrolled per year in
School of Medicine

5
E.g. Men and women with and without hematuria

Nominal Pie Chart - grouping the data

The variable is expressed in words.

METHODS OF RESEARCH: (FINALS) PROBLEM-SOLVING ACTIVITY Summarizing Data and Presenting Data in Tables and Graphs 
BAR CHART
o used to graphically display the nominal and ordinal data in
which the counts or frequencies are shown as bars
o Take note that the bars are separate from each other;
representing different data.
o This is preferred in JOURNALS
o While HISTOGRAM is for Numerical Data

Ordinal Pie Chart - incorporates the concept of ranking

PICTOGRAPH
o It appeals more to the aesthetic approach in presenting
results
o The same concepts and idea
o Creative illustrations may also be used to reinforce texts
and word phrases that may give a clearer understanding
to their meaning.
o Again, RARELY used in JOURNALS

The other graphic devices such as pie charts and

pictographs are often used in newspapers, magazines, and
advertising brochures (or documents intended for a layman).

PIE CHARTS Pictograph Nominal

o The main trend is to group the nominal and ordinal results

according to category
o Each category will receive a slice of the pie
o Popular because it is visually appealing and the concept is
understood right away
o LESS preferred in Scientific Journals

6
 (A) Ordinal characteristics are expressed in ranks. The
ranks are treated as though they are the actual values
themselves. Remember: RANKS ARE ORDINALS.
Pictograph Ordinal  ORDINAL CHARACTERISTICS, like nominal characteristics,
are displayed in contingency tables and bar charts.
 It is also appropriate to use with numerical observations
that are skewed with extreme observations.

Situation 5: You need to describe the relationship between

two numerical characteristics in the results section of your
research paper

The relationship between two numerical characteristics is

described by the correlation.
 The mode is the value that appears most often in a set of
(A): Relationships are still part of descriptive statistics.
data.
Not all relationships are correlation; it strictly needs 2

METHODS OF RESEARCH: (FINALS) PROBLEM-SOLVING ACTIVITY Summarizing Data and Presenting Data in Tables and Graphs 
numerical characteristics.  The mode of a discrete probability distribution is the
SCATTERPLOTS value x at which its probability mass function takes its
maximum value.
 Illustrates the relationship between two numerical
characteristics.  In other words, it is the value that is most likely to be
sampled.
THE CORRELATION COEFFICIENT
 The mode of a continuous probability distribution is the
 sometimes called the Pearson Product Moment
value x at which its probability density function has its
Correlation Coefficient,
maximum value, so the mode is at the peak.
 Is one measure of the relationship between two
numerical characteristics, symbolized by X and Y.  Calculation involves rank-ordering the values from
lowest to highest; (The ranks are then treated as though
 It measures the strength between variables and
they were the actual values themselves.)
relationships.
 Normal Coefficient Value: (-1.00 to 1.00)
Ex. IQ & Academic Grades
 If value is in the positive range: the relationship between
the variables is positively correlated or direct (Both
values decrease/increase together)
 If value is in the negative range: the relationship
between the variables is negatively correlated or inverse.
(As one value decreases, the other value increases)
(A) Correlation coefficient is represented by small
letter “r”.
 Ex: The group would like to estimate the relationship
between the patients’ age (in years) and scores in
relation to the NIH Stroke Scale.
(A) Both characteristics are numerical; that is why it is
appropriate to use correlation coefficient.

Situation 6: You need to describe the relationship between

two ordinal characteristics in the results section of your
research paper.
 Here, the result would be 0.1 which would indicate a
THE SPEARMAN RANK CORRELATION (SPEARMAN'S RHO) positive relationship between these two variables.
 is frequently used to describe the relationship between  Although the formula is simple when no ties occur in the
two ordinal characteristics (or one ordinal and one values, the computation is quite tedious.
numerical). (A) 2nd and 3rd columns are ranks that is why we use
 is the nonparametric version of the Pearson product- Spearman’s rho, but if the 1st and 2nd column is used we
moment Correlation. This means that it does not require use correlation coefficient. Remember: mild, moderate
numbers but on a ranking. and severe is still a form of RANK, same with excellent,
 Therefore, the spearman’s coefficient measures the very good, good and poor. They become ranks by
strength of association between two ranked variables.
7
 assigning numbers for them to represent, thus we use 2. ODDS RATIO
Spearman’s rho. - (OR) – Odds ratio
o is the odds that a person with an adverse
Situation 7: You need to describe the relationship between outcome was at risk divided by the odds that a
two nominal characteristics in the results section of your person without an adverse outcome was at
research paper. risk.
The primary interest (in studies with 2 characteristics): o Another way of stating it is: (Odds that the
o Significantly related diseased were exposed / Odds that the
(A) used for Inferential statistics controls were exposed )
o Magnitude of the relationship - The odds ratio provides a way to look at risk in case–
 In studies involving two characteristics, the control studies.
primary interest may be in whether they are - It is a ratio of the likelihood of an even happening
significantly related or the magnitude of the compared to the likelihood of an event not happening
relationship, such as the relationship between a - One example would be in games of chance such as if you
risk factor and occurrence of a given outcome. roll a dice. The odds of rolling a “four” are 1 in 5 even
though the dice has 6 surfaces, meaning there’s 1 chance
Two ratios used to estimate such a relationship are the: that it does happen and 5 other chances that it doesn’t.

METHODS OF RESEARCH: (FINALS) PROBLEM-SOLVING ACTIVITY Summarizing Data and Presenting Data in Tables and Graphs 
(Both often referred to as risk ratios.) - It is also called the cross-product ratio because it can be
(A) Both are also commonly used in epidemiology. defined as the ratio of the product of the diagonals in a 2
1. RELATIVE RISK × 2 table.
- (RR) - Risk ratio - The odds ratio is easy to calculate when the
o is the ratio of the incidence in people with the observations are given in a 2 × 2 table.
risk factor (exposed persons) to the incidence
in people without the risk factor (nonexposed
persons).
o Another way of stating it is: (Probability of
getting a disease if exposed / Probability of Ex. Favorite Color based on personality type:
getting a disease if not exposed)
- It can therefore be found by dividing the EER by the CER.
EXPERIMENTAL EVENT RATE (EER)
- is the proportion of people with the risk factor who have
or develop the disease, or A/(A + B).
CONTROL EVENT RATE (CER)
- is the proportion of people without the risk factor who (A) If the study design is clinical trial or cohort, use relative
have or develop the disease, or C/(C + D). risk. If the study design is case control or cross-sectional
studies, use odds ratio. Remember that.
NOTE: The relative risk is calculated only from a cohort study
or a clinical trial in which a group of subjects with the risk SUMMARY
factor and a group without it are first identified and then
followed through time to determine which persons develop PEARSON’S COEFFICIENT CORRELATION:
the outcome of interest. - determines if there is a strong relationship between two
- Ex. Top reasons men and women why they argue: numerical characteristics (ex. Age & Income).
SPEARMAN’S RANK CORRELATION:
- determines if there is a strong relationship between two
ordinal characteristics.
RELATIVE RISK / ODDS RATIO
- may be used to measure the relationship between two
characteristics.
(A) Tables for Relative risk and Odds ration should always be
in a 2x2 format.
Notetakers:
Example of doc John for relative risk: The association or Kimbongan, Ayriz
relationship of cigarette smoking and lung cancer: 1st divide Gadgad, James Austin
samples into smokers and non smokers. 2nd categorize it as
with lung cancer and without lung cancer. 3rd put it in a 2x2
table. PROOFREADER:
“So lets say the result of the risk ratio is 20 if computed, then chaim|herr|2015
if interpreted, it means that the risk of lung cancer is 20 times
greater in smokers compared to non-smokers (always
compare or I will fail you!).
8
RESEARCH (2F) Estimating Risk: Is there an association?
FINALS Dr. John Anthony Domantay | May 4, 2016

Estimating Risk: Is there and association?

 Review of study designs
 How do we determine wheter a certain disease
is associated with a certain exposure
 Relative risk
 Odds ratio
Review: What research design is this?

 We must dtermine whether there is an excess risk of

the disease in exposed persons.
Difference in the
Ratio of the risks
risks (or incidence
(or incidence rates)
rates)
- Design of a cohort study
Review: What research deisng is this?  We can calculate the ration of the risks (or incidence
rates).
RISK IN THE EXPOSED
RISK IN THE UNEXPOSED

 We can calculate the difference of the risks (or

incidence rates)

- Design of a case-control study RISK IN THE EXPOSED - RISK IN THE UNEXPOSED

Review: What research design is this?
 One approach is to calculate the rate of the attack
rate

- Design of a hypothetical cross-sectional study

 If an assumption exists in a cohort study, how strong
 Regardless of the design used, the objective is to
is it?
assess risk of a disease in association with an
exposure.
What is the ratio of the risk of disease in exposed individuals
to the risk of disease in nonexposed individuals?
Exposure Outcome  The ratio is called the relative risk.
(Characteristic) (Disease)
Again, formula

 Risk can be defined as the probability of an event RISK IN THE EXPOSED

occuring. RISK IN THE UNEXPOSED
 The incidence of a disease in a population is termed
the absolute risk.
 How do we interpret the value of a relative risk? The odds ratio is another measure of association.

We can calculate the relative risk from a cohort study.

How is a case-control study conducted?

Incidence rate of exposed: a / a + b

Incidence rate of unexposed: c / c + d

Hypothetical cohort study: smoking and coronary heart

disease

Example: Coronary heart disease and cigarette smoking

Calculate the relative risk

Relative risk = 1.61

Interpret the relative risk

 The risk of coronary heart disease is 1.61 times
greater among those who smoke, as compared to
those who do not smoke. Calculate the odds ratio
Odds ratio = 1.62

(2F) Estimating Risk: Is there an association?

We interpret the odds ratio just as we interppret the relative
risk.
 The odds of coronary heart disease are 1.62 times
higher among smokers as compared to non-
smokers.

In a case-control study, we cannot calculate the relative risk

directly.

2
 READING ASSIGNMENT been individually matched to a case, resulting in 10 case
 When is the odds ratio a good estimate of relative control pairs (the horizontal arrows indicate the matching of
risk? pairs). If we use these findings to construct a 2x2 table for
When the following three conditions are met: pairs, we obtain the following:

1. When the cases studied are representative, with regard to

history of exposure, of all people with the disease in the
population from which the cases were drawn.
2. When the controls studied are representative, with regard
to history of exposure, of all people without the disease in the
population from which the cases were drawn.
3. When the disease being studied does not occur frequently.

 Examples of calculating odds ratios in case-control

studies: unmatched and matched

Let us assume that this case-control study is done without any

matching of controls to cases, and that we obtain the results
seen in Figure 11-8. Thus, 6 of the 10 cases were exposed and
3 of the 10 controls were exposed. If we arrange these data in
a 2x2 table, we obtain the following:

The odds ratio in this matched pairs is as follows:

 How to interpret odds ratio less than 1

We interpret the odds ratio just as we interpreted the

relative risk. If the exposure is not related to the disease, the
odds ratio will equal 1. If the exposure is positively related to
the disease, the odds ratio will be greater than 1. If the
exposure is negatively related to the disease, the odds ratio
will be less than 1.

(2F) Estimating Risk: Is there an association?

SUMMARY:
 The odds ratio is a useful measure of association, in
both case-control and cohort studies.
 In a cohort study, the relative risk can be calculated
directly
 In a case-control study, the odds ratio is used as an
The odds ratio in this unmatched equals the ratio of the estimate of the relative risk, when the risk of the
cross-products: disease is low.

Notetaker:
Mama D

Proofreader:
Mama H
Let us now look at an example of an odds ratio calculation in
a matched-pairs case-control study (Fig. 11-9). Let us return
to our low-budget study, which included only 10 cases and 10
controls: now our study is designed so that each control has
3
 (2F) Research Proposal
PHARMACOLOGY
Quiz 1 Dr. John Anthony Domantay | October 12, 2015

Format - Generally peer reviewed journal articles

- NO separate section on literature review
I. Title
- Clear and logical
II. Brief background (significance of study)
- Literature review should logically lead to the
III. Research objective (general and specific)
statement of the objectives – this is the gap
IV. Research design (state research design)
- Present only key ideas
V. Population and Sample (just state)
- 20-25 key papers
VI. Data gathering tools (just state)
VII. Data analysis WEBSITE: http://www.phrasebank.manchester.ac.uk/
VIII. References (Vancouver format)

The problem must be based on literature and must use III. Goals and Objectives
protocol (aka research proposal) of SLU-Research Ethics
- Goal: General objectives
Committee(SREC).
o Should be in line with the title, and usually
starts with "to determine..." – Just copy parts
RECOMMENDED FORMAT FOR RESEARCH PROTOCOL BASED of the title
ON WHO FORMAT - Specific: Specific objectives
o First: should be answerable by descriptive
Protocol text specifications
statistics
- 6-8 pages (excluding appendices) o Secondly: Inferential – This will look for
- Bond size 8x11/short significant differences
- Times New Roman 12 font - Simple, specific, NOT vague
- Single-spaced - I will fail you if you do not follow the pattern
- Pagination: page X and Y pages (centred at the
bottom of the page)
- For ethical clearance: Example:
o i.e. for human participants even a survey
Title of the study is:
o One hard copy (together with an e-copy) to
SLU-REC secretariat staff Knowledge and attitudes of medical students regarding
o REO,2/F Burgos Administrative Centre, SLU pharmacology

General objective: to determine knowledge and attitudes of

I. General Information medical students regarding pharmacology
- Protocol title Specific:
- Researcher or principal investigator – This should be
a list, there should be an order to the list: leaders Descriptive:
name first, followed by co-leader then the rest (et al)
a. What are/is the level of knowledge
b. What are the attitudes

II. Background and Rationale Inferential: (talk about association)

- Reason for conducting the research Is there a significant difference in the knowledge and attitudes
- In the light of current knowledge or literature – most of pharmacology students when they are grouped according
important part in the research is the gap in knowledge to:
– this is what we know but this is what we do not know
a. Age
(and this is what you will research) DO NOT LEAVE
b. Sex
THIS OUT.
c. Premedical course
- Equivalent to the introduction in a research paper
d. Etc.
- Should answer the basic questions:
o Why the research needs to be done? I get hypertension if your specific objective number 1 is: is
o What will be its relevance? there a significant difference.... I will fail you!!!!
- Should be fully referenced
 IV. Design VI. Safety of research subjects/participants

- Type of study (provide a complete description of the - How their safety will be ensured
study you are doing) – do not describe an animal - Recording and reporting adverse events and follow-
study as clinical trial it is experimental and do not call up (e.g. Drugs)
a human study as experimental it is a randomised - Research questionnaire can have an adverse effect
control clinical trial (e.g. Sensitive questions)
- Research population or sampling frame – Will have - "no adverse effects are expected due to
to describe the population/sample of the study will administration of the research questionnaire." or " no
be....etc. adverse effects are expected due to the intervention
- Who can take part done."
o Inclusion and exclusion criteria
o Withdrawal criteria for example a person
VII. Data management and statistical analysis
does NOT want to continue the survey.
Data management:
V. Methodology
- Data handling and coding for computer analysis
This should be the longest part of the protocol not the
- This takes place before data is analysed
background and should be detailed including:
- E.g. how will you input the survey answers into the
- Interventions to be made computer?
- Procedures to be used
Data analysis (Refers to statistical tests that we will use):
- Measurements to be take
- Observation to be made - Reasons for selecting sample size – there should be a
- Laboratory investigations to be done basis for selecting your sample size
- Power of the study used
It is better to overwrite than to underwrite because when it is
- Level of significance to be used
time for revision it is easier. You just have to cross out the items
- Procedure for missing or spurious data
that you have to delete rather than being told it lacks detail.
- For qualitative: how will the data be analyzed
This part should be detailed

Intervention:
VIII. Ethical Considerations
- Describe in detail
Even if you are not dealing with human participants there are
- E.g. If it is a drug/device/vaccine
still ethical considerations for experimental animals. There are
- Survey: How did you train the interviewers, what is
guide lines and laws.
included in the questionnaire etc.
- Informed consent
Procedures
- Confidentiality of participants
- Describe in detail – Even if you have to put the - Confidentiality of the data
venipuncture - Potential conflict of interest
- Social science study: Focus group discussion – how did
Informed consent should be described in detail:
you go about this?
- When and where it will be obtained
Standardised procedures or techniques:
- Who will get the consent
- Should be described - How undue pressure will be minimised
PHARMACOLOGY: Research Proposal

- Complete with bibliographic references - Is there any monetary payment

- Cited appropriately
Informed consent form should be in:
- Appendices – include questionnaire if you used it,
focus group discussion guide, different forms used - The appendix
- If applicable it should be in English or in the local
Randomized control trial
dialect
- Randomisation - If ever it is waived or not used it should be justified
- Blinding or full explained
- etc.

2
 IX. Problems anticipated (if any) XIV. Project team and management plan (if any)

If there are none then this is what you should write: - List down the members of the team
- Specify the roles and responsibilities in a matrix (to be
"We do not foresee any major difficulties in implementing this
placed in the appendix)
project."

XV. References (of literature cited in the preceding sections)

X. Dissemination of results and Public policy
Vancouver system of referencing:
What does this mean – you should foresee where you will
eventually publish the study

- Target conferences In the Vancouver Style, a number is assigned to each reference

- Peer-reviewed journals as it is used. Even if the author is named in your text, a number
- Disseminating results to: must still be used. The original number assigned to the
o Participants reference is used each time that reference is cited in the text.
o Affected community The first reference you cite will be numbered 1 in the text, and
o Policy makers the second reference you cite will be numbered 2, and so on.
o Health administrators If you cite reference number 1 again later in the text, you will
o Etc. cite it using the number 1.

Suggestions for dissemination of results and publication policy. Useful website: https://www.citethisforme.com/vancouver

This study is intended to be presented at the research fora

during the:
#TeamPogi
- Research and invention month (SLU)
- APMC-SN regional convention for Luzon Notetakers:
- APMC-SN national convention Abad, Patrick Raymond
- Philippine Association of Academic Biochemists Balansay, Karl Jose
(PAAB) Leung, Brian Anthony
- Philippine Academic Society for Microbiology and
Parasitology (PASMP)
- Philippines Society for Experimental and Clinical
Pharmacology (PSECP)
- SLU research journal

XI. Disclosure of potential conflicts of interest

"The investigators declare that there is no potential conflict of

interest."

XII. Financing of the project and others support

"This research project is self-financed" (to be financed by our

parents haha!!) or
PHARMACOLOGY: Research Proposal

"This study will be financed by the investigators"

XIII. Collaboration with other scientists

"This is a stand-alone project."

3
 (3F) Writing a Research Proposal (Continuation…)
PHARMACOLOGY
Quiz 1 Dr. Domantay | Nov. 13, 2015

*NOTE: Please download the Vancouver Style Guide of the

University of Queensland (pdf) and the other files uploaded “Today I choose life. Every morning when I wake up I
in the Dropbox (Pharmacology folder) since this part of the can choose joy, happiness, negativity, pain... To feel the
lecture was just flashing of pictures/documents of forms. freedom that comes from being able to continue to make
Some texts were highlighted in the Vancouver Style Guide mistakes and choices - today I choose to feel life, not to
(pdf) as emphasized by the Dean. deny my humanity but embrace it.” Kevyn Aucoin

Forms used in conducting Studies: (Standard Templates)

Informed Consent Form

o There are templates to use:
 For Clinical Studies/Trials
 Qualitative Surveys (adults)
 Parental consent
*NOTE: These forms are also included in the
compiled files.

Gantt Chart
o found or part of the appendices
o shows the time table of the study
NT: Taclobao-Fernandez
Protocol Review Application Form
*NOTE: Photos of this form are included in the compiled files

Types of Review:
1. Full board review
 Will take a month
 Review by all members of the panel
 Example: study involving clinical trials with
human participants

2. Expedited review
 Review by one or some members of the
panel (not the whole board/panel)
 Will take only a few weeks
 Example: Survey

PROTOCOL EVALUATION FORM

- Protocol Document Review
o First part of the protocol evaluation form
o A study should be technically sound for it to
be ethically sound
- Vulnerable participants:
o Children
o Pregnant women
o Elderly
*NOTE: Again, please check the uploaded forms
 (1F) Writing an Outline of a Research Paper
PHARMACOLOGY
FINALS Quiz # 1 Dr. John Domantay| April 21, 2016

Starting to write is very difficult. METHODS

- Explains how you went about answering the main
IMRD Format study question
INTRODUCTION - Detailed enough to enable readers to:
- What is your main study question and why it is a. Judge whether the methods were appropriate
important for answering the study question
Include the following: b. Judge any weaknesses in methodology that
 Why the research was started could influence the interpretation of the results
o what is known c. Repeat the study if you wish to do so
o what are the gaps
 What contributions you believe your paper will Subheadings:
add to current knowledge a. Study design
 The main study question and objectives b. Setting and subjects/participants
(primary and secondary) which include: c. Measurement: outcomes, covariates
o brief specifications of the study population d. Study size
o exposure and outcomes e. Action taken to address potential sources of
- Last part of the introduction bias (if applicable)
DO NOT include:
 Detailed explanation of basic terms RESULTS
 Exhaustive review of the subject area - Presents data that supports the answer to the main
 Exhaustive review of current literature study question
 Results - Data enables readers to judge the validity of your
 Conclusions conclusions
- Directly support the answer to the main study
INTERNATIONALLY ACCEPTED GUIDELINES question
STROBE Statement Checklist - Only present data, DO NOT INTERPRET
STROBE Statement Explanation and Include: (refer to guidelines)
Elaboration
- For observational studies: cross-sectional, case DISCUSSION
control and cohort *Treat the discussion and conclusion separately
DISCUSSION
CONSORT 2010 Checklist - Interpret the findings and critically evaluate
CONSORT 2010 Explanation and Elaboration your work
- For human clinical trials - Take into account any limitations in
methodology (strengths vs weaknesses)
ARRIVE guidelines - Elaborate on the strengths
- Animal Research Reporting In Vitro Experiments - Others (see guidelines)
- Newest
Information included:
For microorganisms ie bacteria - The provisional answer given by your data to
- Modify ARRIVE or CONSORT guidelines to fit the main research question (results are
the study summarized in the first paragraph)
(Please refer to the guidelines for reference) - Evaluation of methods, including any possible
sources of bias or confounding
- STROBE focuses on limitations and strengths
Cautious interpretation:
- Presentation and evaluation of evidence from
other papers that support or contradict your
findings
- An attempt to explain any difference between
your findings and previous research
- Discussion of mechanisms by which A could
lead to B but avoid over interpretation

CONCLUSION
- Gives the final answer to main study question
- The implications of answer
Include:
a. Generalizing of your findings
b. Theoretical implications (including suggestions
for future research in the field 
Recommendations)
c. The practical implications (policy and clinical
practice)
- Last paragraph

Other documents:
Structure of writing: APA format
- Only for appearance of the paper
- Please refer to the APA manual for the structure
- Observe proper spacing
- Shows how tables and graphs look like and
placements of titles
Referencing: Vancouver format

ICMJE
- Recommendations for the Conduct, Reporting,
Editing and Publication of Scholarly Work in

1F PHARMACOLOGY: Writing an Outline of a Research paper 

Medical Journals
- Important: Part 4: Manuscript Preparation and
Submission

Note takers:
Sarah B.
Aileen P.

Proof reader:
Tate <3

2
 Annals of Internal Medicine Academia and Clinic
The Strengthening the Reporting of Observational Studies in
Epidemiology (STROBE) Statement: Guidelines for Reporting
Observational Studies
Erik von Elm, MD; Douglas G. Altman, DSc; Matthias Egger, MD; Stuart J. Pocock, PhD; Peter C. Gøtzsche, MD; and Jan P. Vandenbroucke, MD,
for the STROBE Initiative

Much biomedical research is observational. The reporting of such empirical evidence and methodological considerations. The work-
research is often inadequate, which hampers the assessment of its shop and the subsequent iterative process of consultation and re-
strengths and weaknesses and of a study’s generalizability. The vision resulted in a checklist of 22 items (the STROBE Statement)
Strengthening the Reporting of Observational Studies in Epidemi- that relate to the title, abstract, introduction, methods, results, and
ology (STROBE) Initiative developed recommendations on what discussion sections of articles. Eighteen items are common to all 3
should be included in an accurate and complete report of an study designs and 4 are specific for cohort, case– control, or cross-
observational study. We defined the scope of the recommendations sectional studies. A detailed Explanation and Elaboration document
to cover 3 main study designs: cohort, case– control, and cross- is published separately and is freely available at www.annals.org
sectional studies. We convened a 2-day workshop in September and on the Web sites of PLoS Medicine and Epidemiology. We
2004, with methodologists, researchers, and journal editors, to draft hope that the STROBE Statement will contribute to improving the
a checklist of items. This list was subsequently revised during sev- quality of reporting of observational studies.
eral meetings of the coordinating group and in e-mail discussions Ann Intern Med. 2007;147:573-577. www.annals.org
with the larger group of STROBE contributors, taking into account For author affiliation, see end of text.

M any questions in medical research are investigated in

observational studies (1). Much of the research into
the cause of diseases relies on cohort, case– control, or
Reporting Trials (CONSORT) Statement was developed
in 1996 and revised 5 years later (12). Many medical jour-
nals supported this initiative (13), which has helped to
cross-sectional studies. Observational studies also have a improve the quality of reports of randomized trials (14,
role in research into the benefits and harms of medical 15). Similar initiatives have followed for other research ar-
interventions (2). Randomized trials cannot answer all im- eas—for example, for the reporting of meta-analyses of
portant questions about a given intervention. For example, randomized trials (16) or diagnostic studies (17). We es-
observational studies are more suitable to detect rare or late tablished a network of methodologists, researchers, and
adverse effects of treatments and are more likely to provide journal editors to develop recommendations for the report-
an indication of what is achieved in daily medical practice ing of observational research: the Strengthening the Re-
(3). porting of Observational Studies in Epidemiology
Research should be reported transparently so that (STROBE) Statement.
readers can follow what was planned, what was done, what
was found, and what conclusions were drawn. The credi- AIMS AND USE OF THE STROBE STATEMENT
bility of research depends on a critical assessment by others
The STROBE Statement is a checklist of items that
of the strengths and weaknesses in study design, conduct,
should be addressed in articles reporting on the 3 main
and analysis. Transparent reporting is also needed to judge
study designs of analytical epidemiology: cohort, case–
whether and how results can be included in systematic
control, and cross-sectional studies. The intention is solely
reviews (4, 5). However, in published observational re-
to provide guidance on how to report observational re-
search, important information is often missing or unclear.
search well; these recommendations are not prescriptions
An analysis of epidemiologic studies published in general
for designing or conducting studies. Also, while clarity of
medical and specialist journals found that the rationale be-
reporting is a prerequisite to evaluation, the checklist is not
hind the choice of potential confounding variables was of-
an instrument to evaluate the quality of observational re-
ten not reported (6). Only a few reports of case– control
search.
studies in psychiatry explained the methods used to iden-
tify cases and controls (7). In a survey of longitudinal studies
in stroke research, 17 of 49 articles (35%) did not specify See also:
the eligibility criteria (8). Others have argued that without
sufficient clarity of reporting, the benefits of research might Web-Only
be achieved more slowly (9), and that there is a need for STROBE: Explanation and Elaboration paper by
guidance in reporting observational studies (10, 11). Vandenbroucke and colleagues
Recommendations on the reporting of research can Conversion of graphics into slides
improve reporting quality. The Consolidated Standards of
www.annals.org 16 October 2007 Annals of Internal Medicine Volume 147 • Number 8 573

Downloaded From: http://annals.org/ on 04/23/2016

 Academia and Clinic STROBE Statement

Here, we present the STROBE Statement and explain expertise to help write the Explanation and Elaboration
how it was developed. In a detailed companion paper, the paper and sought feedback from more than 30 people, who
Explanation and Elaboration article (18 –20), we justify the are listed at the end of this paper. We allowed several weeks
inclusion of the different checklist items and give method- for comments on subsequent drafts of the paper and re-
ological background and published examples of what we minded collaborators about deadlines by e-mail.
consider transparent reporting. We strongly recommend
using the STROBE checklist in conjunction with the ex- STROBE COMPONENTS
planatory article, which is available freely at www.annals
The STROBE Statement is a checklist of 22 items that
.org and on the Web sites of PLoS Medicine (www.plos
we consider essential for good reporting of observational
medicine.org) and Epidemiology (www.epidem.com).
studies (Table). These items relate to the article’s title and
abstract (item 1), the introduction (items 2 and 3), meth-
DEVELOPMENT OF THE STROBE STATEMENT ods (items 4 –12), results (items 13–17), and discussion
sections (items 18 –21) and other information (item 22 on
We established the STROBE Initiative in 2004, ob-
funding). Eighteen items are common to all 3 designs,
tained funding for a workshop, and set up a Web site
while 4 (items 6, 12, 14, and 15) are design-specific, with
(www.strobe-statement.org). We searched textbooks, bib-
different versions for all or part of the item. For some items
liographic databases, reference lists, and personal files for
(indicated by asterisks), information should be given sepa-
relevant material, including previous recommendations,
rately for cases and controls in case– control studies, or
empirical studies of reporting, and articles describing rele-
exposed and unexposed groups in cohort and cross-sec-
vant methodological research. Because observational re-
tional studies. Although presented here as a single check-
search makes use of many different study designs, we felt
list, separate checklists are available for each of the 3 study
that the scope of STROBE had to be clearly defined early
designs on the STROBE Web site.
on. We decided to focus on the 3 study designs that are
used most widely in analytical observational research: co-
hort, case– control, and cross-sectional studies. IMPLICATIONS AND LIMITATIONS
We organized a 2-day workshop in Bristol, United The STROBE Statement was developed to assist au-
Kingdom, in September 2004. Twenty-three individuals thors when writing up analytical observational studies, to
attended this meeting, including editorial staff from Annals support editors and reviewers when considering such arti-
of Internal Medicine, BMJ, Bulletin of the World Health cles for publication, and to help readers when critically
Organization, International Journal of Epidemiology, JAMA, appraising published articles. We developed the checklist
Preventive Medicine, and The Lancet, as well as epidemiol- through an open process, taking into account the experi-
ogists, methodologists, statisticians, and practitioners from ence gained with previous initiatives, in particular CON-
Europe and North America. Written contributions were SORT. We reviewed the relevant empirical evidence as
sought from 10 other individuals who declared an interest well as methodological work, and subjected consecutive
in contributing to STROBE but could not attend. Three drafts to an extensive iterative process of consultation. The
working groups identified items deemed to be important to checklist presented here is thus based on input from a large
include in checklists for each type of study. A provisional number of individuals with diverse backgrounds and per-
list of items prepared in advance (available from our Web spectives. The comprehensive explanatory article (18 –20),
site) was used to facilitate discussions. The 3 draft check- which is intended for use alongside the checklist, also ben-
lists were then discussed by all participants and, where pos- efited greatly from this consultation process.
sible, items were revised to make them applicable to all 3 Observational studies serve a wide range of purposes,
study designs. In a final plenary session, the group decided on a continuum from the discovery of new findings to the
on the strategy for finalizing and disseminating the confirmation or refutation of previous findings (18 –20).
STROBE Statement. Some studies are essentially exploratory and raise interest-
After the workshop, we drafted a combined checklist ing hypotheses. Others pursue clearly defined hypotheses
including all 3 designs and made it available on our Web in available data. In yet another type of study, the collec-
site. We invited participants and additional scientists and tion of new data is planned carefully on the basis of an
editors to comment on this draft checklist. We subse- existing hypothesis. We believe the present checklist can be
quently published 3 revisions on the Web site and 2 sum- useful for all these studies, since the readers always need to
maries of comments received and changes made. During know what was planned (and what was not), what was
this process, the coordinating group (i.e., the authors of the done, what was found, and what the results mean. We
present paper) met on 8 occasions for 1 or 2 days and held acknowledge that STROBE is currently limited to 3 main
several telephone conferences to revise the checklist and to observational study designs. We would welcome extensions
prepare the present paper and the Explanation and Elabo- that adapt the checklist to other designs—for example,
ration paper (18 –20). The coordinating group invited 3 case-crossover studies or ecological studies—and also to
additional co-authors with methodological and editorial specific topic areas. Four extensions are now available for
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 STROBE Statement Academia and Clinic

Table. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Statement: Checklist of Items That
Should Be Addressed in Reports of Observational Studies

Item Item Recommendation

Number
Title and abstract 1 (a) Indicate the study’s design with a commonly used term in the title or the abstract.
(b) Provide in the abstract an informative and balanced summary of what was done and what was found.
Introduction
Background/ 2 Explain the scientific background and rationale for the investigation being reported.
rationale
Objectives 3 State specific objectives, including any prespecified hypotheses.
Methods
Study design 4 Present key elements of study design early in the paper.
Setting 5 Describe the setting, locations, and relevant dates, including periods of recruitment, exposure, follow-up, and data
collection.
Participants 6 (a) Cohort study: Give the eligibility criteria, and the sources and methods of selection of participants. Describe
methods of follow-up.
Case–control study: Give the eligibility criteria, and the sources and methods of case ascertainment and control
selection. Give the rationale for the choice of cases and controls.
Cross-sectional study: Give the eligibility criteria, and the sources and methods of selection of participants.
(b) Cohort study: For matched studies, give matching criteria and number of exposed and unexposed.
Case–control study: For matched studies, give matching criteria and the number of controls per case.
Variables 7 Clearly define all outcomes, exposures, predictors, potential confounders, and effect modifiers. Give diagnostic criteria,
if applicable.
Data sources/ 8* For each variable of interest, give sources of data and details of methods of assessment (measurement). Describe
measurement comparability of assessment methods if there is more than one group.
Bias 9 Describe any efforts to address potential sources of bias.
Study size 10 Explain how the study size was arrived at.
Quantitative 11 Explain how quantitative variables were handled in the analyses. If applicable, describe which groupings were chosen,
variables and why.
Statistical 12 (a) Describe all statistical methods, including those used to control for confounding.
methods (b) Describe any methods used to examine subgroups and interactions.
(c) Explain how missing data were addressed.
(d) Cohort study: If applicable, explain how loss to follow-up was addressed.
Case–control study: If applicable, explain how matching of cases and controls was addressed.
Cross-sectional study: If applicable, describe analytical methods taking account of sampling strategy.
(e) Describe any sensitivity analyses.
Results
Participants 13* (a) Report the numbers of individuals at each stage of the study—e.g., numbers potentially eligible, examined for
eligibility, confirmed eligible, included in the study, completing follow-up, and analyzed.
(b) Give reasons for nonparticipation at each stage.
(c) Consider use of a flow diagram.
Descriptive data 14* (a) Give characteristics of study participants (e.g., demographic, clinical, social) and information on exposures and
potential confounders.
(b) Indicate the number of participants with missing data for each variable of interest.
(c) Cohort study: Summarize follow-up time—e.g., average and total amount.
Outcome data 15* Cohort study: Report numbers of outcome events or summary measures over time.
Case–control study: Report numbers in each exposure category or summary measures of exposure.
Cross-sectional study: Report numbers of outcome events or summary measures.
Main results 16 (a) Give unadjusted estimates and, if applicable, confounder-adjusted estimates and their precision (e.g., 95%
confidence intervals). Make clear which confounders were adjusted for and why they were included.
(b) Report category boundaries when continuous variables were categorized.
(c) If relevant, consider translating estimates of relative risk into absolute risk for a meaningful time period.
Other analyses 17 Report other analyses done—e.g., analyses of subgroups and interactions and sensitivity analyses.

Discussion
Key results 18 Summarize key results with reference to study objectives.
Limitations 19 Discuss limitations of the study, taking into account sources of potential bias or imprecision. Discuss both direction and
magnitude of any potential bias.
Interpretation 20 Give a cautious overall interpretation of results considering objectives, limitations, multiplicity of analyses, results from
similar studies, and other relevant evidence.
Generalizability 21 Discuss the generalizability (external validity) of the study results.
Other information
Funding 22 Give the source of funding and the role of the funders for the present study and, if applicable, for the original study
on which the present article is based.

*Give such information separately for cases and controls in case– control studies, and, if applicable, for exposed and unexposed groups in cohort and cross-sectional studies.

An Explanation and Elaboration article (18 –20) discusses each checklist item and gives methodological background and published examples of transparent reporting. The
STROBE checklist is best used in conjunction with this article (freely available at www.annals.org and on the Web sites of PLoS Medicine [www.plosmedicine.org] and
Epidemiology [www.epidem.com]). Separate versions of the checklist for cohort, case– control, and cross-sectional studies are available on the STROBE Web site (www.strobe-
statement.org).

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 Academia and Clinic STROBE Statement

the CONSORT Statement (21–24). A first extension to We welcome suggestions for the further dissemination of
STROBE is under way for gene– disease association stud- STROBE—for example, by re-publication of the present
ies: the STROBE Extension to Genetic Association studies article in specialist journals and in journals published in
(STREGA) initiative (25). We ask those who aim to de- other languages. Groups or individuals who intend to
velop extensions of the STROBE Statement to contact the translate the checklist to other languages should consult the
coordinating group first to avoid duplication of effort. coordinating group beforehand. We will revise the check-
The STROBE Statement should not be interpreted as list in the future, taking into account comments, criticism,
an attempt to prescribe the reporting of observational re- new evidence, and experience from its use. We invite read-
search in a rigid format. The checklist items should be ers to submit their comments via the STROBE Web site
addressed in sufficient detail and with clarity somewhere in (www.strobe-statement.org).
an article, but the order and format for presenting infor-
mation depends on author preferences, journal style, and From the Institute of Social and Preventive Medicine, University of
the traditions of the research field. For instance, we discuss Bern, Bern, Switzerland; Centre for Statistics in Medicine, University of
Oxford, Oxford, United Kingdom; University of Bristol, Bristol, United
the reporting of results under a number of separate items, Kingdom; London School of Hygiene and Tropical Medicine, Univer-
while recognizing that authors might address several items sity of London, London, United Kingdom; Nordic Cochrane Centre,
within a single section of text or in a table. Also, item 22, Copenhagen, Denmark; and Leiden University Hospital, Leiden, the
on the source of funding and the role of funders, could be Netherlands.
addressed in an appendix or in the methods section of the
article. We do not aim at standardizing reporting. Authors Note: The following individuals have contributed to the content and
of randomized clinical trials were asked by an editor of a elaboration of the STROBE Statement: Douglas G. Altman, Maria
Blettner, Paolo Boffetta, Hermann Brenner, Geneviève Chêne, Cyrus
specialist medical journal to “CONSORT” their manu-
Cooper, George Davey-Smith, Erik von Elm, Matthias Egger, France
scripts on submission (26). We believe that manuscripts Gagnon, Peter C. Gøtzsche, Philip Greenland, Sander Greenland, Claire
should not be “STROBEd,” in the sense of regulating style Infante-Rivard, John Ioannidis, Astrid James, Giselle Jones, Bruno Le-
or terminology. We encourage authors to use narrative el- dergerber, Julian Little, Margaret May, David Moher, Hooman Momen,
ements, including the description of illustrative cases, to Alfredo Morabia, Hal Morgenstern, Cynthia D. Mulrow, Fred Paccaud,
complement the essential information about their study, Stuart J. Pocock, Charles Poole, Martin Röösli, Dietrich Rothenbacher,
and to make their articles an interesting read (27). Kenneth Rothman, Caroline Sabin, Willi Sauerbrei, Lale Say, James J.
Schlesselman, Jonathan Sterne, Holly Syddall, Jan P. Vandenbroucke,
We emphasize that the STROBE Statement was not
Ian White, Susan Wieland, Hywel Williams, and Guang Yong Zou.
developed as a tool for assessing the quality of published
observational research. Such instruments have been devel- Acknowledgments: The authors thank Gerd Antes, Kay Dickersin,
oped by other groups and were the subject of a recent Shah Ebrahim, and Richard Lilford for supporting the STROBE Initia-
systematic review (28). In the Explanation and Elaboration tive. They also thank the following institutions that have hosted working
paper, we used several examples of good reporting from meetings of the coordinating group: Institute of Social and Preventive
studies whose results were not confirmed in further re- Medicine, University of Bern, Bern, Switzerland; Department of Social
Medicine, University of Bristol, Bristol, United Kingdom; London
search—the important feature was the good reporting, not
School of Hygiene and Tropical Medicine, London, United Kingdom;
whether the research was of good quality. However, if Nordic Cochrane Centre, Copenhagen, Denmark; and Centre for Sta-
STROBE is adopted by authors and journals, issues such as tistics in Medicine, University of Oxford, Oxford, United Kingdom.
confounding, bias, and generalizability could become more Finally, they thank the 6 reviewers who provided helpful comments on a
transparent, which might help temper the overenthusiastic previous draft of this paper.
reporting of new findings in the scientific community and
popular media (29) and improve the methodology of stud- Grant Support: The workshop was funded by the European Science
ies in the long term. Better reporting may also help to have Foundation. Additional funding was received from the Medical Research
Council Health Services Research Collaboration and the National
more informed decisions about when new studies are Health Services Research & Development Methodology Programme.
needed and what they should address.
We did not undertake a comprehensive systematic re- Potential Financial Conflicts of Interest: None disclosed.
view for each of the checklist items and subitems or do our
own research to fill gaps in the evidence base. Further, Requests for Single Reprints: Erik von Elm, MD, Institute of Social
although no one was excluded from the process, the com- and Preventive Medicine, University of Bern, Finkenhubelweg 11, CH-
position of the group of contributors was influenced by 3012 Bern, Switzerland; e-mail, [email protected].
existing networks and was not representative in terms of
Current author addresses are available at www.annals.org.
geography (it was dominated by contributors from Europe
and North America) and probably was not representative
in terms of research interests and disciplines. We stress that
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research should be seen as evolving documents that require BMJ. 2004;328:39-41. [PMID: 14703546]
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health care. BMJ. 1996;312:1215-8. [PMID: 8634569] accurate reporting of studies of diagnostic accuracy: The STARD Initiative. Ann
3. Papanikolaou PN, Christidi GD, Ioannidis JP. Comparison of evidence on Intern Med. 2003;138:40-4. [PMID: 12513043]
harms of medical interventions in randomized and nonrandomized studies. 18. Vandenbroucke JP, von Elm E, Altman DG, Gøtzsche PC, Mulrow CD,
CMAJ. 2006;174:635-41. [PMID: 16505459] Pocock SJ, et al., for the STROBE Initiative. Strengthening the Reporting of
4. Jüni P, Altman DG, Egger M. Systematic reviews in health care: Assessing the Observational Studies in Epidemiology (STROBE): explanation and elaboration.
quality of controlled clinical trials. BMJ. 2001;323:42-6. [PMID: 11440947] Ann Intern Med. 2007;147:W-164.
5. Egger M, Schneider M, Davey Smith G. Spurious precision? Meta-analysis of 19. Vandenbroucke JP, von Elm E, Altman DG, Gøtzsche PC, Mulrow CD,
observational studies. BMJ. 1998;316:140-4. [PMID: 9462324] Pocock SJ, et al., for the STROBE Initiative. Strengthening the Reporting of
6. Pocock SJ, Collier TJ, Dandreo KJ, de Stavola BL, Goldman MB, Kalish Observational Studies in Epidemiology (STROBE): explanation and elaboration.
LA, et al. Issues in the reporting of epidemiological studies: a survey of recent PLoS Med. 2007;4:e297.
practice. BMJ. 2004;329:883. [PMID: 15469946] 20. Vandenbroucke JP, von Elm E, Altman DG, Gøtzsche PC, Mulrow CD,
7. Lee W, Bindman J, Ford T, Glozier N, Moran P, Stewart R, et al. Bias in Pocock SJ, et al., for the STROBE Initiative. Strengthening the Reporting of
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8. Tooth L, Ware R, Bain C, Purdie DM, Dobson A. Quality of reporting of 21. Ioannidis JP, Evans SJ, Gøtzsche PC, O’Neill RT, Altman DG, Schulz K,
observational longitudinal research. Am J Epidemiol. 2005;161:280-8. [PMID: et al.; CONSORT Group. Better reporting of harms in randomized trials: an
15671260] extension of the CONSORT statement. Ann Intern Med. 2004;141:781-8.
9. Bogardus ST Jr, Concato J, Feinstein AR. Clinical epidemiological quality in [PMID: 15545678]
molecular genetic research: the need for methodological standards. JAMA. 1999; 22. Campbell MK, Elbourne DR, Altman DG; CONSORT group. CON-
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14. Plint AC, Moher D, Morrison A, Schulz K, Altman DG, Hill C, et al. Does Networks. A road map for efficient and reliable human genome epidemiology.
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16. Moher D, Cook DJ, Eastwood S, Olkin I, Rennie D, Stroup DF. Improv- 28. Sanderson S, Tatt ID, Higgins JP. Tools for assessing quality and suscepti-
ing the quality of reports of meta-analyses of randomised controlled trials: the bility to bias in observational studies in epidemiology: a systematic review and
QUOROM statement. Quality of Reporting of Meta-analyses. Lancet. 1999; annotated bibliography. Int J Epidemiol. 2007;36:666-76. [PMID: 17470488]
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 Annals of Internal Medicine
Current Author Addresses: Drs. von Elm and Egger: University of Dr. Gøtzsche: The Nordic Cochrane Centre, Rigshospitalet, Depart-
Bern, Institute of Social and Preventive Medicine, Finkenhubelweg 11, ment 7112, Blegdamsvej 9, DK-2100 Copenhagen Ø, Denmark.
CH-3012 Bern, Switzerland. Dr. Vandenbroucke: Department of Clinical Epidemiology, Leiden Uni-
Dr. Altman: Centre for Statistics in Medicine, Wolfson College Annexe, versity Medical Center, PO Box 9600, 2300 RC Leiden, The Nether-
Linton Road, Oxford OX2 6UD, United Kingdom. lands.
Dr. Pocock: Medical Statistics Unit, London School of Hygiene and
Tropical Medicine, Keppel Street, London WC1E 7HT, United King-
dom.

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The ARRIVE guidelines
Animal Research: Reporting In Vivo Experiments
Carol Kilkenny1, William J Browne2, Innes C Cuthill3, Michael Emerson4 and Douglas G Altman5
1
The National Centre for the Replacement, Refinement and Reduction of Animals in Research, London, UK , 2School of Veterinary Science,
University of Bristol, Bristol, UK, 3School of Biological Sciences, University of Bristol, Bristol, UK, 4National Heart and Lung Institute, Imperial College
London, UK, 5Centre for Statistics in Medicine, University of Oxford, Oxford, UK

ITEM RECOMMENDATION

TITLE 1 Provide as accurate and concise a description of the content of the article as possible.

ABSTRACT 2 Provide an accurate summary of the background, research objectives, including details of
the species or strain of animal used, key methods, principal findings and conclusions of
the study.

INTRODUCTION
Background 3 a. Include sufficient scientific background (including relevant references to previous
work) to understand the motivation and context for the study, and explain the
experimental approach and rationale.
b. Explain how and why the animal species and model being used can address the
scientific objectives and, where appropriate, the study’s relevance to human biology.
Objectives 4 Clearly describe the primary and any secondary objectives of the study, or specific
hypotheses being tested.

METHODS
Ethical statement 5 Indicate the nature of the ethical review permissions, relevant licences (e.g. Animal
[Scientific Procedures] Act 1986), and national or institutional guidelines for the care and
use of animals, that cover the research.
Study design 6 For each experiment, give brief details of the study design including:
a. The number of experimental and control groups.
b. Any steps taken to minimise the effects of subjective bias when allocating animals to
treatment (e.g. randomisation procedure) and when assessing results (e.g. if done,
describe who was blinded and when).
c. The experimental unit (e.g. a single animal, group or cage of animals).
A time-line diagram or flow chart can be useful to illustrate how complex study designs
were carried out.
Experimental procedures 7 For each experiment and each experimental group, including controls, provide precise
details of all procedures carried out. For example:
a. How (e.g. drug formulation and dose, site and route of administration, anaesthesia
and analgesia used [including monitoring], surgical procedure, method of euthanasia).
Provide details of any specialist equipment used, including supplier(s).
b. When (e.g. time of day).
c. Where (e.g. home cage, laboratory, water maze).
d. Why (e.g. rationale for choice of specific anaesthetic, route of administration, drug
dose used).
Experimental animals 8 a. Provide details of the animals used, including species, strain, sex, developmental
stage (e.g. mean or median age plus age range) and weight (e.g. mean or median
weight plus weight range).
b. Provide further relevant information such as the source of animals, international strain
nomenclature, genetic modification status (e.g. knock-out or transgenic), genotype,
health/immune status, drug or test naïve, previous procedures, etc.

The ARRIVE guidelines: Animal Research: Reporting In Vivo Experiments

 ITEM RECOMMENDATION
Housing and husbandry 9 Provide details of:
a. Housing (type of facility e.g. specific pathogen free [SPF]; type of cage or housing;
bedding material; number of cage companions; tank shape and material etc. for fish).
b. Husbandry conditions (e.g. breeding programme, light/dark cycle, temperature,
quality of water etc for fish, type of food, access to food and water, environmental
enrichment).
c. Welfare-related assessments and interventions that were carried out prior to, during,
or after the experiment.
Sample size 10 a. Specify the total number of animals used in each experiment, and the number of
animals in each experimental group.
b. Explain how the number of animals was arrived at. Provide details of any sample size
calculation used.
c. Indicate the number of independent replications of each experiment, if
relevant.
Allocating animals to 11 a. Give full details of how animals were allocated to experimental groups, including
experimental groups randomisation or matching if done.
b. Describe the order in which the animals in the different experimental groups were
treated and assessed.
Experimental outcomes 12 Clearly define the primary and secondary experimental outcomes assessed (e.g. cell
death, molecular markers, behavioural changes).
Statistical methods 13 a. Provide details of the statistical methods used for each analysis.
b. Specify the unit of analysis for each dataset (e.g. single animal, group of animals,
single neuron).
c. Describe any methods used to assess whether the data met the assumptions of the
statistical approach.

RESULTS
Baseline data 14 For each experimental group, report relevant characteristics and health status of animals
(e.g. weight, microbiological status, and drug or test naïve) prior to treatment or testing.
(This information can often be tabulated).
Numbers analysed 15 a. Report the number of animals in each group included in each analysis. Report absolute
†
numbers (e.g. 10/20, not 50% ).
b. If any animals or data were not included in the analysis, explain why.
Outcomes and estimation 16 Report the results for each analysis carried out, with a measure of precision (e.g.
standard error or confidence interval).
Adverse events 17 a. Give details of all important adverse events in each experimental group.
b. Describe any modifications to the experimental protocols made to reduce adverse
events.

DISCUSSION
Interpretation/scientific 18 a. Interpret the results, taking into account the study objectives and hypotheses, current
implications theory and other relevant studies in the literature.
b. Comment on the study limitations including any potential sources of bias, any
†
limitations of the animal model, and the imprecision associated with the results .
c. Describe any implications of your experimental methods or findings for the
replacement, refinement or reduction (the 3Rs) of the use of animals in research.
Generalisability/ 19 Comment on whether, and how, the findings of this study are likely to translate to other
translation species or systems, including any relevance to human biology.
Funding 20 List all funding sources (including grant number) and the role of the funder(s) in the
study.

The ARRIVE guidelines: Animal Research: Reporting In Vivo Experiments

 The guidelines are intended to: How might these guidelines be used?
 Improve reporting of research using animals. The guidelines provide a checklist for those preparing or
reviewing a manuscript intended for publication.
 Guide authors as to the essential information to
include in a manuscript, and not be absolutely
prescriptive. References

 Be flexible to accommodate reporting a wide 1. Kilkenny C, Browne WJ, Cuthill IC, Emerson M, Altman DG
range of research areas and experimental (2010) Improving Bioscience Research Reporting: The
protocols. ARRIVE Guidelines for Reporting Animal Research. PLoS Biol
8(6): e1000412. doi:10.1371/journal.pbio.1000412
 Promote reproducible, transparent, accurate, 2. Schulz KF, Altman DG, Moher D, the CONSORT Group
comprehensive, concise, logically ordered, well (2010) CONSORT 2010 Statement: updated guidelines for
written manuscripts. reporting parallel group randomised trials. BMJ 340:c332.
 Improve the communication of the research
findings to the broader scientific community. Acknowledgements
The NC3Rs gratefully acknowledges the expertise and
The guidelines are NOT intended to: advice that all the contributors have given to developing
 Promote uniformity, stifle creativity, or encourage the guidelines. We would particularly like to acknowledge
authors to adhere rigidly to all items in the the contribution of the NC3Rs Reporting Guidelines Working
checklist. Some of the items may not apply to all Group† – Professor Doug Altman, Centre for Statistics in
studies, and some items can be presented as Medicine, University of Oxford UK, Professor David Balding,
tables/figure legends or flow diagrams (e.g. the Department of Epidemiology & Public Health, Imperial
numbers of animals treated, assessed and College, London UK, Professor William Browne, Department
analysed). of Clinical Veterinary Science, University of Bristol UK,
Professor Innes Cuthill, School of Biological Sciences,
 Be a guide for study design and conduct. University of Bristol UK, Dr Colin Dunn, Editor Laboratory
However, some items on the checklist, such as Animals (Royal Society of Medicine press), Dr Michael
randomisation, blinding and using comparator Emerson, National Heart and Lung Institute, Imperial
groups, may be useful when planning College, London UK, Dr Stella Hurtley, Senior Editor Science,
experiments as their use will reduce the risk of Professor Ian McGrath, Editor-in-Chief British Journal of
bias and increase the robustness of the research. Pharmacology (Wiley Blackwell Publishers) and Dr Clare
Stanford, Department of Psychopharmacology, University
What kind of research areas do the guidelines College, London UK. We would also like to thank NC3Rs
apply to? grant holders, the Medical Research Council, Biotechnology
and Biological Sciences Research Council (BBSRC),
 The guidelines will be most appropriate for
Wellcome Trust, Parkinson’s Disease Society, British Heart
comparative studies, where two or more groups
Foundation and their grant holders and funding committee
of experimental animals are being compared;
members who provided feedback on the guidelines; and
often one or more of the groups may be
Kathryn Chapman and Vicky Robinson (both NC3Rs) for
considered as a control. They apply also to studies
their help with the manuscript.
comparing different drug doses, or, for example,
where a single animal is used as its own control †Please note: that the working group members who
(within–subject experiment). contributed to these guidelines were advising in their
 Most of the recommendations also apply to personal capacity and their input does not necessarily
studies that do not have a control group. represent the policy of the organisations with which they
are associated.
 The guidelines are suitable for any area of
bioscience research where laboratory animals are Funding
used.
The reporting guidelines project was funded by the
Who are the guidelines aimed at? National Centre for the Replacement, Refinement and
Reduction of Animals in Research (NC3Rs).
 Novice and experienced authors
 Journal editors
 Peer reviewers
 Funding bodies

The ARRIVE guidelines: Animal Research: Reporting In Vivo Experiments

 CONSORT 2010 checklist of information to include when reporting a randomised trial *

Item Reported
Section/Topic No Checklist item on page No
Title and abstract
1a Identification as a randomised trial in the title
1b Structured summary of trial design, methods, results, and conclusions (for specific guidance see CONSORT for abstracts)
Introduction
Background and 2a Scientific background and explanation of rationale
objectives 2b Specific objectives or hypotheses

Methods
Trial design 3a Description of trial design (such as parallel, factorial) including allocation ratio
3b Important changes to methods after trial commencement (such as eligibility criteria), with reasons
Participants 4a Eligibility criteria for participants
4b Settings and locations where the data were collected
Interventions 5 The interventions for each group with sufficient details to allow replication, including how and when they were
actually administered
Outcomes 6a Completely defined pre-specified primary and secondary outcome measures, including how and when they
were assessed
6b Any changes to trial outcomes after the trial commenced, with reasons
Sample size 7a How sample size was determined
7b When applicable, explanation of any interim analyses and stopping guidelines
Randomisation:
Sequence 8a Method used to generate the random allocation sequence
generation 8b Type of randomisation; details of any restriction (such as blocking and block size)
Allocation 9 Mechanism used to implement the random allocation sequence (such as sequentially numbered containers),
concealment describing any steps taken to conceal the sequence until interventions were assigned
mechanism
Implementation 10 Who generated the random allocation sequence, who enrolled participants, and who assigned participants to
interventions
Blinding 11a If done, who was blinded after assignment to interventions (for example, participants, care providers, those

CONSORT 2010 checklist Page 1

 assessing outcomes) and how
11b If relevant, description of the similarity of interventions
Statistical methods 12a Statistical methods used to compare groups for primary and secondary outcomes
12b Methods for additional analyses, such as subgroup analyses and adjusted analyses
Results
Participant flow (a 13a For each group, the numbers of participants who were randomly assigned, received intended treatment, and
diagram is strongly were analysed for the primary outcome
recommended) 13b For each group, losses and exclusions after randomisation, together with reasons
Recruitment 14a Dates defining the periods of recruitment and follow-up
14b Why the trial ended or was stopped
Baseline data 15 A table showing baseline demographic and clinical characteristics for each group
Numbers analysed 16 For each group, number of participants (denominator) included in each analysis and whether the analysis was
by original assigned groups
Outcomes and 17a For each primary and secondary outcome, results for each group, and the estimated effect size and its
estimation precision (such as 95% confidence interval)
17b For binary outcomes, presentation of both absolute and relative effect sizes is recommended
Ancillary analyses 18 Results of any other analyses performed, including subgroup analyses and adjusted analyses, distinguishing
pre-specified from exploratory
Harms 19 All important harms or unintended effects in each group (for specific guidance see CONSORT for harms)
Discussion
Limitations 20 Trial limitations, addressing sources of potential bias, imprecision, and, if relevant, multiplicity of analyses
Generalisability 21 Generalisability (external validity, applicability) of the trial findings
Interpretation 22 Interpretation consistent with results, balancing benefits and harms, and considering other relevant evidence
Other information
Registration 23 Registration number and name of trial registry
Protocol 24 Where the full trial protocol can be accessed, if available
Funding 25 Sources of funding and other support (such as supply of drugs), role of funders

*We strongly recommend reading this statement in conjunction with the CONSORT 2010 Explanation and Elaboration for important clarifications on all the items. If relevant, we also
recommend reading CONSORT extensions for cluster randomised trials, non-inferiority and equivalence trials, non-pharmacological treatments, herbal interventions, and pragmatic trials.
Additional extensions are forthcoming: for those and for up to date references relevant to this checklist, see www.consort-statement.org.

CONSORT 2010 checklist Page 2

 Black -Slides Integration Session – 1st sem
Blue Italics- Audio
Green – additional notes from slides SLU SOM - Batch 2018 Integration Team

GUIDE QUESTIONS
Outline:
- Patient’s profile
What structures are involved in fluid and electrolyte
- To be discussed: 1 absorption in the intestines? (describe both gross
 Anatomy and microscopic structures)
 Physiology - Anatomical basis of absorption
 Clinical manifestations
 Total quantity of fluid absorbed each day in the
 Clinic-pathological correlation
 Etiology and laboratory tests intestines is 8-9 liters
 Pharmacology/ management  The total quantity of fluid that must be absorbed
 Epidemiologic investigation each day by the intestines is equal to the ingested
fluid plus that which is secreted in the various
Patient’s Profile gastrointestinal secretions
 All but 1.5 liters are absorbed in the small intestine
Patient’s profile leaving only 1.5 liters to pass through the ileocecal
valve into the colon each day.
Male 3 - Year - old

Chief Complaints:

Fever Vomiting Diarrhea

Social and environmental history:

Several classmates in the

No adult members of the
same day care center were
household are ill SMALL INTESTINES
also sick
- the small intestine has an average length of 22 feet and is
divided into 3 parts : duodenum, jejunum and ileum
Past medical history: - The structures important for absorption of water and
electrolytes in the small intestines include Valvulae
No significant events conniventes, Villi, and microvilli

Physical examination:

Temperature 37.9°C

Heart rate Tachycardic

Mucous membranes Dry

Appearance Sunken eyeballs

Non-tender with hyperactive

Abdomen
bowel sounds

Laboratory test:

Watery consistency
Stool Exam

No blood

No fecal leukocytes
- (picture) - absorptive surface of the small intestinal mucosa -
many gross folds called Valvulae conniventes (or folds of
Kerckring or Plicae circulares); they increase the surface area of
the absorptive mucosa by about threefold.
- These folds extend circularly most of the way around the
intestine; especially well developed in the duodenum and
jejunum - each fold is covered by minute structures called Villi
- Located on the epithelial surface of the small intestine up
to the ileocecal valve are millions of small villi.

- Intestinal glands and the intestinal lumen - lined by

goblet and absorptive cells, with a small number of
enteroendocrine cells
- Colonocytes – Absorptive cells
- Goblet cells – produce lubricating mucus

High power view of colonocytes and goblet cells.

Red box – colonocytes with irregular microvilli
Yellow box - goblet cell which functions to produce mucus
in the intestines.
Orange box – dilated intercellular spaces with
interdigitating leaflets of cell membrane indicating active
fluid absorption in the lumen of the large intestine. (TEM-
LARGE INTESTINES transmission electron microscope)
- Has a greater diameter than the small intestines
- Wall contains haustrations – series of large sacs What mechanisms are involved in fluid and
2
electrolyte absorption in the intestines?
- Water and electrolytes may cross the intestinal
INTEGRATION SESSION – 1ST SEM

epithelial cells by either transcellular or paracellular

routes

Water Osmosis via paracellular route

Electrolytes Transcellular or paracellular
- Active and passive transports

2
− There are 2 major mechanisms by which water and Potassium Small intestine:
electrolytes may cross the intestinal epithelial cells these are - Passive diffusion via paracellular route
either through transcellular or paracellular route. Large intestine:
- 90 – 95% of water absorption takes place in the small
- K+ secretion in the lumen via K+
intestine though osmosis via paracellular route. (which
channels is driven by basolateral Na-K-
means that water pass through the junctions to be absorbed)
o Absorption of water is entirely dependent on absorption ATPase pumps
of solutes, primarily Na
+ - Stimulated by aldosterone
- Transcellular – Passage from the lumen, through the cell, to Calcium Passive from lumen into the cell
the blood. (paracellular routes)
- Electrolyte absorption makes use of either trancellular or Intracellularly:
paracellular routes with the aid of active and passive - Ca-binding proteins
transporters Cell to blood:
- Ca – ATPase
- Na – Ca exchange

*Calcitriol-dependent expression
- Potassium is absorbed through the small intestine passively
and through the large intestine through secretion in the
lumen via K channels driven by basolateral Na-K atpase
pumps which is stimulated by aldosterone
- Calcium also is passively absorbed into the cell through
ELECTROLYTES paracellular route
Sodium Small intestine: - It can also be absorbed through trancellular route. With this
- Na+ - glucose cotransport it needs Ca- binding protein which is produced by Calcitriol.
- Na+ - amino acid cotransport This is the reason why absorption of Ca is said to be Vit. D
dependent
- Na+ - H+ exchange
- For calcium, vitamin D is needed for absorption. Vitamin D
Colon:
will produce a calcium binding protein which is calbindin.
- Passive diffusion via Na+ channels Intracellularly, calcium will bind with binding proteins where
- Stimulated by aldosterone it can either be for storage or excretion. For excretion, the
Chloride Small intestine: calcium are released and then it will bind with Calcium
- Passive diffusion via paracellular route ATPase or Sodium-calcium exchanger to be excreted in the
- Cl – HCO3 antiporter blood.
- Na+ - Cl cotransport
Colon:
- Cl – HCO3 antiporter

- When it comes to the absorption of electrolytes this would

involve absorption through the small intestine and in the
colon.
- Na Is pumped out of the cell against its electrochemical
gradient by the Na K pump into the basolateral membranes
- Chloride is absorbed in the small intestine through passive
diffusion via paracellular route and through these
transporters
- It is also absorbed in the colon through Cl-HCHO3 antiporter
What electrolyte abnormality is expected in this
3
patient? (explain)

Electrolyte abnormalities
1) Metabolic alkalosis
INTEGRATION SESSION – 1ST SEM

2) Metabolic acidosis
3) Hypokalemia
4) Hyponatremia
5) Hypochloremia

3
 What are the mechanisms underlying the clinical
4
manifestations of this patient?

Recall:

- To properly manage our patient it is important that we

investigate what brought about the manifestations. As we
recall, the patient had fever, vomiting, diarrhea, tachycardia,
dry mucous membranes and sunken eyeballs, which we can
cluster as signs and symptoms of Acute Gastroenteritis or A-G-
E.

Acute gastroenteritis
- “AGE” is the number one cause of consult in the
Aldosterone affects the Principal cell pediatric emergency room of the Philippine General
- Na reabsorption consequently leads to K secretion Hospital – Pediatric Infectious Disease Society of the Philippines
- It also affects Alpha intercalated cell. Journal
- Aldosterone stimulates H- adenosine triphosphatase
which facilitates the secretion of H Risk Factors
- Increase in the aldosterone will cause the reabsorption of - AGE: 5 years old
Na and water in return there will be a subsequent - CROWD EXPOSURE: attends day care center
secretion of K -> hypokalemia - Our patient’s age is a significant risk factor
- It is an established fact that children 5 years of age and
below, are more vulnerable to different diseases given their
less developed immunity.
- At this age group, ACUTE GASTROENTERITIS IS ALSO
COMMON.

- Secondly, the patient had crowd exposure where he could

have contracted the pathogen causing his condition.

Hypokalemia
INTEGRATION SESSION – 1ST SEM

Suppoorted by a study published in the Journal of Pediatric

Infectious Diseases last 2011, Entitled “Viral etiology and incidence
of acute gastroenteritis in young children attending day-care
centers.”

4
 -

INTEGRATION SESSION – 1ST SEM

5
 What etiologic agent is most likely responsible for - Rotavirus is a virus that infects the bowels, causing a
5 gastroenteritis (inflammation of the stomach and bowels).
the patient’s condition?
Rotavirus is the most common cause of severe diarrhea among
Acute Diarrhea: Watery, without blood, pus, or mucus infants and pre-school children throughout the world. Infection
is caused by person-to-person contact, such as touching
This means that the etiologic agent is minimally invasive. The
contaminated hands or feces.
most common causes of minimally invasive diarrhea are ff:
(arranged from the most common to the least common)
What diagnostic test will you request to confirm your
diagnosis and to rule out other differential diagnoses?
For letter B, they are responsible for watery diarrhea which
The 2 most common tests that we can rationally request from
maybe caused by preformed toxins rather than bacteria that
the emergency room if the patient will present with acute
is why it is less invasive.
diarrhea are CBC and fecalysis.
A. B. C.
Virus Preformed Toxins: Parasites
1. Complete Blood Count
Bacteria
Rotavirus Staphylococcus aureus Cryptosporidium
Etiologic agent Possible Results
Astrovirus Bacillus cereus Giardia lamblia
Viral Decrease in neutrophils
Calicivirus Clostridium perfringens
Increased lymphocytes
Clostridium difficile
Bacterial Increased neutrophils
Vibrio cholerae
Decreased lymphocytes
Eschericia coli
Parasitic Increased eosinophil
How can we rule out the different etiologic agents for this
- Blood panel which measures the quantity of all the different
case?
types of cells namely Red Blood cells, White Blood cells and
Pre-formed toxins: Bacterial Platelets
Ettiologic agent Rule out - Routine Screen test which aids in the diagnosis of different
Staphylococcus aureus Projectile vomiting, diseases such as acute and chronic infection of different
infrequent diarrhea etiologies, dehydration, fluid loss, etc.
Duration: <1 day - White Blood Cell Count (WBC) is the total number of white
Bacillus cereus Duration: <1 day blood cells. A high WBC usually means that the body is
Clostridium perfringens Fever is uncommon fighting an infection. Five types of white blood cells:
neutrophils, lymphocytes, monocytes, eosinophils and
Duration: <1 day
basophils. These are reported as a percentage of the WBC.
Clostridium difficile Associated with anti-biotic
use
2. Fecalysis
Vibrio cholerae Rice watery stool
Escherichia coli No vomiting or fever Etiologic agent Possible Result
Viral Watery, without blood, pus, or
Parasitic infection: mucus
Etiologic agent Rule out Bacterial Non-bloody or bloody mucoid
Giardia lamblia Diarrhea, stomach cramps, stool. Presence of leukocytes, red
gas blood cells, and pus cells
Duration: days to weeks Parasitic Non-bloody or bloody stool.
Cryptosporidium Mucosa inflammed, with Presence of eggs, trophozoites, or
infiltration of neutrophils, adult worms
macrophages and
lymphocytes
Should anti-diarrheal or antibiotics be given to this
6
patient? How should you manage this patient?
This leads us to the conclusion that the etiologic agent in this
case is a virus. Among pediatric patients, the most implicated Should anti-diarrheal or antibiotic be given to this
INTEGRATION SESSION – 1ST SEM

virus that causes diarrhea is the rotavirus. patient?

Rotavirus - NO
o Anti-diarrheal
o Antibiotic medications
Anti-diarrheals are not given because it has been shown in
studies that these drugs will not have beneficial effects in
acute viral gastroenteritis and may pose side effects such
drowsiness and nausea.

6
Antibiotic medications has no indications in the patient’s case. o Did the students eat something similar at one time
prior to the onset of the S/S?
Symptoms of viral infections usually go away  - In order to make a hypothesis, first know the possible sources
How should you manage this patient? of infection, mode of onset (is it explosive{single exposure or
o Primary goal: multiple exposure} or gradual{spread follows the route of travel
or movement of people}), pattern of spread (is it common
 Reduce symptoms
source patters, propagated, or mixed)
 Prevent complications
o Replace fluids and electrolytes as estimated by the
4) Hypothesis testing
degree of dehydration
- Determine the attack rate and the vehicle of infection
o Oral rehydration therapy for ongoing loses in ions or
- Attack rate – amount of pupils who have been infected
electrolytes.
with the disease compared to the pupils who were not
 Homemade Oresol therapy
affected by the disease but have undertaken the same
 1 liter – safe drinking water
activity.
 8 teaspoons – sugar - Determine the attack rate to measure the frequency of disease
 1 teaspoon - salt - In here we should know what the students ate, drank and
Identify the number who got ill and who were not ill
What steps will you undertake in order to further - It is used primarily in observational case control approach to
7 investigate the report that other pupils from the day food borne-outbreak to identify the vehicle to infection
care center are suffering from watery stools?
5) Conclusion and practical application
1. Define the problem - Evaluation of the results of the
2. Appraisal of the existing information investigation
3. Hypotheses formulation - Initiate control measures:
4. Hypotheses testing (general control measures and
5. Conclusion and practical application measures for sick person)
o General control measures
1) Define the problem  Wash hands regularly
- Verify the case diagnosis of the with soap and water
pupils who suffered from watery  Maintain a clean living environment
stools  Facilities should be adequate to allow
- Determine if the disease is common residents to bathe at least twice weekly
in this area  Laundry facilities should be available to allow
- Determine if the outbreak is appropriate laundering of clothes and bed
epidemic or due to new awareness lines
of endemic disease  Maintaining good personal hygiene including
the following
2) Appraisal of the existing information  Follow good hygienic practices
- Time: to determine the time of  Do not share eating utensils or drinking
exposure, the incubation period, and containers
the route of spread. This is important  Do not share personal toilet articles
to know if the disease is an epidemic
or not. o Measures for sick person
- Place: is it only in the day care  Provide information about gastroenteritis and
center? If not, provide a spot map to its symptoms (including whether they have fever
observe distribution of cases or bloody diarrhea) to determine if medical care is
- Person: the pupils are the ones necessary.
who were affected. Did the pupils eat  Separate sick person from other residents
or drink something or was there another factor in play all until 24 hours after nausea and vomiting and
diarrhea stop
INTEGRATION SESSION – 1ST SEM

together?
 Sick children should be accompanied by only
one responsible adult. The same adult should
3) Hypotheses formulation stay with the child until 24 hours after
- Formulate a hypothesis based on the source, type, mode symptoms stop. If possible, put them in a
of onset, and route of spread separate room or, alternatively, place sick
o What caused it? people in a separate section of the evacuation
 It is a hypothesis on the source, type and route of center away from evacuation center residents
spread. Is there a person (index case) that brought who are not sick. Designated areas should
the infection into the day care center? Is it the have full time staff supervision to ensure that
parents/guardians of the pupils, or teachers? the area is properly cleaned and appropriately
7
 supplied. Dr. Clavio
 Provide residents with plastic bags to contain - Tignan ninyo, the department of family and community
vomit and to dispose of diapers medicine subjects are actually very important and you
 Provide residents with supplies to clean up spills can now see the linkage between the basic sciences, and
especially vomit and stool also the department of family and community medicine
 Eg. Small bathroom trash can liners 

- Initiate specific follow-up surveillance All of the Instructors said

“Congratulations and Very Good!!!!! ”

References:
2018 Integration Team
Powerpoint presentation
& Audio of Reporting.

Comments from Instructors:

Dr. Cinio
- My only suggestion would be off course, uhh regarding
the digestive system diba? it is a very complicated
system and you were given guide questions specifically to
know the absorption regarding the small intestine and
the colon okay, so what do you think, which of the two is
more for the function of absorption?
o Small? Large? See now so these questions will
now guide us of course to be more specific and
detailed to able to correlate the first question to
the next regarding the function, diba?

Dr. Jimmy //TEAMSURGERY2018 

- I think it is important that she had identified the risk
factors for this patient which is the age
- I’m always emphasizing the role of the age in
determining the specific etiologic agent
- It is more believable because the journals taken are in the
Philippine setting
- And to add to the CPC, a reason why we do not treat
viral infections because there is such a thing as internal
repair for the enterocytes
o The enterocytes that are mature are the ones
destroyed by the organism and then the young/
immature enterocytes which are secretory will
replace them, okay? So the repair there is
important because it will have a bearing on the
treatment.
- For the CBC, it is very good that the reporter identified
that in viral infections, your WBC, specially your
INTEGRATION SESSION – 1ST SEM

lymphocytes will increase but your neutrophils will

decrease, but in actual practice later on, you will know
that during a state of dehydration, still your neutrophils
will be increased so be careful with interpreting your CBC
especially in cases of dehydration.
- I am very glad they/the presentor did not over-request
laboratory tests because we all know that there are
specific tests for viral identification but for this case it is
not indicated actually

8
RESEARCH (1F) INTEGRATION SESSION
FINALS April 6, 2016

Patient’s Profile Classification of Hypertension

This is a case of a 51 y/o man comes to the physician’s
office for routine physical examination. At his last
examination 3 years ago, he was advised to modify his
lifestyle because his blood pressure was 140/90mmHg. At
the current visit, his blood pressure is 150/100mmHg. The
patient is overweight (body mass index 28kg/m 2) and he
has smoked one pack of cigarettes per day for the past 30
years.

1. What is the most likely diagnosis? Justify. “Hypertension is a multifactorial disorder, resulting from the
cumulative effects of multiple genetic polymorphisms and
Stage 1 Primary Hypertension interacting environmental factors. HPN doubles the risk of
“Why PRIMARY? Aside from the fact that 90-95% of all cases is cardiovascular diseases, including Coronary Heart Disease,
PRIMARY, another consideration would be the risk factor Congestive Heart Failure, ischemic and hemorrhagic stroke,
mentioned in the case: SMOKING AND OBESITY” renal failure, and peripheral arterial disease.”

Basis of Diagnosis: 2. What structures comprise the microscopic anatomy of an

artery?

Arteries are divided into three types based on their size and
structural features
(1) large or elastic arteries,
- including the aorta, the major branches of the
aorta (the innominate, subclavian, common
carotid, and iliac arteries), and the pulmonary
arteries;

“Overweight: The more you weigh the more blood (2) medium sized or muscular arteries,
you need to supply oxygen and nutrients to your tissues. As the - comprising smaller branches of the aorta (e.g.,
volume of blood circulated through your blood vessels the coronary and renal arteries); and
increases, so does the pressure on your artery walls.”
“Male as a risk factor: Comparing males and (3) small arteries
premenopausal women, males have a higher risk for - (≤2 mm in diameter) and arterioles (20 to 100
cardiovascular diseases because of the protective effect of µm in diameter), within tissues and organs.
hormones in the premenopausal women. A study conducted
in 2013 by the FNRI and Dept. of Science and Tech, shows the
prevalence of HPN based on AGE AND SEX”
“In adults, 50-59 y/o, Males have a higher prevalence
of HPN than females of the same age group”
“And in some readings, it changes by aging, wherein,
postmenopausal women tend to have a higher risk to have
HPN, since, as we can recall, there is a significant role of the
hormones of PRE-MENOPAUSAL women in the context of HPN”
Arteries and veins: have a tunica intima, tunica media, and structures may penetrate to the outer part of the
tunica externa (or adventitia), media.
An artery has a thicker tunica media and relatively narrow 3. ARTERIOLES are microvessels with a
lumen. a. tunica intima that consists only of the
endothelium, in which the cells may have
Different Layers of the Blood vessel rounded nuclei.
1. INTIMA b. They have tunica media with only one or two
- normally consists of a single layer of endothelial layers of smooth muscle, and
cells sitting on a basement membrane underlaid c. usually thin, inconspicuous adventitia
by a thin layer of extracellular matrix; the intima d. The smallest arteries branch as arterioles, which
is demarcated from the media by the internal have one or two smooth muscle layers and
elastic lamina. indicate the beginning of an organ's
2. MEDIA microvasculature
- of vessels on the arterial side of the circulation
varies in structure according to functional 3. What regulatory factors affect arterial blood pressure?
demands.
3. ADVENTITIA Factors affecting Blood Pressure:
- consists of loose connective tissue containing 1. Left Ventricular Stroke Volume
nerve fibers and the vasa vasorum (literally • volume of blood ejected by LV during each
“vessels of the vessels”), small arterioles that are contraction
responsible for supplying the outer portion of the • Affected by:
media of large arteries with oxugen and o Preload – load the stretches the cardiac
nutrients. muscles prior contraction, volume of Blood
in the RV at the end of diastole
Three types of ARTERIES o Myocardial Contractility – increases during
SNS stimulation, decreases when blood flow
1. LARGE ELASTIC ARTERIES - help to stabilize the blood or oxygen delivery to myocardium is
flow. (Aorta and its large branches) impaired.
a. Intima - thicker than the corresponding tunic of o Afterload – vascular resistance against
a muscular artery. which the ventricle must contract
b. Media- consists of elastic fibers and a series of
concentrically arranged, perforated elastic 2. Distensibility of aorta and large arteries
laminae whose number increases with age 3. Peripheral Vascular Resistance
allowing these vessels to expand during systole 4. Volume of blood in the arterial system
and recoil during diastole, a property that serves
to propel the blood towards the tissues. BLOOD PRESSURE REGULATION
c. Between the elastic laminae are smooth muscle Blood pressure - function of cardiac output and peripheral
cells, reticular fibers, proteoglycans, and vascular resistance, both of which are influenced by multiple
glycoproteins. genetic and environmental factors.
d. The tunica adventitia is relatively
underdeveloped. Contains the vasa vaosrum
2. MUSCULAR ARTERIES - can control blood flow to organs
by contracting or relaxing the smooth muscle cells of the
tunica media.
a. Intima has a very thin subendothelial layer and
the internal elastic lamina, the most external
component of the intima, is prominent (Figure
11–11).
b. Media have more prominent smooth muscle
cells which are intermingled with a variable
number of elastic lamellae (depending on the
 Cardiac output is a function of stroke volume and heart
size of the vessel) as well as reticular fibers and
(1F) INTEGRATION SESION

rate.
proteoglycans. An external elastic lamina, the
o The most important determinant of stroke
last component of the media, is present only in
volume is the filling pressure, which is regulated
the larger muscular arteries.
through sodium homeostasis and its effect on
c. Adventitia consists of connective tissue.
blood volume.
Lymphatic capillaries, vasa vasorum, and nerves
o Heart rate and myocardial contractility (a
are also found in the adventitia and these
second factor affecting stroke volume) are both
regulated by the α-and β-adrenergic systems,
2
 which also have important effects on vascular
tone.
o Peripheral resistance is regulated predominantly
at the level of the arterioles by neural and
hormonal inputs.

 Vascular tone reflects a balance between:

o vasoconstrictors (including angiotensin II,
catecholamines, and endothelin)
 VASOPRESSIN (ADH)
o vasodilators (including kinins, prostaglandins,
and nitric oxide).
 Local factors:
o Resistance vessels also exhibit autoregulation,
whereby increased blood flow induces
vasoconstriction to protect tissues against
hyperperfusion.
o fine-tuned by tissue pH and hypoxia to
accommodate local metabolic demands.
“Another mechanism lifted from the book of Robbins, RENIN-
“Apart from the humoral and neural factors affecting the ANGIOTENSIN-ALDOSTERONE AND ATRIAL NATRIURETIC
Peripheral Resistance, there are Vascular Reflexes as cited in PEPTIDE mechanism”
the book of Berne and Levy”
 Factors released from the kidneys, adrenals, and
Vascular Reflexes affecting Peripheral Resistance myocardium interact to influence vascular tone and to
 Arterial Baroreceptors regulate blood volume by adjusting sodium balance.
o stretch receptors located in the carotid sinuses  The kidneys and heart contain cells that sense
and in the aortic arch The carotid sinuses are the changes in blood pressure or volume.
slightly widened areas at the origins of the  In response, these cells release circulating effectors
internal carotid arteries. that act in concert to maintain normal blood pressure.
o changes in carotid sinus pressure evoke greater  Kidneys influence peripheral resistance and sodium
changes in systemic arterial pressure and excretion/retention primarily through the renin-
peripheral resistance angiotensin system.
o play a key role in short term adjustments in
blood pressure in response to relatively abrupt Renin
changes in blood volume, cardiac output, or  proteolytic enzyme produced by renal
peripheral resistance juxtaglomerular cells, myoepithelial cells that
 Cardiopulmonary Baroreceptors. surround the glomerular afferent arterioles.
o receptors are located in the atria, ventricles, and  released in response to low blood pressure
pulmonary vessels. RAAS MECHANISM STEPS:
o are innervated by vagal and sympathetic afferent 1. cleaves plasma angiotensinogen to angiotensin I,
nerves. which in turn is
o Activation : initiate a reflex that lowers arterial 2. converted to angiotensin II by angiotensin-converting
blood pressure by inhibiting the vasoconstrictor enzyme (ACE), mainly a product ofvascular
center in the cerebral medulla. endothelium.
Inhibits the release of angiotensin, aldosterone, 3. Angiotensin II raises blood pressure by:
and vasopressin (antidiuretic hormone) a. inducing vascular contraction,
b. Stimulating aldosterone secretion by the
“It is essential to note that activation of these baroreceptors adrenal gland, and
plays in the regulation of blood volume is apparent in the c. increasing tubular sodium resorption.
body’s responses to hemodynamic changes. “ 4. Adrenal aldosterone
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5. increases blood pressure by increasing sodium

resorption (and thus water) in the distal convoluted
tubule, which increases blood volume.

Myocardial natriuretic peptides are released from atrial

and ventricular myocardium in response to volume
expansion; these inhibit sodium resorption in the distal renal

3
tubules, thus leading to sodium excretion and diuresis. They
also induce systemic vasodilation.
The kidney also produces a variety of vascular relaxing
substances (including prostaglandins and NO) that presumably
counterbalance the vasopressor effects of Angiotensin

4. What are the pathogenic mechanisms involved in the

development of the patient’s condition?

HYPERTENSION
• A disorder with multiple genetic and environmental
contributions.
• Majority (90% to 95%): idiopathic
• Infrequently, hypertension has an underlying
endocrine basis

 Mutations affecting proteins that influence sodium

reabsorption
o Liddle syndrome

Mechanisms of Essential Hypertension

 Genetic factors
o Influenced by blood pressure regulation
o several single-gene disorders cause
relatively rare forms of hypertension (and
hypotension) by altering net sodium
reabsorption in the kidney.
 Reduced renal sodium excretion in the presence of
normal arterial pressure
o key initiating event in essential hypertension
and, indeed, a final common pathway for the
pathogenesis of hypertension. Decreased
sodium
Pathogenesis of Secondary Hypertension o excretion may lead sequentially to an
“Renal stenosis  decreased glomerular flow and pressure in increase in fluid volume, increased cardiac
the afferent arteriole of the glomerulus. This induces renin output, and peripheral vasoconstriction,
secretion, which, as already discussed, increases vascular tone thereby elevating blood pressure.
and blood volume via the angiotensin-aldosterone pathway” o At the higher blood pressure, enough
additional sodium is excreted by the kidneys
Single-gene disorders to equal intake and prevent further fluid
 Gene defects affecting enzymes involved in retention. Thus, a new steady state of
aldosterone metabolism (e.g., aldosterone synthase, sodium balance is achieved (“resetting of
11β-hydroxylase, 17α-hydroxylase deficiency) pressure natriuresis”), but at the expense of
o Primary hyperaldosteronism- “one of the an increase in blood pressure.
most common causes of secondary
hypertension”
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 Vasoconstrictive influences
o Vasoconstrictive influences, such as factors
that induce vasoconstriction or stimuli that
cause structural changes in the vessel wall,
can lead to an increase in peripheral
resistance and may also play a role in
essential hypertension.
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  Environmental factors PREANALYTICAL CONSIDERATIONS
o Environmental factors, such as stress, o Fasting is about 8-12h
obesity, smoking, physical inactivity, and o Exercise, drinking, and smoking is not allowed
heavy salt consumption are all implicated in o Interferences: ascorbic acid, bilirubin, UA, hemolysis
hypertension. Indeed, the evidence linking o HbA1c: shortened RBC survival, opiate and alcohol use
dietary sodium intake with the prevalence of o OGTT: the patient must be ambulatory; should be on an
hypertension in different populations is unrestricted diet of >100g CHO/day for at least 3 days
particularly impressive. prior to testing.
o Sampling: Plasma>Serum

5. What laboratory tests should be requested? OBESITY AND DM = INSULIN RESISTANCE

HbA1c is a result of an irreversible nonenzymatic glycosylation
1. LIPID PROFILE reaction of hemoglobins that represents an index of glucose
 Confers major risks in developing CVD, DM levels for approx. 120 d, and thus constitute a primary
 TOTAL CHOLESTEROL, TRIGLYCERIDES, LDL, HDL diagnostic tool not only in the diagnosis, but more importantly
 Most analyzers employ enzymatic methods in the monitoring of long term glycemic status in DM patients.
 Interferences: Ascorbic acid, hemolysis FPG is the more common test that is used to diagnose DM.
 PRE-ANALYTIC CONSIDERATIONS We also use OGTT wherein we first take the baseline
o In TAG and indirect LDL determinations, fasting glucose level of a patient and thereafter let him drink a
fasting is required for about 8-12 hours standard glucose solution, afterwhich at the 2nd hr, we collect
o Diet - Postprandial states not only increases blood samples. This test is used to determine how well the
TAG but also decreases HDL and LDL body metabolizes glucose over a standard period of time,
transiently. however it is not generally recommended for routine clinical
o Postural considerations - The position of use. The classical symptoms of DM include, but not limited to,
patient must be standardized for the 3Ps: polyuria, polydipsia, and polyphagia
venepuncture. Reclining from a standing
position causes water from extravascular 3. CREATININE CLEARANCE
compartment to move intravascularly and o Nephropathy, CVD
dilute these molecules that will likely cause o End product of muscle metabolism derived from
decrease. creatine
“Dyslipidemia in this group of patients, meaning those who o Most common monitor used for GFR:
have a multiple risk factors like obesity, smoking, and o Fairly constant rate of production
hypertension, actually further predisposes themselves not only o It is freely filtered by the glomerulus
CVD but also DM, since obesity aids in the progression of insulin o It is not reabsorbed, and only a small amount is
resistance, among other factors. secreted.
Now routinely, lipid profile consist of TC, TAG, LDL, o Production = Excretion
and HDL. It is worth noting that increased LDL confers a o Both plasma and urine creatinine are determined.
separate, independent risk. It is the most atherogenic, and
cholesterol-rich among the lipoproteins and it plays a direct 4. URINALYSIS
role in atherogenesis. HDL, is involved in the reverse cholesterol o Diabetic Nephropathy, CVD
pathway, meaning it transports excess cholesterol from o Microalbuminuria, glucose
peripheral tissues to the liver” o Urine Reagent Strip
o Random or first morning specimens
2. BLOOD GLUCOSE
Albumin is the major serum protein that is found in normal
 Diabetes Mellitus
urine. The majority of albumin is not filtered, and whatever is
 Fasting/non-fasting specimens filtered is reabsorbed. In the presence of glomerular disease

GLYCOSURIA
 HYPERGLYCEMIA, RENAL TUBULAR
DYSFUNCTION
 RENAL THRESHOLD: 160 – 180 mg/dL
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 FASTING FOR 2 HOURS POSTPRANDIAL IS

REQUIRED
Glycosuria occurs in two scenarios: one, in the context of
hyperglycemia; two, in patients who have renal tubular
dysfunction.
In hyperglycemia, the increase in glucose in the blood means
a proportional increase in the amount of glucose that is
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filtered by the kidneys, and whenever the renal threshold for 6. How should this patient be managed? (Discuss)
glucose reabsorption is exceeded, then normal being…, the
surplus is dumped into the urine, and thus presenting as clinical Non-pharmacologic: LIFESTYLE MODIFICATION
glycosuria, In renal tubular dysfunction, the glomerular • All smokers should stop smoking.
membrane is intact, however the active transporters of glucose • Overweight patients should attempt weight reduction.
in the PROXIMAL TUBULE are compromised. Thus the normal • Alcoholic drinkers should moderate their
glucose that is filtered and reabsorbed, is now excreted by the consumption.
kidneys, also leading to glycosuria. • Moderation of dietary sodium.
Pharmacologic: ANTI-HYPERTENSIVE DRUGS
5. SERUM ELECTROLYTES
o DIETARY THERAPY
o High levels of dietary minerals (K+,Ca++,Mg++) are
known to lower BP
6. HEMATOCRIT
o Most important determinant of whole blood viscosity
o Blood viscosity affect total peripheral resistance to
blood flow
o Not an important independent correlate of blood
pressure in general population
7. 12 lead ECG
o End organ damage
o LVH, CAD, Arrythmias and CHF
o According to the Framingham Study, hypertension
accounts for about one quarter of heart failure cases.

Uncontrolled and prolonged elevation of BP can lead to a

variety of changes in the myocardial structure, coronary
vasculature, and conduction system of the heart. These 7. How can this condition be prevented?
changes in turn can lead to the development of left ventricular (Include programs of the DOH)
hypertrophy (LVH), coronary artery disease (CAD), various
conduction system diseases, and systolic and diastolic Healthy diet
dysfunction of the myocardium.  Promoting proper nutrition
One criteria, for example, measure the depth of S wave in  Reducing salt intake to less than 5 g of salt per day.
the V1/V@ lead, adding to that the amount of R peak in the v5-  reducing saturated and total fat intake
v6 leads. An amount that is greater than >35mm is said to be
diagnostic of LVH

8. MISCELLANEOUS TESTING
 More extensive testing for identifiable causes is not
generally indicated, unless:
 BP control is not achieved, or,
 The clinical and routine laboratory evaluation
strongly suggests an identifiable secondary
cause.
 HS-CRP AND HOMOCYSTEINE
The Framingham Heart Study cohort demonstrated that those
with a LDL value within the range associated with low
cardiovascular risk, who also had an elevated HS-CRP value,
had a higher cardiovascular event rate as compared to those
with low CRP and high LDL cholesterol. Other studies also have
shown that elevated CRP is associated with a higher
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cardiovascular event rate, especially in women.74 Elevations in

homocysteine have also been linked higher cardiovascular risk;

6
Avoiding harmful alcohol use
 Limit intake to no more than one standard drink a
day.
Physical activity
o Regular physical activity
o Promotion of physical activity

Stopping tobacco use

Managing stress in a healthy way.
Weight reduction

DEPARTMENT OF HEALTH:
• Improve adherence to drug therapy
• Empathy increases patient’s trust, motivation, and
adherence to therapy
• Consider patient’s cultural beliefs and individual
attitudes

DOH PROGRAMS
• BANTAY PUSO, BANTAY PRESYON
• DOH HYPERTENSION CLUB

This intervention will help facilitate risk assessment of

community members and ensure regular follow-up of
diagnosed hypertensive patients. A patient consults the
nearest health center or primary health care facility to undergo
assessment, screening and management.
Once diagnosed, the patient will be enrolled in the
club. As a benefit, the patients can have access to DOH drugs
for hypertension. As members the patient will be included in
activities that promote healthy lifestyle so that their blood
pressure can be controlled.

Notetaker: CALARA, Kevin

Proofreader: chaim|herr|2016

#RoadToMD #ThirdYearNaTayo! #VNeck

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