Health System

Research
 Health System Research
 Pharmaceutical care focuses on outcomes
oriented pharmacy practice that requires the
pharmacist to work in collaboration with the
patient and the patient’s other healthcare
providers with an objective of promoting
patient’s health, prevent occurrence of disease,
and to access, monitor, initiate and modify
medication use to assure a safe and effective
drug therapy .
 The goal of pharmaceutical care is to optimize the drug therapy,
achieve positive clinical outcomes and improve patient’s health-
related quality of life within a realistic economic expenditure. To
achieve an effective pharmaceutical care services, interventional
investigations are necessary. The findings of such interventions will
help practitioners to provide the improved care services to the
patients.
 Health System Research
 Various research studies were carried out
worldwide to access the pharmacist’s
knowledge regarding the professional
responsibilities, the need for pharmaceutical
care and influence of pharmaceutical care on
health outcomes and health economics.
 Literature suggest that in relation to a drug therapy patients visits a
pharmacist more frequently (5-8 times) than their physicians. Thus
pharmacists are having better opportunities to interact with patients,
understand their health related issues and provide suitable solutions
for improved outcomes.
 Health System Research

 Health system research may include assessment

methods/designs that measures the local health
needs and evaluate the effectiveness of services in
meeting those needs.
 Health system research using various scientific
methods may be considered as a course of critical
inquiry leading to the discovery of fact or information
that increases our understanding of human health and
disease.
 Scientific method is a systematic body of procedures
and techniques applied in carrying out investigation or
experimentation targeted at obtaining new
knowledge.
 Health System Research

 Pharmacy practice research is defined as

“Research/investigational process
attempted to understand knowledge of
pharmacy and the way in which it is
practiced, in order to support the objectives
of pharmacy practice and to ensure that
pharmacists knowledge and skills being
effectively utilized in solving the health
related problems and meets the health
related needs of a population.”
 Health System Research
 Pharmacy practice research should preferably be
performed systematically on realistic issues that can
help both pharmacists and the patients. If the
practicing pharmacists are involved in pharmacy
practice research, the pharmacists will experience
the following benefits:
 Improved care patient might be the ultimate goal.
 Positive
Contribution to the ongoing health system
research process.
 Personal and professional gain during a research
process.
 evidence based development of a new service.
 Strengthen the quality of the provided services.
 Health System Research
 In 1967, WHO in collaboration with epidemiology
and communication sciences teams introduced
research.
 In 1978, global advisory committee on medical
research and sub-committee on health services
was established.
 In 1980’s-1990’s WHO considered health system
research as an organization and given a mandate
for future work.
 In 1994 and onward, Adhoc committee was
formed at global forum and aligns which
submitted its report to WHO, under the definition
of health system development strategies for the
 Health System Research
1. Stimulate the new generation for enquiry of latest
evidence based knowledge.
2. Promote the utilization of knowledge for improved
performance of health system.
3. Capacity building amongst researchers, policy makers
and other stake holders for the use of health related
information.
 Health system research is now a multidisciplinary field of
scientific investigations that studies how social factors,
financial systems, organizational structure, health care
technologies, personal behavior, quality and cost of
health care and ultimately our health and well beings are
inter related with each other.
 Health system research in based on three operationally
interlinked categories i.e. biomedical, health services and
 Health System Research
Research

Type A (Empirical & Theoretical) Type B (Basic & Applied)

Empirical Theoretical
Research Research Applied
Basic Research
Observation & Research
Qualitative or
Experience Quantitative

Epidemiologic a) Identification of the Problem oriented

al studies Investigation
population of interest, i.e. Investigation
without defined goal
b) Measurement of variables or specified purpose
on a defined
i.e. Selected Characteristic problem
c) Statistical testing of
hypothesis
 Epidemiological Health System Research

studies
A. Experimental Studies
Experimental studies randomize patients to either the treatment or the control group.
Experimental studies are ones where researchers introduce an intervention/treatment and
study the effects. In majority of the experimental studies one or more groups receiving
particular treatment or intervention (treatment group) are compared with a group
unexposed to that particular intervention (Placebo) or compared with a group exposed to
the best available treatment (control) group

Advantages
1. The ability to manipulate or assign independent variables e.g. in
clinical trials cases of a specific disease are deliberately assigned in
random order, or by matching to treatment and to control groups.
2. The ability to randomize subjects to treatment and control groups.
3. The ability to control and eliminate sources of other factors interfering
with the association under study.
4. The ability to ensure temporality. Experimental studies feasibly
determine which variables precede and which are the consequences
of the intervention.
5. The ability to replicate findings.
 Experimental Epidemiological studies

studies
Disadvantages
1. Lack of reality. In most human situations, it is impossible to randomize all risk
factors except those under examination.
2. Difficulties in extrapolation. Results of experiments in animal models, cannot
readily be extrapolated to human populations.
3. Ethical problems. In human experimentation, It is unethical to test the efficiency
or side-effects of new treatments without critical evaluation in a small group of
human subjects.
4. Difficulties in manipulating the independent variable. e.g. It is virtually impossible
to randomly assign smoking habits to the treatment and control groups.
5. Non-representativeness of samples. Many experiments are carried out on
volunteers, who are not necessarily representative of the huge population
6. Experimental approach is suffer from several sources of selection bias.
7. it is often not feasible to subject human beings to experimental studies.
8. Careful choice of the outcome variable, the sample selection, allocation process
and the statistical analysis procedures is essential for the success of the
experiment.
 Experimental Epidemiological studies

studies
Purpose of
experiment
The design of experiments serves the purpose of ensuring valid data
relevant to the hypothesis under test as economically (maximum
statistical power with minimum cost and inconvenience) as possible. The
experimental studies are based on two variables i.e. independent
variable (X) and dependent variable (Y)
For a successful conduction of comparative experimental studies it is
necessary that
 The only difference between the two groups is that of an intervention
 Existence of sufficiently large number of members/units in the
comparative groups
 Appropriate statistical methods are used to obtain the finding i.e. to
identify the relationship of the treatment/intervention with the
outcomes (drug effects).
 Epidemiological studies
Experimental studies
Flow
chart
 Epidemiological studies
Experimental studies
Procedu
re
 Reference population/target population is the population exhibiting the generalized
characteristic of the interest to which the experiment applies e.g. In a clinical trial of AZT for
AIDS patients, all potential patients diagnosed with AIDS would be included in this group.
 Once the reference population is identified, one has to determine if this entire population is
to be included in a study, or only a sample is available. If a sample, the best choice for this
study population would be to obtain a simple random sample (especially if the study is
reasonably large), so that there will be no bias in the selection of study subjects.
 Once the potential group of subjects is determined, ‘informed consent’ is obtained from the
participants before they are subjected to experiments.
 After allocation of the subjects to the experiment and control groups, they are followed for a
specified period of time under strict conditions, and the outcome of the experiment is carefully
documented. The outcome may be a dichotomous event such as a cure of the disease, relief of pain,
etc., or it could be measured as a continuous variable, such as a reduction in blood pressure, or
intervals of recurrence.
 The measured outcome are then compared among the groups using appropriate statistical methods.
 Epidemiological studies
Experimental studies
Types
Randomize Clinical Trials (RCT)
 Also named as Randomized clinical trial, Controlled clinical trial or Double blind clinical trials.
 Eligible people are randomly assigned to one of two or more groups. One group receives the
intervention (such as a new drug) while the control group receives either nothing/inactive
placebo or commercially available best treatment. The researchers then study what
happens to people in each group. Any difference in outcomes can then be linked to the
intervention.
 Types of Clinical Trials:
I. Prophylactic Trials: Testing of an intervention for prevention of a disease e.g.
immunization, contraception
II. Therapeutic Trials: Testing of efficacy/effectiveness of treatment/intervention
III. Safety Trials: Testing of side effects e.g. side effects of oral contraceptives
 Risk-factor Trials: Proving the cause of a disease by inducing it with the putative/causative
agent in animals, or withdrawing the agent (e.g. smoking) through cessation.
 Experimental studies
Randomize Clinical Trials (RCT)
 Experimental studies
Randomize Clinical Trials (RCT)
 Phases of Clinical Trials
Clinical trials explore testing new methods for diagnosing, treating, or preventing health conditions.
The goal is to determine whether the drug (medications, medication combinations, new uses for
existing medications or medical devices) is both safe and effective.
Pre-clinical studies:
 Pre clinical studies are conducted in labs on human cell cultures or animal models.
 Pre clinical studies are used to determine safety, efficacy and optimized dose/dose variation
within a population.
 Randomize Clinical Trials (RCT)

Clinical studies are conducted on human volunteers.

Phase 0: Performed on very small number of people (< 15).
 Phase I: (Effect of medication is checked in about 20 to 80 people).
 Include those volunteers who initially receive a fraction of the anticipated dose.
volunteers occupy research beds.
 Volunteers are closely/critically monitored for effects on body functions, such as
hepatic, cardiovascular, renal, gastrointestinal and endocrinal functions. The
metabolism of the drug may also be investigated at this stage.
 This phase, which is of short duration (usually one or two months).
 Requires high technology in biochemistry, pharmacology and endocrinology,
and varied medical expertise.
 Need access to highly developed laboratory facilities.
 Experimental studies
Randomize Clinical Trials (RCT)
 Phase II: Involves testing or assessment following strict criteria in several hundred
volunteers/participants (100 to 300).
 Phase II include
i. Assessment of the effectiveness of the drug or device,
ii. determination of appropriate dosage, and
iii. investigation of its safety.
iv. Further information on the pharmacology, especially the dose-response relationship of the
drug, is also collected.
 Randomize Clinical Trials (RCT)

 Phase III: Approximately 3,000 participants (patients).

 Also called classical phase ‘clinical trial’ since it is performed on
patients, after approved consent.
 Performed on both in & out patients with intensive monitoring and
follow-up.
 Phase III include
i. Assessment of the effectiveness of the drug or device,
ii. determination of appropriate dosage, and
iii. assessment of the drug or device safety upon its continued use in a
larger and more heterogeneous population.
 Requires proper planning, organization & adherence to strict
predeveloped protocols.
 Requires advanced laboratory technology.
 Results are investigated by regulatory authorities for licensing of new
product or device for general public use
 Experimental studies
Randomize Clinical Trials (RCT)
Factors influencing the Phase III clinical trials (Design and Analysis)
a. The agent, treatment or experimental factor
b. Conditions to be treated
c. The target population
d. Ethical issues
e. Outcomes to be measured
f. Side-effects
g. Study instrumentsSingle
blind
h. Blinding Only the patient is unaware about the
Double
treatment
blind
Both the investigator and patient are unaware
i. Stopping rule
j. Plans for analysis
k. Selective attrition
l. Methods for ensuring the integrity of the data
m. The choice of design
 Experimental studies
Randomize Clinical Trials (RCT)
 Phase IV: Huge population/general public use.
 Although the drugs or devices has been approved for general public use following
successful Phase III trials, however governmental , WHO and other agencies, subject
drugs/devices to phase IV that involve trials in a normal field conditions.
 Re-assessment of effectiveness, safety, acceptability and continued use of the drugs or
devices under normal field conditions.
 Phase IV clinical trails requires proper facilities, training, and supervision.
 Although this phase is carried out under normal or close to normal conditions, however it
requires additional epidemiological and biostatistical skills, and research requirements
such as record-keeping and computer facilities.

Purpose: The intervention in a clinical trial may include:

a. drugs for prevention, treatment or palliation b. surgical procedures or rehabilitation
procedures
c. clinical device d. lifestyle habits e. medical counselling
f. risk factors g. hospital services h. communication
approaches
 Experimental studies
Community Intervention Trials (CITs)
 CITs are usually carried out in hospitals or clinics, and are usually directed at a
patient group with specific health conditions.
Benefits: CITs are performed to evaluative strategies to study community health
services e.g.
I. Assessment or evaluation of needs
II. Design evaluation
III. Efficiency or process evaluation
IV. Effectiveness or impact evaluation
V. system evaluation
 The classic example of a community intervention trial is a vaccine testing. Some
communities will be randomly assigned to receive the vaccine, while other
communities will either not be vaccinated, or will be vaccinated with a placebo.
 Another example is the introduction of iron-fortified salt in anaemic patients
community to reduce the incidence of anaemia in the community.
 In RCT randomization is done among individuals while in CITs randomization is
 Experimental studies
Community Intervention Trials (CITs)

Limitations
1.Blinding is not possible
2.Contamination: Contamination occurs when individuals from one of
the experimental groups receive the intervention from the other
experimental group.
3.Co-interventions: when some other interventions, probably unknown
to the investigators of this trial or otherwise, are simultaneously
introduced
4.Reduced sample size: The effective sample size is the number of
communities, not the number of people in these communities.
Non-Randomize control trials:

In non randomize control trials researchers measures the outcome for

programmed participants and non-participant with random
assignment.
 Experimental studies
Community Intervention Trials (CITs)
 Epidemiological studi
Observational
Studies
Observational studies observe patients either on or not on the
treatment of interest to find out the association between
exposure and disease.
OR
Observational studies are ones where researchers observe
the effect of a intervention/treatment without trying to
change who is or isn’t exposed to it.
OR
In observational studies, the primary goal is to establish a
relationship or association between a ‘risk factor’ (etiological
agent) and an outcome (disease).
Descriptive studies
When an observational study is not structured formally as an analytical
or experimental study, i.e. when it is not aimed specifically to test a
hypothesis, it is called a descriptive study, and belongs to the
observational category of studies.

Analytical studies
In this type of study, hypothesis testing is the primary tool of inference.
The basic approach in analytical studies is to develop a specific, testable
hypothesis, and to design the study to control any extraneous variables
that could potentially confound the observed relationship between the
studied factor and the disease. The approach varies according to the
specific strategy used.
 Observational Studie
Descriptive
Studies
 Most descriptive studies allows the generation of
hypotheses, which can then be tested by
analytical/observational or experimental designs. A
survey based study, for example a prevalence
survey, could also be defined as a descriptive study
e.g. Effect of smoking on lung cancer, effect of
obesity in developing CVS complications and
Evaluation of impact of pollen in the incidence of
asthma.
 In descriptive studies, morbidity or mortality in the
population is examined, and its occurrence and
distribution in population groups according to (1)
characteristics of persons, (2) characteristics of
place, and (3) characteristics of time, are illustrated.
 The numbers of events (mortality or morbidity) are enumerated and
the population at risk identified. Rates, ratios and proportions are
calculated as measures of the probability of events. Comparison of
the measures of probability across subgroups of populations is
performed to identify the variables (time, place and person) that
might explain the variability in mortality and morbidity within and
between population groups.
 Descriptive studies also involve the collection, analysis and
interpretation of data. Both qualitative and quantitative techniques
may be used, including questionnaires, interviews, observations of
participants, and service statistics, as well as documents describing
communities, groups, situations, programs and other individual or
ecological units. The distinctive feature of this approach is that its
primary concern is with description rather than with the testing of
hypotheses or proving causality.
 Observational Studies
Descriptive Studies

Types

Epidemiological
Community diagnosis description of disease
Case Series
or needs assessment occurrence

Based on reports
Identify existing needs and to Involve the collection of data
of a series of cases
provide baseline data for the on the occurrence and
of a specific
conduct of further working/research. distribution of disease in
condition, or a
It involves data collection on existing populations according to
series of treated
health problems, programs, specific characteristics of
cases, with no
achievements, limitations, high individuals, place and time
specifically
prevalence, or groups at highest or possible familial
allocated control
risk. characteristics
group.
 Descriptive Observational Studies
Studies
Types
Descriptive cross-sectional Ecological
studies or Community studies
surveys

A cross-section encompasses the data

collection on entire population or its
When the unit of observation is an
proportion (sample). Here both the
aggregate (e.g. family, clan or
disease and its cause are known and
school) or an ecological unit (a
involve assessment regarding the disease
village, town or country) the study
distribution, disability, pathological
becomes an ecological descriptive
condition, immunological condition,
study.
nutritional status, fitness, or intelligence,
etc.
 Observational Studies
Analytical Studies
Types

Cross
Case Control
Sectional Cohort studies
studies
Studies

Only exposure is present (or

Disease is known Both the disease
in other word risk factor is
but cause is and cause are
known) which may lead to a
unknown. known
particular disease in future.
Prospective cohort studies
Historical/Retrospective cohort stu
Prognostic cohort studies
 Observational Studies
Case Control
 It is designed primarily studies
to establish the causes of diseases by investigating
associations between exposure to a risk factor and the occurrence of disease.
 Simple however retrospective based on the exposure histories of cases and
controls.
 In this type of study, researcher investigates an association by contrasting the
exposure of a series of cases of the specified disease with the exposure pattern of
carefully selected control groups free from that particular disease.
 The risk factor is something that happened or began in the past, presumably
before disease onset, e.g. smoking, or a previous infection or medication.
Information about the exposure is obtained by taking a history and/or from
records. Occasionally, the suspected factor or attribute is a permanent one, such
as blood group, which can be ascertained by clinical or laboratory investigation.
 A higher frequency of the attribute or risk factor among cases than among
controls indicates its association with a disease condition.
 Observational Studies
Case Control
studies
 Case Control studies Observational Studies

Selection of cases
 A case of the study should be clearly defined with regard to the histological type and specific
disease characteristics, such as date of diagnosis, geographical location, etc. This design is
particularly efficient for rare diseases and allows a reasonable number of cases to be included in
the study, because all cases that fit the study criteria in a particular setting within a specific
period are usually included.
 The selection of cases should be such that the study results are reliable and valid. For these
reasons, the following guidelines should be used when selecting cases in a case-control study
a. The criteria for inclusion in the study (what constitutes a case) and criteria for exclusion from the
study must be clearly specified; this will improve the validity of the results;
b. The sources of cases may be:
- all cases admitted to or discharged from a hospital, clinic, or private
practice within a specified period;
- all cases reported or diagnosed during a survey or surveillance
program within a specified period;
- - incident or newly diagnosed cases;
- - incident cases in an ongoing cohort study or in an
- occupational cohort (sometimes called a nested case control study)
- deaths with a record of causes of death, and fulfilling other criteria for
the study;
- - case units with a prescribed health outcome;
c. If the number of cases is too large, a probability sample may be used;
d. Cases selected for the study should be representative of all cases of
the disease under consideration.
 Case Control studies Observational Studies

Selection of controls
A. The sources of comparison groups may be:
• a probability sample of a defined population, from where a cases are drawn.
• a sample of patients admitted to, or attending the same institution as the cases.
• a sample of relatives or associates of the cases (neighbourhood controls).
• a group of persons selected from the same source population as the cases, and matched with
the cases for potentially confounding variables (third variable effecting both independent &
dependent variables)
• on other risk factors (other than the one under consideration);
B. The selection of controls may involve matching on other risk factors:
• Matching means that cases and controls have the same (or very similar) characteristics other
than the disease and the risk factor being investigated.
• The characteristics are those that would confound the effect of the putative risk factor, The
characteristics are known to have an association with the disease, and may be associated with
the risk factor being studied.
C. The number of control groups may vary. Multiple controls provide
 Case Control studies Observational Studies

Collection of data on exposure and other factors

 Often data are collected through interviews, questionnaires and/or examination of records.
Occasionally, clinical and laboratory examinations are carried out, but often this is not possible, in
case of past/death cases. The following precautions should be taken during data collection
• observation should be objective, or, well standardized;
• blinding should be adopted i.e. the investigator or interviewer should not know whether a subject is
in the case or control group.
• the same procedures, e.g. interview and setting, should be used for all groups.
Multifactorial case-control studies
The common form of case-control study addresses one main factor or attribute at a time. however,
Multifactorial case-control studies involve investigation of several exposure factors at the same
time in the same/single study.

Advantages of case-control studies

 Feasible when the disease being studied occurs only rarely, e.g. cancer of a specific organ;
 Relatively efficient, requiring a smaller sample than a cohort study
 little problem with attrition, as when follow-up requires periodic investigations and some subjects
refuse to continue to cooperate
 sometimes they are the earliest practical observational strategy for determining an association
 Case Control studies Observational Studies

Disadvantages and biases of case-control studies

 Absence of epidemiological denominators (population at risk)
 Temporality appears as a serious problem particularly where it is not possible to determine
whether the attribute led to the disease/condition, or vice versa.
 Greater risk of bias in the selection of cases and controls particularly using a single control
group that’s itself is related to the risk factor under investigation.
 Difficult or impossible to obtain information on exposure if the recall period is long.
 Selective survival may bias the comparison as there is no way of ascertaining whether the
exposure was the same for those who died and those who survived.
 Most of these studies are performed in hospitals so they are liable to
Berkson’s fallacy, or the effect of differing admission policies and
rates.
 Measurement biasness may exist, including selective recall and
misclassification (putting cases in the control group, or vice versa);
there is also the possibility of the Hawthorne effect: with repeated
interviews, respondents may be influenced by being under study.
 case-control studies are incapable of disclosing other conditions
related to the risk factor: for example, in a study of the side-effects of
oral contraceptives, one has to know their side-effects before a case-
control design can be set up.
 Observational Studies
Cross Sectional studies
 In an analytical cross-sectional study, the
investigator measures exposure and disease
simultaneously in a representative sample
of the population.
 Cross-sectional studies measure the
association between the exposure variable
and existing disease (prevalence), while
cohort studies, measures the rate of
developing disease (incidence).
 Rare diseases, conditions of short duration,
or diseases with high case fatality are often
not detected by the one-time snapshot of
the cross sectional study. Therefore, cross-
sectional studies are more appropriate for
measuring the relationship between fairly
permanent characteristics in individuals and
chronic diseases or stable conditions.
 Observational Studies
Cross Sectional studies

Advantages of cross-sectional studies

The following are some advantages of cross-sectional studies:
 Cross-sectional studies have the great advantage over case-control studies of starting
with a reference population from which the cases and controls are drawn.
 They can be short-term, and therefore less costly than prospective studies.
 They are the starting point in prospective cohort studies for screening out already
existing conditions.
 They provide a wealth of data that can be of great use in health systems research.
 They allow a risk statement to be made, although this is not precise.
Disadvantages of cross-sectional studies
 They provide no direct estimate of risk.
 They are prone to bias from selective survival.
 Since exposure and disease are measured at the same point in time, it is not
possible to establish temporality (i.e. whether the exposure or presence of a
 Observational Studies
Cohort studies
Prospective cohort studies
 The common strategy of cohort studies is to start with a reference
population (or a representative sample thereof), some of whom have
certain characteristics or attributes relevant to the study (exposed
group), with others who do not have those characteristics (unexposed
group).
 Both groups should, at the outset of the study, be free from the
condition or conditions under consideration. Both groups are then
observed over a specified period to find out the risk each group has of
developing the condition(s) of interest.
 In a conventional cohort study, an initial cross-sectional study is often
performed to exclude persons with the outcome of interest (disease) and
to identify the cohort that is free from the disease.
Design features
A. Selection of cohort
I. A community cohort of specific age and sex;
II. An exposure cohort, e.g. radiologists, smokers, users of oral
contraceptives;
III. A birth cohort, e.g. school entrants;
IV. An occupational cohort, e.g. miners, military personnel;
V. A marriage cohort;
VI. A diagnosed or treated cohort, e.g. cases treated with radiotherapy,
surgery, hormonal treatment.
 Observational Studies
Cohort studies
 Observational Studies
Cohort studies
B. Data to be collected
I. Data on the exposure of interest to the study hypotheses
II. Data on the outcome of interest to the study hypotheses
III. Characteristics of the cohort that might confound the association
under study.
C. Methods of data collection
IV. Interview surveys with follow-up procedures
V. Medical records monitored over time
VI. Medical examinations and laboratory testing
VII. Record linkage of sets with exposure data and sets with outcome data,
e.g. work history data in underground mines with mortality data from
national mortality files.
Measures of frequency
 Two methods are commonly used in cohort studies to measure the
incidence of the disease (condition) under investigation
a. Cumulative incidence
b. Incidence density (person-time approach)
 Observational Studies
Cohort studies
A. Cumulative incidence
 This index of disease frequency is based on the total population at risk which at the start of study
was free of the disease under investigation. The incidence of the disease is calculated for each
class of exposure to the risk factor, and the ratio of effected persons to the total population at risk
was determined during a specified observation period.
 the term ‘cumulative incidence’ has been applied since this incidence measure provides an
estimate of the probability or risk of developing disease among all members of the group who
were included in the study at its initiation and were at risk of disease.
 Cumulative incidence is a proportion, not a rate, and can vary from 0 to 1, that is, no less than 0%
and no more than 100% of the population at risk can acquire the disease.
B. Incidence density (person-time approach)
 This approach is an improvement over the conventional measure of
incidence, because it takes into consideration both the number
observed and the duration of observation for each individual.
 Thus, if 30 individuals were observed as follows: 10 for two years, 5
for three years, and 15 for four years, they would contribute
(10x2)+(5x3)+(15x4) = 95 person-years of observation, which would
become the denominator.
 The numerator is the number of new cases observed in these groups
over the specified period of time.
 This gives an incidence rate per person-year, called the incidence
density. Person-years do not represent the number of persons: 400
person-years of observation could represent 400 persons each
observed for one year, or 40 persons each observed for 10 years.
 Two drawbacks of this measure are that the exact time when the
disease occurs often cannot be ascertained, and that the rate of
disease development over time is not necessarily constant.
 Cohort studies Observational Studie

Advantages of cohort studies

 Because of the presence of a defined population at risk, cohort studies allow the possibility of
measuring directly the relative risk of developing the condition.
 In a cohort study, it is known that the characteristic precedes the development of the disease,
since all the subjects are free of disease at the beginning of the study; this allows for a
conclusion of cause-effect relationship (a necessary, but not sufficient, condition).
 Because the presence or absence of the risk factor is recorded before the disease occurs, there is
no chance of bias being introduced due to awareness of being sick as in encountered in case-
control studies.
 There is also less chance of encountering the problem of selective survival or selective recall,
although selection bias can still occur because some subjects who contracted the disease will
have been eliminated from consideration at the start of the study.
 Cohort studies are capable of identifying other diseases that may be related to the same risk
factor.
 Unlike case-control studies, cohort studies provide the possibility of estimating attributable risks,
thus indicating the absolute magnitude of disease attributable to the risk factor.
 If a probability sample is taken from the reference population, it is possible to generalize from
the sample to the reference population with a known degree of precision.
 Cohort studies Observational Studie

Disadvantages of cohort studies

 These studies are long-term and are not always feasible
 They are relatively inefficient for studying rare conditions.
 They are very costly in time, personnel, space and patient follow-up.
 Sample sizes required for cohort studies are extremely large, especially for infrequent conditions; it is usually
difficult to find and manage samples of this size.
 The most serious problem is that of attrition, or loss of people from the sample or control during the course of the
study as a result of migration or refusal to continue to participate in the study. The higher the proportion lost (say
beyond 10-15%) the more serious is the potential bias.
 There may also be attrition among investigators who may lose interest, leave for another job, or become
involved in another project.
 Over a long period, many changes may occur in the environment, among individuals or in the type of
intervention, and these may confuse the issue of association and attributable risk.
 Over a long period, study procedures may influence the behavior of the persons investigated (Hawthorne effect).
This problem is more likely to occur in studies involving repeated contact with participants, as in studies of diet or
the use of contraceptives. The participants may modify their diet or shift to another contraceptive method.
Behavioral changes are also a serious problem in opinion surveys, acceptability studies and psychological
investigations.
 A serious ethical problem may arise particularly when the exposed population is manifesting significant disease
symptoms before the completion of follow-up period.
 Cohort studies Observational Studie

Historical/Retrospective cohort studies

 A historical cohort study depends upon the availability of records that allow reconstruction of the
exposure of cohorts to a suspected risk factor and follow-up of their mortality or morbidity over
time. In other words, although the investigator was not present when the exposure was first
identified, he reconstructs exposed and unexposed populations from records, and then proceeds
as though he had been present throughout the study.
 In a prospective cohort study, the investigators or their substitutes are typically present from the
beginning to the end of the observation period. However, it is possible to maintain the
advantages of the cohort study without the continuous presence of the investigators, or having
to wait a long time to collect the necessary data, through the use of a historical or retrospective
cohort study.
Advantages
 All of the relevant variables may not be available in the original records.
 It may be difficult to ascertain that the study population was free from the
condition at the start of the comparison. This problem does not exist if we
are concerned with deaths as indicators of disease.
 Attrition problems may be serious due to loss of records, incomplete
records, or difficulties in tracing or locating all of the original population for
further study.
 These studies require ingenuity in identifying suitable populations and in
obtaining reliable information concerning exposure and other relevant
factors. Examples of such population groups include members of health
insurance plans, military personnel, industrial groups (such as miners),
professional groups, members of a trade union, etc.
 Cohort studies Observational Studie

Prognostic cohort studies

Prognostic cohort studies are a special type of cohort study used to
identify factors that might influence the prognosis after a diagnosis or
treatment. These follow-up studies have the following features
 The cohort consists of cases diagnosed at a fixed time, or cases
treated at a fixed time by a medical or surgical treatment,
rehabilitation procedure, psychological adjustment or vocational
adjustment.
 By definition, such cases are not free of a specified disease, as in the
case of a conventional cohort study (but are free of the ‘outcome of
interest’).
 The outcome of interest is usually survival, cure, improvement,
disability, vocational adjustment, or repeat episode of the illness, etc.