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Module 9 - Experimental Studies - PowerPoint

The document outlines the principles and methodology of experimental studies in epidemiology, highlighting their role as the gold standard in research. It details the process of conducting these studies, including hypothesis formation, randomization, treatment allocation, and outcome assessment, while addressing ethical considerations and issues related to study design. Additionally, it emphasizes the importance of blinding, compliance, and the analysis of data to ensure valid results.

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16 views20 pages

Module 9 - Experimental Studies - PowerPoint

The document outlines the principles and methodology of experimental studies in epidemiology, highlighting their role as the gold standard in research. It details the process of conducting these studies, including hypothesis formation, randomization, treatment allocation, and outcome assessment, while addressing ethical considerations and issues related to study design. Additionally, it emphasizes the importance of blinding, compliance, and the analysis of data to ensure valid results.

Uploaded by

jenna dabaja
Copyright
© © All Rights Reserved
We take content rights seriously. If you suspect this is your content, claim it here.
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Download as PPTX, PDF, TXT or read online on Scribd
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EXPERIMENTAL STUDIES

PH 803 Epidemiology and Public Health


Robert L. Wahl, DVM, MS
[email protected]
Epidemiological studies are either observational or
experimental.
• Observational studies are considered “natural”
experiments
• Experimental studies are considered true
experiments
1. Defining feature of experimental studies:
Investigator assigns exposure to study subjects

A) Experimental studies most closely resemble controlled laboratory


experiments and serve as models for the conduct of observational
studies.

B) They are the gold standard of epidemiological research. They have


high status and validity, and can pick up small and modest effects
2. Overall conduct of an Experimental Study
A) Hypothesis formed

B) Study subjects recruited based on specific criteria and their


informed consent is sought

C) Eligible and willing subjects are randomly allocated to


receive one of the two or more interventions being
compared

D) Study groups are monitored for specific outcomes being


studied
• First occurrence of disease,
• Recurrence of disease,
• Recovery from disease and
• Side effects of the disease and of treatments
E) Rates of the outcome in the various groups are compared
3. Ways to categorize experimental studies

Individual versus community


• Treatment allocated to individual OR entire community

Do women with stage I breast cancer, given a lumpectomy


alone, survive as long without recurrence of disease as
women given a lumpectomy plus radiation?

Does fluoride in the water supply decrease the frequency of


dental caries in a community compared to a similar
community without such water treatment?
3. Ways to categorize experimental studies

Preventive versus therapeutic


• Prophylactic agent is given to healthy or high-risk individual to
prevent disease
OR
• Treatment given to diseased individuals to reduce risk of recurrence
and improve survival and quality of life

• Does tamoxifen lower the incidence of breast cancer in women with


high-risk profiles as compared with high-risk women not given
tamoxifen?
OR
• Do combinations of two or three antiretroviral drugs prolong survival
of AIDS patients as well as regimens of single drugs?
4. Selection of study population

A) Reference population - general group to whom results of a trial


should be applicable (hopefully, all humans but some restrictions
may apply)

B) Study or experimental population – people who are considered


for enrollment in a trial, i.e., potential participants
Reference Population

Study or Experimental Population

Population Non-Participants
Hierarchy
Participants

Treatment Allocation

Treatment Group Comparison Group

Cooperators Non-Cooperators Cooperators Non-Cooperators


5. Issues to be considered

A. Size, size, size - not just number of people in the trial, but how
many endpoints (outcomes under study) are being examined

B. Restrictions on who is eligible (eligibility criteria)

• Substantive: What group are you interested in?

• Logistics: What group is accessible? Who will comply with


study protocol? How feasible is complete and accurate
follow-up of the subjects?

• Characteristics of volunteers: How does the study population


differ from reference population?
6. Allocation of treatment
A. Should be random assignment
• DEFINITION: each individual has the same chance of
receiving each possible “treatment”

B. Some examples of random allocation


• Random number table: as each subject is enrolled, a
number is assigned from the random number table
• Assign even numbers to treatment A and odd to
treatment B
• Toss a coin for each subject: heads=A, tails=B

C. Some examples of nonrandom allocation


• Alternate assignment of treatments
• Assignment by day of the week
6. Allocation of treatment

D. Goal of randomization

• To achieve baseline comparability between compared groups


on factors related to outcome

• Essence of good comparison between “treatments” is that the


compared groups are the same EXCEPT for the “treatment.”

• This is important because any group of individuals will vary in


response to a “treatment” based upon their sex, age, overall
health, severity of illness.

• The investigator knows some of these (like severity of illness


by different demographics), but there are many unknown
factors that are also relevant.
6. Allocation of treatment

D. Goal of randomization (cont.)

• The compared groups should have the same distribution


of all these characteristics.

• This is what randomization can accomplish: the equal


distribution of known and unknown factors that are
relevant to response to the treatment (i.e., cofactors and
confounders)

• The larger the groups, the better randomization


works
EXAMPLE: CAPRIE STUDY

Clopidogrel Group Aspirin Group


N = 9,599 N = 9,586

% Male 72 72

% White 95 95

% Current Smoker 29 30

% Prior 51 51
Hypertension
% Stable Angina 22 22
Example: Maternal-Infant HIV Transmission Study
Zidovudine Placebo Group
Group
N = 239 N = 238
Median Age at entry 25 yrs 25 yrs

% White 48 38

Gestational age at
entry
% 14-26 weeks 52 50

% > 26 weeks 48 50

Mean CD4 count at 560 538


entry
7. Use of placebo and blinding

A) Goals

• Placebos are used to make the groups as comparable as


possible (recall the laboratory experiment)

• Blinding: subjects do not know if they are receiving treatment


or placebo (single blind); neither subjects nor investigators know
who is receiving treatment or placebo (double blind).

• Purpose of blinding: To avoid bias in ascertainment of outcome

• Placebo allows study to be blinded


8. Maintenance and assessment of compliance
A. Study requires active participation and cooperation of
participants but deviations from the protocol will occur related
to side effects, illness, level of interest, and length of follow-up

B. Noncompliance makes the compared groups more alike, which


reduces the ability of the investigator to detect a difference
between the groups (i.e., diminishes study power)

C. Strategies to enhance compliance exist at the design phase


(e.g., pick an interested group and design a simple protocol)
and during the study itself (e.g., frequent contact with subjects,
incentives to continue, such as free check-ups, etc.)
9. Ascertaining the outcome

A) Goals

• High follow-up rates: don’t lose people

• Uniform follow-up for compared groups: must be equally


vigilant in follow-up in all compared groups

B) The penalty of non-uniform ascertainment of


outcome is BIAS
10. Analysis of data from experimental studies

Data set up: familiar 2 x 2 table

Disease: Disease: Total


YES No
Treatment a b a+b

Placebo c d c+d

Total a+c b+d a+b+c+d

Measure of treatment effect: RR or RD


11. Important issues in experimental
studies
A. Ethical considerations

• Equipoise: Must be genuine doubt about efficacy of


treatment yet sufficient belief that it may work

• Stopping rules: What if it becomes apparent, before


the trial is over, that the new treatment is beneficial
(and should not be withheld from the placebo group)
or is toxic (and treatment should be withdrawn)?
11. Important issues in experimental studies

B. Planning for an informative result: if the study finds no


difference between compared treatments, do you
believe it? Or was there a difference but the study was
not powerful enough to detect it? Initial consideration is
study size.

C. Analyzing by intention to treat: As the saying goes…


once randomized, always analyzed.

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