Managerial Epidemiology
Helpm31990
51589_PPTx_CH08.pptxChapter 8
Experimental Study Designs
Learning Objectives (abridged)
State how study designs compare with respect to validity of causal inference
Distinguish between a controlled experiment and a quasi-experiment
Describe the scope of intervention studies
Define the term controlled clinical trials and give examples
Explain the phases in testing a new drug or vaccine
Learning Objectives (abridged)
Discuss blinding and crossover in clinical trials.
Define what is meant by community trials.
Discuss ethical aspects of experimentation with human subjects.
True Experimental Studies
Most convincing for conferring evidence of associations between risk factors and outcomes
Manipulation of study factor and randomization of subjects
An example is a randomized clinical trial.
Women’s Health Initiative
Hormone Replacement Therapy (HRT)
Epidemiologic studies had shown that HRT use had significant benefits against coronary heart disease.
Clinical trials had failed to demonstrate any benefit.
Large body of epidemiologic research had observed that women who took HRT had elevated risks of breast cancer.
Women’s Health Initiative
Hormone Replacement Therapy (HRT)
To resolve the question of risks versus benefits of HRT, a clinical trial was conducted.
Demonstrated that:
the epidemiologic findings on cancer were generally accurate
the benefits on cardiovascular disease had been overestimated
Results
Use of HRT decreased 40%-80% after the trial was stopped
Quasi-Experiment/Community Trial
Ranked immediately below controlled experiments in rigor
Investigator is unable to randomly allocate subjects to the conditions.
There may be contamination across the conditions of the study.
Intervention Studies
An investigation involving intentional change in some aspect of the status of subjects
Used to test efficacy of preventive or therapeutic measures
Manipulation of the study factor and randomization of study subjects
Intervention Studies
Two categories:
Clinical trials (focus on the individual)
Community trial or community intervention (focus on the group or community.
NOTE: Controlled clinical trials may be conducted both at the individual and community levels.
Clinical Trials: Definition
A research activity that involves the administration of a test regimen to humans to evaluate its efficacy and safety
Wide variation in usage:
The first use of the term was for studies in humans without any control treatment
Now denotes a rigorously designed and executed experiment involving RANDOM ALLOCATION of test and control treatments
Characteristics of Clinical Trials
Carefully designed and rigidly enforced protocol
Tightly controlled in terms of eligibility, delivery of the intervention, and monitoring out outcomes
Duration ranges from days to years
Participation is generally restricted to a highly selected group of individuals.
Characteristics of Clinical Trials
Once subjects agree to participate, they are randomly assigned to one of the study groups, e.g., intervention or control (placebo)
History of Clinical Trials
In 1537, Ambroise Paré applied experimental treatment for battlefield wounds.
East India Shipping Company (1600) found that lemon juice protected against scurvy.
James Lind (1747) used the concurrently treated control group method.
History of Clinical Trials
Edward Jenner’s efforts to develop a smallpox vaccine in the late 18th century
Most recent historical developments include the use of multicenter trials.
Instrumental in the development of treatments for infectious diseases and recently in chronic diseases that are of noninfectious origin
Prophylactic and Therapeutic Trials
A prophylactic trial evaluates the effectiveness of a substance that is used to prevent disease; it can also involve a prevention program.
A therapeutic trial involves the study of curative drugs or a new surgical procedure to improve the patient’s health.
Outcomes of Clinical Trials
Referred to as clinical end points
May include rates of disease, death, or recovery
The outcome of interest is measured in the intervention and control arms of the trial to evaluate efficacy--these must be measured in a comparable manner.
Examples of Clinical Trials
Medical Research Council Vitamin Study—studied role of folic acid in preventing neural tube defects.
South Bronx, NY, STD Program—evaluated effectiveness of education efforts to prevent spread of sexually transmitted diseases (STDs).
Blinding (Masking)
To maintain the integrity of a study and reduce the potential for bias, the investigator may utilize one of two popular approaches:
Single-blind design: subject unaware of group assignment
Double-blind design: Neither subject nor experimenter is aware of group assignment
Phases of Clinical Trials
Before a vaccine, drug, or treatment can be licensed for general use, it must go through several stages of development.
This lengthy process requires balance to:
protect the public from a potentially deleterious vaccine
satisfy the urgent needs for new vaccines
Stages in the Development of A Vaccination Program
Pre-licensing evaluation of vaccine
Phase I trials: Safety of adult volunteers
Phase II trials: Immunogenicity and reactogenicity in the target population.
Phase III trials: protective efficacy
Post-licensing evaluation
Safety and efficacy of vaccine
Disease surveillance
Serologic surveillance
Measurement of vaccine coverage
Phase IV Trials
There can be more than three phases in a clinical trial.
Phase IV trials involve post-marketing research to gather more information about risks and benefits of a drug.
Randomization
Method of choice for assigning subjects to the treatment or control conditions of a clinical trial.
Non-random assignment may cause mixing of the effects of the intervention with differences (e.g., demographic) among the participants of the trial.
Crossover Designs
Any change of treatment for a patient in a clinical trial involving a switch of study treatments
In planned crossovers a protocol is developed in advance, and the patient may serve as his or her own control.
Unplanned crossovers exist for various reasons, such as patient’s request to change treatment.
Ethical Aspects of Human Experimentation
Benefits must outweigh risks.
Ethical issues:
Informed consent
Withholding treatment known to be effective
Protective the interests of the individual patient
Monitoring for side effects
Deciding when to withdraw a patient
Reporting the Results of Clinical Trials
The CONSORT Statement is a protocol that guides the reporting of randomized trials by providing a 22-item checklist and a flowchart.
Summary of Clinical Trials
Strengths:
Provide the greatest control over:
the amount of exposure
the timing and frequency of exposure
the period of observation
Ability to randomize reduces the likelihood that groups will differ significantly.
Summary of Clinical Trials (cont’d)
Limitations:
Artificial setting
Limited scope of potential impact
Adherence to protocol is difficult to enforce
Ethical dilemmas
Community Trials
Community intervention trials determine the potential benefit of new policies and programs
Intervention: Any program or other planned effort designed to produce changes in a target population
Community refers to a defined unit, e.g., a county, state, or school district
Community Trials (cont’d)
Start by determining eligible communities and their willingness to participate
Collect baseline measures of the problem to be addressed in the intervention and control communities
Use a variety of measures, e.g., disease rates, knowledge, attitudes, and practices
Community Trials (cont’d)
Communities are randomized and followed over time
Outcomes of interest are measured
Examples of Community Trials
North Karelia Project
Minnesota Heart Health Program
Stanford Five-City Project
Pawtucket Heart Health Program
Community Intervention Trial for Smoking Cessation (COMMIT)
Project Respect
Summary of Community Trials: Advantages
They represent the only way to estimate directly the impact of change in behavior or modifiable exposure on the incidence of disease.
Summary of Community Trials: Disadvantages
They are inferior to clinical trials with respect to ability to control entrance into study, delivery of the intervention, and monitoring of outcomes.
Fewer study units are capable of being randomized, which affects comparability.
They are affected by population dynamics, secular trends, and nonintervention influences.
Four Stages of Evaluation
Formative: Will all plans and procedures work as conceived?
Process: Is the program serving the target group as planned?
Impact: Has the program produced any changes among the target group?
Outcome: Did the program accomplish its ultimate goal?
Overview of Quasi-Experimental Study Designs
| Type of Study Design | Group(s) | Pretest | Intervention | Posttest |
| Posttest only | Intervention | O | X | X |
| (has only one group) | ||||
| Pretest/Posttest | Intervention | X | X | X |
| (has only one group) | ||||
| Pretest/Posttest/Control | Intervention | X | X | X |
| (has two groups) | Control | X | O | X |
| Solomon Four-Group | Intervention 1 | X | X | X |
| (has four groups) | Intervention 2 | O | X | X |
| Control 1 | X | O | X | |
| Control 2 | O | O | X |
Note. O = not used; X = used.
Quasi-Experimental Designs
Posttest only--observations are made only after the program has been delivered.
Pretest/Posttest--baseline and follow-up observations are made.
Pretest/Postest/Control--observations are made in both intervention and control groups before and after the program.
Quasi-Experimental Designs (cont’d)
Solomon Four-Group assignment:
Used to overcome the Hawthorne Effect.
Uses four equivalent groups, two intervention and two control:
Two are observed before and after intervention.
Two are observed only after intervention.
