1 / 35

Chapter 8

Chapter 8. Experimental Study Designs Revised by Susan Bailey, Ph.D. Learning Objectives (abridged). State how study designs compare with respect to validity of causal inference. Define the term controlled clinical trials . Define what is meant by community trials.

vincent-ford
Télécharger la présentation

Chapter 8

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Chapter 8 Experimental Study Designs Revised by Susan Bailey, Ph.D.

  2. Learning Objectives (abridged) • State how study designs compare with respect to validity of causal inference. • Define the term controlled clinical trials. • Define what is meant by community trials.

  3. Hierarchy of Study Designs:Validity for Etiologic Inference

  4. Experimental Studies • Most rigorous design: greatest control over the research setting. • Manipulation of study factor and random assignment. • An example is a randomized clinical trial. • Typically implemented as intervention studies (controlled or quasi-experimental).

  5. 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.

  6. Intervention Studies • Used to test efficacy of preventive or therapeutic measures. • Two categories: • Controlled clinical trials • Community interventions • Multicenter trials--results from several researchers are pooled.

  7. History of Clinical Trials • Earliest recorded clinical trial • Old Testament • Daniel followed a diet of pulses (beans) and water rather than a diet of meat and wine recommended by King Nebuchadnezzar II • Daniel remained healthy while his companions became ill

  8. 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.

  9. Clinical TrialsDefinition • A planned experiment that assesses the efficacy of a treatment in man. • Outcomes in treated group are compared with outcomes in an equivalent control group. • Participants in both groups are enrolled, treated, and followed over the same time period.

  10. Characteristics of Clinical Trials • Assess the efficacy of a treatment. • Carefully designed and rigidly enforced protocol. • Random assignment of subjects to study groups (intervention and control). • Placebo given to control group.

  11. Characteristics of Clinical Trials (cont’d) • Eligibility rules carefully defined and rigidly enforced. • Subjects are randomly assigned to one of the study groups, e.g., intervention or control (placebo). • More than one experimental intervention can be run in parallel.

  12. Schematic Diagram of a Clinical Trial

  13. 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.

  14. Outcomes of Clinical Trials • Referred to as clinical end points. • May include rates of disease, death, or recovery. • Outcomes must be measured in a comparable manner in the intervention and control conditions.

  15. 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).

  16. 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.

  17. 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 helps to protect the public, yet at the same time delays access to needed pharmaceutical agents for critically ill patients, such as those afflicted with AIDS or cancer.

  18. Phases of Clinical Trials for New Vaccines • Phase I--tests a new vaccine in adult volunteers (fewer than 100 volunteers). • Phase II--expands testing to a group of 100 to 200 subjects (from the targeted population). • Phase III (the main test)--assesses the efficacy of the vaccine in the target population.

  19. 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 systematic differences (e.g., demographic) among the participants of the trial.

  20. 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.

  21. Example of a Crossover Design WashoutPeriod

  22. Ethical Aspects of Human Experimentation • Benefits must outweigh risks. • Ethical issues: • Informed consent • Withholding treatment • Sequential designs are used as a solution. • Monitoring for side effects • Can be circumvented by using animals. • Deciding when to withdraw a patient • Protecting the interests of patients

  23. 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.

  24. 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.

  25. Summary of Clinical Trials (cont’d) • Limitations: • Artificial setting • Limited scope of potential impact • Adherence to protocol is difficult to enforce. • Ethical dilemmas

  26. 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.

  27. 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.

  28. Community Trials (cont’d) • Communities are randomized and followed over time. • Outcomes of interest are measured.

  29. 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

  30. Summary of Community Trials: Advantages • Represent the only way to estimate directly the impact of change in behavior or modifiable exposure on the incidence of disease.

  31. Summary of Community Trials: Disadvantages • 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. • Affected by population dynamics, secular trends, and nonintervention influences.

  32. 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?

  33. Overview of Quasi-Experimental Study Designs Note. O = not used; X = used.

  34. 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.

  35. 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.

More Related