Experimental design originated in agricultural research and influenced laboratory and industrial research before being applied to trials of pharmaceuticals in humans. Experimental design is characterized by control of the experimental process to reduce experimental error, replication of the experiment to estimate variability in the response, and randomization. For example, in comparing the yields of two varieties of corn, the experimenter uses the same type of corn planter and the same fertilizer and weed control methods in each test plot. Multiple plots of ground are planted with the two varieties of corn. The assignment of a seed variety to a test plot is randomized.
Clinical trial design has its roots in classical experimental design, yet has some different features. The clinical investigator is not able to control as many sources of variability through design as a laboratory or industrial experimenter. Human responses to medical treatments display greater variability than observations from experiments in genetically identical plants and animals or measuring the effects of tightly-controlled physical and chemical processes. And of course, ethical issues are paramount in clinical research. To study a clinical response with adequate precision, a trial may require lengthy periods for patient accrual and follow-up. It is unlikely to enroll all the study subjects on the same day. There is an opportunity for study volunteers to decide to no longer participate.
Each of these issues will be considered as we extend the classical experimental design to clinical trials.
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- State 6 general objectives that will be met with proper trial design.
- Name at least 6 sources of potential bias in clinical studies.
- Suggest design strategies to reduce bias, variability and ‘placebo effects’ in a proposed clinical study.
- Compare and contrast the following study designs with respect to the ability of the investigator to minimize bias: Case report or case series, database analysis, prospective cohort study, case-control study, parallel design clinical trial, crossover clinical trial.
- Identify the experimental unit in a proposed study.
- Differentiate between Phase I - IV trials.
- Recognize features that should be described in a written protocol for a clinical trial.
- Recognize confounding in a clinical study proposal.
- Identify characteristics and purposes of translational studies.