In part 2 of this interview, Benjamin Djulbegovic, MD, PhD, discusses the uncertainty principle in clinical trials. Dr. Djulbegovic is associate professor of medicine, Divisions of Blood and Marrow Transplantation, H. Lee Moffitt Cancer Center and Research Institute at the University of South Florida, Tampa.
Oncology News International: What are the ethical implications of the uncertainty principle?
Dr. Djulbegovic: An ethical issue arises in the assessment of the quality of the preexisting knowledge. In recent years, increasing evidence points to systematic review and meta-analysis, when possible, as the best method for research synthesis of available knowledge regarding a given treatment. The logical question then becomes: Is it ethical to perform a trial if it is not preceded by systematic review and meta-analysis?
A second question relates to the choice of the control group. We should bear in mind that any testing of medical treatments is an exercise in comparison. Basing trials on the uncertainty principle addresses this important issue in the design of a clinical trial—the choice of an adequate comparator for the intervention under investigation.
Studies violate the uncertainty principle when the intervention and the control or comparison group are known in advance to be nonequivalent in their effects on the outcomes of main interest. Even if a study is properly reported, extra caution might be needed in its interpretation if the choice of the comparator treatment was not based on uncertainty about the relative value of the treatments being assessed.
The main point here is that explicit acknowledgment of uncertainty prior to the trial is the only mechanism that we have to ensure a proper choice of an adequate control group. Studies can meet all other quality criteria regarding conduct and design and can still be biased if the control group was inferior or inadequate.
For example, we recently found that for every single quality criterion analyzed, industry-sponsored studies are equal to or better than publicly sponsored studies. Yet, industry-sponsored studies were more biased because they more often chose an inferior control group in their trials (as evidenced by increased percentage of placebo/no therapy comparators in the industry-sponsored studies).
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Part 1 appeared in the November 2001 issue of Oncology News International.