June 13, 2012, Vol 307, No. 22
Viewpoint | June 13, 2012
Adaptive Clinical Trials – A Partial Remedy for the Therapeutic Misconception?
William J. Meurer, MD, MS; Roger J. Lewis, MD, PhD; Donald A. Berry, PhD
There is a common “therapeutic misconception” among patients considering participation in clinical trials.1 Some trial participants and family members believe that the goal of a clinical trial is to improve their outcomes—a misperception often reinforced by media advertising of clinical research.2 Clinical trials have primarily scientific aims and rarely attempt to collectively improve the outcomes of their participants. The overarching goal of most clinical trials is to evaluate the effect of a treatment on disease outcomes.3 Comparisons are usually made with placebo for conditions having no established treatments and with standard care for conditions having effective treatments. Any benefit to an individual trial participant is a chance effect of randomization and the true, but unknown, relative effects of the treatments. Available evidence is conflicting regarding whether patients receive some benefit from simply participating in a clinical trial.3 Thus, even though serving as a research participant is essentially an altruistic activity, many clinical trial volunteers do not participate in research out of altruism.4 An adaptive clinical trial design can be used to increase the likelihood that study participants will benefit by being in a clinical trial…
Viewpoint | June 13, 2012
Adaptive Trials in Clinical Research – Scientific and Ethical Issues to Consider
Rieke van der Graaf, PhD; Kit C. B. Roes, PhD; Johannes J. M. van Delden, MD, PhD
Interest in the use of adaptive trial design has increased among clinical investigators, pharmaceutical companies, and regulatory authorities. Adaptive trials are randomized clinical trials that allow for adaptations in the study design while the study is being conducted. Modifications as a study is being conducted can include changes in sample size, adjustments in medication dosage, or changes in the number of treatment groups. Adaptive trials can often decrease drug development time, which can have clinical and economic advantages.
Adaptive trials also have certain ethical advantages because fewer participants are assigned to the inferior procedure or drug compared with trials with fixed designs. For instance, in the ASTIN trial, researchers conducted an adaptive phase 2 dose response trial to determine whether a neutrophil inhibitory factor improved recovery in patients with acute ischemic stroke; it did not. However, this trial needed to enroll 966 patients, compared with the need to enroll 1080 patients if a traditional design had been used. Furthermore, the adaptive design made it possible to stop the trial early for futility.1
However, certain features of adaptive trials may create some potential scientific and ethical challenges.2 This Viewpoint explores several ethical issues that researchers and participants in adaptive trials should consider…