What Should Be Done About Bias and Misconduct in Clinical Trials?

In recent years, highly publicized litigation and new U.S. Food and Drug Administration (FDA) reporting requirements have given researchers an unprecedented opportunity to “peek inside the statistical black box”4 and examine data on drug product safety and efficacy that were previously unreported in peer-reviewed literature. The resulting proliferation of research on clinical trial conduct (and misconduct) has confirmed what many managed care pharmacy professionals have known for years—physicians often unknowingly rely on suboptimal information in making prescribing decisions. As the above quotations illustrate, among the most troubling problems is the reporting of incomplete or erroneous information in communications targeted to physicians, including clinical trials published in the peerreviewed literature. For example: • A 2008 analysis of new drug application trials approved by the FDA from 2001-2002 found that 22% were unpublished at least 5 years after their completion, and the odds of publication were multiplied by a factor of 4.8 for trials with favorable results, compared with trials with unfavorable results.5 • A 2008 analysis of FDA-registered clinical trials for antidepressants approved from 1987-2004 found that 97% with favorable results, but only 8% with unfavorable results, were published.6 • A 2007 analysis of promotional detailing visits for gabapentin from 1995-1999 found that 46% led to physician intention to prescribe or recommend the drug, and 38% of those visits involved discussions in which the “main message” was at least 1 off-label use.7 Various components of the health care system, including government regulators, journal editors, and pharmaceutical manufacturers, are cobbling together a patchwork of solutions to the problem of inaccurate “evidence” about the efficacy and safety of prescription drugs. But will their efforts be sufficient to encourage What Should Be Done About Bias and Misconduct in Clinical Trials?