Enrollment in clinical trials is crucial to continued scientific discovery and improved patient care. However, public trust in clinical trials has diminished in recent years due to a few well-publicized deaths and serious adverse events (AEs) that occurred in phase I/II trials. Minimizing risks of serious injury and death during clinical research may increase the willingness of patient-subjects to participate in clinical trials. This is particularly relevant since adverse drug reactions account for more than 100,000 patient deaths per year in hospitals in the United States.
While clinical trials identify benefits and common side effects of drugs, their practical size limits the likelihood of detecting all but the most common AEs prior to drug approval. Similarly, clinical trials limit the profile of patients who test new drugs. As a result, more than half of all new drugs have serious undetected toxicities at the time of their initial FDA approval.
FDA outside of the clinical trial setting is low, and these reports are often of poor quality. Failure to detect occurrences of serious AEs with novel cancer agents in the clinical trial setting may result in continued use of these agents in ongoing and future clinical trials without the necessary insight about the true toxicity profile, and subsequent clinical trial participants can be injured or die from these toxicities.
With improved pharmaco-vigilance practices, it may be possible to improve the detection of serious AEs during clinical trials—before the drug is approved and widely available.
Role of IRBs
One means of improving AE detection is through improved Institutional Review Board (IRB) mechanisms. IRB oversight of medication safety is an especially important issue in oncology clinical trials due to the expected toxicity of cancer drugs, the large number of cancer patients who participate in clinical trials, the high frequency of comorbidity, the difficulty in distinguishing drug toxicity from underlying disease in cancer patients, and the importance of clinical trials in both clarifying the optimal uses of novel cancer agents and improving post- marketing assessments of safety.
Physician investigators routinely report information on serious AEs through reports to IRBs, Data Safety Monitoring Boards (if applicable), and pharmaceutical sponsors, who submit required safety reports to the FDA. In fact, one of the most important ways the IRB safeguards clinical trial participants is by ensuring there is an adequate data and safety monitoring plan related to a study.
Flood of Reported AEs
In the 1990s, drug companies extended the regulatory requirements issued by the government and began to require that all serious AEs of a drug under investigation be reported to the investigators’ local IRB, including reports from other study sites and from other studies with the investigational drug. This led to a flood of paperwork and adverse event reports— many of them overlapping—that have overwhelmed chronically underfunded IRBs. For example, one large center reported receiving more than 10,000 reports per year with only one primary person available to read and interpret the reports.