A Closing Thought: Prescribing Fixes for a Broken System

Arthur L. Caplan, Ph.D., chair of the University of Pennsylvania's Department of Medical Ethics, expressed his frank views about issues that are ailing the drug industry today during his DIA Keynote Address in mid-June.

He began by recounting the circumstances surrounding the well-known 1999 death of Jesse Gelsinger, a subject in a gene therapy trial of a drug to treat OTC deficiency-a rare metabolic disease that prevents the body from properly processing protein and which is frequently fatal in infants.

Attendees exchanging ideas at DIAs 40th Annual Meeting, held at the Washington Convention Center in DC.

Caplan conceded that there were problems connected with the University of Pennsylvania trial, even though two separate IRBs as well as the NIH were involved. He also emphasized that although both the lead scientist and the university had possible conflicts of interests, they were nonetheless motivated to "save babies and do good."

Pointing to such issues as poor informed consent, ineffective peer review, and conflicts of interest, Caplan suggested several steps to help fix a " broken system ."

First, he says, the industry must do a better job collecting basic data on human subjects and adhering to accepted GCP protocols during clinical trials. "We have better data on animals than we have on people," Caplan lamented.

Attendees exchanging ideas at DIA's 40th Annual Meeting, held at the Washington Convention Center in DC.

Second, he advocates splitting the functions of the IRBs and DSMBs. Ethics committees, he argues, are overwhelmed and should focus on monitoring informed consent while the DSMBs should oversee data compliance. To better utilize IRB resources, Caplan favors increased audits at pivotal trials and fewer, more random audits in low-risk studies. When problems are uncovered in less critical trials, however, he says there should be heavier sanctions levied.

Third, Caplan favors creation of a central registry of adverse events: "Disclosure is great; transparency is greater."

Attendees exchanging ideas at DIAs 40th Annual Meeting, held at the Washington Convention Center in DC.

Finally, he believes a flexible, worldwide compensation policy for payouts to those affected by adverse events would help, cautioning, " One size does not fit all ."

It would be unrealistic to believe Caplan's solutions will be implemented in the near term. Nevertheless, these issues provide for provocative discussion in the ongoing dialogue over stronger subject protections in clinical trials.-Rob Davidson