Centralized and Uniform Research Ethics Review
A more efficient alternative to FDA oversight is available: uniform scrutiny of all ongoing clinical trials by a single regulatory body. To be sure, the OIG’s recommendations: creation of a comprehensive clinical trials database and IRB registry to facilitate identification of ongoing studies and their associated IRBs; development of a mechanism to track all site inspections; and procurement of legal authority to cover all participants in the management and conduct of a trial, including CROs and associate research personnel should be implemented.
Responsibility for managing these data sources and exercising this expanded legal authority need not be vested in the FDA alone. It would be preferable to develop a central, unified ethics organization responsible for ensuring regulatory compliance in all clinical trials subject to FDA jurisdiction. At a high level of abstraction, this organization’s role would mirror the oversight function of the Office of Human Research Protections (OHRP) but involve a wider operational scope and require greater authority.
Either created anew or subsumed within OHRP, this entity would be exclusively responsible for ensuring that research ethics requirements have been satisfied. The organization’s first task would be to promulgate a uniform set of regulations applicable to all research with human subjects, regardless of whether funded privately or by the government. The source of funding, be it governmental, academic, or industrial, should be irrelevant to the question of ethical treatment of human subjects.
It might also be appropriate for this organization to accredit and periodically recertify select IRBs, both institutional and private, for industry-sponsored trials, in addition to generating a standardized set of guidelines encompassing data-safety monitoring procedures, adverse event reporting obligations, and detailed conflict-of-interest rules—all issues of special relevance to research within FDA’s purview.
It is appropriate for the FDA to retain its authority to sanction noncompliance with applicable federal regulations. This is a quasi-judicial function that requires no fact finding. As such, it should not impose the magnitude of administrative burden we fear might debilitate the agency further. Rather, the organization we propose could accept this burden, incorporate the BiMo inspection function, and take responsibility for investigating violations, compiling data on noncompliance, and reporting offenders to FDA for recommended disciplinary action. Of course, no federal rules require IRB representatives to visit trial sites or inspect research centers; the new organization could seek to fill this gap by codifying an inspection requirement.
Finally, a central ethics organization could assuage mounting concerns about the impartiality of private, for-profit IRBs and CROs. At present, a single privately run IRB performs the ethics review of more than half of all new drug applications to the FDA. This private IRB has been singled out for ethics violations on a number of occasions.
Similarly, CROs currently run a majority of the pharmaceutical industry’s drug trials. In 1991, about 80% of industry-sponsored drug trials were conducted by academic researchers at universities. By 2005, 75% of all clinical trials sponsored by pharmaceutical companies were set in private test centers or doctor’s offices.
Given these volumes, it is vital for maintaining public trust in research that federal overseers investigate reports that CROs take liberties with ethics guidelines to remain attractive business propositions, e.g., recruiting vulnerable study subjects without an adequate explanation of risks, employing unqualified or unlicensed clinicians to administer study drugs at private test centers, or simply maintaining incomplete or illegible records.
Our proposed ethics organization could do so by promoting transparency in CRO operations, enforcing accountability of CRO personnel for mishandling human subjects and clarifying how pharmaceutical firms employing CROs should be held responsible for violations at their test sites.
We have proposed one solution to the FDA’s apparent lack of institutional capacity to monitor clinical trial sites aggressively. There may be others. Admittedly, the role of our proposed ethics organization demands further specification. In addition, there are drawbacks to such an approach. But an alternative approach must be found because the evidence strongly implies that protecting human subjects may be outside the perimeter of FDA’s traditional, and likely future, competencies.