Enforcement statistics suggest an increase in violative conduct identified by the Agency in its oversight of clinical investigations and predicted an "increased attention by the FDA to the conduct of human studies by clinical investigators and to the monitoring of such studies by company sponsors."
Dramatic recent developments support these observations and presage further potentially wide-reaching consequences for the clinical research and pharmaceutical industries. Clinical research organizations (CROs) and company sponsors received FDA Warning Letters in April and May 1999 related to the inadequate monitoring of clinical investigations following equally deficient inspection results at clinical study sites. A high-profile prosecution of the former president and primary researcher of a now defunct clinical research organization received wide and significant press coverage. The case is described in detail on the front pages of the May 16th and 17th editions of the New York Times as part of a two-part report on the clinical research industry. Reportedly, the defendant was recently sentenced to 15 months in prison and ordered to repay $800,000 to several pharmaceutical companies stemming from an elaborate, fraudulent scheme that involved the falsification of patient records, fabrication of test results and submission of case report forms on entirely fictitious patients. Alarmingly, it is reported that the company conducted almost 200 clinical studies.
Equally alarming is the perception that such violations are part of a trend and reflect serious deficiencies in the system for testing experimental drugs. For example, the New York Times report raises questions on a shift in the research base used by pharmaceutical companies from career researchers at academic centers to thousands of private-practice doctors, "for whom testing has become a sideline for making money." Further questions are raised with respect to the elevated fees and bonuses paid to clinical researchers by pharmaceutical sponsors, which handsomely reward the accelerated accrual of the greatest possible number of patients. Such fees, which can reach $4,500 per patient enrolled, are subject to confidential agreements between the researchers and the CROs or pharmaceutical companies, and are not subject to regulatory scrutiny by FDA, Institutional Review Boards (IRBs) or any State agency. This unregulated incentive structure has been blamed for the inappropriate enrollment of patients in investigational studies, the use of inexperienced clinical investigators and for encouraging fraudulent activity. Based in part on concerns that, in some cases, patient safety has been compromised, the American Medical Association has weighed in that bonuses in clinical research that are contingent on rapid enrollment are "inappropriate, potentially illegal, and certainly unethical."
Such high-profile enforcement actions and significant press coverage are sure to revive recent interest in the U.S. Congress, which already had expressed concern regarding the effectiveness of the IRB system, to propose: additional safeguards designed to protect the integrity of the clinical research process and the safety of patents. Regulatory agencies will become even more vigilant, as is reflected by the May 1999 ban, now lifted, on new enrollment for federally funded human medical research at Duke University Medical Center following troubled inspections by the National Institutes of Health's Office for Protection from Research Risks, which has jurisdiction over clinical research that is funded by the federal coffer. Similar bans had been levied in 1998 on Rush Presbyterian Hospital in Chicago and the West Los Angeles Veterans Administration Hospital.
In addition to addressing practices that may lead to compliance problems, industry must brace itself for tremendous public scrutiny of its role in the apparent shortcomings of the clinical research system. Sponsors should diligently monitor clinical investigations, choose competent investigators and reexamine potentially troubling fee arrangements. Industry as a whole may consider the development of a voluntary consensus standard that sets forth guidelines on appropriate incentive programs for clinical investigators and that complies with federal Antitrust laws. Ignoring the early warning signals sets the stage for compliance problems down the line, potential civil and criminal liability and the creation of a more onerous regulatory system by regulators and legislators in response to perceived excesses of the pharmaceutical and clinical research industries.
If you have any questions or comments about any of the foregoing, please contact:
Robert G. Pinco
202-452-7901
pincorg@bipc.com
Edward John Allera
202-452-7985
alleraej@bipc.com
Donald E. Segal
202-452-7959
segalde@bipc.com
Mark M. Yacura
202-452-7949
yacuramm@bipc.com
Todd H. Halpern
205-452-7963
halpernth@bipc.com