On January 12, 2009, the Department of Health and Human Services Office of Inspector General (OIG) issued a report that was deeply critical of the U.S. Food and Drug Administration’s (FDA) oversight of clinical investigators’ financial disclosure.1 Under FDA’s financial disclosure regulation,2 the agency requires clinical investigators and study sponsors to submit information about investigators’ financial interests to assist the agency in determining whether those interests could potentially introduce bias into the outcome of clinical studies.3
Although the collection of financial information has become a routine part of clinical trials conducted under Investigational New Drug applications, the FDA has apparently not made review of potential financial conflicts a priority; the agency has taken relatively little public action related to financial conflicts as they pertain to clinical studies and new drug approvals. This is the case even as members of Congress and the media have for several years drawn increasing attention to the financial ties between the pharmaceutical industry and the physicians who perform services for the industry.
As an example of Congressional concern in this area, in 2007 Senator Charles Grassley introduced his Physician Payments Sunshine Act, which would have required broad disclosure of the financial ties between the drug industry and healthcare professionals. The OIG Report is likely to intensify the concerns of Senator Grassley and other members of Congress and could trigger additional congressional action on financial disclosure.
The OIG Report
The OIG Report contains five findings that call into question the rigor of the processes used to collect, report, and assess financial disclosure information. Specifically, the OIG found that:
- Only one percent of clinical investigators disclosed a financial interest.
- The FDA cannot determine whether sponsors have submitted financial information for all clinical investigators.
- 42 percent of FDA-approved marketing applications were missing financial information.
- The FDA did not document a review of any financial information for 31 percent of marketing applications.
- Neither the FDA nor sponsors took action for 20 percent of marketing applications with disclosed financial interests.4
In reaction to the five findings listed above, the OIG issued a series of recommendations that it urged FDA to promptly implement. In particular, the OIG recommended that FDA should:
- Ensure that sponsors submit complete financial information for all clinical investigators.
- Use a complete list of clinical investigators to check that sponsors have submitted financial information for all clinical investigators.
- Check that sponsors have submitted all required attachments to financial forms.
- Update guidance to sponsors regarding the due diligence exemption.
- Add a review of financial information to the onsite inspection protocol.
- Ensure that reviewers consistently review financial information and take action in response to disclosed financial interests.
- Require that all centers consistently use a template that includes a prompt to document a review of financial information.
- Provide additional guidance and training to reviewers.
- Require that sponsors submit financial information for clinical investigators as part of the pretrial application process.5
Observations and Suggestions
If implemented, the cumulative effect of these recommendations would most certainly be greater scrutiny on the financial ties between the sponsors and investigators who conduct clinical studies on pharmaceuticals.
Additionally, the OIG’s final recommendation – requiring the submission of financial information as part of the “pretrial application process” – could result in substantial delays in the initiation of clinical trials. Under the present system, sponsors collect financial disclosure information during study initiation and throughout the course of the study. This data is not reported to the FDA until such time that the sponsor submits a New Drug Application (NDA) or Biologics License Application
(BLA).6 However, as the FDA stated in its response to the OIG’s recommendations, taking this approach “may very well have the unintended effect of adding to the complexity and cost of the clinical trial enterprise with no commensurate gain in the protection of human subjects or the quality of the data. Moreover, implementing this recommendation would add a significant burden to FDA’s administrative and review staff.” 7
In response to a previous OIG report on FDA’s oversight of clinical trials,8 the agency established the “Human Subject Protection / Bioresearch Monitoring Modernization Initiative.” Under this initiative, the agency has been reviewing all aspects of its oversight of clinical studies. In its response to the recent OIG Report, the agency has stated that it will consider OIG’s recommendations in the context of this initiative.9
Members of Congress reacted immediately to the OIG Report and were troubled by FDA’s rejection of some of the findings and recommendations in the Report. In particular, Senator Grassley and Representative Maurice Hinchey expressed an intention to introduce legislation to address investigator financial interests and require drug companies to publicly report payments to physicians. Senator Grassley is expected to re-introduce his Physician Payments Sunshine Act in the very near future.
In anticipation of additional agency and congressional action in response to the OIG’s recommendations, which we believe is highly likely, pharmaceutical and biotechnology companies should consider taking the following steps:
- Sponsors should carefully assess their policies and procedures related to compliance with FDA’s financial disclosure regulation. Sponsors should also periodically audit their compliance with these policies and procedures.
- As required by regulation,10 drug companies should carefully describe in their NDAs and BLAs what steps they took to minimize any bias that may have resulted from financial ties to their investigators. For example, a sponsor might describe how it minimized the potential for bias by the use of an independent data monitoring committee.
- Finally, sponsors should anticipate that, in the future, FDA inspectors will more closely examine financial disclosure documentation during clinical Good Clinical Practice inspections.
Regardless of how the FDA ultimately responds to the OIG’s recommendations, it is clear that the financial ties between the drug industry and physicians will continue to be more closely scrutinized in the future by both the FDA and the Congress.