Washington Editor

WASHINGTON - As the Washington parlor games of predicting who will be the next FDA chief continued this week, the agency got hit yet again with another failing grade from the Health and Human Services Office of Inspector General (OIG).

In a new report, government auditors said the FDA failed to adequately monitor the financial ties between clinical investigators and the companies whose products they tested in trials.

Manufacturers are required to disclose to the FDA in their marketing applications all clinical investigators' potential financial conflicts. Financial interests between clinical investigators and drug and device makers create a potential for bias that may compromise the safety of patients and the integrity of research data, the OIG noted.

In a review of 118 marketing applications for drugs, biologics and medical devices approved by the FDA in 2007, auditors said 23 percent were missing the required financial forms or attachments and 42 percent lacked complete financial information. Federal regulations permit manufacturers to indicate in their applications that they acted with due diligence but were unable to obtain financial information from a clinical investigator. However, if a company claims the exemption, it must explain why it was unable to obtain the investigators' financial information.

The OIG said companies used the due diligence exemption in 28 percent of the marketing applications approved in 2007. However, for most of those, the firms failed to provide the required explanation for not getting the information.

Auditors noted that the Journal of the American Medical Association reported that up to 28 percent of academic researchers had financial interests in medical companies. Yet, the OIG said, only 1 percent of clinical investigators in the applications reviewed disclosed a potential financial conflict.

Among marketing applications with disclosed financial interests, 24 percent were missing the companies' actions to minimize potential bias resulting from disclosed financial interests, the OIG said, and 18 percent with disclosed financial interests were missing detailed descriptions of those potential conflicts.

The OIG said it found "a number of limitations" in the FDA's oversight, leaving the agency unable to determine whether companies submit financial information for all clinical investigators. The OIG noted that the FDA does not keep a complete list of all clinical investigators. Therefore, the auditors said, the agency cannot determine whether manufacturers have submitted complete financial information for all of them. In addition, the OIG noted that the FDA does not use onsite inspections to confirm that submitted financial information is complete. In 31 percent of the applications, FDA reviewers failed to document whether they reviewed any financial information.

Auditors said that in 20 percent of the applications, neither the FDA nor manufacturers took action about the potential financial conflicts of interest. And when regulators did act, OIG said, those actions were inconsistent.

OIG noted that the FDA's Center for Drug Evaluation and Research, which used a consistent review template, was better than the agency's biologics or device centers about documenting potential conflict information.

The OIG made several recommendations to the FDA for fixing its problems, including using a complete list of clinical investigators to check that companies have submitted financial information for all clinical investigators and making sure that the firms have submitted all required attachments to financial forms. Auditors also suggested that the FDA update its due-diligence exemption guidance and add a review of financial information to its onsite inspection protocol. The OIG also said that the agency needs to better ensure that reviewers are consistently reviewing financial information and taking action in response to potential conflicts.

The government auditors also suggested that the FDA require companies to submit clinical investigators' financial information earlier, as part of the pretrial application process rather than with their marketing applications. However, regulators disagreed with that recommendation, responding that the agency had no mechanism in place to ensure that manufacturers are in fact collecting financial information before beginning clinical trials.

The FDA also said it would take significant additional effort for the agency to collect and review financial information during the pretrial application process. However, it noted that firms are required to collect the investigators' financial information before the start of a clinical trial.

Temporary Chiefs

President-Elect Barack Obama is replacing most of the heads of the federal health care agencies with acting chiefs until his new leaders are confirmed.

Frank Torti, the FDA's chief scientist, will step in next Tuesday as acting commissioner until a new head is named and confirmed by the Senate.

Rumors have circulated for weeks about who Obama will pick to lead the agency, with such names being suggested as former Office of Women's Health Director Susan Wood, who quit the agency in protest over the FDA's appearance that it was dragging feet on making a decision about emergency contraception, and longtime critic Steven Nissen, chief of cardiology at the Cleveland Clinic Foundation.

Others speculated to take the FDA helm include former Vermont Gov. Howard Dean, who is a medical doctor.

Centers for Disease Control and Prevention Director Julie Gerberding, who announced last week that she was leaving, will be replaced temporarily by William Gimson, the agency's chief operating officer.

Acting Administrator Kerry Weems also next week will be leaving the Center for Medicare & Medicaid Services, with Charlene Frizzera, the agency's chief operating officer, taking the helm temporarily. However, Carolyn Clancy, director of the Agency for Healthcare Research and Quality, will reportedly be staying on for the time being.

National Institutes of Health Director Elias Zerhouni already stepped down last October. NIH's Deputy Director Raynard Kington has been filling the job for the past few months in an acting capacity. (See BioWorld Today, Sept. 29, 2008.)