Missing information, loopholes and weak oversight hamper efforts to uncover financial conflicts by researchers who test experimental drugs before companies seek U.S. government approval, an internal watchdog finds.
As a result, the Food and Drug Administration's screening system is unreliable, the Health and Human Services inspector general's office said in a report being released Monday.
"We found a number of limitations in FDA's oversight, leaving FDA unable to determine whether (drug companies) submit financial information for all clinical investigators," the report said. Investigators examined 118 new drug applications approved by the FDA in 2007.
Because scientists can be tempted by profits, the government requires disclosure of possible conflicts involving clinical researchers who review medications before drug companies seek FDA approval.
In all, 42 percent of the applications lacked complete financial information and not even 1 percent of researchers disclosed possible conflicts. Such limitations "could result in FDA being unaware of a clinical investigator's financial interest, and thus unable to gauge its potential bias on clinical trial results," the report said.
The agency acknowledged the need for improvements while also disagreeing with some of the inspector general's findings and recommendations.
Loophole in disclosure requirements
Drug companies hire outside scientists and doctors to test the safety and effectiveness of medications under development. Such tests provide raw data for the FDA to later decide whether to approve a drug. The process, which uses human patients as medical guinea pigs, is supposed to be governed by strict scientific and ethical rules, including financial disclosure.
The issue is not scientists' compensation for supervising drug development tests, but the conflicts that could arise from other rewards, such as honoraria, grants and stock options.
Disclosure requirements were put in place after the 1999 death of a teenager in an experimental gene therapy trial. Among other problems with that clinical trial, it turned out that many of the scientists had financial ties to the drug company.
The inspector general's report found that in 2007 only 206 of 29,691 clinical investigators disclosed potential financial conflicts. By comparison, a study published in the Journal of the American Medical Association reported that between 23 percent and 28 percent of university researchers had financial ties to industry.
Also, the FDA cannot easily check whose financial information is missing because the agency does not maintain a complete list of clinical investigators.
For those scientists who did report, the most common financial rewards were consulting fees or honoraria, with a midpoint payment of $47,252. The highest was a $3.9 million donation to the institution that one researcher was affiliated with. Neither was identified.
Among those who received company stock, the median value was $65,000 and the highest grant was worth $148,751.
The report traced some of the reporting problems to a loophole in the disclosure requirements. Drug companies are supposed to gather the financial information from their researchers and submit it to the FDA. But they do not have to submit any information if they certify they used "due diligence" and were unable to collect it.
The inspector general's office said the FDA should crack down so that exemption can only be used in rare cases.
The report also concluded that financial information gets to the FDA too late in the process. Companies submit the data with their application for a drug's approval. By that stage, clinical tests are complete.