Sola Fide with Drugs

© Awakenedeye | Dreamstime.com

© Awakenedeye | Dreamstime.com

Between May of 1999 and July of 2002, a researcher employed at the Stratton Veterans Affairs Medical Center in Albany New York falsified documents in a clinical trial drug study that contributed to the death of a subject. The researcher “knowingly and willfully” misrepresented the results of a blood chemistry analysis to qualify an individual with impaired kidney and liver function for the study. As Charles Seife reported, the study subject died as a direct consequence of the first dose of the treatment. “The researcher pleaded guilty to fraud and criminally negligent homicide and was sentenced to 71 months in prison.”

Although this episode is described in detail in FDA documents as well as court documents,none of the publications in the peer-reviewed literature associated with the chemotherapy study in which the patient died have any mention of the falsification, fraud, or homicide. The publications associated with 2 of the 3 other studies for which the researcher falsified documents also do not report on the violations.

This was just one of the four case examples described by Seife in his JAMA Internal Medicine article, “Research Misconduct Identified by the US Federal Drug Administration.” His study sought to identify publications describing clinical trials to which the FDA had given its severest warning (an OAI—official action indicated—warning) after doing routine inspections. Once the published articles were identified, Seife tried to determine if there was any subsequent acknowledgement of the violation.

From the documents he and his students gathered together, they found approximately 600 clinical trials mentioned as potentially having OAI violations. They then submitted requests for the FDA OAI notifications through the Freedom of Information Act. Because of extensive redactions (censoring for legal or security purposes), most of the trials in the documents could not be identified. When key information was available, they were able to identify 101 trials with one or more OAI grades. From these, they were able to glean 57 trials with 1 or more FDA inspections of a trial site with evidence of “significant departure from good clinical practice.” These violations included actions such as: underreporting adverse events, violations of protocol, violations of recruitment guidelines, and various forms of scientific misconduct.

In 22 of these trials (39%), the FDA cited researchers for falsification or submission of false information; in 14 (25%), for problems with adverse events reporting; in 42 (74%), for failure to follow the investigational plan or other violations of protocol; in 35 (61%), for inadequate or inaccurate recordkeeping; in 30 (53%), for failure to protect the safety, rights, and welfare of patients or issues with informed consent or institutional review board oversight; and in 20 (35%), for violations not otherwise categorized. Examples of uncategorized violations include cases in which the investigators used experimental compounds in patients not enrolled in trials, delegated tasks to unauthorized personnel, or otherwise failed to supervise clinical investigations properly.

The 57 clinical trials in their study had resulted in 78 articles published in peer-reviewed journals. “Of these 78 articles, only 3 publications (4%) included any mention of the FDA inspection violations despite the fact that for 59 of those 78 articles (76%), the inspection was completed at least 6 months before the article was published.”

This led Seife to conclude in: “Are Your Medications Safe?” that for more than a decade, the FDA has shown a pattern of burying the details of scientific fraud and misconduct. “The agency doesn’t notify the public, the medical establishment, or even the scientific community that the results of a medical experiment are not to be trusted.” So no one finds out which data is bogus; “which drugs might be on the market under false pretences.” The FDA has repeatedly hidden evidence of scientific fraud from the public, from its trusted scientific advisors—even as they were attempting to decide whether or not a new drug should be allowed on the market. They even stonewalled a congressional panel investigating a case of fraud regarding a dangerous drug.

The sworn purpose of the FDA is to protect the public health, to assure us that all the drugs on the market are proven safe and effective by reputable scientific trials. Yet, over and over again, the agency has proven itself willing to keep scientists, doctors, and the public in the dark about incidents when those scientific trials turn out to be less than reputable. It does so not only by passive silence, but by active deception. And despite being called out numerous times over the years for its bad behavior, including from some very pissed-off members of Congress, the agency is stubbornly resistant to change. It’s a sign that the FDA is deeply captured, drawn firmly into the orbit of the pharmaceutical industry that it’s supposed to regulate.

Seife’s research and conclusions are disturbing on so many levels. The FDA knows about dozens of scientific papers whose data are questionable, but the agency had said and done NOTHING. Even when itself is “shocked at the degree of fraud and misconduct in a clinical trial.” Seife said the most common excuse given by the FDA is that revealing which drugs’ approval relied upon tainted data, would compromise “confidential commercial information” that could hurt the drug companies if it was revealed. Another excuse is that the FDA doesn’t want to confuse the public by revealing misconduct that in the FDA’s judgment, doesn’t “pose an immediate risk to public health.”

The FDA wants you to take it on faith that its officials have the public’s best interest at heart. Justification through faith alone [sola fide] might be just fine as a religious doctrine, but it’s not a good foundation for ensuring the safety and effectiveness of our drugs.