Despite the Food and Drug Administration (FDA)’s assurance that it would make its compliance and enforcement activities more transparent, many of the agency’s published reports of scientific findings didn’t note occurrences of research misconduct and other violations, a recent study finds.
Researchers at New York University (NYU) in New York City sifted through data compiled between 1998 and 2003 and identified 57 clinical trials that received the highest level of violations for reasons that included poor record keeping, false information, failure to disclose adverse effects, and poor patient safety. Only three of the 78 studies analyzed in the study, published in this week’s issue of JAMA Internal Medicine, noted the infractions.
In one case of research misconduct, a report stated that all patients saw improvements in their condition when, in fact, one person had a foot amputation less than two weeks after treatment. In another case, the final report didn’t disclose that the FDA found an entire clinical trial to be unreliable. The NYU study also highlighted an instance of research misconduct that led to a patient’s death.
Dr. Robert Steinbrook, an editor-at-large at JAMA Internal Medicine, told Reuters that the recent revelations — which come less than a week after FDA Commissioner Margaret Hamburg announced her resignation — have caused alarm among doctors and research journal publishers, two groups that rely on the published findings to make informed decisions.
“This study highlights some disturbing examples where articles were published and information was lacking and this would be a concern to readers,” Steinbrook, who is affiliated with the Yale School of Medicine in New Haven, CT, said. “What this does is call attention to a communication issue.”
The communication issue that Steinbrook mentions may stem from “publication bias” — defined as the tendency of researchers, editors, and pharmaceutical companies to tout the positive outcomes of research while sweeping the negative findings under the rug. That could create an outcome that advances their agenda, whether it’s securing a medication’s place on the market or telling a specific narrative about a health issue.
This issue is not new to the FDA, an agency that has long enjoyed a profitable relationship with pharmaceutical companies. The passage of the Prescription User Drug Fee Act in 1992 sped up the drug approval process using fees collected from Big Pharma companies. The increased workload caused deficiencies within the federal agency’s drug approval process, including the manner in which researchers conduct clinical trials.
A 2005 report found that nearly 20 percent of authors in clinical drug trials said they personally knew of lies made in research going back at least 10 years. In 2007, the agency attempted to curb publication bias with the passage of the Food and Drug Administration Acts, which would require researchers to register clinical trials of FDA-regulated products at ClinicalTrials.gov.
The mandate, however, did little to compel researchers to fully disclose the findings of their studies, positive or negative. A 2009 investigation published in Nature, an international weekly science journal, found that fewer than half of studies published in peer-reviewed journals followed these guidelines. Of the clinical trials that complied with the regulations, the findings of more than 50 percent of them didn’t make it into academic journals, mainly because investigators didn’t think that the negative results would interest readers.
Handling investigations into potentially faulty research in-house often allows the FDA to keep the drugs in question on pharmacy shelves, even with no additional evidence of their safety or efficacy. Such was the case in early 2010 when the federal agency zeroed in a Houston-based pharmaceutical research firm that tested more than 100 drugs, including chemotherapy compounds and prescription painkillers. While FDA officials determined more than 1,400 drug trials conducted within a span of five years to be tainted, industry officials remained reluctant to issue recalls and retest the medication out of fear of “alarm[ing] the public and the providers for a large portion of drugs.”
“If there are problems with the scientific studies, as there have been in this case, then the FDA’s review of those problems needs to be transparent,” David Kessler, who sat at the helm of the FDA from 1990 to 1997, told ProPublica in 2013. “Putting its reviews in public view would let the medical community understand the basis for the agency’s actions. The FDA may be right here, but if it wants public confidence, they should be transparent. Otherwise it’s just a black box.”
Whenever the FDA actively investigates allegations of researchers’ wrongdoing, investigators generate a host of documents — including 483 Forms, Establishment Inspection Reports, and Warning Letters — that often leave observers asking more questions. The edits of key portions of the documents can make it difficult for those who read them to decipher the name and sponsor of the study, the drug involved in the clinical trial, and the effect of the misconduct on the reliability of the results.
Earlier this week, Charles Seife, lead author of the new JAMA study, described his attempt to gather data from 600 FDA clinical trial investigation documents in an article published on Slate. He said that his team of university students ultimately found the information they sought in less than 100 reports. In the piece, Seife calls on the FDA to stop protecting drug companies and excusing the actions of those who manufacture scientific findings, saying that the agency has lost the public trust by putting patients at risk.
“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,” Seife writes. “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. 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.”