When the FDA encounters instances of scientific misconduct, it buries the evidence. A recent investigation sheds light on the extent of the problem.
The U.S. Food and Drug Administration – the agency tasked with protecting public health via regulation of everything from food safety to prescription drugs – occasionally encounters serious instances of misconduct in biomedical research. According to an investigation published in the latest issue of the Journal of the American Medical Association, these cases include
...falsification or submission of false information... problems with adverse events reporting... protocol violations... inadequate or inaccurate recordkeeping... failure to protect the safety of patients and/or issues with oversight or informed consent... [among other violations]
Study author Charles Seife, an acclaimed science writer and professor of journalism at NYU, writes that "the FDA has no systematic method of communicating these findings to the scientific community, leaving open the possibility that research misconduct detected by a government agency goes unremarked in the peer-reviewed literature." In the course of his investigation, he identified fifty seven published clinical trials for which an FDA inspection of the trial site had turned up "significant evidence" for at least of the aforementioned problems.
The problem with these problems is that they are not reported. At least, not in any meaningful way. "The FDA has no systematic method of communicating these findings to the scientific community," writes Seife, "leaving open the possibility that research misconduct detected by a government agency goes unremarked in the peer-reviewed literature." By failing to make this information readily available, the FDA compromises the ability of scientists, doctors, and the public – that means you – to remain informed about scientific trials fraught with misconduct.
The most troubling thing about the FDA's reticence about these matters is that it is characterized by more than silence. As Seife writes in a supplemental piece published at Slate, the FDA is engaged in "active deception." This is something the FDA has been accused of in the past. In his piece, Seife describes the process by which he and his students dug up even more damning evidence of the FDA's surreptitious practices:
My students and I looked at FDA documents relating to roughly 600 clinical trials in which one of the researchers running the trial failed an FDA inspection. In only roughly 100 cases were we able to figure out which study, which drug, and which pharmaceutical company were involved. (We cracked a bunch of the redactions by cross-referencing the documents with clinical trials data, checking various other databases, and using carefully crafted Google searches.) For the other 500, the FDA was successfully able to shield the drugmaker (and the study sponsor) from public exposure.
It's not just the public that's in the dark. It's researchers, too. And your doctor. As I describe in the current issue of JAMA Internal Medicine, my students and I were able to track down some 78 scientific publications resulting from a tainted study—a clinical trial in which FDA inspectors found significant problems with the conduct of the trial, up to and including fraud. In only three cases did we find any hint in the peer-reviewed literature of problems found by the FDA inspection. The other publications were not retracted, corrected, or highlighted in any way. In other words, the FDA knows about dozens of scientific papers floating about whose data are questionable—and has said nothing, leaving physicians and medical researchers completely unaware. The silence is unbroken even when the FDA itself seems shocked at the degree of fraud and misconduct in a clinical trial.
Such was the case with the so-called RECORD 4 study. RECORD 4 was one of four large clinical trials that involved thousands of patients who were recruited at scores of clinical sites in more than a dozen countries around the world. The trial was used as evidence that a new anti-blood-clotting agent, rivaroxaban, was safe and effective. The FDA inspected or had access to external audits of 16 of the RECORD 4 sites. The trial was a fiasco. At Dr. Craig Loucks' site in Colorado, the FDA foundfalsified data. At Dr. Ricardo Esquivel's site in Mexico, there was "systematic discarding of medical records" that made it impossible to tell whether the study drug was given to the patients. At half of the sites that drew FDA scrutiny—eight out of 16—there was misconduct, fraud, fishy behavior, or other practices so objectionable that the data had to be thrown out. The problems were so bad and so widespread that, contrary to its usual practice, the FDA declared the entire study to be "unreliable." Yet if you look in the medical journals, the results from RECORD 4 sit quietly in The Lancet without any hint in the literature about falsification, misconduct, or chaos behind the scenes. This means that physicians around the world are basing life-and-death medical decisions on a study that the FDA knows is simply not credible.
Read the rest of Seife's piece at Slate. Read the results of his and his students' investigation in the latest issue of JAMA. Seife has also made all primary documents for the exposé available on his website.