Failing the Drug Test: Fraud and Misconduct in Corporate Clinical Trials
A recent Government Accounting Office (GAO) report warns that the FDA can take years to bar corrupt researchers from oversight of clinical drug trials. The GAO report unveils a litany of irresponsible, dishonest, and sometimes deadly practices committed by dozens of physicians and researchers charged with testing new drugs for safety and efficacy.
Pharmaceutical companies spend billions every year on research and studies on new drugs in development. So conducting drug tests has become big business for corporate contract research organizations. And with the influx of money, often the medical ethics of researchers goes out the window, in favor of the business ethics model that puts profits ahead of science, patient safety and public health.
The GAO report and more than a decade of warnings from medical experts inside and outside the medical scientific community calls into question the safety of drugs used by millions of people worldwide. For example, more than 5.6 million people have taken the Aventis antibiotic Ketek since it was approved in 2004, despite fraudulent tests conducted by several clinical investigators. Experts warn that the drug carries an almost four-times greater risk of potentially lethal liver failure than other antibiotics. In 2007, a physician and former FDA regulator told Congress that the FDA approved the antibiotic despite the flawed studies “…knowing that it could kill people from liver damage and that tens of millions of people would be exposed to it.”
The GAO report is chilling reading for anyone taking prescription drugs. The GAO reviewed eighteen FDA debarment proceedings against clinical study researchers, and 52 disqualification proceedings (debarment generally follows from criminal behavior, while disqualification can occur after repeated or deliberate failure to comply with FDA rules or repeatedly submitting false information). More than half of the debarment cases took more than four years (an additional two debarment cases were not included in the review, as one investigator died during the agency review, and another was off the hook because FDA learned about the relevant crime that would have triggered a debarment past its five year time limit).
The GAO report notes debarment cases in which investigators stole study funds, received illegal Medicare kickbacks, falsifyied X-rays and lab tests to fraudulently show efficacy, manipulated test results, and/or committed fraud relating to data submissions, patient records, and even creating patient records for non-existent patients. It also shows disqualification cases that included the following abuses:
- A participant in a drug study died, likely from treatment with the experimental drug. The investigator enrolled the patient even though he suffered impaired liver and renal function that should have disqualified him; the investigator then altered lab results to make it appear that the participant was eligible for enrollment.
- Three participants were given an experimental vaccine that was developed by an unapproved process and not authorized for use in human subjects. One of the three died from the drug.
- In a study of an experimental vaccine for infants, investigators failed to document the occurrence and follow-up of serious adverse events (including hospitalizations).
- An investigator failed to report deaths and serious adverse effects of an experimental drug for months, even though the institutional review board (IRB) specifically required immediate reporting of any adverse effects. Another investigator took nearly two years to report that a patient in another study suffered acute kidney failure.
- An investigator filed case reports on 200 patients in a drug study who, it was later determined, never took part in the study.
- A physician kept two sets of medical records for the same patients: one for the experimental drug trial he oversaw, the other for his private practice. The latter records showed several study participants had health conditions that should have excluded them from the study.
- An investigator sold untested drugs to “unauthorized personnel” overseas without approval to export or sell the drug.
Corporate for-profit labs, called contract research organizations (CROs), collaborate with pharmaceutical companies to develop study protocols, and connect them with networks of physicians to recruit patients as study participants (human guinea pigs). The American Medical Students Association journal New Physician called CROs “one-stop testing service centers for drug and biotech manufacturers (that) have been raking in billions of dollars each year.” But as the journal noted, in contrast to independent academic studies, the close relationship that for-profit CROs have with Big Pharma leads inevitably to conflicts of interest and abuses. As an editor of the Annals of Internal Medicine put it, drug companies use CROs to maintain total control (and avoid independent oversight) of drug trials: “In the worst cases, the drug firms design the trial, explain to physicians how to carry it out, analyze the study, do not let researchers see all of the data, and then control the publication.”
A piece on the recent GAO report in the New York Times notes the case of Dr. Robert Fiddes, which the paper covered more extensively in a 1999 report. Studies Fiddes conducted at his for-profit test lab, Southern California Research Institute (later known as American Pharmaceutical Research Inc.), were riddled with fraud, from falsified records to rigged tests to invented patients. For one trial that required urine samples, Fiddes found a lab employee whose urine matched the trial criteria, and substituted the employee’s urine for samples from real trial participants – paying the employee $25 per sample. The recent Times piece highlighted a Fiddes study coordinator involved in the fraud who is still permitted to work on drug trials simply because FDA failed to take appropriate and timely steps to bar her.
On the same day the Times reported on the GAO report, a Montana women was awarded $3.2 million in her case against Novartis, for a life-long disability she suffers as a result of taking the company’s bone-building drug, Zometa. Zometa and Merck’s Fosamax are bisphosphonates, a class of drugs linked to osteonecrosis of the jaw (ONJ), a disease causing a disfiguring and irreversible breakdown of the jawbone and loss of teeth. Referring to Merck’s drug trials of Fosamax, the leading expert on the relationship between bisphosponates and ONJ, Dr. Robert Marx of the University of Miami Medical School, said the drug company failed to adequately test the drug and that proper testing “could’ve predicted this might occur.”