A top health fraud prosecutor recently announced that clinical trial fraud will be a major priority of the U.S. Department of Justice (DOJ). Speaking at a Food and Drug Law Institute conference last month, Deputy Assistant Attorney General Arun Rao characterized the DOJ’s enforcement of clinical trial fraud cases as “aggressive”, citing two recent actions we’ll return to in a moment.
In his remarks, Rao noted that
[f]raud in clinical trials poses significant risks to the American public. The FDA relies on the veracity of clinical trial data when making drug approval determinations, with the ultimate goal of ensuring that all FDA-approved drugs are safe and effective for their approved indications. Fabricated clinical trial data can have dangerous consequences if relied upon by the FDA, drug researchers and medical doctors when making material decisions about the safety, efficacy and clinical use of drug products.
Rao supervises the DOJ’s Consumer Protection Branch, which brings criminal and civil actions to enforce health and safety-related laws, including the Food, Drug and Cosmetic Act.
SBM has covered dodgy clinical trials from the beginning, many involving “alternative” treatments that had no business being studied in the first place, such as the “Gonzalez Regimen” for cancer, Burzynski’s “antineoplastons”, what seems like umpteen thousand acupuncture trials, and most recently David Weinberg’s critique of US Stem Cell’s dubious efforts. Here, though, as much as we might wish the Department of Justice would show some interest in such matters, we’re talking about the more traditional type of fraud where, in a riff on the illegal drug trade, proceeds from fake studies of legit drugs are used to purchase luxury vehicles in South Florida.
The “Unlimited Medical Research” that wasn’t
According to the DOJ, Unlimited Medical Research, a Miami, Florida, company, was one of several firms hired by a pharmaceutical firm (identified elsewhere as GlaxoSmithKline [GSK]) to conduct a clinical trial designed to investigate the safety and efficacy of an asthma medication in children. From about 2013 to 2016, employees of the company falsified records to make it appear as though pediatric subjects made scheduled visits to Unlimited Medical Research, received physical exams from a clinical investigator, took study drugs as required, and received payments for their participation. Actually, none of this happened: children were not given exams, they did not take the study drugs, and they were not paid. In fact, there were no children at all. Employees, including a medical doctor who served as the primary investigator for the trial, fabricated the entire thing in a scheme to defraud the pharmaceutical company. The doctor used patients’ personal information from her private medical practice to create false information to be entered into case histories for the trial.
The purpose of the study was to measure the long-term safety of the inhaled asthma medication Advair Diskus in patients 4-11 years old. Results were published in the New England Journal of Medicine. According to GSK, once it became aware of possible misfeasance by Unlimited Medical Research, it excluded the fraudulent data from studies and reports and reported its suspicions to the FDA and Institutional Review Boards, hence the prosecutions.
There’s more than meets in eye in that published study and GSK’s response to the fraud, as you shall see.
Five individuals were charged in the scheme. The medical doctor plead guilty to one count of conspiracy to commit wire fraud and was sentenced to 60 months in prison and ordered to pay a $174,000 forfeiture. The study coordinator also plead guilty to conspiracy to commit wire fraud and was sentenced to 30 months in prison. At least one other person is scheduled for trial this year.
In another case mentioned in Deputy Assistant AG Rao’s remarks, a Coral Gables, Florida, medical doctor, a nurse practitioner, and two others were charged last March in a six-count indictment with crimes including wire fraud and money laundering. According to the indictment, from 2014 to 2016, the defendants fabricated clinical trial data while working at a Miami medical clinic, Tellus Clinical Research. The fraudulent trials were for drugs treating opioid dependency, irritable bowel syndrome, and diabetic nephropathy.
The indictment charges that the defendants knowingly enrolled subjects that failed to meet eligibility requirements, falsified lab results and medical records, and falsely represented that the trial participants were taking the drugs under study when, in fact, they weren’t. Personal information from friends and family were used to create fake profiles of trial participants and the drugs under study were tossed. Payments from pharmaceutical companies were used, among other things, to purchase a Land Rover.
Three defendants have plead guilty. In August, the nurse practitioner was sentenced to 46 months in prison and his co-defendant to 30 months. Both were ordered to pay just over $2 million in restitution. The third defendant, who faces up to 20 years in prison, will be sentenced next week.
Two additional recent incidents of alleged criminal clinical trial fraud not mentioned in Rao’s speech came to light in researching this post, courtesy of an international group of experts who run Rxisk.org, which they describe as an
independent website where you can research prescription drugs and report a drug side effect — identifying problems and possible solutions when it might still be possible to intervene and find a solution.
In July, 2020, an Ohio federal grand jury returned a 19-count indictment against eight defendants who worked for a company called Clinical Research Solutions [CRS], charging them with a scheme to defraud eight pharmaceutical companies and the FDA. A trial is scheduled for July of this year.
According to the DOJ, the defendants, one of whom is an MD specializing in allergies and immunology, agreed with pharmaceutical companies (who are unnamed) to conduct clinical trials of various drugs. Per the indictment, the defendants broke the law by
enrolling subjects in clinical trials under fictitious names, enrolling past subjects without their knowledge, and enrolling other subjects who did not meet pre-established criteria. In addition, the defendants allegedly fabricated and falsified medical records, informed consent forms, and other documentation for fictitious study subjects. . . [The] defendants were able to enrich themselves in this scheme by billing the [clinical trials’] sponsoring agencies for the time and participation of these fictitious subjects.
These schemes, as despicable as they are, pale in comparison to clinical trial fraud carried out by Sami Anwar, who, between 2013 and 2018, according to the DOJ,
directed and carried out a conspiracy to have his companies fraudulently pose as legitimate human clinical research trial sites and provide of false clinical research trial data regarding drug safety and drug efficacy to dozens of drug companies and, through them, the Food and Drug Administration (FDA). The false clinical research data . . . included safety data on dozens of different drugs and medicines designed to treat a wide variety of diseases and conditions including, but not limited to, heart disease, diabetes, asthma, pediatric illnesses, adolescent smoking, cirrhosis, scabies, depression, and opioid addiction to name just a few, according the evidence presented at [his] trial, [which] . . . indicated that Sami Anwar and his companies received over $5.6 million dollars from the fraud.
Anwar, who trained as a doctor in Pakistan but was not licensed in the U.S., forged the signatures of actual doctors he employed, whom he instructed to falsify records to admit dozens of ineligible research subjects. They falsified electrocardiograms and vital signs, obtained blood specimens from Anwar’s employees or stole them from patients of his medical center, and fabricated trial participant diary entries. Anwar and his employees disposed of study medications, falsely recording them as having been administered per the trial protocol, and stole opioids intended for study subjects.
According to a local newspaper, a three-year-old girl, who actually had eczema, was enrolled in a study for a new topical medication for scabies. The medication left her permanently scarred. A teenager, enrolled in study of a smoking cessation drug that Pfizer researchers worried might increase suicidal feelings, was hospitalized for attempted suicide. Another man died while participating in two different clinical trials at the same time.
Employees testified at Anwar’s trial that he not only directed the fraud but engaged in threats, retaliation, and intimidation in order to hide his crimes. They testified that Anwar filed false police reports, made false allegations to the Washington State Department of Health and the FDA, threatened them at their homes and at work, slashed their tires, and stalked them in order to prevent them from cooperating with the authorities.
In 2019, a federal jury found Anwar guilty of 47 counts of wire fraud, mail fraud, conspiracy, fraudulently obtaining controlled substances, and furnishing false material information to the Drug Enforcement Administration. He was sentenced to over 28 years in prison and he and his companies ordered to pay more than $7.5 million in restitution and forfeitures, the judge remarking that that “the extent of the fraud is astounding” and that Anwar had “endangered countless lives”. Anwar has appealed his conviction.
How did they get away with it?
[A]ll these people [charged with clinical trial fraud] were working for multinational drug companies, doing the kind of research that gets published in top peer-reviewed journals. The kind of research that your doctor and mine rely on when deciding what treatments we ought to have.
The frauds went undetected for years: CRS [the Ohio firm] worked for seven companies before the eighth one noticed something wasn’t quite right. Tellus Research [in Miami] hummed along unnoticed until the CEO, Ms. Font, used the company account to buy herself a Range Rover.
When FDA inspections finally closed down Zain Research, Sami Anwar simply opened a new research center, in the same small town, at the same address, and was hired anew.
How the hell did that happen?
The answer, according to the blog posts’ author, Johanna Ryan, is “Contract Research Organizations: the Ubers of clinical research”. Most pharmaceutical giants, she says, rely on Contract Research Organizations (CROs), large commercial brokers that recruit and manage the hundreds of local sites and doctors in a “gig economy” of medical research. CROs “offer help with everything from designing the studies to writing up the research papers and pitching the newly-approved drug to doctors”.
She compares the doctors in this system, who work as independent contractors, to drivers who transport passengers one day for Uber and pizza the next day for Door Dash. If the drive is dangerous or the pizza arrives cold, Uber and the pizza parlor can deny responsibility, claiming it’s the driver’s fault. Likewise, she says, contract doctors provide similar plausible deniability for pharmaceutical companies. Thus,
when Dr. Bencosme [of Unlimited Medical Research] was arrested, the system allowed GSK to position themselves as victims not suspects. “As soon as we became aware of possible clinical trial fraud we conducted an internal investigation; excluded the data from the studies and reports, and reported the potential fraud to the FDA,” they told reporters. Parexel [the CRO managing the trials for GSK] for its part, sniffed that it had “no affiliation” with Unlimited Medical Research.
But it was Parexel who signed up Dr. Bencosme, as well as the Ohio doctor charged with fraud, to conduct the drug trials in the first place.
As for that NEJM article publishing the study results, Ryan points out it is unlikely that any of the authors in academic medicine
actually gave an inhaler to a patient and watched what happened. They simply signed off on the results of research done by 530 or so local doctors [in 32 countries]: some skilled, some unskilled; some extremely ethical, some not exactly.
It’s good to know that the DOJ is prioritizing clinical trial fraud, but if Ryan is correct in her analysis, the drug trial system is ripe for abuse by unethical players. Until that system is reformed, the DOJ can only come in and mop up the crime scene, and that’s only for the ones who get caught.