When a clinical study on asthma launched in late 2019 in Louisiana, Patricia M. (not her real name) signed up. But she was not completely honest about her eligibility.
"One of the criteria was you can't have taken prednisone steroids in the past two or three weeks. But I actually had taken prednisone a few days before, so I lied and said I hadn't," she tells Medscape Medical News. Otherwise, she says, "that would have put me out of the study."
For another study, on severe allergies and nasal polyps, Patricia omitted her medication history.
"They were testing different nasal sprays to see how well they would shrink nasal polyps. They wanted to try Nasacort [Sanofi]. I was actually already using Nasacort, but I told them I wasn't," she says.
"I didn't feel good about it. I'm usually an honest person," she adds. "But the study paid $400."
Researchers checked her driver's license, required a note from her physician, photos of her prescription medications, and requested permission to access her health portal. "If you don't have asthma, diabetes, or hypertension, you're not going to be able to fake it and get into a study," Patricia says.
For researchers, these so-called 'professional study subjects' are much more than a nuisance. Their deception can ruin the chances of an otherwise effective agent reaching the market, potentially dashing the hopes and jeopardizing the health of real patients living with a variety of acute and chronic illnesses.
Misrepresentation of medical conditions, failing to accurately disclose the medications they are taking, or fabricating a clinical response to an agent in development can also skew skews results — in some cases enough to invalidate outcomes and even halt further research.
Janette P., who also agreed to share her story only on the condition of anonymity, admits she has lied to get into paid clinical trials.
She has enrolled in three studies over the past 5 years. "They don't come up all that often, and a lot of them I'm not willing to do. If they want to test something new on me, I say no."
The first study evaluated an off-label use of botulinum toxin. She didn't receive payment "but there was free treatment."
She has since enrolled in a subsequent study of botulinum toxin, this time evaluating a formulation that does not require reconstitution prior to injection. The investigators take blood work, perform an ECG and run other tests on a regular basis, she says.
With the exception of the first unpaid study, the 67-year-old former teacher from Arizona supplements her retirement with the money she makes from participating in medical research and focus groups.
Like Patricia, she lied about being treatment naive. "One of the questions was 'Have you ever had Botox?' And I said no," Janette says. "I wanted to get into the study. I wanted free Botox, so I participated. And I got paid — so why wouldn't I?"
Janette has also lied about her age.
"At age 65, a lot of the opportunities go away," she says. So far, no one has checked her identification. "If you're not going to make me prove my age, I'm going to tell you I'm younger."
Using deception, she says, "was a little uncomfortable, but it was not difficult."
Beyond income generation, both Patricia and Janette believe they are contributing to medical research and society in general, by participating in these studies.
Chris W., a California man in his mid-40s who also asked that we not disclose his last name, says he has never qualified for participation in a study by duplicitous means, but he has encountered individuals who have.
"I've met some great people, and I've met some crazy people too," he said. Some people enter trials with good intentions and others "don't feel like the rules apply to them," he tells Medscape Medical News.
Clinical trials offer a welcome income stream that he has used consistently over the past decade to support himself and pay off debt.
But beyond the money, he says, he's doing it as a way to help and make a difference. One trial for an Alzheimer's drug netted him $31,000 and the feeling of being useful.
"Because my grandmother has Alzheimer's, that one hit closer to home," he says. "It's a nice paycheck, but at the end of the day, if you can help further a drug that they could give to your grandmother and help her … [or] give her a better quality of life…it's just great."
He recently completed screening for another Alzheimer's study. This one pays $10,000. He calls lucrative trials like these, which provide him with more financial freedom, "a blessing."
"You Caught Me"
Individuals who participate in clinical trials under false pretences — whether it involves lying about their identity, health history or concurrent enrollment in multiple studies — not only skew research outcomes but risk their own health and safety.
Unlike studies involving conditions like hypertension — where potential participants undergo objective biological screens at trial entry — studies investigating conditions such as depression, anxiety, and chronic pain that typically rely on self-reported symptoms are more susceptible to fraud.
"One subject went to multiple sites — seven that I know of — over the course of less than 12 months, often concurrently, negatively affecting several [psychiatric] studies simultaneously," Thomas Shiovitz, MD, a psychiatrist and founder of California Neuroscience Research Medical Group Inc, Sherman Oaks, California, tells Medscape Medical News.
When confronted, the fraudulent study subject said, "You caught me!" reports Shiovitz, who is also President of CTS database LLC, a commercial clinical trial subject database company.
Deception from other professional subjects can be more obvious.
"I was doing clinical trials and I was running into people who were just lying to me. It was blatant when I looked at their medical records," says Eric Devine, PhD, assistant professor of psychiatry at Boston University School of Medicine.
"It was even people coming back that I knew who had a different identity, giving me a different name or different details because they wanted to screen into one of my studies," Devine adds. "So I started doing a lot of gatekeeping to try to keep people out who threaten the validity of the study, but who also pose a threat to themselves."
A study of 100 individuals conducted by Devine and colleagues showed 75% who had participated in two or more studies in the previous year reported deceiving researchers about their health status.
Almost one third concealed health problems, 28% did not report prescribed medications, and 20% withheld information about recreational drug use. Furthermore, 25% of the sample reported exaggerating their symptoms in order to qualify for a study and 14% pretended to have a relevant health condition.
Devine also uncovered evidence of a "research kingpin" who tipped off professional subjects and advised them how to improve their chances of getting into one of Devine's studies.
"A kingpin made a run on our study because our reimbursement was [so high]. We were paying $60 at baseline," Devine says, "but they had to pay her $40 to find out what they needed to do to qualify."
When Devine and colleagues lowered the reimbursement for screening, "all of our people disappeared overnight."
Some individuals treat clinical trial enrollment as a job, Devine says, and they are very organized about it. He cited the Just Another Lab Rat website, an online community that features clinical trial locations, enrollment status, and study criteria.
"In their forums, they talk pretty openly about how they game us. It's no secret," Devine says.
Many professional subjects worry about being shut out of clinical trials. Forum moderator 'Vark' flags companies like Verified Clinical Trials (VCT) and others that check for deception. He warns forum members about which trials to avoid if they plan on bending the rules to enroll.
"A Real Headache"
Kerri Weingard, ANP, MS, BSN, founder and chief operating officer of VCT, estimates that 14% to 25% of subjects apply for enrollment at US research sites in a way that violates study criteria.
Some, having previously enrolled in a study for patients with a specific condition, alter their history and later apply to a subsequent trial as healthy controls, she says. For instance, a person who enrolls in a diabetes study in January, completes the trial, and then enrolls in a trial in May of the same year as a healthy control, claiming he or she has no medical conditions.
"That's one of the biggest things we see across CNS [central nervous system trials]. When you think about depression, schizophrenia, bipolar disorder, panic disorder or anxiety, they tell one site they have one of these disorders, and, because they want to earn money…they also go to a healthy volunteer unit," Weingard says. "They tell that site they've never had any of the conditions."
In a 2019 talk at the American Society of Clinical Psychopharmacology meeting, Weingard presented a study of 113 CNS trials. The total population included 10,092 participants screened by VCT between August 2016 and March 2019.
Of 498 total inclusion or exclusion protocol violations, 91 individuals violated the washout period, 45 attempted to qualify for another study at the same site and 25 others at a different site, and 42 were caught trying to dual enroll in more than one study.
But there are potential solutions.
Use of subject registries like CTS, VCT and others is "an easy way to eliminate some low-hanging bad apples," Shiovitz says. "Using a subject registry takes less than 5 minutes and is undertaken prior to more time-consuming or invasive procedures." Monitored dosing and pharmacokinetic sampling are also good ideas, he says.
Shiovitz and colleagues conducted a study examining the impact of professional subjects on migraine studies entitled, "A Real Headache: Professional Subjects in Migraine Trials."
They identified 2192 subjects in the CTS database who applied for migraine research. They found almost 19% tried to enroll to another study site over an 18-month period. Of this group, 24% tried to apply to another migraine trial. The remaining 76% applied for major depression, schizophrenia, and healthy volunteer studies among others.
Naive vs Nefarious
Unlike those who intentionally bend the rules to enter a clinical trial, another category of 'professional subjects' is more naive than nefarious. Many people do not understand that they cannot simultaneously participate in multiple clinical trials, says Weingard.
"We give them these 20-page informed consents, and we expect them to absorb and understand all the rules we set."
Although money remains a common motivator, Devine, Weingard, and others note that some participants act out of clinical desperation. Alzheimer's disease is a prime example.
"People are desperate to find something that will stop, or at least slow down, this fatal disease that they, or a loved one has," says Keith Fargo, PhD, director of scientific programs and outreach at the Alzheimer's Association in Chicago.
Desperate to receive a potentially life-saving treatment, Fargo says, these individuals sometimes travel hundreds of miles to enroll at multiple study sites, trying to increase their chances of being randomized to a non-placebo group of the trial.
In her ASCP presentation, Weingard cited a patient who enrolled in a bipolar disorder study at one site, then travelled 17 miles to enroll a second time at a different site for the same study. VCT flagged the attempt.
Undeterred, the same person drove to yet a third site and tried again, traveling a total 37 miles on the same day.
Some subjects use an old-school approach and bring false identification to trial enrollment.
"It's very easy for a professional research subject to game the system," Weingard notes. "I could go to a research site with my sister's ID — she's a real person and we look a lot alike — and I can participate in two trials and no one is going to catch me."
"If you pay $50 to $100 for a fake ID and you enroll in a study that pays $2000 or $2500, it's definitely worth it," says Devine.
Technology to the Rescue?
Some researchers are turning to companies emerging in this space that offer to use artificial intelligence (AI), biometrics, and other advanced technology to minimize enrollment of professional subjects in clinical trials.
"Digital technologies, including AI technologies, that allow for the remote capture of patient data are increasingly being leveraged by pharma to speed up research, improve data quality and vastly augment our understanding of patient behavior and how patients respond to treatment outside of the clinic," Amanda Paley, director of strategic solutions clinical research at AiCure, a company that incorporates artificial intelligence in advanced data analytics, tells Medscape Medical News in an email.
Paley notes the strategy can help address the deceptive enrollment, something she says is an "endemic problem in the industry."
But although individual clinical trial companies offer solutions, there is no centralized enrollment database. That, Devine says, is what the field really needs. Just as researchers have to register at clinicaltrials.gov, there should be a national, centralized database registration in clinical trials.
"That can sound very 'Big Brother-ish' because then you are probably tracking people with biometrics to prevent fraud," Devine says. "But think about the quality of our information — it can either be lifesaving or not. Do we really want to take a chance with medicine as a science, and leave it up to 'Well, I hope we didn't have too many professional subjects in this trial?' "
Biometrics is probably a smart way to handle some of the issues related to professional subjects, he added. VCT and clinical RSVP, for example, offer fingerprint scanning to help researchers flag professional subjects.
Preventing patients from simultaneous enrollment in multiple studies doesn't just protect the research — it protects the patient too, Devine says.
Someone who receives treatment for a condition he or she actually has, for example, risks potential side effects against the benefit of responding to therapy. But someone pretending to have a disease has no potential clinical gain to offset those side effects.
Weingard agrees, noting that side effects, serious adverse events, and even deaths have occurred in study subjects participating in multiple clinical trials. This makes it impossible to determine whether such events are caused by a specific single agent or a drug interaction.
Professional subjects can also skew trial results by reporting exemplary compliance while not actually taking the treatment at all. "Your ability to separate active treatment from placebo is diminished," Shiovitz says.
"Pandora's Box" on the Horizon
David McCann, PhD, and colleagues from the National Institute on Drug Abuse, describe another kind of subject, one they call "destined to succeed." Such individuals pretend to have a condition, enroll in a trial, and report symptoms that quickly resolve.
Remission, they find, is easier to fabricate than disease. Such behavior, McCann notes, can substantially increase the statistical placebo response rate, while decreasing the size of an observed effect.
A growing body of literature suggests 30% of professional study subjects do not take the study drug according to protocol, Paley notes. People who over-report adherence skew the data researchers collect during a study, she says.
When the investigators look at the results, they can misinterpret the effect of a particular drug and put future patients as risk. In addition, such false results can and have caused drug trials to fail, in some cases preventing a potentially useful drug from gaining approval and reaching the market.
"These subjects intentionally over-report adherence," Paley says. "Not only does this interfere with the integrity of the data but it may lead to incorrect interpretation of trial results, placing future patients at risk."
Or, she says, it could cause trial to fail, preventing progress of what might otherwise have been a potentially successful drug.
Even once all these problems have been addressed, Weingard sees another potential danger on the horizon — online trial enrollment.
"We're going to see a huge shift to virtual trials within the next 2 to 3 years. The doctor will interact with the participant on video, and everything for the trial will be shipped to the home."
When this happens, she says, individuals won't have to present at research sites. Doing everything virtually, Weingard says, "will open a 'Pandora's Box' if steps are not taken to prevent or minimize enrollment in multiple trials."
Shiovitz is president of CTSdatabase LLC. Devine receives funding from NIH — NIAAA and NIDA — for doing clinical trials. Weingard is founder and COO of Verified Clinical Trials. Fargo has disclosed no relevant financial relationships. Paley is director of strategic solutions clinical research at AiCure.
Medscape Medical News © 2020
Cite this: Lies and Desperation: How, Why 'Professional Study Subjects' Skew Clinical Research - Medscape - Jul 14, 2020.