By John Carlos Diaz, GeoSera Consulting
Clinical research patients are compensated for their participation in clinical trials. The compensation is based on the burden the trial imposes on the patient and is vetted through an institutional review board, so patients are not overly influenced by financial gain to enroll. Unfortunately, in some therapeutic areas and types of clinical trials, the compensation for enrolling in one or more clinical trials or at multiple research sites is enough to influence patients to join more than one contemporaneously and expose themselves to multiple investigational products or multiple doses of one investigational product. In other cases, patients may participate in several clinical trials but never actually take the investigational product, providing false answers and data just to remain in the trial. These “professional patients” are a growing threat to the safety of patients in clinical research and the data integrity of trials. (Even HBO’s show Vice highlighted professional patients in a season 6 episode called “Lab Rat Nation.”)
With increasing pressures to recruit subjects in a timely fashion along with the abundance of social media, research participants have increased the incidence of simultaneously enrolling in more than one clinical trial at a time. Many patients do not have the money or insurance to obtain proper medical care and choose to go from study to study for their medical care. There are also circumstances in which a patient innocently enrolls in a clinical trial without understanding the impact to his health. The impact and danger of combining multiple investigational products can be steep. Additionally, the cost of screening and enrolling poor-quality duplicate subjects is significant, especially if the study fails to prove efficacy or if adverse events occur that require the trial to be repeated.
My Experience With Professional Patients
My career started in clinical pharmacology, where I worked exclusively in Phase 1 clinical trials. Phase 1 trials have a small number of patients and extensive pharmacokinetic blood draws and generally require patients to stay at a clinical research unit overnight or for multiple nights. The data obtained from pharmacology studies is used to guide the pharmaceutical company in how to create a clinical development plan for the drug product, so it is important to have high-quality data from the Phase 1 trials.
One issue with Phase 1 studies is patients are compensated for their time. Since the studies generally have extensive overnight stays at a clinical research unit, patients are provided significant compensation for their time and effort. You can see the problem arising. Since patients are provided significant financial reimbursement for their effort in a short period of time, they are enticed to enroll in multiple Phase 1 studies at once or to not wait the mandatory washout period from their last exposure to an experimental product.
My career progressed to late-stage clinical research specializing in the central nervous system, specifically psychiatry (bipolar, substance use disorder, schizophrenia, sleep/wake), migraine, and all types of pain such as neuropathic, chronic, acute/post-operative, and breakthrough cancer pain clinical trials. One benefit of working in these indications is many patients are eager to participate in clinical research. However, one downside is the entrance criteria and trial endpoints for clinical trials in these indications tend to be subjective, patient-reported, and/or clinician-rated. Therefore, patients understand how to properly answer trial questions, so they can enter or stay in a clinical trial. Patients are compensated for their time in late-stage clinical trials like patients in Phase 1 clinical trials.
The Need for Proactive Prescreening
Most quality Phase 1 clinical research units have some sort of proactive prescreening approach to enrolling patients. These sites utilize a research subject database that monitors a subject’s study participation history to ensure safety and data quality. Frankly, it would be difficult for me to approve the use of a Phase 1 unit without it having some sort of proactive prescreening measures in place.
In 2010, I was the lead on an efficacy, placebo-controlled trial where the company was following the 505(b)(2) regulatory pathway for a drug that had been on the market for years with a known safety and efficacy profile. The company created a formulation of the drug that extended the duration of effect. The goal of following the 505(b)(2) pathway is to speed up the regulatory approval process. As the clinical team rushed to enroll patients and lock the database as quickly as possible, certain tasks were not incorporated into the trial, such as proactive prescreening. After database lock, the clinical team learned the efficacy, placebo-controlled trial for a drug known to treat the indication well failed to meet the efficacy endpoints. The team was shocked. Once the data was unblinded post-database lock, the team learned four patients who were randomized to the placebo arm received treatment for their disease; thus, these four showed a placebo response and caused the study to fail.
After multiple site audits and conversations with workers at the research site, it was determined these four patients most likely were professional patients. Unfortunately, the company could not exclude these patients from the final statistical analysis, and the result of a failed study for a product with a known safety and efficacy profile remained. The company had to repeat the study, basically doubling the original cost. The failed study cost the company tens of millions of dollars. Also, since the study had to be repeated, the regulatory approval time was delayed by years, thus reducing the revenue that was to be generated by sales of the drug. Finally, after the study was repeated and had positive endpoints and the drug received approval, the company deemed the drug not commercially viable since during the delay in approval, multiple 505(b)(2) drugs with similar indications were approved. The market for this indication was saturated, and the company did not want to commit sales and marketing resources and funds to promote a drug with so much competition. Basically, including four professional patients in a clinical trial stopped a drug from getting to patients.
The hard costs of a failed clinical trial are easily quantifiable, but there are costs that are much more difficult to quantify such as lost time to market to generate sales of the investigational product and damage to the company’s stock price and investor confidence. Eliminating professional patients should not only be the research sites’ responsibility but also the responsibility of the pharmaceutical or biotech company. Professional patients are becoming more educated on how to enter clinical trials due to social media. And, due to the financial compensation and cost of healthcare, professional patients are very interested in enrolling in clinical trials. Incorporating a proactive prescreening service such as a research subject database is vital to eliminating professional patients from your clinical trial. There needs to be adequate awareness and protection across all phases of clinical trials research from phase 1 through 3 to prevent data quality issues and improve research volunteer safety.
About the Author
John Carlos Diaz has been in the pharmaceutical industry for 20 years, with operational experiences in preclinical drug metabolism and pharmacokinetics, clinical pharmacology/Phase 1, adult/pediatric, global Phase 2 to 4, and investigator-initiated trials. Currently, Diaz is using his experience and clinical research network to execute clinical trials for pharma companies, clinical research sites, clinical trial service providers, and CROs. You can reach him at email@example.com or 484-568-3952.