Offering incentives, often financial, is common practice in many clinical research studies. The rationale is obvious: Patients are more likely to give up their time in exchange for compensation or reimbursement.
While debate persists about the ethical implications of enticing patient participation through incentives, another concern is the integrity of study results. This is particularly true in the case of a self-selecting population of participants.
In this post, we explore how incentives are used and how they might influence bias in a self-selecting population.
The FDA now recognizes the difference between compensation and reimbursement. The former refers to payment received in exchange for time given, while the latter concerns travel, food and accommodation costs expended through participation.
When it comes to offering incentives, the goal is to ensure balance between undue influence and just compensation. It’s important to remember that incentives are often vital prerequisites for people to participate in research. Without it, trials could be far less diverse.
Selection bias threatens any research. Statistical consultant Peter Flom, Ph.D., points to a poll conducted by the Literary Digest regarding the expected 1936 election results between Franklin D. Roosevelt and Alf Landon. The sample polled was restricted to people who owned cars or had phones, which at the time was a clear indicator of personal wealth. The prediction was that Landon would win; however, Roosevelt was of course elected with one of the largest majorities of any presidential election.
Clinical trials also run the risk of selection bias. Studies that only test men or certain demographics or healthy people, for example, will likely skew results.
Another concern is self-selection bias, which refers to when research participants are able to decide on their own whether or not to participate.
If motivated to join in the research, they could well distort the results by being non-representative of the entire target population or concealing information that would impact the study, research consultant Paul J. Lavrakas, Ph.D., explains.
Incentivizing patients has been a practice in the US for almost 200 years. There’s a famous case, for example, of the patient in 1820 with a gunshot wound to the stomach that had not completely healed. Gastric physiologist William Beaumont offered payment by way of food, shelter and money to examine the contents of that patient’s stomach for one year, explain Ahmad Wijdan and Moeen Al-Sayed at King Faisal Specialist Hospital and Research Center in Saudi Arabia.
In the 1920s and 1930s, payment and compensation became more common and continues today. The debate surrounding the ethics of payment and the potential effects on research results also continues.
The researchers argue that financial incentives are the primary factor encouraging healthy participants to enroll in phase I trials, but this becomes less so in phase II and phase III trials. Wijdan and Al-Sayed add that financial incentives likely play a bigger role in developing countries compared with trials in developed countries.
However, they note the issue of enrollment bias, which could lead to more people of lower socioeconomic status self-selecting to participate. The result is a potential bias that jeopardizes the research’s generalizability, depleting its scientific and social value.
While compensating trial participants may lead to patients deceiving staff about eligibility, the amount of that compensation has no effect.
Researchers examined that question with a randomized survey of 2,275 nationally representative adults. The question itself was simple: whether respondents had a flu shot in the last six months. Academic attorney-bioethicist Holly Fernandez Lynch, J.D., was on the research team which found that paying participants for participation — those amounts varied between $5, $10 and $20 — may be associated with deception; however, higher payment may not lead to increased deception.
When participants were told that a recent vaccination was required to meet the eligibility criteria and were offered a $5 incentive, 16.6 percent more people deceived researchers than those who were told that having a vaccination was not a requirement. When a $10 incentive was offered, the rate of deception climbed to 21 percent but dropped to 15.4 percent with the $20 incentive.
The reality is there are people who might be regarded as professional research participants, earning up to $40,000 a year. Consequently, the argument that incentives could affect research results or encourage patients to engage in risky studies is convincing.
Researchers at the Hastings Center refer to a US study in which 75 percent of professional research participants withheld information to qualify for participation. Some participants also provided false information, concealed contraindications and even practiced self-harm. These “professional patients,” often participating in multiple and simultaneous studies, could impact findings of studies that pay lower incentives as they take quick routes into studies with higher incentives, researchers explain.
Another problem that arises with incentives is that patients will perceive a trial with higher incentives as having greater risks. While this is not a surprising finding, the concern is patients might incorrectly rate the risk of a low-paying incentive as also being low.
When incentives are offered, regardless of the amount, researchers argue that it could lead to oversampling of patients from disadvantaged soci-economic backgrounds, and thus potentially impact study results.
While countries such as South Africa provide a fixed rate for participation in trials and Brazil bans incentives altogether, the US through the NIH offers incentives in proportion to inconvenience units — measurements of pain, discomfort or inconvenience patients experience.
Would patients being paid to participate in clinical trials be blinded to the potential risks because of the incentive? This was the question Dr. John P. Bentley and P.G. Thacker at the University of Mississippi set out to answer.
Students at a US pharmacy school were given a hypothetical recruitment notice, informed consent form for the study and a questionnaire. Five variables were assessed in the questionnaire, which included willingness to participate, willingness to participate without financial incentive, likelihood not to reveal restricted activities, likelihood not to reveal negative effects, and risk rating.
Bentley and Thacker found that the students were more likely to participate when payment was offered, and this did not depend on risk levels. Respondents were also more likely not to reveal restricted activities, but showed no inclination to conceal negative effects from researchers.
While the conclusions of the study are not particularly surprising, the study could not prove that payments blind participants to the risk involved. However, Thacker and Bentley noted that a concern arises in which the potential for payments could diminish the integrity of a study’s findings.
Making money from clinical trials can be an appealing option for some, but it’s important to be aware of participants being motivated primarily by money. They should be treated with caution.
Consider college-age students, two percent of whom earn money from participating in clinical trials. This number climbs to seven percent when students are in a financial crisis, explains Ashleigh Mutton at Save the Student, a student financial advice site.
She says student participation in clinical trials is not uncommon in the UK, telling her readers that they should be fine on the age requirement, but need to be healthy non-smokers that don’t drink too much. She offers the caveat, we assume in good humour, that many students would be discounted because of the last factor.
However, it does call into question how many students might deceive researchers on this point and how that could impact study results.
While students may often be motivated by money, senior citizens tend not to be. Dr. Patricia Winokur, executive dean of the University of Iowa’s Carver College of Medicine, says the elderly are driven by a desire to give back to society and/or try a new therapy to treat their disease.
It’s not just senior citizens eschewing financial gain from trial participation, of course, but the broader population, too. Kate Gillies and Derek Stewart, at Cochrane UK, say that some participants who have been sent gift vouchers as recognition for taking part in a study have rejected them. In fact, the vouchers have been returned, sometimes with a letter attached asking that the money be spent on further research rather than thank you notes.
Still, people are more likely to participate in research when there is a financial incentive offered. The problem, as highlighted above, is that evidence suggests some people would deceive researchers to ensure they will be accepted in the study, potentially impacting the integrity of results.
Attached to incentives is how the amounts involved might allow misperceptions of study risks and lead to people participating who might not have had they known the true risks involved. Incentives remain an important component of recruiting patients and researchers will need to safeguard against biases that can arise because of it.
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