Each year, scores of clinical trials are delayed because participant recruitment proves more difficult than trial directors imagined.
That’s why trial recruitment teams put considerable energy into communicating their studies to relevant demographics. In many cases, additional incentives are offered to recruit people who might not have participated otherwise.
This is an effective way to get people to sign up for some trials, but poses ethical and practical questions about whether incentives skew outcomes. Those questions are perhaps less clear-cut than they would seem, too.
So, let’s dig into those ethical and practical questions. Understanding incentives and their ripple effects can help clinical trial directors design more informed recruitment strategies.
What Motivates Trial Participants?
This conversation needs to begin with participant motivations. Those inform both the effectiveness of a particular incentive structure and illuminate the diversity of participant needs.
The team at Trialfacts has a useful list of what motivates trial participants. These include:
- People want to learn about their bodies and their own health.
- People want to contribute to society.
- People seek compensation or perks.
- People seek improvement in their own wellness
In theory, a well-promoted trial could recruit a diverse set of participants simply because people bring their own diverse needs to the trial. That’s a good thing because, as Kate Shaw, founder and CEO of Innovative Trials points out, patient diversity is the key to a successful trial.
The problem, she says, is most patients in clinical trials are white, middle-class people. “Relationships are vital in encouraging more patients of all ethnicities to participate in clinical trials,” Shaw says.
“Many people are introduced to trials through their physician, so strong links with them are necessary. The industry also needs to look at how it is engaging with more locally-based community and patient advocacy groups.”
Recruitment channels are an important part of this conversation because there seems to be a correlation between participants’ motivations and how they get connected with a trial.
In 2012, a team of researchers led by Maulik Sumantbhai Doshi, from the Department of Clinical Pharmacology at Seth GS Medical College in Mumbai, found that healthy trial participants are primarily motivated by financial reward and learn about studies through friends or relatives. By contrast, patient participants are overwhelmingly referred to trials by their treating physicians.
Already, it’s clear to see how motivation, health and recruitment channels can impact who gets selected to participate in a trial. Before we tackle the thorny question of incentivization, though, we must address the more fundamental ways recruitment can impact trial representation.
Clinical Trial Recruitment Must Focus on Representation
Whether you are recruiting participants via social media or through relationships you have with HCPs, your message affects your trial’s diversity. As such, this is something that requires careful planning, write Katrina Kubicek and Marisela Robles from the University of Southern California.
“A single word can turn someone away,” they write. “Certain colors and images (or lack thereof) can draw or discourage potential participants. For example, among the Latino community, using the term ‘investigacion’ for research can bring about suspicion or fear, as it sounds like an investigation of their residential status will be conducted.
“... The best way to develop recruitment tools is to work alongside your target population and/or with people that work day-to-day with that population. You can do so by conducting focus groups, convening an advisory board or partnering with a community organization that can provide feedback and give you suggestions.”
This all speaks to the point Shaw makes about diversity in clinical trials. Even things like language barriers — perceived or otherwise — or the promotional language used can skew a participant pool, says Soumya J. Niranjan, Ph.D., an assistant professor of health services administration at The University of Alabama at Birmingham and first author of a 2020 research paper into racial biases in clinical trials.
It’s against this backdrop of potential biases that we must talk about incentives and how they persuade or further dissuade participants from different ethnic, linguistic and socioeconomic backgrounds.
Pluralism and Personalization in Clinical Trial Recruitment
For effective recruitment in general, then, it appears tailored messaging is needed across several channels to reach a diverse participant pool. That’s exactly what University of Florida researcher Elizabeth Flood-Grady and her team conclude in a March 2020 paper on audience segmentation in recruitment.
“[C]ustomizing (i.e., tailoring, personalizing) messages about recruitment and consent on the basis of prospective participant's beliefs, attitudes, needs, and preferences can improve recruitment and consent procedures,” they write.
Along those same lines, it appears that customizing incentives helps diversify the candidate pool. University of Washington researchers Gary Hsieh and Rafal Kocielnik note that a single type of incentive can homogenize the participant group. However, when a variety of incentives are on the table — e.g. direct payments, lottery entry, charitable contribution — that choice “may help attract participants from different strata of the population,” they write.
At this point, it’s worth noting that the FDA draws a distinction between compensation and reimbursement. Reimbursing travel and lodging costs, for example, might open a trial up to new groups of participants. Hsien and Kocielnik note, though, that having some kind of incentive further widens the aperture beyond “those who value the task intrinsically and/or incur low costs from participation.”
In other words, incentives are still important for ensuring a diverse sample size among participants.
3 Challenges With Recruitment Incentives
The benefits of offering incentives come with their own costs, however. Three major drawbacks stand out in the research:
- Compensation consistency. As impactful as personalized incentives could be, it creates new variables. As Harvard researchers David M. Swanson and Rebecca A. Betensky write in a 2015 paper: “For consistency across clinical trials, standardization in compensation is essential. Also, use of statistical methods that correct for dependent censoring and adjust for variable compensation structure when it is present should be emphasized more in the clinical literature.”
- Perception of risk. David Fogel, chief scientist at Trials.ai, notes how “a high remuneration is often associated in patients' minds as being associated with a perception of higher risk in the trial.” That perception of risk can undercut recruitment efforts.
- Crowding out. TL Zutlevics from Women’s and Children’s Health Network in Adelaide, Australia, writes that providing compensation for something a person might otherwise do for free has the effect of diminishing the person’s desire to perform that act. That effect could skew gender representation in a trial, as Zutlevics cites from the literature.
Of course, randomized controls and a thorough anticipation of systemic biases factor into the design of most trials. What the points above suggest is there are several dimensions to account for when analyzing how the presence or absence of incentives could bias a trial’s research outcomes.
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