Expense reimbursement model aims to ‘level playing field’ for clinical trial participation

Clinical trials, superficially speaking, might seem custom-made for low-income patients with cancer.

Participation gives patients access to cutting-edge investigational therapies and hope for life-prolonging treatment that otherwise would be unavailable.

But despite free drugs and follow-up care, the social and financial costs of clinical trial participation often are the deciding factor for low-income patients — the group with the overall lowest participation rate.

Joseph M. Unger, PhD, health services researcher and biostatistician at Fred Hutchinson Cancer Research Center in Seattle, and Mark E. Fleury, PhD, principal of policy development and emerging science at American Cancer Society Cancer Action Network, asked what could be done to increase low rates of cancer clinical trial participation, particularly among patients with socioeconomic challenges.

In an article published in June in JAMA Oncology, they proposed that all patients be reimbursed for out-of-pocket expenses associated with participating in clinical trials, including insurance copays, coinsurance, time away from work and travel.

“The common reason given for not reimbursing patients for their participation in trials is the desire to avoid undue influence on patients’ decision-making about treatment choices, as articulated in the U.S. Common Rule for the Protection of Human Subjects,” Unger and Fleury wrote. “The concern is that a payment inducement might alter participants’ assessment of potential risks or impair their judgement.”

A chief concern with the reimbursement model has been that it would skew research toward lower-income patients, Unger and Fleury noted. But this emphasis has had the unintended consequence of inducing an income disparity in trial participation. They argued that the “greater ethical challenge” is increasing participation among these patients.

Breaking down barriers

Clinical trial participation rates are notoriously low among patients with cancer.

A previous analysis by Unger and colleagues estimated the overall trial participation rate among patients with cancer at about 8.1%; Unger believes this rate can be improved significantly.

“Structural and clinical barriers were the reasons why three out of four patients do not participate in trials,” he told HemOnc Today. “Patients need better access to trials in their communities, and trial eligibility criteria need to be streamlined or modernized to make trials more accessible to patients with well-managed comorbid conditions.”

Unger said there is little available research on socioeconomic barriers to clinical trial participation, mostly because clinical trials typically do not collect this information.

Five years ago, Unger and colleagues created a questionnaire to explore patient-reported socioeconomic issues, and the data showed that Americans who make less than $50,000 per year are 30% less likely to participate in clinical trials than those with higher incomes.

“There are issues around participation in clinical trials that differentially impact lower-income patients,” Unger said.

It is these often-unaccounted-for barriers that motivated Unger and Fleury to propose a reimbursement model.

“It has long been felt that providing reimbursement or a payment, even just to level the playing field, might be imposing some undue influence on patients,” he said. “In our assessment, it has led to the current situation where we have an income disparity among clinical trial participants. It’s unfair, not just for those who suffer the income disparity, but for all patients because it hinders the advancement of clinical trial research.”

When asked what the reimbursement model would entail, Unger told HemOnc Today that it would need to be “carefully calibrated” to avoid overcompensation of low-income patients and thereby potentially fulfilling its critics’ prophesies. The aim is to make it easier for low-income patients to participate, not to incentivize them.

“The idea is that removing financial concerns as a factor in trial participation will level the playing field and raise trial participation rates for lower-income patients in particular, because these patients are more often fearful about the financial implications of clinical trial participation,” he explained. “I would make this approach uniform across the entire U.S. clinical trial system, so we don’t end up incentivizing patients to participate in one type of trial or another depending on the trial’s sponsorship. It’s critical that if such a system were to develop, it is applied as a uniform process.”

A ‘higher degree of burden’

R. Donald Harvey, PharmD, BCOP, FCCP, FHOPA, a pharmacist by training who also is director of the phase 1 clinical trials section at Winship Cancer Institute of Emory University, firmly believes that the low overall participation rate in cancer clinical trials needs to be addressed.

Harvey presented study data at this year’s ASCO Annual Meeting regarding clinical trial participation. His group found that current criteria excluded nearly 48% of patients in a study sample of more than 10,000 people, whereas broadened participation criteria recommended by ASCO would have excluded only 1.5% of the sample. These broadened criteria would allow more patients to participate in trials without interfering with the safety or efficacy of the drug being tested, Harvey and colleagues concluded.

Harvey has worked to expand Emory’s phase 1 program to provide treatments to patients who have exhausted their therapy options, but he told HemOnc Today that participation rates among low-income patients across phases of trials and across the country remain far less robust.

“I don’t think our trials are reflective, oftentimes, of the total socioeconomic spectrum of our country,” he said. “The reasons for this are multifactorial, depending on socioeconomics as well as referral patterns and level of engagement in the clinical research enterprise from a variety of perspectives.”

Harvey agrees with the concept of a reimbursement model for lower-income patients, citing the same indirect costs as Unger, including transportation and time away from work. He also noted some other demands of clinical trials on participants, many of whom are caregivers themselves, either for their children or elderly relatives.

“We create a burden on patients across the spectrum of trials, with a higher degree of burden in early-phase trials where we ask patients to come to trial centers frequently, spending multiple hours on multiple days at our centers,” Harvey explained, adding that patients “do this at a cost to themselves and their families.”

He acknowledged there are ethical issues that must be addressed with proposed reimbursements, but that any program — if implemented systematically and uniformly — would not affect study results. Providing expense reimbursement would only “reduce the barriers to participation,” Harvey said.

Martin Gutierrez, MD, chief of the thoracic oncology division and phase 1 clinical trials section at Hackensack Meridian’s John Theurer Cancer Center, said that more clinical trial participants would be desirable, but he doesn’t believe reimbursement would promote greater participation among low-income patients.

“The truth is that many sponsors already reimburse or provide for travel expenses to participate in trials, so I’m not sure that offering reimbursement of expenses to potential low-income participants would improve the overall trial participation rate,” he told HemOnc Today.

Gutierrez trained at the NCI, where he worked on clinical trials.

“We used to reimburse patients for travel expenses all of the time. Or we used to provide them with travel across the board. This did not necessarily result in better enrollment in clinical trials,” he said.

Gutierrez believes the largest barriers to participation among lower-income individuals may be the ancillary services that are needed to participate.

“The social worker, the nutrition, the case manager, navigation through the systems — these are actually the most limiting factors preventing clinical trial enrollment, in my opinion,” Gutierrez said. “If you make less than $50,000 per year, then you will likely need some type of social services to continue your cancer care. It’s not just a matter of travel time and expenses.”

Gutierrez said he finds a reimbursement scheme acceptable to promote greater clinical trial participation, assuming the reimbursement is offered to all patients, regardless of income level.

“If you are going to reimburse for expenses, then I think you need to do it across the board. You cannot be selective,” he said. “Otherwise the perception could be one of coercion among that group. If reimbursement were offered, then there would have to be some definitive, well-defined guidelines about what and how much will be reimbursed.”

In the name of cancer research

The form and timing of any reimbursements for low-income patients would likely have the greatest impact on clinical trial participation, according to Unger. He confirmed Gutierrez’s assertion that many trial sponsors already cover travel expenses to participate, and that internal review boards overseeing the trials agree to this because they do not see it as an undue incentive to participate.

“But there are some operational and functional challenges with the way reimbursement operates,” Unger said. “For example, if you have a patient who is being asked to front the money for a hotel stay, food or gas, and then wait to be reimbursed, then the timing of that reimbursement is critical.

“The optimal approach would be that patients have things prepaid for them — a concierge service rather than a reimbursement model,” he added.

Unger noted both ethical and operational issues must be addressed within a concierge model.

“If we really want to get serious about helping people come onto trials from a financial perspective, then the best scenario is that the resources people need to participate are paid for and provided up front,” he added.

Unger provided a tempered response when asked if instituting any reimbursement model would have the intended effect of increasing clinical trial participation among low-income patients.

“My hope is that the answer is yes; my fear is that the answer is no,” he said. “Any barrier we remove is a good move and will improve participation opportunities for some, but I’m concerned that participation in trials is more than just a financial challenge for some people. There’s a mistrust of the trial system for some, or a mistrust of clinical research as a whole, that has nothing to do with finances, but could be related to income levels.”

Gutierrez echoed this response, asserting that there is a layered decision-making process behind clinical trial participation.

“I don’t think the barrier to participation among low-income patients is the actual cost — it’s the social aspects. It’s the transportation, the family support, the time commitment, the lack of available social workers or case managers,” he said. “The complexities regarding whether to participate go beyond a certain dollar amount.”

Despite what may be limited return on the investment, Harvey endorsed the proposal by Unger and Fleury with the belief that every patient counts in the name of cancer research.

“I think this is something we should move forward independently of other factors that may limit clinical trial participation,” he said. “The number of patients who participate in trials in the adult oncology setting is already too low, and any barriers we can remove are important. We just need to realize there is no one barrier that we can remove that will solve the problem.” – by Drew Amorosi

References:

Harvey RD, et al. Abstract LBA108. Presented at: ASCO Annual Meeting; May 31-June 4, 2019; Chicago.

Unger JM and Fleury ME. JAMA Oncol. 2019;doi:10.1001/jamaoncol.2019.0141.

Unger JM, et al. J Clin Oncol. 2013;doi:10.1200/JCO.2012.45.4553.

Unger JM, et al. J Natl Cancer Inst. 2019;doi:10.1093/jnci/djy221.

For more information:

Martin Gutierrez, MD, can be reached at John Theurer Cancer Center, 92 Second St., Hackensack, NJ 07601; email: martin.gutierrez@hackensackmeridian.org.

R. Donald Harvey, PharmD, BCOP, FCCP, FHOPA, can be reached at Winship Cancer Institute of Emory University, 1365 Clifton Road, Atlanta, GA 30322; email: rdharve@emory.edu.

Joseph M. Unger, PhD, can be reached at Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N, M3-C102, P.O. Box 19024, Seattle, WA 98109-1024; email: junger@fredhutch.org.

Disclosures: Gutierrez reports speakers bureau roles with Bristol-Myers Squibb and Merck. Harvey reports consultant/advisory roles with Bristol-Myers Squibb, Genentech, Spectrum Pharmaceuticals and Takeda, and institutional research funding from AbbVie, Amgen, AstraZeneca, Bristol-Myers Squibb, Boston Biomedical, Calithera Biosciences, Celgene, Corvus Pharmaceuticals, Eli Lilly, Five Prime Therapeutics, Genmab, Halozyme, Incyte, Merck, Nektar, Novartis, Pfizer, Rgenix, Sanofi, Takeda, Tesaro and Xencor. Unger reports no relevant financial disclosures.