Low trial participation rates slow development of myelodysplastic syndrome treatments
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Clinical trials have played a key role in the development of targeted treatments that have improved outcomes for patients with cancer.
Despite the clear benefits of these trials, up to 86% fail to meet their enrollment targets, and about 20% close early due to recruitment failure.
Myelodysplastic syndromes (MDS) are among the diseases for which development of new therapies has been hindered by low clinical trial enrollment, according to Charlotte K. Brierley, MD, Wellcome Trust clinical research fellow at University of Oxford, who led a study published in Cancer on MDS trial participation.
“[Although] recruitment is a challenge across the board for clinical trials, there are specific challenges for the MDS patient population,” Brierley told Healio. “MDS are heterogenous disorders that predominantly affect older, often comorbid patients, and as about 20% of MDS are therapy-related, patients frequently have a history of another cancer. Strict diagnostic criteria, restrictions on age, comorbidities and history of another cancer all frequently form part of trial eligibility criteria.”
Age and affluence
Brierley and colleagues identified 1,919 patients with MDS treated at five institutions in the MDS Clinical Research Consortium between 1991 and 2017. They compared the characteristics of patients who enrolled in MDS clinical trials with those of patients who did not enroll in trials.
Among all patients, 449 (23%) participated in an interventional clinical trial. Trial participants appeared more likely to be men (71% vs. 61%; P < .001) and younger (median age, 68 years vs. 69 years; P = .014) than nonparticipants.
“Part of the problem with low accrual to MDS studies is that the median age of patients with MDS is in the 70s,” study author David P. Steensma, MD, associate professor of medicine at Harvard Medical School and Edward P. Evans chair in MDS research at Dana-Farber Cancer Institute, told Healio. “Older patients may have other serious medical problems and may have difficulty traveling. There are also FDA-approved treatments for MDS that work just well enough that the community oncologist might not think it is necessary for the patient to go to the big centers, until it is too late and the patient is too sick to go on a study.”
Researchers observed no correlation between race/ethnicity and likelihood of trial enrollment. However, socioeconomic factors appeared to have an impact, with results showing a higher rate of trial participation among patients who resided in more affluent ZIP codes (median total income, $68,896 vs. $61,241; P < .001).
“The fact that people in more affluent ZIP codes closer to the large centers are more likely to participate in trials seems to indicate that part of the barrier is logistical and financial,” Steensma said. “People may not have the means to travel to the centers for treatment.”
Trials had an overrepresentation of patients with intermediate- and high-risk disease based on the revised International Prognostic Scoring System (P =.004), and trial participants appeared less likely to have therapy-related disease (P < .001).
“Certain MDS subtypes were also overrepresented, such as those with excess blasts, multilineage dysplasia or ring sideroblasts compared with del(5q) and chronic myelomonocytic leukemia,” Brierley said.
According to Steensma, eligibility criteria for clinical trials may inadvertently exclude some patients with MDS.
“There might not be trials open for a particular disease, because many of the disease subtypes are rare,” he said.
Multivariable analysis showed associations of male sex, white race and shorter distance to the trial site with increased likelihood of trial participation.
Improving participation rates
Improving rates of clinical trial participation by patients with MDS likely will require adjustments to trial eligibility criteria, according to Brierley.
“Liberalizing inclusion and exclusion factors and adapting trial design, for example by focusing on genetically defined subtypes for efficacy analyses and investigating the wider patient population for safety analyses, is one route forward,” Brierley said. “This approach is supported by a recent study in leukemia comparing outcomes of patients treated on-trial vs. those who were retrospectively deemed ineligible, which found that both groups had similar safety and efficacy outcomes.”
Brierley added that it is essential to recognize the socioeconomic and cultural factors at play in low MDS trial enrollment. These factors should be considered during the design phase of trials, she said.
“Minority trial participation needs to be actively supported from the trial design phase, and the path to more equitable trial recruitment is being investigated by initiatives such as Enhancing Minority Participation in Clinical Trials, or EMPaCT,” Brierley said. “Strategies to maximize accessibility include involving community providers at the design phase and providing patient navigation assistance throughout the study.”
Steps also need to be taken to make clinical trials more accessible to patients in all locations and circumstances. Brierley said achieving this goal will require time and financial investment.
“Travel time for treatment and its financial and time burden is another barrier, and practical, logistical and potentially financial support could help here,” she said. “These approaches are challenging and potentially costly, but are critical to enhancing trial recruitment, ensuring the generalizability of clinical trial findings and ultimately improving patient outcomes.”
For more information:
Charlotte K. Brierley, BM, BCh, MRCP, can be reached at MRC Weatherall Institute for Molecular Medicine, University of Oxford, John Radcliffe Hospital, Headley Way, Oxford OX3 9DS; email: charlotte.brierley@imm.ox.ac.uk.
David P. Steensma, MD can be reached at Dana-Farber Cancer Institute, Dana Building 2-037, 450 Brookline Ave., Boston, MA 02215; email: david_steensma@dfci.harvard.edu.
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