Opportunities for Participation in Randomized Controlled Trials for Patients with Multiple Myeloma: Trial Access Depends on Restrictive Eligibility Criteria and Patient Expectations

SIMPLE SUMMARY: Over the past decade, randomized controlled trials as an established instrument of evidence-based medicine have contributed fundamentally to the development and approval of new substances. However, it has been frequently shown that less than 5% of adult cancer patients enroll in clinical trials. Barriers to trial participation have been extensively studied, but the rate of trial participation has not changed substantially. In this retrospective analysis, we found that 53% of newly diagnosed multiple myeloma patients met the eligibility criteria, while only 38% of relapsed refractory patients were eligible. Moreover, our data show for the first time that eligible patients tend to become more reluctant to participate over the course of the disease, with 42% of newly diagnosed patients consenting, and only 7% of relapsed/refractory patients consenting. Thus, our results may assist with trial design improvements and address patient expectations and priorities in order to increase enrollment. ABSTRACT: Randomized controlled trials (RCT) are the driver of therapeutic innovations. However, it has been frequently shown that less than 5% of adult cancer patients enroll in clinical trials, although 70% of patients are considered as being willing to participate. Barriers to trial participation have been extensively studied. Although there is evidence that trial participation correlates with improved survival and reduced mortality, the rate of participation has not changed substantially. We provide retrospective data from a single-center analysis of 411 patients with multiple myeloma (MM) who were treated at the University Hospital Duesseldorf in Germany between January 2014 and December 2016. Each patient was analyzed for the real-world possibility of participating in a clinical study, based on the inclusion and exclusion (I/E) criteria and the recruiting period of open studies. The overall rate of study participation was 19%. A total of 53% of NDMM patients were eligible for first-line studies (GMMG-HD6, LenaMain). Of these, 80% consented to enrolment (42% of all). In contrast, only 38% of the RRMM population was eligible (GMMG-Relapse, Castor, Tourmaline, Admyre). Of these, only 22% (7% of all) consented. This was confirmed by virtual analysis, showing that only 29% of all RRMM patients would have been eligible for six internationally recruiting trials leading to later drug approval. The majority of cases were rendered ineligible by only one I/E criterion. The most common criteria were study-specific (prior therapies or refractory disease to a specific drug), kidney disease, and previous malignancy, followed by internal, neurologic, and infectious disease. In summary, this single-center analysis showed that I/E criteria permit study participation for most NNDM patients, with a dramatic decrease in the RRMM population. This is aggravated by the fact that the willingness for study participation also significantly declines in RRMM. Thus, addressing patient expectations and priorities seems to be the most promising approach to increasing patient enrollment in clinical trials.