Randomized Controlled Trials versus Single Cohort Studies in Relapse Refractory Multiple Myeloma

Background: The Randomized Controlled Trial (RCT) is considered the gold-standard for the evaluation of treatment efficacy. For rare or end stage cancers for which there are no effective treatments, or the number of patients is sparse, the use of RCTs for the assessment of efficacy and safety may be difficult. In these circumstances the single cohort study (SC) can be considered as an alternative to the RCT. Purpose: The purpose of this study was to compare the measures of efficacy as assessed with estimates of the Overall Response Rate (ORR) or Overall Survival (OS) obtained in RCT and SC studies that evaluate the same treatments for Relapse Refractory Multiple Myeloma (RRMM). The study also compared the estimates of ORR and OS ratios between treatments estimated in RCTs and extrapolated in SCs for the same treatments of RRMM. Methods: The study utilized data from 42 RCTs and 47 SCs assessing 18 different treatment protocols for RRMM that were identified through a MEDLINE search. Results: The results showed that there were no material differences in the demographics of patients enrolled in RCTs and SCs. The estimates of ORR and OS obtained in RCTs and SCs were comparable. Statistically significant Intra-Class Correlation Coefficient (ICC = 0.618, P = 0.027) was observed for ORR and for OS (ICC = 0.734; P = 0.014) indicating good agreement between RCTs and SCs. Treatment effect size as measured by the ORR and OS ratios (new treatment / control) was ascertained directly from RCTs and extrapolated for SCs based on the control ORR and OS observed in RCTs. There was agreement between RCTs and SCs with respect to the magnitude and direction of the ORR ratios (91% of the studies) and the OS ratios (75% of the studies). With respect to the conclusion regarding the relative efficacy of the new treatment versus the control, there was agreement between RCTs and SCs for 8/11 treatments based on ORR ratios and for 6 / 8 based on OS ratios. Conclusions: The results of this study have shown that for RRMM single cohort studies can be used to assess the efficacy of new treatments, given that sufficient data are available on controls treatments used as standard of care. The results may have implications for the evaluation of treatments of rare and advanced cancers as well as other conditions.