Evaluation and appraisal of randomized controlled trials in myeloma

Purpose: To critically appraise therapeutic innovations tested in randomize d controlled trials (RCTs) in multiple myeloma from 1966-1998. Design: We performed a comprehensive search to identify published RCTs in m ultiple myeloma. Quality dimensions of the design, conduct, analysis and re porting of each trial were assessed. Results: We identified 136 RCTs reported in 114 papers. Overall, therapeuti c efforts in multiple myeloma resulted in a 5% absolute gain in five-year s urvival at a cost of a 0.35% increase in treatment related deaths. Hence on average a patient enrolled in a RCT in myeloma is 14 (5/35) times more lik ely to be helped than harmed. However, when the RCTs were critically apprai sed for key quality dimensions of trials' conduct, we found that only 7% of the trials (10 of 136) were analyzed according to intention-to-treat (ITT) , 9% (12 of 136) reported a power analysis (beta error), 32% (35 of 111) ad equately concealed treatment allocation, 78% (106 of 136) provided a detail ed description of patient withdrawals, and 83% (19 of 22) of the double bli nd RCTs had appropriately described methodology. Conclusions: Therapeutic innovations tested through RCTs have improved the outcomes of patients with multiple myeloma. However, the quality of RCT rep orting and methodology in multiple myeloma could be substantially improved. Most therapeutic strategies in multiple myeloma are based on modest qualit y, low power evidence. Despite these shortcomings our findings suggest pati ents may often clinically benefit from enrollment in clinical trials when a vailable. Patients on average received modest benefit from innovative thera pies tested in RCTs at little additional risk of side effects.