Protocol quality for patient-reported outcomes in multiple myeloma randomized controlled trials according to the SPIRIT-PRO guidelines: A systematic review.

Abstract

e23189 Background: Patient-reported outcomes (PROs) are increasingly incorporated into multiple myeloma (MM) randomized controlled trials (RCTs) to help inform clinical decision making. While it is known that, in general, the quality of PRO components in RCT protocols remains suboptimal, there is no data on adherence to international quality standards (i.e., the SPIRIT-PRO guidelines) in MM RCT protocols. Methods: We performed a systematic review to identify MM RCTs published between January 2014 and June 2023 that utilized the EORTC QLQ-C30 questionnaire. The quality of PRO-specific protocol content was evaluated using the SPIRIT-PRO guidelines, which establish minimum requirements for PRO inclusion in protocols. The framework consists of 16 items: 5 elaborations of the existing SPIRIT checklist and 11 PRO-specific extensions items. Results: Our systematic review identified 35 RCTs encompassing 20,612 patients, with 24 trials (69%) having publicly accessible protocols. The median protocol compliance was 7.5 SPIRIT-PRO items. Compared against SPIRIT-PRO guidelines, 23/24 (96%) protocols included comprehensive PRO assessment schedules, justifying the timing of these evaluations relative to clinical interventions. Specific PRO objectives or hypotheses were reported in 17/24 (71%) of protocols, and 19/24 (79%) specified PRO domains or justified PRO instruments, including measurement properties and patient burden. Procedures for handling deviations from assigned interventions were described in 15/24 (63%) protocols. However, significant gaps were observed: only 2/24 (8%) protocols detailed plans for monitoring PRO data to inform clinical care, specified personnel responsible for PRO content, or included PRO-specific eligibility criteria. Comprehensive plans for data collection modes and settings were present in 12/24 (50%) protocols. Furthermore, 10/24 (42%) outlined PRO-specific research questions or addressed multiplicity to control type I errors. While 14/24 (58%) addressed methods for handling missing data, only 9/24 (38%) described strategies to minimize avoidable missing data. Conclusions: Despite some foundational strengths of existing MM RCT protocols, important gaps exist in PRO methodological specifications, statistical analysis, and clinical interpretation. Our findings may help to better inform PRO implementation in future MM RCT protocols. For example, since missing PRO data can be due to informative censoring, there should be increased attention on considering how to minimize missing data, already at the stage of protocol writing.