Health-Related Quality of Life Instruments for Clinical Trials in AL Amyloidosis: Report from the Amyloidosis Forum HRQOL Working Group

Patient Relat Outcome Meas. 2023 May 18:14:153-169. doi: 10.2147/PROM.S399658. eCollection 2023.


Systemic AL (light chain) amyloidosis is a rare protein misfolding disorder associated with plasma cell dyscrasia affecting various organs leading to organ dysfunction and failure. The Amyloidosis Forum is a public-private partnership between the Amyloidosis Research Consortium and the US Food and Drug Administration Center for Drug Evaluation and Research with the goal of accelerating the development of effective treatments for AL amyloidosis. In recognition of this goal, 6 individual working groups were formed to identify and/or provide recommendations related to various aspects of patient-relevant clinical trial endpoints. This review summarizes the methods, findings, and recommendations of the Health-Related Quality of Life (HRQOL) Working Group. The HRQOL Working Group sought to identify existing patient-reported outcome (PRO) assessments of HRQOL for use in clinical trials and practice deemed relevant across a broad spectrum of patients with AL amyloidosis. A systematic review of the AL amyloidosis literature identified 1) additional signs/symptoms not currently part of an existing conceptual model, and 2) relevant PRO instruments used to measure HRQOL. The Working Group mapped content from each identified instrument to areas of impact in the conceptual model to determine which instrument(s) provide coverage of relevant concepts. The SF-36v2® Health Survey (SF-36v2; QualityMetric Incorporated, LLC) and Patient-Reported Outcomes Measurement Information System-29 Profile (PROMIS-29; HealthMeasures) were identified as instruments relevant to patients with AL amyloidosis. Existing evidence of reliability and validity was evaluated with a recommendation for future work focused on estimating clinically meaningful within-patient change thresholds for these instruments. For sponsors, the context of use-including specific research objectives, trial population, and investigational product under study-should inherently drive selection of the appropriate PRO instrument and endpoint definitions to detect meaningful change and enable patient-focused drug development.

Keywords: PROMIS-29; SF-36v2; drug development; endpoints; patient-reported outcome; rare diseases.

Publication types

  • Review

Grants and funding

The Amyloidosis Forum is funded by ARC. ARC is funded through private/philanthropic donations and grants from for-profit pharmaceutical and biotechnology companies. ARC retains all influence, control, and autonomy over projects for which it has received external support. ARC received grants from AbbVie, Alexion, Caelum, GlaxoSmithKline, and Janssen in support of the Amyloidosis Forum Novel Endpoints and Analyses meeting series. ARC was responsible for designing the meeting series, co-developing each Amyloidosis Forum meeting agenda, establishing multi-stakeholder working groups, production of meeting materials, hosting each virtual meeting, and creating publications. Research reported in this publication was supported by the National Institute on Aging (Award Number R13AG071150), of the National Institutes of Health. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.