Health‐related quality of life assessment in randomised controlled trials in multiple myeloma: a critical review of methodology and impact on treatment recommendations

Abstract

Objectives: Patients with multiple myeloma (MM) often have pronounced symptoms and substantially reduced quality of life. The aims of treatment are to control disease, maximise quality of life and prolong survival. Hence, health‐related quality of life (HRQOL) should be an important end‐point in randomised controlled trials (RCTs) in addition to traditional endpoints. We wanted to evaluate whether trials reporting HRQOL outcomes have influenced clinical decision making and whether HRQOL was assessed robustly according to predefined criteria. Methods: A systematic review identified RCTs in MM with HRQOL assessment as a study end‐point. The methodological quality of these studies was assessed according to a checklist developed for evaluating HRQOL outcomes in clinical trials. The impact of the HRQOL results on clinical decision making was assessed, using published clinical guidelines as a reference. Results: Fifteen publications presenting RCTs with HRQOL as a study end‐point were identified. In 13 trials, the author stated that HRQOL results should influence clinical decision making. We found, however, that the HRQOL data only had a limited impact on published treatment guidelines for bisphosphonates, high‐dose treatment, interferon, erythropoiesis‐stimulating agents and novel agents. Conclusion: The present review indicates that the there are still few RCTs in MM including HRQOL as a study end‐point. Systematic incorporation of HRQOL measures into clinical trials allows for a comparison of treatment arms that includes the patients’ perspective. Before the full impact on clinical decisions can be realised, the quality and methodology of collecting HRQOL data must be further improved and the results rendered more comprehensible to clinicians.

A randomized phase 3 trial of thalidomide and prednisone as maintenance therapy after ASCT in patients with MM with a quality-of-life assessment: the National Cancer Institute of Canada Clinicals Trials Group Myeloma 10 Trial

“…18 These principles were also applied in a review of randomized trials that evaluated HRQoL when testing therapies for patients with multiple myeloma. 19 Kvam et al identified 15 trials and reported that in only 2 trials were efficacy and HRQoL outcomes discordant. 19 Segeren et al compared ASCT with chemotherapy alone and observed superior response rates and time-toprogression outcomes in those undergoing ASCT, 20 but did not detect improvements in event-free survival or OS; HRQoL was worse in those undergoing ASCT.…”

“…19 Kvam et al identified 15 trials and reported that in only 2 trials were efficacy and HRQoL outcomes discordant. 19 Segeren et al compared ASCT with chemotherapy alone and observed superior response rates and time-toprogression outcomes in those undergoing ASCT, 20 but did not detect improvements in event-free survival or OS; HRQoL was worse in those undergoing ASCT. Although potentially supporting a transplantation strategy, the investigators recommended against adoption of their ASCT preparative regimen, which included total body irradiation.…”

How could patient reported outcomes improve patient management in chronic myeloid leukemia?

“…An impact of QoL questionnaires on the outcome of myeloma patients has been confirmed in another study (SUMMIT) evaluating 202 patients with resistant/refractory MM treated with proteasome inhibitor bortezomib. Patients enrolled received four questionnaires (EORTC, QLQ C30, QLQ MY24 e FACT GOG Ntx [24,[28][29][30][31]) at different time points. QoL scores obtained were not only associated with survival, but also with response to treatment, while reported QoL progressively declined in patients with progressive disease [32].…”

Effect of thalidomide with melphalan and prednisone on health-related quality of life (HRQoL) in elderly patients with newly diagnosed multiple myeloma: a prospective analysis in a randomized trial

“…Systematic incorporation of HRQoL measures into clinical trials allows for a comparison of treatment arms that includes the patients' perspective. A review study of showed that there are few randomized clinical trials in MM that include HRQoL as a study end-point [15]. HOVON 49 is, to our knowledge, the first phase III randomized multicenter trial comparing the efficacy of MP vs. MPT combined with a HRQoL assessment.…”