Consortium: PROs Have Key Role in MDS Trials

As new therapeutic options become available to treat myelodysplastic syndromes/neoplasms (MDS), clinical trial designers should carefully incorporate patient-centered outcomes to better reflect the impact of new therapies, according to a new report.

The authors of the report—members of the International Consortium for MDS (icMDS) said factors like health care–related quality of life (HRQOL) and other patient-reported outcomes (PROs) warrant inclusion in trials, but they added that investigators should do more to ensure PRO parameters are rigorously reported. The review was published in the journal Haematologica.¹

The study authors said HRQOL is a key goal of therapy, both because MDS can significantly affect QOL and because QOL improvement may be the best outcome for some patients. The authors noted that MDS is only curable with stem cell transplantation, and many patients are deemed ineligible for the curative procedure due to advanced age or other factors.

Patients and physicians alike support incorporating patient-reported outcome measures inte clinical trials due to their prognostic value | Image Credit: underverse-stock.adobe.com

A study last year found that MDS can have a stark impact on QOL, particularly for vulnerable patients and those with a worse prognosis. High percentages of patients considered vulnerable reported difficulty with prolonged physical activity (88%), walking a quarter mile (74%), and doing heavy housework (68%), that study found.²

The present study authors said both patients and hematologists support the incorporation of PROs into clinical trials, adding that PROs have been found to offer prognostic value in terms of survival and HRQOL outcomes.

“On the other hand, for PRO data to fulfill their potential and help patients and clinicians to make more informed treatment decisions, investigators must be mindful of several dimensions of their collection, from the initial trial setup to publication of study results, as nonrigorous PRO assessments are unlikely to generate meaningful information that can robustly inform patient care,” they cautioned.

The investigators said it is important to carefully select and plan PROs prior to the initiation of a trial, and to pay careful attention to the timing of assessments and the potential for missing PRO data. When data are missing, the authors said it is important to document the reasons for missing data to better inform statistical analysis.

They also discussed specific considerations for collecting and reporting PRO data. For instance, they said time-to-event analyses—which focus on how long it takes for a particular PRO domain to improve to a clinically meaningful degree—can be helpful, but they said such measures need to be carefully planned out. Trial designers should map out what constitutes a clinically meaningful change, and consider how to handle improvements or deteriorations that might reverse over time.

They performed a literature search designed to evaluate how well randomized control trials with PRO end points followed the Consolidated Standards of Reporting Trials guidelines for PROs (CONSORT-PRO). They identified 11 studies of MDS that incorporated PROs, all of which used PROs as a secondary outcome. They found that the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C-C30 was the most used PRO measure, followed by the Functional Assessment of Chronic Illness Therapy assessment. Yet, the authors said the overall adherence to CONSORT-PRO recommendations was “suboptimal.”

“Among the items less frequently addressed were reporting statistical approaches for dealing with missing data, and reporting the number of questionnaires submitted/available for analysis at follow-up time points,” they wrote.

They closed by calling for more rigorous methodology when utilizing PROs as study end points. They said a set of international consensus-based guidelines should be developed around PRO elements for MDS trials and educational initiatives should be launched to explain the importance of PROs.

“The time is ripe for international initiatives that can facilitate a shift toward a more patient-centered MDS drug development process and this initial step by the icMDS will hopefully facilitate this sorely needed transition,” they concluded.

References

1. Efficace F, Buckstein R, Abel GA, et al. Toward a more patient-centered drug development process in clinical trials for patients with myelodysplastic syndromes/neoplasms (MDS): practical considerations from the International Consortium for MDS (icMDS). Hemasphere. 2024;8(5):e69. doi:10.1002/hem3.69

2. Abel GA, Hebert D, Lee C, et al. Health-related quality of life and vulnerability among people with myelodysplastic syndromes: a US national study. Blood Adv. 2023;7(14):3506-3515. doi:10.1182/bloodadvances.2022009000