Article type
Abstract
BACKGROUND:
Clinical trials testing cytoreductive treatments for patients with Philadelphia-negative chronic myeloproliferative neoplasms (CMNs) typically used conventional primary endpoints (eg, spleen volume reduction). However, several desirable and undesirable outcomes should be pursued in curing patients with CMN. Moreover, the outcomes should be also relevant to patients and other stakeholders.
OBJECTIVE:
We aimed at developing novel candidate composite primary outcomes for registrative clinical trials devoted to CMN.
METHODS:
We adapted the Desirability Of Outcome Ranking (DOOR) method originally developed to account for both the efficacy and the drawbacks of antibiotic therapy (Ong, 2023). In order to gain a transparent selection of the outcomes, we dissected the concept of Relevancy of trial Outcomes (RO) into 8 dimensions. An international Expert Panel (EP) was invited to rank Relevancy dimensions and, subsequently, to check the relevance of the listed outcomes. As the final step, operational definitions of the outcomes (eg, endpoint formulation) and association of multiple outcomes into Composite Outcomes (COs) was achieved by Delphi consensus.
RESULTS:
The EP ranked by a Likert scale (1–7) the 4 most important dimensions of RO: meaningfulness, modifiability, reliability, and feasibility. The geometric mean of the scores was calculated for each relevancy dimension and converted into weights. The EP was subsequently asked to check which relevancy dimensions were met by each of 28 listed CMN outcomes. Therefore, a Weighted Relevancy Mean (WRM) was calculated for each outcome. Based on their WRM, the outcomes were clustered into 4 classes. Operational definitions for each outcome were based on the available literature and finely tuned by 2 Delphi rounds. COs were finally developed for each of the 4 classes, and 2 novel COs were proposed.
CONCLUSIONS: DOOR is feasible for developing novel CO for trials testing cytoreductive treatments for blood cancers. Despite the complexity of the method, several advantages were detected, such as transparency and robustness/consistency of the results. Newly proposed COs still need both a data-driven and a patient-driven validation (agreement with patient communities and/or representative) before sharing them with regulatory agencies.
Clinical trials testing cytoreductive treatments for patients with Philadelphia-negative chronic myeloproliferative neoplasms (CMNs) typically used conventional primary endpoints (eg, spleen volume reduction). However, several desirable and undesirable outcomes should be pursued in curing patients with CMN. Moreover, the outcomes should be also relevant to patients and other stakeholders.
OBJECTIVE:
We aimed at developing novel candidate composite primary outcomes for registrative clinical trials devoted to CMN.
METHODS:
We adapted the Desirability Of Outcome Ranking (DOOR) method originally developed to account for both the efficacy and the drawbacks of antibiotic therapy (Ong, 2023). In order to gain a transparent selection of the outcomes, we dissected the concept of Relevancy of trial Outcomes (RO) into 8 dimensions. An international Expert Panel (EP) was invited to rank Relevancy dimensions and, subsequently, to check the relevance of the listed outcomes. As the final step, operational definitions of the outcomes (eg, endpoint formulation) and association of multiple outcomes into Composite Outcomes (COs) was achieved by Delphi consensus.
RESULTS:
The EP ranked by a Likert scale (1–7) the 4 most important dimensions of RO: meaningfulness, modifiability, reliability, and feasibility. The geometric mean of the scores was calculated for each relevancy dimension and converted into weights. The EP was subsequently asked to check which relevancy dimensions were met by each of 28 listed CMN outcomes. Therefore, a Weighted Relevancy Mean (WRM) was calculated for each outcome. Based on their WRM, the outcomes were clustered into 4 classes. Operational definitions for each outcome were based on the available literature and finely tuned by 2 Delphi rounds. COs were finally developed for each of the 4 classes, and 2 novel COs were proposed.
CONCLUSIONS: DOOR is feasible for developing novel CO for trials testing cytoreductive treatments for blood cancers. Despite the complexity of the method, several advantages were detected, such as transparency and robustness/consistency of the results. Newly proposed COs still need both a data-driven and a patient-driven validation (agreement with patient communities and/or representative) before sharing them with regulatory agencies.