Core outcome set measurement for future clinical trials in acute myeloid leukemia: the HARMONY study protocol using a multi-stakeholder consensus-based Delphi process and a final consensus meeting

Abstract

Background Acute myeloid leukemia is the most common acute leukemia in adults with an unacceptably low cure rate. In recent years a number of new treatment strategies and compounds were developed for the treatment of acute myeloid leukemia. There were several randomized, controlled clinical trials with the objective to improve patients’ management and patients’ outcome in acute myeloid leukemia. Unfortunately, these trials are not always directly comparable, as they do not measure the same outcomes and currently there are no core outcome sets that can be utilized to guide outcome selection and harmonization in this disease area. The HARMONY Alliance is a public-private European Network established in 2017, which currently includes 53 partners and 32 associated members from 22 countries. Amongst many other goals of the HARMONY Alliance, Work Package 2 focuses on defining outcomes that are relevant to each hematological malignancy. In accordance, a pilot study will be performed to define core outcome set in acute myeloid leukemia. Methods The pilot study will use a three-round Delphi survey and a final consensus meeting to define a core outcome set. Participants will be recruited from different stakeholder groups, including patients, clinicians, regulators and members of the European Federation of Pharmaceutical Industries and Associations (EFPIA). At the pre-Delphi stage a literature research was conducted followed by several semi-structured interviews of clinical public and private key opinion leaders. Subsequently the preliminary outcome list was discussed in several multi-stakeholder face-to-face meetings. The Delphi survey will reduce the preliminary outcome list to essential core outcomes. After completing the last Delphi round a final face-to-face meeting is planned to achieve consensus about core outcome set in acute myeloid leukemia. Discussion The pilot Delphi as part of HARMONY Alliance aims to define a core outcome set in acute myeloid leukemia based on a multi-stakeholder consensus. Such a core outcome set will help to allow consistent comparison of future clinical trials and real world evidence research and ensures that appropriate outcomes valued by a range of stakeholders are measured within future trials.

2021 Update on MRD in acute myeloid leukemia: a consensus document from the European LeukemiaNet MRD Working Party

“…49 Inter-laboratory tests are being performed within the ELN for MFC, qPCR-based NPM1 analysis and NGS-MRD, and multicenter initiatives are encouraged. 50 Turnaround time, cost, sensitivity and effects of clonal evolution should be compared between these approaches. The recommended MRD cutoffs of the major MRD technologies should be validated in the ELN risk groups, and the value of alternative cut-points should be evaluated.…”

Building a Healthcare Alliance for Resourceful Medicine Offensive Against Neoplasms in Hematology Added Value Framework for Hematologic Malignancies: A Comparative Analysis of Existing Tools

“…The outcomes to be included in the HAVF were determined using the HARMONY lists of outcomes 19 that were generated by multistakeholder groups specifically set up for the development of core outcome sets (COS) for the different HMs. COS were developed by a multistakeholder consensus-based Delphi methodology, 20 following COMET 21 recommendations from the international COS-STAD study. 22 Stakeholders included health service users, health service practitioners, researchers, regulators, drug developer, patients, and patient advocates.…”