OBJECTIVES: Evidence of efficacy for antineoplastic agents may be valued differently by regulatory and health technology assessment (HTA) bodies in the European Union (EU), impacting decision-making and access to novel medicines. A study protocol was developed to identify and harmonise core outcomes prioritised by European regulatory and HTA experts for clinical trials (CTs) investigating leukaemic disorders.

METHODS: The protocol was developed as follows: (1) identification of Phase II to Phase IV CTs registered in the EU Clinical Trials Register database throughout an 11-year period (2007-2017); (2) screening of CTs against inclusion criteria; (3) extraction of efficacy endpoints from selected trials and grouping according to type of measurement; (4) design of the Response Evaluation in Leukaemia (REVALEU) online surveying tool; (5) testing of the tool for content validity by means of the content validity index (CVI) method and for reliability using the test-retest approach; (6) recruitment of regulatory and HTA onco-haematology experts in a two-round e-Delphi process with two independent panels; (7) determination of the outcomes that have reached consensus.

RESULTS: Thirty-six unique efficacy measures were identified from the final data set of CTs (N=431) and grouped into the endpoint clusters of survival (n=5), response rates and biomarkers (n=16), time-to-event (n=6), and other (n=9). The REVALEU tool demonstrated high content validity as shown from the mean scale-level CVI (S-CVI) score of 93% for the assessed domains. Intra-subject reliability was upheld across the tool as confirmed from the Kendall-Tau and Kappa statistical test values (p<0.05). Thirty-six experts were recruited in the e-Delphi process; 24 from configurations and external expertise of the European Medicines Agency (EMA) and 12 from HTA bodies in 9 EU countries.

CONCLUSIONS: The protocol developed will form the basis for the identification of core outcomes, overarching and leukaemia subtype-specific, that are able to support industry stakeholders in obtaining regulatory and reimbursement approvals.