PCN253 DECISION-MAKER PERSPECTIVES ON OUTCOMES STUDIED IN LEUKAEMIA CLINICAL TRIALS: THE RESPONSE EVALUATION IN LEUKAEMIA (REVALEU) STUDY PROTOCOL

Abstract

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. 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. 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-five experts were recruited in the e-Delphi process; 24 from configurations and external expertise of the European Medicines Agency (EMA) and 11 from HTA bodies in 9 EU countries. 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.