Presentation (CTI)

OBJECTIVES: Planned head-to-head trials are unlikely to address all PICOs in EU Joint Clinical Assessment (JCA), necessitating indirect treatment comparisons (ITCs). Pivotal trials are often designed primarily to address regulatory requirements, and ad hoc ITCs for HTA are regularly constrained by pivotal trial limitations or data gaps for comparators. Uncertainties in comparative effectiveness can lead to challenges in achieving reimbursement. To mitigate challenges within the context of JCA, we designed a roadmap for preliminary ITC assessments that manufacturers should initiate before Phase 3 to enable JCA-ready ITCs across PICOs.
METHODS: We reviewed HTA Coordination Group methodological and practical guidelines and designed a roadmap of preliminary investigations that manufacturers should conduct prior to and during the pivotal trial(s). The roadmap ensures evidence generation captures the unique value of an intervention while facilitating fit-for-purpose comparative evidence for JCA.
RESULTS: •The roadmap constitutes five key steps: 1. Targeted searches and PICO simulations to characterise treatment pathways and identify ongoing/planned comparator trials 2. Identification of potential treatment effect modifiers and prognostic factors via literature searches and clinical expert input 3. Formal comparisons of trial design, patient populations and reported outcomes, based on available data, to inform the validity of similarity and homogeneity assumptions in future ITCs 4. Recommendations for pivotal trial key design elements to facilitate consistent comparisons across PICOs concerning comparator arm selection, eligibility criteria, concomitant medications, stratification factors for randomisation, outcome variables and timepoints 5. Recommendations for supplementary evidence generation as needed, including real-world evidence-based external comparators •Feasibility assessments and ITCs should be living and adaptable to incorporate emerging comparator data and Phase 3 results to meet the 100-day timeframe between PICO finalisation and JCA submission
CONCLUSIONS: Our roadmap offers a structured approach for manufacturers to develop a stronger data package for JCA, with ITCs that are carefully planned, methodologically sound and suitable across PICOs.