Presentation (CTI)

OBJECTIVES: HTA agencies are often critical of evidence based on Phase 2 trial data. Concerns around the quality of the evidence, including non-comparative study design, small sample size, and short follow-up, have a negative impact on HTA outcomes and pricing negotiations. Here, we explore whether supporting evidence from Phase 3 randomized controlled trials (RCTs) in earlier lines of therapy can support more positive HTA outcomes.
METHODS: A targeted review of HTA recommendations from Canada, France, Italy and UK in multiple myeloma (MM) and non-Hodgkin lymphoma (NHL) (published on agency websites between 2020-2025) was conducted.
RESULTS: Seven HTA decisions (MM 6, NHL 1) were identified where Phase 3 RCT data were leveraged as supporting evidence in HTA (re-) evaluations by AEMPS, HAS, G-BA and SMC. All HTA agencies criticized the existence of differences between the characteristics of supporting Phase 3 trial populations and the target indications under evaluation. G-BA only considered post hoc subgroup analyses of the efficacy of the intervention in subpopulations matching the target indication, while AEMPS and SMC focused on the outcomes observed in the intention-to-treat (ITT) populations and HAS considered both analyses. Phase 3 trial data were accepted as supportive of Phase 2 trial outcomes and had a positive contribution to three of the seven HTA recommendations. In one case, real-world data appeared to be more influential than the external RCT data on HTA outcomes.
CONCLUSIONS: Evidence from Phase 3 RCTs in earlier lines of therapy can positively influence HTA decisions on indications otherwise supported by non-comparative Phase 2 trial data. If feasible, when planning trials, manufacturers should consider the value of overlapping populations in Phase 2 and 3 trials and the timing of availability of RCT data.