OBJECTIVES: To explore challenges and opportunities related to prespecification of analyses for Health Technology Assessment (HTA) in the context of the upcoming EU HTA regulation.

METHODS: Prespecification is a key technique to strengthen interpretation and evidential value of statistical results. This principle is well understood in the context of confirmatory analyses of clinical trials, which are specified in the clinical trial protocol and/or in a separate statistical analysis plan (SAP) that, as per ICH E9, should be finalized before unblinding. This framework is not yet mandated for the HTA space, where there are often uncertainties related to scope at the time of unblinding and analysis requirements may differ to those that are planned for the clinical study report. We will explore the following questions: When can prespecification strengthen evidential value? What are key operational considerations for SAPs? How can industry and HTA bodies collaborate to maximize the transparency around prespecified analyses?

RESULTS: There is increasing emphasis on the relevance of analysis prespecification for HTA. In 2021, the European Commission passed a new regulation on HTA. In the methods guidelines released by EUnetHTA21[1] (which will serve as the basis for defining the final regulation implementation), there is high value placed on prespecification across many aspects of a submission, from scoping (“This means that a particular research question (the PICO) is prespecified for a given assessment”) to indirect treatment comparisons (“...it is required that all confounders and effect modifiers relevant for adjustment are measured and that the model and covariate selection strategies for adjustment are prespecified and based upon transparent criteria”). It is yet unclear where, when, and how this prespecification should be conducted – revealing need for more detail.

CONCLUSIONS: Prespecification of analyses for HTA will become more relevant, yet we need to be specific in how this is done.