EU HTA Is Like a Box of Chocolates, You Never Know What You Are Going to Get: Necessity for EU PICO Simulations

In the EU HTA process, manufacturers receive a list with the demanded evidence in form of PICOs (Population, Intervention, Comparator, Outcome) 100 days before dossier submission. Since it is a) a key tactical element in EU market access and pricing strategy, and b) operatively defines the dossier content, manufacturers have to anticipate PICOs much earlier. HTA bodies offer an early consultation (JSC) to give a “fair” view on expected PICOs, however, it takes place years before the actual EU assessment process (JCA). This analysis aims to understand the indication-specific dynamics within PICOs over time to educate on what and how to optimally anticipate the PICO scope for the future.

Based on all German HTA procedures from 2011, we analyzed average changes in the PICO scope to allow for extrapolation in less or more dynamic indications. Indications were subdivided into reasonable categories, such as therapy lines, to account for both too small sample sizes and too broad areas of application.

Until Jun 2024 there have been 988 completed HTA procedures in Germany. Especially in oncology, indications such as non-small cell lung cancer (NSCLC) or renal cell carcinoma can be considered dynamic with a change in the PICO scope once every two years (1^st line). The analysis does not include changes in guidelines without related HTA procedures.

Considering the time window until the JCA, even after a JSC it is essential to anticipate upcoming changes in the PICO scope. This is especially important in a dynamic indication. Manufacturers have to build scenarios to foresee and evaluate all potential changes to their PICO scope, such as new subgroups in the treatment cascade, new entries as direct or indirect competitors, complete paradigm shifts, e.g., with gene and cell therapies, and, for all of them, the evolving price spectrum.