Evidence Gap Analysis

Project background

The European HTA Regulation is reshaping the evidence expectations for health technology developers across Europe. With the Joint Clinical Assessment (JCA) process, health technology developers (HTDs) must be prepared to address all requested PICOs in the JCA dossier, even when the final scope becomes available only shortly before submission. For many HTDs, this creates a race against time: understanding what evidence is available, where uncertainty remains, and how remaining gaps can be addressed in a credible and strategic way.

In this context, a HTD turned to Asc Academics for guidance on evidence readiness for the upcoming JCA dossier. Our team assessed the available evidence for each PICO, identified key evidence gaps, and developed practical recommendations for managing areas where evidence was limited or insufficient. By translating a complex and evolving regulatory challenge into a clear evidence roadmap, Asc Academics helped the HTD prepare for the demands of the JCA process and make informed decisions ahead of dossier submission.

Challenges faced

The project presented two important challenges that are becoming increasingly relevant under the European JCA process. The first challenge was the uncertainty created by a rapidly evolving treatment landscape. Approximately one-third of the anticipated comparators were still being investigated in ongoing phase III trials, with no published results available at the time of the assessment. This made it difficult to predict which data would ultimately be available, how robust that evidence would be, and whether it could support the comparative evidence requirements of the future JCA dossier. The second challenge related to the definition of the target population. The intervention trial population was divided into two newly defined subpopulations, whereas the available comparator trials had generally reported outcomes for the broader overall population. As these subpopulations together represented the full population reflected in most clinical trials, the evidence base was not directly aligned with several anticipated population-specific PICO requests.

Together, these challenges created a high risk of evidence gaps across the expected JCA scope. Asc Academics therefore supported the HTD in anticipating where the available evidence was likely to be sufficient, where additional analyses or indirect comparisons could potentially strengthen the dossier, and where limitations would need to be clearly justified in line with JCA expectations.

Our solution

Future comparator evidence

To address the uncertainty around future comparator evidence, we reviewed the available clinical trial protocols to anticipate which data could become available and how these might contribute to the future JCA evidence package. We recommended continuous monitoring of public announcements, congress presentations and full publications. Although early public disclosures and conference materials would not be suitable as evidence sources for the final JCA dossier, they could provide valuable early insight into the likely direction and timing of the evolving evidence base.

Different subpopulations

To address the population challenge, we assessed whether the two cohorts in the intervention trial could be combined to reflect the overall population reported in most comparator trials and whether this is aligned with the EU HTA guidance. In parallel, we recommended monitoring two ongoing EMA assessments in a relevant subpopulation to understand how similar population definitions and evidence limitations might be considered in practice.

Given the rapidly evolving evidence landscape, we advised that the evidence gap analysis should be updated regularly. This ensured that the HTD could continuously refine the JCA strategy, anticipate remaining evidence gaps and prepare scientifically robust justifications where direct evidence was unlikely to be available.

Our impact

The project provided the client with strategic clarity on the evidence gaps most likely to affect the future JCA dossier. By translating these gaps into practical recommendations, we supported the client in strengthening its evidence planning and mitigation strategy ahead of submission.

Rather than treating evidence gaps as isolated limitations, the project helped the HTD understand their potential implications for both the European JCA process and subsequent national HTA assessments. This enabled the client to focus preparation efforts on scientifically robust justifications, targeted additional analyses and, where appropriate, post-hoc assessments to better address anticipated evidence requirements.

By anticipating the likely challenges early, the client was better positioned to prepare a credible and proactive JCA strategy, while also supporting downstream market access planning across Europe.