We’re delighted to share insights from Jaclyn Beca’s recent participation at the Health Technology Assessment International (HTAi) 2024 Annual Meeting in Seville, Spain aimed at enabling innovation, sustainability and collaboration in HTA.
Jaclyn had the opportunity to present recent research examining opportunities to improve assumptions around long-term benefits in early-state cancers. In line with many efforts shared at the conference, it is clear there is much to learn from one another by examining similar issues across HTA agencies.
In this research, we explored how HTA agencies handle long-term benefit assumptions in economic models when looking at early-stage cancers, where benefit is often shown with reduced disease recurrence risks, there is a potential for cure but limited evidence at adoption to assume treatment effects or remission are sustained. To understand the approaches being used, we looked at 49 reimbursement reviews in Canada, the UK and Australia, recognizing there are differences in processes, objectives and local preferences, including the amount of interaction between submitters and HTA agency, and HTA insight into net pricing, which might impact the approach taken to inform appraisals.
Methodologically, we found a high degree of variability in how long-term treatment effect duration or cure assumptions are applied. For example, treatment effects could be assumed to wane immediately or gradually at time points as early as treatment or trial completion or could be sustained indefinitely. Similarly, a cure could be explicitly assumed for all or some patients or not assumed for patients who remain disease-free as of a certain timepoint and could also be assumed to apply at various set times or gradually to a maximum cured proportion. We also noted that treatment benefit waning or cure could be implicit in extrapolated curves, but discussion of the implications, appropriateness and acceptability were inconsistent. Importantly, we found significant variability in the justifications used by submitters and accepted by HTA, including whether supporting evidence was leveraged to inform long-term risks, trends within the trial data were examined, and how the interplay between clinical expert opinion, the disease context, biological rationale, mechanism of action and precedent from prior reviews were considered.
Jaclyn presented data showing significant variability in approaches within and across files both from the perspective of the submitter and HTA agencies and noted that modifications were made to the assumptions in two-thirds of files before acceptance by HTA. She highlighted the importance of enhanced transparency, including the need to illustrate whether and how these assumptions are used to reflect plausible long-term benefits in appraisals. Finally, she emphasized opportunities to improve practices based on these learnings, including the generation of supporting evidence into the potential for cure from a disease perspective, the use of flexible statistical techniques to incorporate supporting evidence and uncertainty, and the value of validation using a life-cycle approach. There is a clear need for shared efforts to establish principles upon which to base assumptions grounded in available evidence. As this issue grows in importance in HTA, we hope these findings will support ongoing collaborative efforts and enhance broader stakeholder discussions to improve appraisal consistency and efficiency in similar contexts.
Download our poster presentation to learn more about “Challenges with Integrating Early-Stage Cancer Trial Endpoints into Economic Models: Review of Canadian and International HTA Recommendations”:
We are grateful to AstraZeneca Canada for providing partial support for this work.
Challenging issues in HTA can make appraisal outcomes unpredictable and contentious. Contact us for further insights on handling long-term benefit assumptions in oncology submissions.
