A Dolon Institute report
Healthcare innovation is advancing rapidly, with gene and cell therapies, tumour-agnostic treatments and personalised medicines creating new opportunities to address serious unmet needs. Yet the evidence required to assess these innovations does not always fit within traditional health technology assessment (HTA) frameworks. When patient populations are small, diseases are rapidly progressing or long-term outcomes cannot feasibly be measured before a decision is required, insisting on conventional “gold standard” evidence can risk delaying access to potentially transformative treatments.
Future-Proofing HTA: The Case for Flexibility in Assessment Frameworks explores how HTA systems can better manage this challenge while maintaining scientific rigour and protecting healthcare sustainability. The paper focuses on a fundamental issue: uncertainty is not always a consequence of insufficient evidence or inadequate research. In some circumstances, it is inherent to the disease, technology or practical realities of evidence generation.
The paper proposes viewing uncertainty as a spectrum, ranging from uncertainty that can reasonably be resolved with additional evidence, through uncertainty that may be acceptable given the potential benefits of treatment, to “irreducible” uncertainty that is unlikely to be eliminated regardless of additional time or investment. This distinction is important because applying the same evidence requirements to every technology can lead to disproportionate barriers for treatments where conventional evidence generation is inherently difficult.
The report argues that the answer is not to lower evidentiary standards, but to make HTA more context-sensitive. This means assessing the nature, magnitude and potential resolvability of uncertainty alongside factors such as disease severity, unmet need, availability of alternatives, ethical considerations and the broader clinical and societal impact of a treatment.
Building on a review of the literature, HTA case studies and input from payers, HTA bodies, clinicians, patients and developers, the paper identifies potential areas where principled flexibility could be applied. These span evidence generation, assessment methodologies and decision-making, including the appropriate use of surrogate endpoints, adaptive trial designs, alternative analytical approaches and conditional reimbursement mechanisms.
Importantly, the proposed approach recognises that decisions are made at a particular point in time. What constitutes reasonable or irreducible uncertainty may change as evidence develops, meaning HTA frameworks need to consider when uncertainty occurs and what can realistically be known at that stage. A multi-stakeholder perspective is also essential to ensure that decisions reflect the real-world trade-offs between patient access, scientific evidence, affordability and incentives for innovation.
The paper ultimately calls for a clearer and more transparent framework for determining when flexibility is justified and how it should be applied, helping HTA bodies balance timely access, evidentiary standards and healthcare sustainability without placing the burden of uncertainty disproportionately on any one stakeholder.