OBJECTIVES: Innovative therapies for rare conditions, including haematological malignancies (HM), encounter difficulties in generating robust evidence to meet regulatory and HTA agencies requirements. This results in high levels of uncertainties leading to non-approval of drug treatments. Understanding the causal factors associated with these uncertainties facilitates the development of appropriate mitigation strategies to ensure timely access for patients to innovative treatments.

Our goal was to understand the range and inter-relationships of uncertainties that specifically impact within HM as viewed from various stakeholder perspectives including industry (market access, trialists), regulatory, and HTA.

RESULTS: The main clinical evidence uncertainties (any text that reported an unresolved issue in the clinical evidence) for 12 innovative HM products from 9 European HTA agencies and the EMA were extracted from source language, publicly available assessment documents (n=74), and categorised into 6 key domains. Uncertainties mentioned within the same report on multiple occasions were included once. Frequencies of uncertainty reporting by domains were HTA dependant and showed indication specific patterns. This information, along with an aggregated consolidated list of individual uncertainties (n=64), were thematically mapped and weighted by participants in a multi-stakeholder-workshop. Key clusters and sub-nodes highlighted key connections between individual uncertainties with links to underlying causal mechanisms. The resulting mind map provides a visual tool for placing uncertainties in context to clinical evidence generation and incorporates various perspectives.

PRACTICAL IMPLICATIONS: The mind map provides a visual representation of HM specific uncertainties. This enables a novel mechanism for rationalizing and recognizing where uncertainties may arise and aid in defining appropriate mitigation strategies that could potentially target numerous linked uncertainties. This work is part of a wider access evidence framework that is being developed about the requirements for market access and reimbursement, specifically focused on the challenges facing innovative HM drugs and the jurisdictional differences across Europe.