Uncertainty management in regulatory and health technology assessment decision-making on drugs: guidance of the HTAi-DIA Working Group

Abstract

Objectives Uncertainty is a fundamental component of decision making regarding access to and pricing and reimbursement of drugs. The context-specific interpretation and mitigation of uncertainty remain major challenges for decision makers. Following the 2021 HTAi Global Policy Forum, a cross-sectoral, interdisciplinary HTAi-DIA Working Group (WG) was initiated to develop guidance to support stakeholder deliberation on the systematic identification and mitigation of uncertainties in the regulatory-HTA interface. Methods Six online discussions among WG members (Dec 2021–Sep 2022) who examined the output of a scoping review, two literature-based case studies and a survey; application of the initial guidance to a real-world case study; and two international conference panel discussions. Results The WG identified key concepts, clustered into twelve building blocks that were collectively perceived to define uncertainty: “unavailable,” “inaccurate,” “conflicting,” “not understandable,” “random variation,” “information,” “prediction,” “impact,” “risk,” “relevance,” “context,” and “judgment.” These were converted into a checklist to explain and define whether any issue constitutes a decision-relevant uncertainty. A taxonomy of domains in which uncertainty may exist within the regulatory-HTA interface was developed to facilitate categorization. The real-world case study was used to demonstrate how the guidance may facilitate deliberation between stakeholders and where additional guidance development may be needed. Conclusions The systematic approach taken for the identification of uncertainties in this guidance has the potential to facilitate understanding of uncertainty and its management across different stakeholders involved in drug development and evaluation. This can improve consistency and transparency throughout decision processes. To further support uncertainty management, linkage to suitable mitigation strategies is necessary.

Response to “UNCERTAINTY MANAGEMENT IN REGULATORY AND HEALTH TECHNOLOGY ASSESSMENT DECISION-MAKING ON DRUGS: GUIDANCE OF THE HTAi-DIA WORKING GROUP”

“…With great interest, we read the article entitled "Uncertainty Management in Regulatory and Health Technology Assessment Decision-Making on Drugs: Guidance of the HTAi-DIA Working Group" by Hogervorst et al (1). We wish to commend HTAi, DIA, and the Working Group for selecting this important topic.…”

Response to uncertainty management in regulatory and health technology assessment decision-making on drugs: guidance of the HTAi-DIA Working Group – author’s reply

“…We welcome the interest of Grimm et al ( 1 ) in the guidance of the HTAi-DIA Working Group that intends to support stakeholder deliberation on the systematic identification and mitigation of uncertainties in the regulatory-HTA interface ( 2 ). In their letter, the authors put forth two arguments.…”

“…It was developed by a cross-sectoral, interdisciplinary Working Group using a deliberate structured process. The steps and various methods deployed are documented in detail in the article ( 2 ). We fully agree with the commentators that much has been written about uncertainty in and outside of the HTA domain.…”

“…The literature that served as a basis for the discussions of the Working Group was, therefore, collected as part of the scoping process to determine the breadth of available information. It was – as clearly mentioned in the article ( 2 ) – not a systematic, but a scoping review. The scoping review in combination with iterative, multi-stakeholder dialogues did, nevertheless, result in similar relevant topics that the commentators also mention in their response (i.e., identification, analysis and communication of uncertainty, and risk tolerance).…”

“…The scoping review in combination with iterative, multi-stakeholder dialogues did, nevertheless, result in similar relevant topics that the commentators also mention in their response (i.e., identification, analysis and communication of uncertainty, and risk tolerance). Details on the scoping review and the included papers, among them the clearly cited TRUST tool 2020, are publicly available as part of the guidance ( 2 ). Furthermore, 10 of the papers referenced by the commentators as missed are cited in our scoping review ( 3 ; 5 – 13 ), whereas four of the papers mentioned by the commentators were published after completion of the final Working Group meeting – as described in the guidance – in September 2022 ( 14 – 17 ).…”