Early Health Technology Assessment during Nonalcoholic Steatohepatitis Drug Development: A Two-Round, Cross-Country, Multicriteria Decision Analysis

Abstract

Background. The assessment of value along the clinical development of new biopharmaceutical compounds is a challenging task. Complex and uncertain evidence has to be analyzed, considering a multitude of value preferences from different stakeholders. Objective. To investigate the use of multicriteria decision analysis (MCDA) to support decision making during drug development while considering payer and health technology assessment (HTA) value concerns, by applying the Advance Value Framework in nonalcoholic steatohepatitis (NASH) and testing for the consistency of the results. Design. A multiattribute value theory methodology was applied and 2 rounds of decision conferences (DCs) were organized in 3 countries (England, France, and Germany), with the participation of national key experts and stakeholders using the MACBETH questioning protocol and algorithm. A total of 51 health care professionals, patient advocates, and methodologists, including (ex-) committee members or assessors from national HTA bodies, participated in 6 DCs in the study countries. Target Population. NASH patients in fibrosis stages F2 to 3 were considered. Interventions. The value of a hypothetical product profile was assessed against 3 compounds under development using their phase 2 results. Outcome Measures. DC participants’ value preferences were elicited involving criteria selection, options scoring, and criteria weighting. Results. Highly consistent valuation rankings were observed in all DCs, always favoring the same compound. Highly consistent rankings of criteria clusters were observed, favoring therapeutic benefit criteria, followed by safety profile and innovation level criteria. Limitations. There was a lack of comparative treatment effects, early evidence on surrogate endpoints was used, and stakeholder representativeness was limited in some DCs. Conclusions. The use of MCDA is promising in supporting early HTA, illustrating high consistency in results across countries and between study rounds.

Early Access to Medicines: Use of Multicriteria Decision Analysis (MCDA) as a Decision Tool in Catalonia (Spain)

“…Recommendations for the use of MCDA as a tool to support decisions in product development focus in early HTA, with few experiences reported [ 37 ]. There is a lack of methodological references to methods aimed to inform decision making on early access to medicines for those patients in need in European countries.…”

Impact of Managed Entry Agreements on availability of and timely access to medicines: an ex-post evaluation of agreements implemented for oncology therapies in four countries

“…More precisely, this study highlights that successful and timely access to oncology therapies is also subject to submission of clinical evidence which presents with minimal uncertainties and is primarily based on clinically relevant instead of surrogate endpoints. Literature has also underscored the importance that HTA decision-makers place on submitting evidence with clinically meaningful outcomes relating to mortality, morbidity, and quality of life [ 43 ]. Even though the use of surrogate measures in cancer medicines’ trials is not associated with an HTA decision to reject a medicine [ 44 ], a gap between the surrogate endpoint and the final clinical endpoint creates additional uncertainty for decision-makers.…”

Impact of Managed Entry Agreements on availability of and timely access to medicines: an ex-post evaluation of agreements implemented for oncology therapies in four countries

“…More precisely, this study highlights that successful and timely access to oncology therapies is also subject to submission of clinical evidence which presents with minimal uncertainties and is primarily based on clinically relevant instead of surrogate endpoints. Literature has also underscored the importance that HTA decision-makers place on submitting evidence with clinically meaningful outcomes relating to mortality, morbidity, and quality of life [42].…”