Case Studies

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

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.

Multiple Criteria Decision Analysis for HTA across four EU Member States: Piloting the Advance Value Framework

Multiple Criteria Decision Analysis (MCDA) has emerged as a methodology for Health Technology Assessment (HTA). However, limited empirical evidence is available on its use by decision-makers; where available, it only comes from single-setting exercises, while cross-country comparative studies are unavailable. This study applies the Advance Value Framework (AVF), an MCDA methodology for HTA based on multi-attribute value theory, through a series of case studies with decision-makers in four countries, to explore its feasibility and compare decision-makers' value preferences and results.

The AVF was applied in the evaluation of three drugs for metastatic, castrate resistant, prostate cancer (abiraterone, cabazitaxel and enzalutamide) in the post-chemotherapy indication. Decision conferences were organised in four European countries in collaboration with their HTA or health insurance organisations by involving relevant assessors and experts: Sweden (TLV), Andalusia/Spain (AETSA), Poland (AOTMiT) and Belgium (INAMI-RIZIV). Participants' value preferences, including performance scoring and criteria weighting, were elicited through a facilitated decision-analysis modelling approach using the MACBETH technique.

Between 6 and 11 criteria were included in each jurisdiction's value model, allocated across four criteria domains; Therapeutic Benefit criteria consistently ranked first in relative importance across all countries. Consistent drug rankings were observed in all settings, with enzalutamide generating the highest overall weighted preference value (WPV) score, followed by abiraterone and cabazitaxel. Dividing drugs' overall WPV scores by their costs produced the lowest “cost per unit of value” for enzalutamide, followed by abiraterone and cabazitaxel. These results come in contrast with the actual country HTA recommendations and pricing decisions.

Overall, although some differences in value preferences were observed between countries, drug rankings remained the same. The MCDA methodology employed could act as a decision support tool in HTA, due to the transparency in the construction of value preferences in a collaborative manner.