OBJECTIVES:

The assessment of long-term (relative) effectiveness of new therapies in health technology assessment (HTA) is often surrounded by uncertainty due to limited follow-up time in pivotal trials. This study assessed the various ways countries weigh and manage this uncertainty.

METHODS:

This cross-country comparative policy analysis included HTA reports of new medicines for the treatment of spinal muscular atrophy (SMA), cystic fibrosis (CF), or hypercholesterolemia. The HTA appraisals of six countries were compared (the Netherlands, the United Kingdom, Germany, France, and the United States of America). HTA reports that were published between January 2014 and May 2022 were included. The analysis focused on three main topics. First, the amount of data available at the time of initial assessment and how this was considered in the appraisal. Second, the number and type of managed entry agreements proposed that were specifically linked to long-term effectiveness uncertainty. Last, whether reassessments yielded a change in recommendations due to larger data availability.

RESULTS:

Preliminary results based on 25% of the documents (12 HTA appraisals, one managed entry document, and three reassessments) showed that pivotal trial duration at time of initial assessment is often short (range 1-24 months). Various countries included different trials, which in some cases led to variance in conclusions regarding the long-term relative effects. Out of seven managed entry agreements that were proposed in the sample, three directly linked to long-term effectiveness uncertainty. All three proposed agreements were outcome-based agreements. In two out of the three reassessments, the recommendation changed, of which one could be linked to the availability of more long-term effectiveness data.

CONCLUSIONS:

Uncertainty due to short follow-up duration at initial assessment was common for medicines included in the cohort. Both outcome-based managed entry agreements and reassessments could provide opportunities for managing, but were used to various degrees.