PHP235 - INDIRECT TREATMENT COMPARISONS (ITC) FOR HTA IN EUROPE – UNDERSTANDING REQUIREMENTS FOR INDUSTRY SUBMISSIONS

Abstract

To issue clinically relevant guidance, health technology assessment (HTA) agencies have to consider care pathways which often evolve rapidly. As a result, for manufacturers, it is challenging, potentially high risk and costly to perform head-to-head trials against the comparator(s) considered most relevant by HTA agencies. One way of addressing this situation is to perform indirect treatment comparisons (ITCs). The objective of our study was to determine the preferred methodologies of HTA agencies across Europe and to ascertain acceptance of ITCs as a source of comparative evidence. A review of published materials was undertaken to analyse the requirements and recommendations of International best practice guidelines (International Society for Pharmacoeconomics and Outcomes Research [ISPOR], European Network for Health Technology Assessment [EUnetHTA]) and HTA agencies in the following European countries: UK, Sweden, Netherlands, Germany and France. HTA agencies differ in the inferences they are willing to accept from ITC. In addition, they have individual preferences for ITC methodologies. Even when it is possible to perform a population-adjusted indirect comparison, not all agencies have the statistical capabilities to understand these more complex approaches. Moreover, most agencies prefer to see the most simple and transparent evidence possible if the differences between trials are small and do not require additional adjustment. Most of the HTA agencies analysed are very open to the use of ITC. Only the G-BA strongly expresses the need for direct evidence and would require compelling arguments to justify not providing head-to-head evidence. ITC is generally accepted as a technique that allows demonstration of noninferiority to a comparator provided the chosen methodology and underlying assumptions are clear and justified. However, HTA agencies are more likely to closely scrutinize submitted data and evaluate statistical significance of results when superiority is claimed.