Real-world studies for the assessment of medicinal products and medical devices

Guide objectives

This methodological guide aims to support and assist the implementation of real-world studies relating to health products, with a view to their evaluation by HAS assessment committees. It aims to provide practical benchmarks relating to methodological aspects to optimise the level of evidence of these studies and confidence in their results.
This guide therefore applies to all real-world studies on health products (medicinal products or medical devices), including those requested by HAS assessment committees (“post-registration studies”). It is aimed at all players involved in the design and implementation of real-world studies on health products: manufacturers, contract research companies, as well as professional organisations and academic teams, which are increasingly frequently involved, particularly in the context of public-private partner-ships.

This guide focuses on:

• observational or real-world studies, which represent the majority of the additional studies re-quested by the HAS;
• pragmatic trials, insofar as they are part of a continuum between randomised clinical trials and observational studies.

This document will not tackle non-pragmatic interventional trials (conventional clinical trials), meta-analyses or network meta-analyses, although these may be requested in the context of post-registra-tion studies. In addition, the methodological aspects of real-world data on epidemiology, the burden of the disease or data collected for the purpose of indirect comparisons will not be detailed in this guide, although this type of data can also contribute to HAS assessments.

The guide is divided into three chapters:

• the first covers research questions that may be raised during the clinical development of a me-dicinal product or a medical device and which may justify the implementation of a real-world study;
• the second details the main HAS recommendations for the implementation of high-quality real-world studies;
• and the third specifies the international methodological references to be taken into account when conducting a real-world study.
  For the practical arrangements concerning document exchanges with the HAS and internal procedures relative to post-registration studies, dedicated instruction sheets are available on the HAS website:
  • For medical devices
  • For medicinal products
  • For health products that are also the subject of requests for additional data from the CEESP, the protocol may be discussed with the HAS’ Economic and Public Health Evaluation Depart-ment (SEESP). The department may also be contacted for the submission of protocols specific to economic analyses or organisational studies.

This document does not provide a “ready-made formula” that can be applied in all circumstances, regardless of the nature of the request, and should be seen as a methodology guide. It is the manu-facturer’s responsibility to propose and adapt its own protocol to implement a relevant real-world study with a view to assessment of health products by the HAS. It is not a binding document.