Orphanet J Rare Dis. 2024 Feb 07. 19(1): 47
Victoria W Dayer,
Michael F Drummond,
Omar Dabbous,
Mondher Toumi,
Peter Neumann,
Sean Tunis,
Nelson Teich,
Shadi Saleh,
Ulf Persson,
Johann-Matthias Graf von der Schulenburg,
Daniel C Malone,
Tay Salimullah,
Sean D Sullivan.
Health technology assessment (HTA) decisions for pharmaceuticals are complex and evolving. New rare disease treatments are often approved more quickly through accelerated approval schemes, creating more uncertainties about clinical evidence and budget impact at the time of market entry. The use of real-world evidence (RWE), including early coverage with evidence development, has been suggested as a means to support HTA decisions for rare disease treatments. However, the collection and use of RWE poses substantial challenges. These challenges are compounded when considered in the context of treatments for rare diseases. In this paper, we describe the methodological challenges to developing and using prospective and retrospective RWE for HTA decisions, for rare diseases in particular. We focus attention on key elements of study design and analyses, including patient selection and recruitment, appropriate adjustment for confounding and other sources of bias, outcome selection, and data quality monitoring. We conclude by offering suggestions to help address some of the most vexing challenges. The role of RWE in coverage and pricing determination will grow. It is, therefore, necessary for researchers, manufacturers, HTA agencies, and payers to ensure that rigorous and appropriate scientific principles are followed when using RWE as part of decision-making.
Keywords: Cell and gene therapy; Coverage determination; Coverage with evidence development; Health technology assessment; Rare disease; Real world evidence