Research Method, Conduct, and Reporting Considerations for Improving the Quality of Non-Hypothesis-Evaluating...

Numerous real-world evidence guidance documents have been published by many regulatory agencies, health technology assessment agencies, and academic groups. These guidances are largely focused on generating unbiased treatment effect estimates from real-world data (RWD) for use in approval and coverage decisions. One of the most prominently cited documents, is a joint ISPOR/ISPE Task Force guidance on the use of RWD for Hypothesis-Evaluating Treatment Effectiveness (HETE) Studies. However, there are a variety of uses of RWD that existing guidance does not explicitly address. Our goal was to assess existing guidance for its relevance to a range of non-HETE analyses.

In this article, we delineate categories of non-HETE applications of RWD. This range of applications includes various types of non-HETE RWD analyses, as well as the use of RWD as inputs into other types of analyses, such as health economic modeling or simulation studies that are not typically considered RWD studies. We then map existing guidance documents to the categories of non-HETE studies to help identify existing resources for analysts interested in conducting these types of analyses.

We identified 13 published guidance documents for detailed review, including documents that outline best practices, provide checklists, or are structured templates. They were selected for their prominence, recency, specific reference to fit-for-purpose real-world evidence generation, or their relevance to specific analysis categories.

We conclude that existing guidance documents, although they were largely developed for HETE studies, are highly useful for the broad range of non-HETE RWD analyses as well.