Due to the changing nature of primary evidence generation, the availability of large patient registries and the introduction of standards for real-world-evidence use by regulatory agencies, healthcare decision making bodies are often asked to consider non-randomized studies (NRS) in the assessments of new health technologies. Unfortunately, integrating the results from NRS into decision making is not straightforward, and requires careful consideration of study quality and applicability.

So far, there is limited guidance on trustworthy integration of randomized and non-randomized evidence, thereby limiting the acceptance of NRS in decision making. To address this concern, the International Society for Pharmacoepidemiology (ISPE) Comparative Effectiveness Research (CER) Special Interest Group (SIG) set out to develop a methodological guidance on selection, appraisal and synthesis of evidence across different study designs. Under the lead of Dr. Grammati Sarri and Dr. Thomas Debray, the ISPE CER-SIG developed a seven-step framework to systematically identify relevant NRS and RCTs, to critically appraise their findings, and to summarize the available evidence using inputs from both study designs. This framework distinguishes between 3 hypothetical (though commonly encountered) scenarios in health care decision-making when heterogeneous sources of evidence are available, and guides researchers/ decision makers to select the most relevant statistical technique for evidence synthesis under each of these scenarios.

In this talk, Dr. Sarri and Dr. Debray will present the framework developed by ISPE CER- SIG and endorsed by ISPE Public Committee and explain how it can be used to produce reliable treatment estimates, facilitate decision making and increase transparency in the use of NRS. Grammati Sarri has a strong epidemiological and HTA background (from previous academic and NICE positions) with an in-depth understanding of RWE challenges and opportunities in the health care decision making from her current role as a RWE Strategy Lead in a private consultancy organisation. Thomas Debray is an assistant professor and leads the innovation, dissemination, and implementation of statistical methods to facilitate evidence synthesis. Together with ISPE CER- SIG, Dr. Sarri and Dr. Debray are engaging with key stakeholders to ascertain what additional steps are necessary to facilitate the synthesis of NRS into decision making.