Practical Issues in the Development of External Comparator Arms Using Real-World Evidence: Pragmatic Solutions or Unacceptable Uncertainties?

PURPOSE: The development of external comparator arms based on real-world data (RWD) is often challenging due to inherent limitations in RWD resulting in substantial uncertainty. Alongside the extensive discussion of uncertainties (e.g., qualitative bias assessment), there is a need for consideration of pragmatic quantitative solutions to data limitations. In this workshop we discuss practical issues and potential pragmatic solutions to data limitations using two case studies and the effect of these on HTA decision making.

DESCRIPTION: Boglarka Szegvari will introduce the limitations of clinical trials for HTA due to trial design, changing treatment algorithms and geographical variation (9 minutes). While innovative trial designs might offer solutions, often RWD is required to fill the data gaps. RWD however is typically limited by the context, method, and purpose of the data collection. Noemi Muszbek and Neil Hawkins will present case studies where inherent data limitations required pragmatic solution (12 minutes each). Noemi Muszbek will discuss patient selection based on prognostic factors and predictors vs. statistical matching within an unanchored indirect comparison, the use of proxy variables for missing patient characteristics and the importance of clinical validations using a case study in cutaneous T-cell lymphoma. Neil Hawkins will talk about issues stemming from truncation and censoring in the survival data and the use of directed acyclic graphs (DAGs) for variable selection and evaluations using a case study in X-linked hypophosphatemia. David Epstein will talk about the opportunities and challenges posed by RWD for HTA (12 minutes). He will review current approaches used in Spain to assess clinical benefit and associated uncertainty, how RWD impacts pricing&reimbursement decisions, and how RWD might be considered in Joint Scientific Consultation.

The workshop will use real-time polling on the experience of audience members of the challenges/opportunities in using RWD and will be invited to share their experiences (15 minutes).