SW-3A - Navigating Around Quicksand: Mapping the Complexities of Externally Controlled Trial (ECT) Designs

Background: In specific settings, a single-arm trial may use an external comparator to provide important information about the expected risk of outcomes when patients cannot be randomized to an internal comparison group due to ethical concerns or feasibility. As with all non-randomized studies, there are several sources of systematic bias that need to be mitigated and additional challenges due to the small sample size that is typical of these studies. How can researchers recognize the clinical settings where an external comparator is appropriate while still addressing the fundamental sources of potential bias?

Objectives: In this symposium, our objectives are to provide a map of the territory around designing and conducting externally controlled trials (ECTs) including the solid ground (foundation, in methodologic terms), several areas of quicksand (significant risk of unmitigated bias), and uncharted regions (specific methodologic areas that require additional study). Scientists seeking a deeper understanding of this challenging study design as well as those designing or conducting ECTs are most likely to benefit from this symposium.

Description: The symposium will include insights from experts who will address each of the following topics: 1) Regulatory perspective on externally controlled trials (Dr Catherine Lerro, FDA, 15m); 2) Biostatistical perspective on what is known about the conditions under which ECTs are likely to face reliability concerns (Dr Gerd Rippin, IQVIA, 15m); and 3) Epidemiologic perspective on specific areas where significant questions remain to be answered about the design and analyses of ECTs to minimize bias (Dr Michele Jonsson Funk, UNC, 15m). A panel discussion (moderated by Dr Jennifer Lund, UNC) will include our speakers and additional panelists (Jennifer Fusco, Epividian; Dr Ann Marie McNeill, AbbVie; Dr Donna Rivera, FDA) who will discuss different crossroads when considering an ECT versus other study designs as well as common pitfalls and real-world experience designing, implementing, and evaluating ECTs.