Table 3.

Summary of Characteristics of External Controls/Comparators

Type of control or comparator*	N (%)—FDA (N = 20)	N (%)—EMA (N = 17)
Baseline-controlled (participants in single-arm trial compared to their own values prior to intervention in a pre-post design)	8 (40)	8 (47)
RWD-based external control arm	9 (45)	8 (47)
EHR	0 (0)	0 (0)
Natural History Cohort+	9 (45)	8 (47)
Claims	0 (0)	0 (0)
Historical control group from prior controlled trial	4 (20)	1 (6)
Benchmark (single-arm data is compared to an aggregate value)	7 (32)	6 (32)

*Some single-arm trials used multiple comparators for context

 + Natural History Cohort sources included prospective cohorts, xretrospective chart reviews, reviews of case reports in the literature, and disease registries