Table 2.

Summary of external controls for submissions involving individual patient-level data

Product	Source(s)	Year(s) of data capture	n	Key methods
Recombinant antithrombin*	Retrospective cohort at US and European sites	From 1997	35	Controls selected using eligibility criteria that matched clinical trial eligibility criteria.
Modified T cells†	European Bone Marrow Transplant database	2000–2013	853	Pair-matched analysis, matched on four key prognostic factors using a 1:4 matching ratio.
Blinatumomab	Six national study groups and five large treatment centres	>1990	1139	Several different matching approaches were applied to three different cohort definitions: two propensity score approaches using inverse probability of treatment weights (IPTW), and a weighted stratified analysis using established prognostic factors.
Blinatumomab	Systematic literature review (24 studies)	NR	2622	Model-based meta-analysis.
Defibrotide sodium	Retrospective chart review from the same sites as uncontrolled interventional trial	NR	32	Propensity score stratification. Strict exclusion for historical controls and a comparison of baseline characteristics.
Defibrotide sodium	Center for International Bone and Marrow Transplant Research	2008–2011	Arm 1=41 Arm 2=55	Observational study involving defibrotide sodium (arm 1) and standard of care (arm 2). Supporting study.

*Included in the Food and Drug Administration (FDA) submission only.

†Modified with a retroviral vector encoding for a truncated form of the human low-affinity nerve growth factor receptor and the herpes simplex I virus thymidine kinase.

NR, not reported.