Table 1.

Condensed criteria for design and analysis of uncontrolled extensions with external controls

Category	Criteria
Data source	Rationale for selection of data source (fitness for purpose) is provided; setting and standard of care are similar to extension
Sampling	Trial inclusion / extension inclusion criteria are replicated in external control Comparison of baseline characteristics allows assessment of selection bias: Exhaustive assessment of key risk factors for the outcome among external control and extension enrollees, stratified by crossovers (where characteristics are assessed at time of extension) and continuers (where characteristics are assessed at original trial enrollment) Achieves adequate balance of baseline characteristics and during follow‐up (with time‐varying exposure assignments)
Outcome	Outcome measurement in external control has similar accuracy, precision, and ascertainment frequency as in the extension Selected outcome is valid in open‐label settings and differential misclassification is unlikely
Exposure	Sufficient detail of external control exposure (especially for active comparator designs) is provided Start of follow‐up for external controls matches that for extensions and avoids bias (e.g., via differences in disease progression or immortal time) Sufficient detail on variation in treatment duration, switching and gaps for both extension and the external controls, and related biases are addressed where appropriate (e.g., avoid ITT for noninferiority findings or analysis of safety outcomes)
Attrition	Provides detail on attrition and missingness to allow assessment of related biases Adequately addresses differential loss to follow‐up and censoring (if informative censoring is suspected)

ITT, intention to treat.