Table 2

External control arm methodology in randomised controlled trials

Study IDIndicationStatistical methods for generating ECAOutcome(s) compared with ECAOutcome timepoint (weeks)Evidence of treatment benefit compared with ECA*Rationale for using an ECA
Hueber et al, 201219CDWeightingEfficacy (CDAI response rate)6NoSmall study sample size
Hyams et al, 201220UCUnadjustedEfficacy (MCS response rate)8YesUnethical to use internal placebo arm
Hodkinson et al, 201321RAUnadjustedEfficacy (DAS 28 response and remission rates)26YesNR
Croft et al, 202122UCUnadjustedEfficacy (MCS remission rate)8, 52YesUnethical to use internal placebo arm advised by regulatory organisations; low recruitment
Hupf et al, 2021†25ASBayesian dynamic borrowingEfficacy (ASAS 20 response rate)6NAECA methodology study
Reed et al, 2021†24RAPropensity score matchingSafety (SAEs)NRNAECA methodology study
Rudrapatna et al, 2021†26CDUnadjustedEfficacy (mean change in CDAI, steroid-free CDAI remission rate)12, 24NAECA methodology study
Wang et al, 2021†27RAPropensity score matchingEfficacy (ACR 20 response rate)12NAECA methodology study
Magnolo et al, 202223PsOBayesian dynamic borrowingEfficacy (PASI 75, PASI 90 & IGA 0/1 response rates)
Safety (AEs)
12YesUnethical to use internal placebo arm; advised by regulatory organisations
Norvang et al, 2022†28RAPropensity score weightingEfficacy (DAS 28 remission rate)24, 52, 104NAECA methodology study
  • *As defined by the included study.

  • †Primary study objective was to examine methodological approaches for complementing prior or concurrent RCT data with external control data.

  • ACR, American College of Rheumatology; AE, adverse event; AS, ankylosing spondylitis; ASAS, Assessment of SpondyloArthritis International Society; CD, Crohn’s disease; CDAI, Crohn’s Disease Activity Index; DAS, Disease Activity Score; ECA, external control arm; IGA, Investigator’s Global Assessment; MCS, Mayo Clinical Score; NA, not applicable; NR, not reported; PASI, Psoriasis Area Severity Index; PsO, psoriasis; RA, rheumatoid arthritis; SAE, serious adverse event; UC, ulcerative colitis.