Component | Specification | Example |
---|---|---|
Prior distributions | • Previous studies on the control rate or treatment effect can be used as prior information • Prior beliefs about the treatment effect should be elicited from experts to inform the strength of the evidence needed to convince them | Two-arm trial of Treatment A versus B (control): • Evidence from three previous trials on rate of outcome under treatment B: 17 %, 25 %, 30 % • Evidence from two studies on treatment effect for different population: RR 0.98 (95 % CI: 0.73–1.3); RR 0.75 (95 % CI: 0.56–1.0) Prior distributions, center (95 % CrI): • Control rate: 25 % (5–55 %) • Skeptical prior for treatment effect: RR 1.10 (0.7–2.0) • Enthusiastic prior for treatment effect: RR 0.85 (0.5–1.0) |
Clinically important treatment effect | • Investigators should specify how big a treatment effect needs to be in order to stop a trial and recommend its use or advise against it | • A relative risk reduction of 15 % or more is needed to recommend treatment A, RR < 0.85 • An absolute increase of 2 % in safety outcome would be unacceptable, RD > 0.02 |
Stopping thresholds | • For each type of monitoring, i.e., safety, efficacy, or futility, the level of confidence to stop the trial early needs to be specified • For most cases, it should be based on a clinically important effect • Efficacy: the trial will stop early if the likelihood of seeing a clinically important effect is very large, even under a skeptical prior • Futility: if the likelihood of a clinically important effect is small even under an enthusiastic prior, the trial would stop early • Safety: the trial would stop if the probability of increasing harm is large enough under an enthusiastic prior | At any preplanned interim analysis, any of these occurrences would make the DSMC consider stopping the trial: • Efficacy under skeptical prior:  Pr(RR < 0.85) > 0.99 • Futility under enthusiastic prior:  Pr(RR < 0.85) < 0.10 • Safety under enthusiastic prior:  Pr(RD > 0.02) > 0.70 |