Sample Size Re-estimation (SSR)
Reporting
Reporting of trials that used SSR
In general, like any other adaptive design, the reporting should adhere to the Adaptive designs CONSORT Extension (ACE) 1, 2. There is poor reporting of SSR aspects in the literature, for example, around 43% (15/35) 3 of regulatory submissions did not describe how a SSR would be performed so they needed further clarifications. In principle, information should be provided to ensure that other researchers will be able to reproduce the SSR Specifically, the reporting should encompass:
- how design parameters were re-estimated;
- the estimates of design parameters that were used in the SSR and method for SSR (e.g., analytical formula);
- the pre-specified decision rules and decisions that were taken at an interim analysis with rationale of any deviations from the plan;
- characteristics of patients recruited before and after SSR;
- any impact of SSR on statistical properties such as type I error rate and estimation of treatment effects including methods used where appropriate (see 4 discussion);
- measures put in place to maintain confidentiality of interim information and to avoid or minimise operational bias.
References
1. Dimairo et al. The Adaptive designs CONSORT Extension (ACE) statement: a checklist with explanation and elaboration guideline for reporting randomised trials that use an adaptive design. BMJ. 2020;369:m115.
2. Dimairo et al. The adaptive designs CONSORT extension (ACE) statement: a checklist with explanation and elaboration guideline for reporting randomised trials that use an adaptive design. Trials. 2020;21(1):528.
3. Lin et al. CBER’s experience with adaptive design clinical trials. Ther Innov Regul Sci. 2015;50(2):195–203.
4. Pritchett et al. Sample size re-estimation designs in confirmatory clinical trials—current state, statistical considerations, and practical guidance. Stat Biopharm Res. 2015;7(4):309–21.
2. Dimairo et al. The adaptive designs CONSORT extension (ACE) statement: a checklist with explanation and elaboration guideline for reporting randomised trials that use an adaptive design. Trials. 2020;21(1):528.
3. Lin et al. CBER’s experience with adaptive design clinical trials. Ther Innov Regul Sci. 2015;50(2):195–203.
4. Pritchett et al. Sample size re-estimation designs in confirmatory clinical trials—current state, statistical considerations, and practical guidance. Stat Biopharm Res. 2015;7(4):309–21.