Table 1 Brief descriptions of a sample of identified confirmatory ADs captured in the review

This is a private-sector-funded two-stage confirmatory AD with sample size re-estimation (SSR) at the first interim analysis applying the methodology proposed by Bauer and Kohne [25] using P value combination procedures. It is a double-blinded RCT investigating the efficacy and safety of a drug Anagrelide Retard in patients with essential thrombocythaemia at certain defined risk criteria.

The MATISSE study is a private-sector-sponsored open-label RCT with an active comparator, adaptive group sequential design (GSD) with SSR at the interim analysis evaluating the efficacy of palifosfamide-tris, in combination with carboplatin and etoposide chemotherapy in chemotherapy naive patients with extensive-stage small-cell lung cancer.

The STAMPEDE study is a phase II/III RCT with a multi-arm multi-stage AD investigating five treatments in combination with hormone therapy for patients with locally advanced or metastatic prostate cancer with options to drop futile arms or add new investigation arms during the trial. The trial is predominantly funded by the UK public sector. Sydes et al. [26, 27] describe the rationale and design aspects of the trial. James et al. [28] present the first interim results with decisions to discontinue certain intervention arms.

The PROPPR study is a GSD with SSR, funded by the public sector in the USA, investigating the effectiveness and safety of transfusing patients with severe trauma and major bleeding using plasma, platelets and red blood cells in a 1:1:1 ratio compared with a 1:1:2 ratio. Baraniuk et al. [29] provide the detailed rationale and design of the trial. The two co-primary outcomes were separately monitored using a two-sided O’Brien and Fleming [30] boundary with Lan and DeMets [31] alpha spending function based on numbers of events for each of the two comparisons. SSR was performed prior to the first efficacy interim analysis. Holcomb et al. [32] report the trial results in the Journal of the American Medical Association.

The PREVAIL study is a private-sector-funded randomised parallel-group double-blind placebo-controlled therapeutic confirmatory multicentre trial with four intervention arms, inclusive of the comparator. The trial is a Bayesian adaptive GSD with two interim analyses, possible SSR after the first or second interim analysis and drop-the-loser approach (option to drop futile intervention arms). Holmes et al. [33] report the results of the trial.

The PRIMO study is a private-sector-funded trial evaluating the effects of a drug (paricalcitol) on cardiac structure and function over 48 weeks in patients with stage 3/4 chronic kidney disease who had left ventricular hypertrophy. The trial is an information-based GSD with SSR. Pritchett et al. [34] provide the design details and rationale, and Thadhani et al. [35] present the findings.

The STAR study is a multi-stage operational seamless II/III RCT publicly funded by the NIHR Health Technology Assessment. The trial investigates the effect of a novel drug-free-interval strategy compared to the standard treatment strategy in the first-line treatment of advanced renal cell carcinoma [36].

FOCUS4 is a MAMS seamless II/III design investigating multiple treatments in multiple population enriched biomarkers in oncology. Kaplan et al. [37] provide a detailed description of the design, its rationale, statistical properties and implementation tools.