Modern clinical trials: Seamless designs and master protocols

Abigail Burdon; Thomas Jaki; Xijin Chen; Pavel Mozgunov; Haiyan Zheng; Richard Baird

doi:10.1002/cam4.71858

Modern clinical trials: Seamless designs and master protocols

Abigail Burdon, Thomas Jaki, Xijin Chen, Pavel Mozgunov, Haiyan Zheng, Richard Baird

Department of Mathematical Sciences

Research output: Contribution to journal › Article › peer-review

Abstract

Background: Drug development is often inefficient, costly and lengthy, yet it is essential for evaluating the safety and efficacy of new interventions. Compared with other disease areas, this is particularly true for Phase II / III cancer clinical trials where high attrition rates and reduced regulatory approvals are being seen. In response to these challenges, seamless clinical trials and master protocols have emerged to streamline the drug development process.

Methods: Seamless clinical trials, characterized by their ability to transition seamlessly from one phase to another, can lead to accelerating the development of promising therapies while Master protocols provide a framework for investigating multiple treatment options and patient subgroups within a single trial.

Results: We discuss the advantages of these methods through real trial examples and the principals that lead to their success while also acknowledging the associated regulatory considerations and challenges.

Conclusion: Seamless designs and Master protocols have the potential to improve confirmatory clinical trials. In the disease area of cancer, this ultimately means that patients can receive life-saving treatments sooner.

Original language	English
Article number	e71858
Number of pages	15
Journal	Cancer Medicine
Volume	15
Issue number	5
Early online date	23 Apr 2026
DOIs	https://doi.org/10.1002/cam4.71858
Publication status	Published - 31 May 2026

Data Availability Statement

Data sharing not applicable to this article as no datasets were generated or analysed during the current study.

Funding

This project has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement no. 965397. HZ's and RB's contribution to this manuscript was supported by Cancer Research UK (RCCCDF-May24/100001). This report is independent research supported by the National Institute for Health and Care Research (NIHR300576). PM and TJ also received funding from the UK Medical Research Council (MC_UU_00040/03). Infrastructure support is acknowledged from the NIHR Cambridge Biomedical Research Centre (BRC-1215-20014) and Cambridge Experimental Cancer Medicine Centre.

Funders	Funder number
Cancer Research UK	RCCCDF-May24/100001
Medical Research Council	MC_UU_00040/03
National Institute for Health and Care Excellence	NIHR300576
NIHR Cambridge Biomedical Research Centre	BRC-1215-20014

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

adaptive designs
efficient trials
interim analysis
master protocols
seamless phase II/III

ASJC Scopus subject areas

Radiology Nuclear Medicine and imaging
Oncology
Cancer Research

Access to Document

10.1002/cam4.71858Licence: CC BY

https://arxiv.org/abs/2405.06353Licence: CC BY

Cite this

@article{99185bf87883493696b6829c680fc592,

title = "Modern clinical trials: Seamless designs and master protocols",

abstract = "Background: Drug development is often inefficient, costly and lengthy, yet it is essential for evaluating the safety and efficacy of new interventions. Compared with other disease areas, this is particularly true for Phase II / III cancer clinical trials where high attrition rates and reduced regulatory approvals are being seen. In response to these challenges, seamless clinical trials and master protocols have emerged to streamline the drug development process. Methods: Seamless clinical trials, characterized by their ability to transition seamlessly from one phase to another, can lead to accelerating the development of promising therapies while Master protocols provide a framework for investigating multiple treatment options and patient subgroups within a single trial. Results: We discuss the advantages of these methods through real trial examples and the principals that lead to their success while also acknowledging the associated regulatory considerations and challenges. Conclusion: Seamless designs and Master protocols have the potential to improve confirmatory clinical trials. In the disease area of cancer, this ultimately means that patients can receive life-saving treatments sooner.",

keywords = "adaptive designs, efficient trials, interim analysis, master protocols, seamless phase II/III",

author = "Abigail Burdon and Thomas Jaki and Xijin Chen and Pavel Mozgunov and Haiyan Zheng and Richard Baird",

year = "2026",

month = may,

day = "31",

doi = "10.1002/cam4.71858",

language = "English",

volume = "15",

journal = "Cancer Medicine",

issn = "2045-7634",

publisher = "John Wiley and Sons Inc.",

number = "5",

}

TY - JOUR

T1 - Modern clinical trials

T2 - Seamless designs and master protocols

AU - Burdon, Abigail

AU - Jaki, Thomas

AU - Chen, Xijin

AU - Mozgunov, Pavel

AU - Zheng, Haiyan

AU - Baird, Richard

PY - 2026/5/31

Y1 - 2026/5/31

N2 - Background: Drug development is often inefficient, costly and lengthy, yet it is essential for evaluating the safety and efficacy of new interventions. Compared with other disease areas, this is particularly true for Phase II / III cancer clinical trials where high attrition rates and reduced regulatory approvals are being seen. In response to these challenges, seamless clinical trials and master protocols have emerged to streamline the drug development process. Methods: Seamless clinical trials, characterized by their ability to transition seamlessly from one phase to another, can lead to accelerating the development of promising therapies while Master protocols provide a framework for investigating multiple treatment options and patient subgroups within a single trial. Results: We discuss the advantages of these methods through real trial examples and the principals that lead to their success while also acknowledging the associated regulatory considerations and challenges. Conclusion: Seamless designs and Master protocols have the potential to improve confirmatory clinical trials. In the disease area of cancer, this ultimately means that patients can receive life-saving treatments sooner.

AB - Background: Drug development is often inefficient, costly and lengthy, yet it is essential for evaluating the safety and efficacy of new interventions. Compared with other disease areas, this is particularly true for Phase II / III cancer clinical trials where high attrition rates and reduced regulatory approvals are being seen. In response to these challenges, seamless clinical trials and master protocols have emerged to streamline the drug development process. Methods: Seamless clinical trials, characterized by their ability to transition seamlessly from one phase to another, can lead to accelerating the development of promising therapies while Master protocols provide a framework for investigating multiple treatment options and patient subgroups within a single trial. Results: We discuss the advantages of these methods through real trial examples and the principals that lead to their success while also acknowledging the associated regulatory considerations and challenges. Conclusion: Seamless designs and Master protocols have the potential to improve confirmatory clinical trials. In the disease area of cancer, this ultimately means that patients can receive life-saving treatments sooner.

KW - adaptive designs

KW - efficient trials

KW - interim analysis

KW - master protocols

KW - seamless phase II/III

UR - https://www.scopus.com/pages/publications/105036512394

U2 - 10.1002/cam4.71858

DO - 10.1002/cam4.71858

M3 - Article

C2 - 42026863

AN - SCOPUS:105036512394

SN - 2045-7634

VL - 15

JO - Cancer Medicine

JF - Cancer Medicine

IS - 5

M1 - e71858

ER -

Modern clinical trials: Seamless designs and master protocols

Abstract

Data Availability Statement

Funding

UN SDGs

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

STEEP: Statistically efficient methods for precision medicine trials

IDENT: Improving design and analysis of oncology trials Evaluating new Targeted Therapies

Cite this

Modern clinical trials: Seamless designs and master protocols

Abstract

Data Availability Statement

Funding

UN SDGs

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Projects

STEEP: Statistically efficient methods for precision medicine trials

IDENT: Improving design and analysis of oncology trials Evaluating new Targeted Therapies

Cite this