Testing Many Treatments Within a Single Protocol over 10 years at MRC Clinical Trials Unit at UCL: Multi-arm, Multi-stage Platform, Umbrella and Basket Protocols

Overview

Journal Clin Trials

Publisher Sage Publications

Date 2017 Aug 24

PMID 28830236

Citations 39

Authors

Mahesh Kb Parmar

Matthew R Sydes

Fay H Cafferty

Babak Choodari-Oskooei

Ruth E Langley

Louise Brown

Patrick Pj Phillips

Melissa R Spears

Sam Rowley

Richard Kaplan

Nicholas D James

Timothy Maughan

Nicholas Paton

Patrick J Royston

Affiliations

Soon will be listed here.

Abstract

There is real need to change how we do some of our clinical trials, as currently the testing and development process is too slow, too costly and too failure-prone often we find that a new treatment is no better than the current standard. Much of the focus on the development and testing pathway has been in improving the design of phase I and II trials. In this article, we present examples of new methods for improving the design of phase III trials (and the necessary lead up to them) as they are the most time-consuming and expensive part of the pathway. Key to all these methods is the aim to test many treatments and/or pose many therapeutic questions within one protocol.

Citing Articles

Tumor-Agnostic Therapies in Practice: Challenges, Innovations, and Future Perspectives.

Wu S, Thawani R Cancers (Basel). 2025; 17(5).

PMID: 40075649 PMC: 11899253. DOI: 10.3390/cancers17050801.

Developing an adaptive platform trial for evaluation of medical treatments for Crohn's disease.

Noor N, Radford S, Choodari-Oskooei B, Gordon M, Hart A, Hepburn T Nat Rev Gastroenterol Hepatol. 2025; .

PMID: 40045038 DOI: 10.1038/s41575-025-01052-0.

Revolutionizing ovarian cancer therapy by drug repositioning for accelerated and cost-effective treatments.

Villegas-Vazquez E, Marin-Carrasco F, Reyes-Hernandez O, Baez-Gonzalez A, Bustamante-Montes L, Padilla-Benavides T Front Oncol. 2025; 14:1514120.

PMID: 39876896 PMC: 11772297. DOI: 10.3389/fonc.2024.1514120.

Why and how should we simulate platform trials? Learnings from EU-PEARL.

Meyer E, Mielke T, Bofill Roig M, Freitag M, Jacko P, Krotka P BMC Med Res Methodol. 2025; 25(1):12.

PMID: 39819305 PMC: 11740366. DOI: 10.1186/s12874-024-02453-6.

Review article: Primer for clinical researchers on innovative trial designs for emergency medicine.

Lee K, Middleton M, Mahar R Emerg Med Australas. 2024; 37(1):e14532.

PMID: 39552367 PMC: 11744427. DOI: 10.1111/1742-6723.14532.

References

Djulbegovic B, Kumar A, Glasziou P, Miladinovic B, Chalmers I . Medical research: Trial unpredictability yields predictable therapy gains. Nature. 2013; 500(7463):395-6. PMC: 3819120. DOI: 10.1038/500395a. View

Vale C, Burdett S, Rydzewska L, Albiges L, Clarke N, Fisher D . Addition of docetaxel or bisphosphonates to standard of care in men with localised or metastatic, hormone-sensitive prostate cancer: a systematic review and meta-analyses of aggregate data. Lancet Oncol. 2016; 17(2):243-256. PMC: 4737894. DOI: 10.1016/S1470-2045(15)00489-1. View

James N, de Bono J, Spears M, Clarke N, Mason M, Dearnaley D . Abiraterone for Prostate Cancer Not Previously Treated with Hormone Therapy. N Engl J Med. 2017; 377(4):338-351. PMC: 5533216. DOI: 10.1056/NEJMoa1702900. View

Parmar M, Barthel F, Sydes M, Langley R, Kaplan R, Eisenhauer E . Speeding up the evaluation of new agents in cancer. J Natl Cancer Inst. 2008; 100(17):1204-14. PMC: 2528020. DOI: 10.1093/jnci/djn267. View

Korn E, Freidlin B . Outcome--adaptive randomization: is it useful?. J Clin Oncol. 2010; 29(6):771-6. PMC: 3056658. DOI: 10.1200/JCO.2010.31.1423. View

Coyle C, Cafferty F, Rowley S, MacKenzie M, Berkman L, Gupta S . ADD-ASPIRIN: A phase III, double-blind, placebo controlled, randomised trial assessing the effects of aspirin on disease recurrence and survival after primary therapy in common non-metastatic solid tumours. Contemp Clin Trials. 2016; 51:56-64. PMC: 5127874. DOI: 10.1016/j.cct.2016.10.004. View

Kaplan R, Maughan T, Crook A, Fisher D, Wilson R, Brown L . Evaluating many treatments and biomarkers in oncology: a new design. J Clin Oncol. 2013; 31(36):4562-8. PMC: 4394353. DOI: 10.1200/JCO.2013.50.7905. View

James N, Sydes M, Mason M, Clarke N, Anderson J, Dearnaley D . Celecoxib plus hormone therapy versus hormone therapy alone for hormone-sensitive prostate cancer: first results from the STAMPEDE multiarm, multistage, randomised controlled trial. Lancet Oncol. 2012; 13(5):549-58. PMC: 3398767. DOI: 10.1016/S1470-2045(12)70088-8. View

Berry D . The Brave New World of clinical cancer research: Adaptive biomarker-driven trials integrating clinical practice with clinical research. Mol Oncol. 2015; 9(5):951-9. PMC: 4516171. DOI: 10.1016/j.molonc.2015.02.011. View

10.

James N, Sydes M, Clarke N, Mason M, Dearnaley D, Spears M . Addition of docetaxel, zoledronic acid, or both to first-line long-term hormone therapy in prostate cancer (STAMPEDE): survival results from an adaptive, multiarm, multistage, platform randomised controlled trial. Lancet. 2016; 387(10024):1163-77. PMC: 4800035. DOI: 10.1016/S0140-6736(15)01037-5. View

11.

Sydes M, Parmar M, James N, Clarke N, Dearnaley D, Mason M . Issues in applying multi-arm multi-stage methodology to a clinical trial in prostate cancer: the MRC STAMPEDE trial. Trials. 2009; 10:39. PMC: 2704188. DOI: 10.1186/1745-6215-10-39. View

12.

Mason M, Clarke N, James N, Dearnaley D, Spears M, Ritchie A . Adding Celecoxib With or Without Zoledronic Acid for Hormone-Naïve Prostate Cancer: Long-Term Survival Results From an Adaptive, Multiarm, Multistage, Platform, Randomized Controlled Trial. J Clin Oncol. 2017; 35(14):1530-1541. PMC: 5455701. DOI: 10.1200/JCO.2016.69.0677. View

13.

OQuigley J, Conaway M . Continual Reassessment and Related Dose-Finding Designs. Stat Sci. 2011; 25(2):202-216. PMC: 3128794. DOI: 10.1214/10-STS332. View

14.

Rothwell P, Wilson M, Price J, Belch J, Meade T, Mehta Z . Effect of daily aspirin on risk of cancer metastasis: a study of incident cancers during randomised controlled trials. Lancet. 2012; 379(9826):1591-601. DOI: 10.1016/S0140-6736(12)60209-8. View

15.

Bratton D, Parmar M, Phillips P, Choodari-Oskooei B . Type I error rates of multi-arm multi-stage clinical trials: strong control and impact of intermediate outcomes. Trials. 2016; 17(1):309. PMC: 4930581. DOI: 10.1186/s13063-016-1382-5. View

16.

Torre L, Bray F, Siegel R, Ferlay J, Lortet-Tieulent J, Jemal A . Global cancer statistics, 2012. CA Cancer J Clin. 2015; 65(2):87-108. DOI: 10.3322/caac.21262. View

17.

de Bono J, Logothetis C, Molina A, Fizazi K, North S, Chu L . Abiraterone and increased survival in metastatic prostate cancer. N Engl J Med. 2011; 364(21):1995-2005. PMC: 3471149. DOI: 10.1056/NEJMoa1014618. View

18.

Langley R, Burdett S, Tierney J, Cafferty F, Parmar M, Venning G . Aspirin and cancer: has aspirin been overlooked as an adjuvant therapy?. Br J Cancer. 2011; 105(8):1107-13. PMC: 3208483. DOI: 10.1038/bjc.2011.289. View

19.

Liu S, Lee J . An overview of the design and conduct of the BATTLE trials. Chin Clin Oncol. 2015; 4(3):33. DOI: 10.3978/j.issn.2304-3865.2015.06.07. View

20.

Parker C, Sydes M, Mason M, Clarke N, Aebersold D, de Bono J . Prostate radiotherapy for men with metastatic disease: a new comparison in the Systemic Therapy in Advancing or Metastatic Prostate Cancer: Evaluation of Drug Efficacy (STAMPEDE) trial. BJU Int. 2013; 111(5):697-9. DOI: 10.1111/bju.12087. View