Early phase clinical trials in oncology: Realising the potential of seamless designs

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

doi:10.1016/j.ejca.2023.05.005

Early phase clinical trials in oncology: Realising the potential of seamless designs

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

Department of Mathematical Sciences

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

4 Citations (SciVal)

Abstract

Background: The pharmaceutical industry's productivity has been declining over the last two decades and high attrition rates and reduced regulatory approvals are being seen. The development of oncology drugs is particularly challenging with low rates of approval for novel treatments when compared with other therapeutic areas. Reliably establishing the potential of novel treatment and the corresponding optimal dosage is a key component to ensure efficient overall development. A growing interest lies in terminating developments of poor treatments quickly while enabling accelerated development for highly promising interventions. Methods: One approach to reliably establish the optimal dosage and the potential of a novel treatment and thereby improve efficiency in the drug development pathway is the use of novel statistical designs that make efficient use of the data collected. Results: In this paper, we discuss different (seamless) strategies for early oncology development and illustrate their strengths and weaknesses through real trial examples. We provide some directions for good practices in early oncology development, discuss frequently seen missed opportunities for improved efficiency and some future opportunities that have yet to fully develop their potential in early oncology treatment development. Discussion: Modern methods for dose-finding have the potential to shorten and improve dose-finding and only small changes to current approaches are required to realise this potential.

Original language	English
Article number	112916
Journal	European Journal of Cancer
Volume	189
Early online date	13 May 2023
DOIs	https://doi.org/10.1016/j.ejca.2023.05.005
Publication status	Published - 1 Aug 2023

Bibliographical note

Funding Information:
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 ( RCCPDF\100008 ). 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_00002/14 ). Infrastructure support is acknowledged from the NIHR Cambridge Biomedical Research Centre ( BRC-1215-20014 ) and Cambridge Experimental Cancer Medicine Centre .

Funding Information:
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 (RCCPDF\100008). 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_00002/14). Infrastructure support is acknowledged from the NIHR Cambridge Biomedical Research Centre (BRC-1215-20014) and Cambridge Experimental Cancer Medicine Centre.

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 ( RCCPDF\100008 ). 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_00002/14 ). Infrastructure support is acknowledged from the NIHR Cambridge Biomedical Research Centre ( BRC-1215-20014 ) and Cambridge Experimental Cancer Medicine Centre . 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 (RCCPDF\100008). 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_00002/14). Infrastructure support is acknowledged from the NIHR Cambridge Biomedical Research Centre (BRC-1215-20014) and Cambridge Experimental Cancer Medicine Centre.

Keywords

Dose-determination
Efficient trials
Model-based designs

ASJC Scopus subject areas

Oncology
Cancer Research

UN SDGs

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

Access to Document

10.1016/j.ejca.2023.05.005Licence: CC BY

Cite this

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title = "Early phase clinical trials in oncology: Realising the potential of seamless designs",

abstract = "Background: The pharmaceutical industry's productivity has been declining over the last two decades and high attrition rates and reduced regulatory approvals are being seen. The development of oncology drugs is particularly challenging with low rates of approval for novel treatments when compared with other therapeutic areas. Reliably establishing the potential of novel treatment and the corresponding optimal dosage is a key component to ensure efficient overall development. A growing interest lies in terminating developments of poor treatments quickly while enabling accelerated development for highly promising interventions. Methods: One approach to reliably establish the optimal dosage and the potential of a novel treatment and thereby improve efficiency in the drug development pathway is the use of novel statistical designs that make efficient use of the data collected. Results: In this paper, we discuss different (seamless) strategies for early oncology development and illustrate their strengths and weaknesses through real trial examples. We provide some directions for good practices in early oncology development, discuss frequently seen missed opportunities for improved efficiency and some future opportunities that have yet to fully develop their potential in early oncology treatment development. Discussion: Modern methods for dose-finding have the potential to shorten and improve dose-finding and only small changes to current approaches are required to realise this potential.",

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

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AU - Burdon, Abigail

AU - Chen, Xijin

AU - Mozgunov, Pavel

AU - Zheng, Haiyan

AU - Baird, Richard

N1 - Funding Information: 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 ( RCCPDF\100008 ). 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_00002/14 ). Infrastructure support is acknowledged from the NIHR Cambridge Biomedical Research Centre ( BRC-1215-20014 ) and Cambridge Experimental Cancer Medicine Centre . Funding Information: 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 (RCCPDF\100008). 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_00002/14). Infrastructure support is acknowledged from the NIHR Cambridge Biomedical Research Centre (BRC-1215-20014) and Cambridge Experimental Cancer Medicine Centre.

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N2 - Background: The pharmaceutical industry's productivity has been declining over the last two decades and high attrition rates and reduced regulatory approvals are being seen. The development of oncology drugs is particularly challenging with low rates of approval for novel treatments when compared with other therapeutic areas. Reliably establishing the potential of novel treatment and the corresponding optimal dosage is a key component to ensure efficient overall development. A growing interest lies in terminating developments of poor treatments quickly while enabling accelerated development for highly promising interventions. Methods: One approach to reliably establish the optimal dosage and the potential of a novel treatment and thereby improve efficiency in the drug development pathway is the use of novel statistical designs that make efficient use of the data collected. Results: In this paper, we discuss different (seamless) strategies for early oncology development and illustrate their strengths and weaknesses through real trial examples. We provide some directions for good practices in early oncology development, discuss frequently seen missed opportunities for improved efficiency and some future opportunities that have yet to fully develop their potential in early oncology treatment development. Discussion: Modern methods for dose-finding have the potential to shorten and improve dose-finding and only small changes to current approaches are required to realise this potential.

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JO - European Journal of Cancer

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ER -

Early phase clinical trials in oncology: Realising the potential of seamless designs

Abstract

Bibliographical note

Funding

Keywords

ASJC Scopus subject areas

UN SDGs

Access to Document

Other files and links

Fingerprint

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

Cite this

Early phase clinical trials in oncology: Realising the potential of seamless designs

Abstract

Bibliographical note

Funding

Keywords

ASJC Scopus subject areas

UN SDGs

Access to Document

Other files and links

Fingerprint

Projects

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

Cite this