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A Quantitative Process for Enhancing End of Phase 2 Drug Development Decisions

Sabin, Antony James; (2020) A Quantitative Process for Enhancing End of Phase 2 Drug Development Decisions. Doctoral thesis (Ph.D), UCL (University College London). Green open access

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Abstract

The objectives of the phase 2 stage in a drug development programme are to evaluate the safety and tolerability of different doses, select a promising dose range and look for early signs of activity. At the end of phase 2 (EOP2), a decision to initiate phase 3 studies involves the commitment of considerable resources and associated costs. This multi-factorial, critical business decision is made by balancing the current condition of a sponsor organisation’s portfolio, the future cost of development, the competitive landscape, and the expected safety and efficacy benefits of a new therapy. The decision process needs to be efficient, effective and evidentially supported. This PhD presents a practical, formalised and quantitative approach for enhancing the EOP2 decision process. This process ensures that a consistent and explicit evidence-based approach is used to inform decisions for new drug candidates. Broadly following this process will help statisticians increase their strategic influence in drug development programmes. Embedded within the process is a predominantly bayesian approach to predicting the probability of efficacy success (PoS) in a future (frequentist) phase 3 programme at the end of phase 2. Also included are early predictions of the outcomes of indirect treatment comparisons and future treatment ranking between the investigational treatment and alternative treatments either already approved or still in development. Moreover, the incorporation of qualitative factors into the decision making process, and the implementation of a PoS framework when limited or no prior clinical data is available is discussed. The entire process is illustrated using an example from the pancreatic cancer indication, with further supporting examples of predicting the PoS provided for gastric cancer, soft tissue sarcoma, non-small cell lung cancer and ovarian cancer. Additionally, the utility of the PoS framework in practice is highlighted through a review of the PoS for 63 completed phase 3 studies.

Type: Thesis (Doctoral)
Qualification: Ph.D
Title: A Quantitative Process for Enhancing End of Phase 2 Drug Development Decisions
Event: UCL (University College London)
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Copyright © The Author 2020. Original content in this thesis is licensed under the terms of the Creative Commons Attribution 4.0 International (CC BY 4.0) Licence (https://creativecommons.org/licenses/by/4.0/). Any third-party copyright material present remains the property of its respective owner(s) and is licensed under its existing terms. Access may initially be restricted at the author’s request.
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy > Pharmacology
URI: https://discovery.ucl.ac.uk/id/eprint/10113237
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