Bridging the gap
: using evidence synthesis to incorporate information from drug development into Health Technology Appraisal and beyond

Student thesis: Doctoral ThesisDoctor of Philosophy (PhD)


Within the drug development process, drugs are first tested in preclinical trials consisting of animal and/or in vitro studies, followed by several phases of clinical trials in humans. For a new drug to be licensed it must pass through regulatory approval and, for it to be reimbursed by a national healthcare provider such as the UK NHS, be assessed in a Health Technology Appraisal (HTA). Treatments may subsequently be evaluated and recommended as part of national or international guidelines.

Synthesis of evidence is performed at different points throughout this process, but often in relative isolation and using different methodologies. Furthermore, available evidence can be sparse, which poses challenges for robust synthesis, particularly if such analyses are intended to inform decision-making.
This thesis aims to characterise the use of evidence synthesis within drug development and reimbursement, and to explore which sources of data may be useful at different points for decision-making by addressing the following questions:

1. What are the barriers to using evidence synthesis to support translation of research findings from preclinical studies to human trials?
2. What robust methods can we use to incorporate dose-response and time-course information into evidence synthesis?
3. Can we use early phase evidence to connect evidence networks in reimbursement decision-making?
4. Which tools may be helpful for evidence synthesis of drug development trials?

The thesis includes published papers and software to explore these questions, including developing and evaluating a framework for explicitly modelling dose-response and time-course relationships using Model-Based Network Meta-Analysis (MBNMA). The integrative chapter places these developments in the context of other work, discusses strengths and limitations of proposed approaches, and suggests future research that could build upon the work in the thesis.
Date of Award21 Mar 2023
Original languageEnglish
Awarding Institution
  • The University of Bristol
SupervisorDavid M Phillippo (Supervisor) & Nicky J Welton (Supervisor)


  • evidence synthsis
  • NMA
  • HTA
  • drug development

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