Gert van Valkenhoef

PhD project & thesis

Project

My PhD research at the Department of Epidemiology, University Medical Center Groningen and at the Faculty of Economics and Business, University of Groningen started in April 2009 and culminated in the defense of my PhD thesis

• G. van Valkenhoef, "Making better use of clinical trials: computational decision support methods for evidence-based drug benefit-risk assessment", Bibliotheek van de Rijksuniversiteit Groningen, Groningen, The Netherlands. [eprint] [preprint]

on 19 December 2012 (cum laude / with honor — a distinction awarded to only 6% of theses in the Medical Sciences). This thesis was produced in the context of the Escher Project (T6-202), a project of the Dutch Top Institute Pharma. The Escher Project brings together university and pharmaceutical partners with the aim of energizing pharmaceutical R & D by identifying, evaluating, and removing regulatory and methodological barriers in order to bring efficacious and safe medicines to patients in an efficient and timely fashion. The project focuses on delivering evidence and credibility for regulatory reform and policy recommendations.

• Pictures of the defence ceremony

My activities and responsibilities during the project included the following:

• Research: 8 published journal papers, 1 conference paper, 1 research report. Presented at 6 international and 10+ national conferences and scientific meetings.
• Software: ADDIS decision support system, GeMTC software for network meta-analysis, "hitandrun" R package, and others.
• Management: managed a small team of up to 4 software developers, developing the ADDIS decision support system (September 2009 - present).
• Teaching: (co-)supervised 2 MSc and 2 BSc thesis projects, gave a short course on mixed treatment comparisons and decision analysis at the School of Pharmacy, University of Eastern Finland.
• Courses: Multi-Parameter Evidence Synthesis (Bristol & Leicester University), Drug Development & Approval (TI Pharma), Drug Discovery & Development Cycle (TI Pharma), Systematic Review & Meta-Analysis (VUMC), Epidemiology and Applied Statistics (UMCG), Scientific Visualization (UoG), Multi-Criteria Decision Analysis (MCDA) summer school (2010), Service and Software Architectures, Infrastructures and Engineering (SSAIE) summer school (2009).

Thesis: Making better use of clinical trials

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Health care policy decision makers routinely evaluate the health impact of alternative treatment options. Here benefit-risk assessment is key, consisting of weighing the favorable effects (benefits) and unfavorable effects (risks) of the alternatives. For example, before a new drug is allowed on the market, regulators evaluate its benefit-risk balance in comparison to placebo or competing drugs.

Ideally, benefit-risk assessments are based on the best available evidence, typically meaning randomized controlled trials. However, finding the evidence and explicitly linking it to the assessment is complicated by several factors. First, the results of clinical trials are mainly made available in text-based documents that can not be processed automatically. Second, the data from these trials must be combined into a consistent basis for benefit-risk analysis. Third, quantitative decision models are required to directly link decisions to the underlying evidence and to make trade-off decisions explicit.

This thesis addresses these topics through the development of the Aggregate Data Drug Information System (ADDIS), an integrated system for decision support based on databases of structured clinical trials data. Novel algorithms are presented to automate network meta-analysis to combine clinical trials' results and multi-criteria decision models are developed to support benefit-risk assessment.

ADDIS is open source software, available from http://drugis.org/.