Extrapolation of economic outcomes beyond trial follow-up, are there additional challenges in paediatric trials?

During the health technology appraisal process, evidence is considered pertaining to both the clinical effectiveness and cost-effectiveness of an intervention. Economic analyses frequently require lifetime costs and outcomes of treatment, however clinical trials rarely extend beyond a few years and are often conducted over much shorter periods¹. As such, extrapolation or modelling approaches are often required to reduce time horizon bias in cost-effectiveness estimates. Extrapolation of data beyond trials has attracted interest in a non-paediatric-specific setting², however, there are some challenges which may be unique to the paediatric setting. While there is increasing availability and use of specific paediatric questionnaires and tariff values, there has been less consideration as to how utility values, and the costs associated with paediatric (or adult) services, are applied appropriately in extrapolating, or modelling results as the patient transitions to adulthood³. Moreover, while there is extensive research in extrapolating pharmacological treatment effect from adults to children⁴, there has been little attention to the reverse in the context of transitioning from paediatric to adult indications, doses and treatment regimens. Adult and paediatric populations are often considered separately in trial conduct and analysis; however, the quality and generalisability of outcomes in paediatric trials has potential to be enhanced by considering data generated from trials in adult populations at age-appropriate points when estimating results over the longer time horizon. As extrapolation approaches often draw from clinical data in addition to economic data, this potential for integration extends beyond the specific health economic outcomes.

The studentship will begin with a review of paediatric trial reports which have an accompanying health economics analysis. This will seek to identify the scope of approaches and assumptions used in extrapolating the health economic results. A series of simulations will be used to consider the relationships between time horizons, discount rates and the convergence of incremental outcomes in light of alternative approaches to and valuations of ongoing incremental costs and benefits, and future risks. A trial-based case study (e.g. the SANAD clinical trials of anti-seizure medicines) will be used to illustrate the impact of different approaches on estimates of cost-effectiveness. Consensus methodology such as the Delphi method will be used to draw together the results of the analyses with recommendations and perspectives from a panel of stakeholders, in order to produce recommendations for future best practice.

This studentship will be supervised by a team with expertise in trial-based economic analyses (including paediatric trials), economic modelling, trial methodology, medical statistics, and paediatric clinical pharmacology. The lead supervisor will be Dr Catrin Plumpton (Bangor University), co-supervised by Prof. Dyfrig Hughes (Bangor University), Prof. Paula Williamson (University of Liverpool) and Dr Dan Hawcutt (University of Liverpool).

The potential for placements will be discussed during the studentship. Options may include placement with co-supervisors, or HTA bodies. Opportunities for PPI input will be explored, and will include representation (e.g. parents, carers or young people) in the consensus exercise.

HOW TO APPLY

You are applying for a PhD studentship from the MRC TMRP DTP. A list of potential projects and the application form is available online at:

http://www.methodologyhubs.mrc.ac.uk/about/tmrp-doctoral-training-partnership/

Please complete the form fully. Incomplete forms will not be considered. CVs will not be accepted for this scheme.

Please apply giving details for your first choice project. You can provide details of up to two other TMRP DTP projects you may be interested in at section B of the application form.

Before making an application, applicants should contact the project supervisor to find out more about the project and to discuss their interests in the research before 09 January 2023.

The deadline for applications is 4pm (GMT) 16 January 2023. Late applications will not be considered.

Completed application forms must be returned to: [Email Address Removed]

Informal enquiries may be made to Dr Catrin Plumpton - [Email Address Removed]