Applying a Multidimensional Appraisal Framework to Personalised Prevention: Pre-treatment DPYD Genotyping For Fluoropyrimidine Chemotherapy in Finland : National application of a framework co-created within the PROPHET consortium
Kannan, Pragathy (2026)
2026
Kansanterveystieteen maisteriohjelma - Master's Programme in Public Health
Yhteiskuntatieteiden tiedekunta - Faculty of Social Sciences
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Hyväksymispäivämäärä
2026-05-29
Julkaisun pysyvä osoite on
https://urn.fi/URN:NBN:fi:tuni-202605276461
https://urn.fi/URN:NBN:fi:tuni-202605276461
Tiivistelmä
Background
Personalised prevention aims to reduce disease burden and treatment-related harm by tailoring interventions to individual biological, behavioural and contextual characteristics. Despite increasing use of biomarker-guided prevention strategies, existing appraisal approaches often struggle to capture their full value. Traditional HTA approaches focus primarily on clinical effectiveness and economic efficiency, while less importance is given to implementation feasibility, equity and system-level impacts. This creates a policy-level appraisal gap for personalised prevention interventions.
Objectives
The aim of this thesis was to develop and apply a hybrid appraisal approach for personalised prevention by integrating HTA and HIA perspectives, and to test its policy relevance through a national case study of pre-treatment DPYD genotyping prior to fluoropyrimidine chemotherapy in Finland.
Methods
The study adopted a mixed-methods design. A structured literature synthesis was conducted to identify conceptual and methodological approaches to personalised prevention appraisal. This informed the development and application of a hybrid Health Technology Assessment (HTA) – Health Impact Assessment (HIA) framework. This framework was applied to a national case study in Finland using multiple data sources, including registry-derived aggregates, decision-analytic modelling outputs adapted for the Finnish context, surveys of oncologists and laboratory professionals, semi-structured patient interviews, and policy and guidance documents. The appraisal was structured across four analytical domains: clinical effectiveness and safety, economic value, implementation feasibility, and equity and distributional considerations.
Results
DPYD genotyping was already widely adopted in Finland, with a high baseline testing rate prior to fluoropyrimidine treatment. Modelled outcomes indicated modest incremental reductions in severe toxicity and treatment-related mortality when moving from current practice to full systematic genotyping, reflecting this high baseline uptake. Published economic evidence consistently supported the cost-effectiveness or cost savings of prospective DPYD testing. Implementation findings highlighted variation in laboratory turnaround times, workflow integration and regional logistics, despite high professional acceptability. Equity considerations were primarily related to differences in timeliness of testing and potential gaps in variant coverage relevant to the Finnish population. Patient interviews indicated high trust in clinical recommendations but limited awareness of testing.
Conclusions
This thesis demonstrates that a hybrid HTA–HIA appraisal approach provides added value when evaluating personalised prevention interventions, even in settings with strong clinical evidence and mature implementation. The findings show that the real-world effectiveness of personalised prevention interventions is co-determined by health system implementation conditions and therefore cannot be fully understood through clinical and economic evidence alone. Effective appraisal requires integration of clinical, economic, organisational and equity dimensions within a single policy-oriented framework. The findings further underline the importance of system readiness, monitoring and equity-sensitive evaluation for the sustainable scaling of personalised prevention strategies.
Personalised prevention aims to reduce disease burden and treatment-related harm by tailoring interventions to individual biological, behavioural and contextual characteristics. Despite increasing use of biomarker-guided prevention strategies, existing appraisal approaches often struggle to capture their full value. Traditional HTA approaches focus primarily on clinical effectiveness and economic efficiency, while less importance is given to implementation feasibility, equity and system-level impacts. This creates a policy-level appraisal gap for personalised prevention interventions.
Objectives
The aim of this thesis was to develop and apply a hybrid appraisal approach for personalised prevention by integrating HTA and HIA perspectives, and to test its policy relevance through a national case study of pre-treatment DPYD genotyping prior to fluoropyrimidine chemotherapy in Finland.
Methods
The study adopted a mixed-methods design. A structured literature synthesis was conducted to identify conceptual and methodological approaches to personalised prevention appraisal. This informed the development and application of a hybrid Health Technology Assessment (HTA) – Health Impact Assessment (HIA) framework. This framework was applied to a national case study in Finland using multiple data sources, including registry-derived aggregates, decision-analytic modelling outputs adapted for the Finnish context, surveys of oncologists and laboratory professionals, semi-structured patient interviews, and policy and guidance documents. The appraisal was structured across four analytical domains: clinical effectiveness and safety, economic value, implementation feasibility, and equity and distributional considerations.
Results
DPYD genotyping was already widely adopted in Finland, with a high baseline testing rate prior to fluoropyrimidine treatment. Modelled outcomes indicated modest incremental reductions in severe toxicity and treatment-related mortality when moving from current practice to full systematic genotyping, reflecting this high baseline uptake. Published economic evidence consistently supported the cost-effectiveness or cost savings of prospective DPYD testing. Implementation findings highlighted variation in laboratory turnaround times, workflow integration and regional logistics, despite high professional acceptability. Equity considerations were primarily related to differences in timeliness of testing and potential gaps in variant coverage relevant to the Finnish population. Patient interviews indicated high trust in clinical recommendations but limited awareness of testing.
Conclusions
This thesis demonstrates that a hybrid HTA–HIA appraisal approach provides added value when evaluating personalised prevention interventions, even in settings with strong clinical evidence and mature implementation. The findings show that the real-world effectiveness of personalised prevention interventions is co-determined by health system implementation conditions and therefore cannot be fully understood through clinical and economic evidence alone. Effective appraisal requires integration of clinical, economic, organisational and equity dimensions within a single policy-oriented framework. The findings further underline the importance of system readiness, monitoring and equity-sensitive evaluation for the sustainable scaling of personalised prevention strategies.