Health economic considerations for pharmacogenomic services in the United Kingdom: The Centre for Excellence in Regulatory Science and Innovation in Pharmacogenomics

As National Health Services (NHS) across the United Kingdom face mounting pressures, pharmacogenomics presents a rare opportunity to improve patient outcomes, reduce care expenditure and promote economic growth. The Centre for Excellence in Regulatory Science and Innovation in Pharmacogenomics (CERSI PGx), led by Professor Sir Munir Pirmohamed of the University of Liverpool, was established in 2025 to work with multiple stakeholders, including UK regulators and industry, to develop pathways for implementing pharmacogenomic services. A key focus is on developing evidence on the value of pharmacogenomics—both to the NHS and beyond. Conventional health technology assessment (HTA) methods provide a foundation for evaluating health technologies, including pharmacogenomics, and focus primarily on quantifying health and cost outcomes associated with specific therapeutic strategies at the individual level. Most HTA agencies, including the National Institute for Health and Care Excellence (NICE) in the United Kingdom, adopt a healthcare system perspective and assess whether a given technology represents good value-for-money relative to the health opportunity cost of reimbursement. Within CERSI PGx, UK-specific pharmacogenomic guidelines, accessible via a dedicated, open-access repository, are being developed. These are not intended to replicate the Clinical Pharmacogenetics Implementation Consortium or the Dutch Pharmacogenetics Working Group guidelines, but rather to provide a UK focus, especially in relation to clinical practice within the NHS, patient eligibility and cost-effectiveness. They aim to offer practical, evidence-based guidance to prescribers. The health economic evidence for these guidelines is drawn from targeted reviews of the literature and presented within structured summaries. This undertaking is facilitated via a growing body of economic evidence supporting the implementation of single-gene pharmacogenomic tests. The majority of economic evaluations identified in a systematic review concluded that pharmacogenomic testing was cost-effective, cost-saving or dominant (i.e., health-improving and cost-saving).1 In relation to CYP2C19 genotyping prior to clopidogrel, for example, a UK-based analysis adopting an NHS perspective found that both laboratory-based and point-of-care testing strategies generated more quality-adjusted life years (QALYs) and lower costs over a lifetime than no testing for patients with ischaemic stroke or transient ischaemic attack.2 In another evaluation again over a lifetime and from an NHS perspective, routine testing for HLA-A*31:01 was cost-effective at £12 808 per QALY gained, in reducing the incidence of cutaneous adverse drug reactions in patients with epilepsy being prescribed carbamazepine.3 Single-gene tests are often cost-effective through their improvement in treatment efficacy or the avoidance of adverse drug reactions and associated costs. However, single-gene testing may not be the most cost-effective solution. The high prevalence of pharmacogenomic variants (>99%) and the likelihood of patients being prescribed medicines with actionable pharmacogenomic biomarkers (80% over 20 years in primary care) might reasonably mean that panel testing is expected to be more efficient. Yet, while there is evidence to support the clinical effectiveness of implementing panel tests,4 evidence of the cost effectiveness of pre-emptive and multigene testing is limited.1 One UK-based evaluation of a panel of HLA pharmacogenes relevant to five commonly prescribed drugs found cost-savings to the NHS over a patient's lifetime, irrespective of the individual cost-effectiveness of each drug–gene pair.5 Within CERSI PGx, the methodological challenge of assessing the value of a test that applies to multiple medicines for a range of diseases and over time is being approached via a meta-model of economic evaluations of single-gene tests. The cost-effectiveness of each drug–gene pair thus becomes dependent upon the incident prescribing of the drug and the likelihood that future prescribing decisions are made on the basis of information from the panel. The strategy (ies) chosen for implementing panel testing introduce further analytical complexity and have important economic implications. Population screening at birth, or when people reach an ‘at-risk’ age (as in vaccination programmes), is conceptually and operationally very different from screening at the point where a prescribing decision needs to be made. Additionally, panels that are comprehensive will offer different value from those that are specific to disease (e.g., cardiovascular, mental health and cancer) or context (e.g., primary care). These challenges associated with accurately modelling testing strategies are accompanied by difficulties in capturing the full value of upscaling pharmacogenomics in the United Kingdom. Consideration of broader elements of value is gaining traction in public health interventions such as vaccines and potentially curative treatments including cell and gene therapies.6 In the case of vaccination programmes, significant population-level benefits are realised, including productivity gains for both patients and caregivers, reduction in preventable healthcare resource use and macroeconomic benefits for society. A cross-country analysis of four vaccination programmes against seasonal influenza, pneumococcal disease, herpes zoster and respiratory syncytial virus found that when accounting for the full spectrum of benefits, these programmes can return up to 19 times their initial investment.7 For cell and gene therapies, which have the potential to transform the management of chronic and rare conditions, discussion has focused on how economic value is defined and whether consideration of perspective and outcomes should be broadened.6 Cited elements include disease severity, insurance value, carer and family spillover and scientific innovation. As a paradigm-shifting approach to prevention and personalised medicine, the case for routine pre-emptive pharmacogenomic testing similarly extends beyond the health benefits derived from improved personalised medicines. Relevant impacts may include benefits to the health system, in terms of reduced iatrogenic disease and reduced demand for services, and health-related benefits to the economy, in terms of reduced absenteeism and increased productivity. The analytical challenge is greater in this context than considering health outcomes alone. While HTA is a structured approach to inform healthcare resource allocation, value assessments for justifying investment in pharmacogenomics in general—from R&D, regulatory pathways and genomics infrastructure, to clinical training and testing guidance—require a societal perspective to also capture increased productivity, reduced informal care burden and wider macroeconomic benefits. There is currently no evidence quantifying the broader societal impacts of widespread pharmacogenomics adoption. CERSI PGx addresses this by drawing learnings from existing frameworks to ensure its broader societal value is appropriately captured and reflected in policy and investment decisions. The Wider Societal Impacts framework, for example, views health as both a form of human capital and an input into further capital production,8 and estimates net societal contribution as the difference between an individual's resource production and consumption. Social return on investment, which offers a stakeholder-oriented framework evolved from the principles of cost–benefit analysis,9 quantifies social value across multiple domains and presents the result as a return ratio (e.g., £3 of social value generated per £1 invested). This aspect of the work of CERSI PGx seeks to inform investment decisions about pharmacogenomics beyond the allocation of existing NHS resources. For this purpose, the appropriate methodological guide in the UK is The Green Book,10 issued by HM Treasury and designed to guide the appraisal of public expenditure programmes. This demands a different decision-making perspective to HTA, one that considers the real-world circumstances of dynamic disease populations, flexible budgets and short-term spending and investment settlements. The rationale for investing in pharmacogenomics lies in the potential for a shift from reactive to pre-emptive (panel) testing, which could transform prescribing practices in favour of personalised care. In line with single gene testing, this is likely to improve patient outcomes and reduce ADRs. However, a system-wide shift that results in more people being tested for more pharmacogenes creates opportunities for significant economies of scale and scope, with an expansion of capacity and the creation of spillover benefits that cannot be attributed to specific reimbursement decisions or individual patient groups. Such system-wide changes can support the life sciences sector by stimulating industrial expansion, creating highly skilled employment opportunities, increasing investment in research and development and fostering innovation. These factors collectively drive broader economic activity and national income growth, linking advances in pharmacogenomics directly to macroeconomic benefits beyond those arising from patient-level health and non-health impacts. Crucially, this perspective aligns with current national priorities, such as the 10-Year Health Plan for England and the UK Life Sciences Sector Plan. However, realising these benefits requires overcoming barriers related to current reimbursement frameworks, operational feasibility and infrastructure development, justifying strategic investment to enable a system-wide shift toward comprehensive, pre-emptive pharmacogenomic testing integrated into routine care. Outputs from CERSI PGx will be communicated with relevant stakeholder groups and policy-makers via dissemination activities. As the evidence base for pharmacogenomics continues to grow, economic evaluation will play a pivotal role in informing implementation decisions. Traditional HTA methods are essential, although challenges remain. The choice of evaluation perspective significantly influences which costs and benefits are captured. Data gaps, particularly in electronic health records, limit the ability to track long-term outcomes across care pathways, while the distinction between reactive and pre-emptive testing requires nuances in economic modelling. HTA approaches serve a specific purpose but are limited in their ability to assess the full impact of a system-wide shift to pre-emptive testing and to demonstrate a case for investment. Broader analytical frameworks enable the inclusion of cross-sectoral benefits and better reflect the societal impacts of pharmacogenomics. These have an important role in informing policies to realise the transformative potential of pharmacogenomics across the NHS and the UK economy. All authors drafted the manuscript, gave their final approval of the version to be published and agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. We acknowledge the funding received from Innovate UK (MC_PC_24034) for the Centre of Excellence in Regulatory Science and Innovation in Pharmacogenomics (CERSI PGx). CERSI PGx is managed by the University of Liverpool and includes the following additional partners: The University of Manchester, Bangor University, Queen Mary University of London, JS O'Brien Business Solutions Ltd, Office of Health Economics, British Pharmacological Society and Alderley Lighthouse Labs Ltd. D.A.H. is co-chair of the NHS England Pharmacogenomics Test Evaluation Working Group and chair of the NHS Wales National Pharmacogenomics Group. C.O.P. declares no conflicts of interest. H.F., G.H., and C.S. are employed by the Office of Health Economics (OHE), which receives funding from a variety of commercial and charitable bodies that may have an interest in the content of this manuscript.