A patient's genetic makeup can determine whether a prescribed medicine works or causes harm, and this study will analyse NHS data to find out how many people could benefit from genetically guided prescribing. The problem is that drug effectiveness and safety vary widely between individuals, partly because of inherited differences in how the body processes medications. While testing for these genetic variants is possible, the NHS lacks clear evidence on which patients should be prioritised, how many prescriptions are already affected, and what the current costs of adverse drug reactions are. The researchers will examine a large population-based cohort of adults registered with GP practices, using linked hospital and mortality data to identify who is taking medicines eligible for pharmacogenetic optimisation, estimate how often prescribing is potentially inappropriate, and model the direct costs of adverse reactions. If successful, this work could help the NHS target pharmacogenetic testing to the patients who would benefit most, reducing avoidable harm and health inequalities while informing prescribing decisions for many commonly used medications.
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Research question There is considerable variability in the effectiveness and safety of medicines among individuals. This variability stems in part from genetic differences that influence how drugs are absorbed and metabolised. It is now possible to test for this genetic variability for specific medicines and use this information to inform prescribing decisions (hereafter pharmacogenetic-prescribing ). We aim to determine which patients would benefit most from prioritised pharmacogenetic testing, the scale of pharmacogenetic prescribing in the NHS, and to assess the extent of prescription and adverse drug reaction (ADR)-related costs from prescribing that could be improved with wider pharmacogenetic testing. Background To improve patient outcomes and reduce avoidable health inequalities, it is essential to develop strategies that reduce the impact of genetic variation on drug response. Up to 99% of patients prescribed a medicine in the NHS may carry a "pharmacogenetic" variant. One promising approach is "pharmacogenetic" prescribing, which uses an individual's genetic information to guide medicine selection and dosing. Despite this, there is significant uncertainty about how pharmacogenetics should be implemented in the English NHS. Aims and Objectives We aim to identify the number and type of patients who may be eligible for targeted pharmacogenetic prescribing. We will also assess the current scale of pharmacogenetic prescription and adverse drug reaction (ADR)-related costs in the English NHS. To achieve this, we will analyse which patient characteristics influence the use of medicines eligible for pharmacogenetic-optimised prescribing across different populations, estimate the potential to improve prescribing using population-level genetic data, describe the prevalence of ADRs and links with Multiple Long-Term Conditions (MLTCs), and analyse costs of current-prescribing versus pharmacogenetic-prescribing. Methods The study employs a population-based cohort design. The cohort consists of adults registered with GP practices in the Clinical Practice Research Datalink (CPRD) Aurum database from 2006 to 2023 with at least two-years of continuous follow-up data. The CPRD data is linked to Hospital Episode Statistics(HES) and Office of National Statistics (ONS) data. We will describe pharmacogenetic-medicine exposure in this cohort, and identify patient characteristics associated with this exposure thus identifying patients potentially eligible for targeted pharmacogenetic testing. Using data on allele frequency and functionality, we will estimate the scale of potentially inappropriate prescribing of pharmacogenetic medicines. We will describe the prevalence of ADRs in primary and secondary care, and also the prevalence of drug intolerance, drug allergies, treatment termination, and drug-switching. We will also focus this analysis on patients with MLTCs. We will model the direct costs associated with improved prescribing and reduced ADRs. Timelines We propose a 15-month project. Our established Patient and Public Involvement group, which helped develop this application, will be consulted again to ensure a rapid project start. Additionally, initial feasibility assessments and the code to create the cohort are nearly complete which will enable prompt project initiation. Anticipated Impact and Dissemination The research has the potential to inform prescribing decisions for many commonly used medications. The co-applicants have excellent links to dissemination, education and implementation networks including via the NHSE s pharmacogenomic and medicines optimisation "Genomic Network of Excellence".
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