PHOENIX: a study protocol for a pilot randomised controlled trial of pre-emptive pharmacogenomic panel testing in acute care settings with health economic evaluations.

چکیده اصلی

INTRODUCTION: Pharmacogenomic (PGx) panel testing may reduce adverse drug reactions (ADRs), treatment failures and downstream healthcare use by aligning prescribing with germline genetic variation. The PREPARE trial reported an approximately 30% reduction in clinically relevant ADRs using a pre-emptive multigene panel, but its open-label design, patient-reported endpoint and subsequent methodological critiques limit its use for National Health Service (NHS) decision-making. Whether panel-based PGx delivers benefit in acute NHS secondary care, where prescribing is time-critical, patients are older and multimorbid and outcomes can be linkage-adjudicated, remains unknown. METHODS AND ANALYSIS: PHOENIX is a pragmatic, pilot, parallel-group, individually randomised controlled trial with blinded outcome adjudication, in NHS Greater Glasgow and Clyde (NHSGGC) hospitals and NHS Golden Jubilee National Hospital. Adults newly prescribed an eligible PGx-relevant index drug are identified through a data-driven screening system integrating electronic prescribing, community prescribing linkage and record review and randomised 1:1 to PGx-guided care or standard care with delayed PGx testing. In the intervention arm, buccal-swab DNA is genotyped (Clinical Laboratory Improvement Amendments/College of American Pathologist (CLIA/CAP)-accredited laboratory) and a Clinical Pharmacogenetics Implementation Consortium (CPIC)/Dutch Pharmacogenetics Working Group (DPWG)-based report returned within approximately 10 days; results are research-use-only. The trial aims to recruit 2000-4000 participants constrained by a fixed operational end-date (30 September 2026). The primary outcome is index-drug-related ADR or treatment failure within 3 months, adjudicated using Common Terminology Criteria for Adverse Events (CTCAE) V.6 and validated causality tools, with deterministic linkage via the West of Scotland Safe Haven. Secondary outcomes include ADR severity, hospitalisations, mortality, actionable prescribing uptake, biomarker levels, EuroQol 5-Dimension 5-Level questionnaire (EQ-5D-5L) and healthcare utilisation. The primary analysis is intention-to-treat logistic regression adjusted for stratification factors; a within-trial cost-utility analysis estimates cost per quality-adjusted life year (QALY). ETHICS AND DISSEMINATION: Approved by Scotland A Research Ethics Committee (24/SS/0064; IRAS 344412; NHS R&I INGN24MG113). Co-sponsors are NHSGGC and the University of Glasgow. Findings will be disseminated via peer-reviewed publication, conferences, patient and public involvement and engagement-co-produced lay summaries and the trial website. TRIAL REGISTRATION NUMBER: NCT06907784.

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