Minimising Adverse Drug Reactions and Verifying Economic Legitimacy-Pharmacogenomics Implementation in Children (MARVEL- PIC): protocol for a national randomised controlled trial of pharmacogenomics implementation
- Author(s)
- Conyers, R; Halman, A; Moore, C; Stenta, T; Felmingham, B; Collier, L; Khatri, D; Spelman, T; Williams, E; Dyas, R; Kotecha, RS; Jessop, S; Mateos, MK; Swen, J; Elliott, DA;
- Details
- Publication Year 2024-05-16,Volume 14,Issue #5,Page e085115
- Journal Title
- BMJ Open
- Publication Type
- Protocol
- Abstract
- INTRODUCTION: DNA-informed prescribing (termed pharmacogenomics, PGx) is the epitome of personalised medicine. Despite international guidelines existing, its implementation in paediatric oncology remains sparse. METHODS AND ANALYSIS: Minimising Adverse Drug Reactions and Verifying Economic Legitimacy-Pharmacogenomics Implementation in Children is a national prospective, multicentre, randomised controlled trial assessing the impact of pre-emptive PGx testing for actionable PGx variants on adverse drug reaction (ADR) incidence in patients with a new cancer diagnosis or proceeding to haematopoetic stem cell transplant. All ADRs will be prospectively collected by surveys completed by parents/patients using the National Cancer Institute Pediatric Patient Reported [Ped-PRO]-Common Terminology Criteria for Adverse Events (CTCAE) (weeks 1, 6 and 12). Pharmacist will assess for causality and severity in semistructured interviews using the CTCAE and Liverpool Causality Assessment Tool. The primary outcome is a reduction in ADRs among patients with actionable PGx variants, where an ADR will be considered as any CTCAE grade 2 and above for non-haematological toxicities and any CTCAE grade 3 and above for haematological toxicities Cost-effectiveness of pre-emptive PGx (secondary outcome) will be compared with standard of care using hospital inpatient and outpatient data along with the validated Childhood Health Utility 9D Instrument. Power and statistics considerations: A sample size of 440 patients (220 per arm) will provide 80% power to detect a 24% relative risk reduction in the primary endpoint of ADRs (two-sided α=5%, 80% vs 61%), allowing for 10% drop-out. ETHICS AND DISSEMINATION: The ethics approval of the trial has been obtained from the Royal Children's Hospital Ethics Committee (HREC/89083/RCHM-2022). The ethics committee of each participating centres nationally has undertaken an assessment of the protocol and governance submission. TRIAL REGISTRATION NUMBER: NCT05667766.
- Publisher
- BMJ
- Keywords
- Humans; Child; *Drug-Related Side Effects and Adverse Reactions/prevention & control; *Pharmacogenetics; Prospective Studies; Randomized Controlled Trials as Topic; Neoplasms/drug therapy/genetics; Multicenter Studies as Topic; Precision Medicine/economics; Hematopoietic Stem Cell Transplantation; Genetics; Implementation Science; Paediatric oncology; Pharmacists; Pharmacology; Polypharmacy
- Department(s)
- Laboratory Research; Health Services Research
- Publisher's Version
- https://doi.org/10.1136/bmjopen-2024-085115
- Open Access at Publisher's Site
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Creation Date: 2024-07-04 04:37:31
Last Modified: 2024-07-04 04:49:35