How can genetic testing improve medication safety and effectiveness in Aboriginal and Torres Strait Islander people with chronic diseases?

Participants will undergo pharmacogenomic testing using a blood sample (~5 mL) to identify genetic variants that influence medication response. Participants will attend screening, consent, intervention, and follow-up appointments over approximately 24 weeks. The intervention consists of: Screening phase During standard clinical appointments, clinicians or Clinical Coordinators identify potentially eligible patients who are prescribed an index medication and invite them to participate in the study. Interested participants are referred to an Aboriginal Health Worker (AHW) or Research Nurse, who contacts potential participants and arranges a study information appointment. Appointment 1 (Screening) The AHW/Research Nurse explains the study and provides the Participant Information and Consent Form (PICF). Participants who are not interested are not contacted further. Appointment 2 (Recruitment/Consent – Week 1) The AHW/Research Nurse conducts the consent interview and obtains informed consent. Participants who do not consent are withdrawn from further study procedures. Appointment 3 (Intervention – Week 2–3) Participants attend pathology collection for blood sample collection (~5 mL). Blood samples undergo pharmacogenomic sequencing using a targeted gene panel. Clinical Coordinators administer baseline electronic questionnaires and collect relevant clinical information from electronic health records. Where required, samples are sent to a National Association of Testing Authorities (NATA)-accredited laboratory for validation of clinically actionable findings. The study includes participants prescribed selected medications associated with chronic disease management and known pharmacogenomic relevance. These include: Mental illness • Paroxetine • Venlafaxine • Risperidone • Sertraline Cardiovascular disease (CVD), Chronic Kidney Disease (CKD), and Hypertension • Atorvastatin • Simvastatin Acute pain management • Celecoxib Appointment 4 (Following sequencing and validation – approximately Week 3 onwards) Where clinically actionable pharmacogenomic findings are identified, a report summarising the results and clinical recommendations will be provided to the treating clinician. Medication adjustments may be made based on these results. Pharmacogenomic results and established clinical guidelines will be used by clinicians to guide both initial prescribing decisions and any subsequent prescriptions during the follow-up period. Pharmacogenomic results are returned to treating clinician and participants are informed of any medication dose or selection changes guided by pharmacogenomic findings. Treating clinicians may adjust medications using pharmacogenomic results alongside internationally recognised guidelines including the Clinical Pharmacogenetics Implementation Consortium (CPIC) and the Dutch Pharmacogenetics Working Group (DPWG) guidelines, where clinically applicable. Participants are informed during the consent process that only clinically actionable pharmacogenomic results will be returned. If no clinically actionable variants are identified, or findings do not meet criteria for return, participants will not receive an individual pharmacogenomic report and will continue receiving standard clinical care. No medication changes will be made where no actionable findings are identified. The intervention is delivered within hospital and community healthcare settings, including Toowoomba Hospital, Logan Hospital, and Carbal Medical Services. Clinical Coordinators, Research Nurses, and clinicians are responsible for study procedures, while Aboriginal Health Workers provide culturally appropriate support to participants throughout recruitment, consent, and follow-up. Follow-up (Week 12) Clinical Coordinators follow up participants and conduct Week 12 surveys. Additional appointments with treating clinicians may be arranged if required. Final Follow-up (Week 24) Clinical Coordinators conduct final Week 24 follow-up surveys. Additional clinician appointments may be arranged if required. Intervention adherence and fidelity will be monitored through participant follow-up surveys, review of medication changes, and relevant medical record review. Participants who undergo medication adjustments will be followed for a six-month period to monitor the frequency and severity of adverse drug reactions. Adverse events will be assessed using a standardised clinical grading scale, focusing on events rated as moderate to severe. Participants may withdraw from the study at any time.