Minimising Adverse Drug Reactions and Verifying Economic Legitimacy - Pharmacogenomics Implementation in Children (MARVEL-PIC)
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 入组人数
- 441
- 试验地点
- 10
- 主要终点
- Reduction in the number of adverse drug reactions (ADRs)
研究概览
简要总结
A prospective, open, randomised implementation study in paediatric cancer patients. The study aims to determine whether a personalised approach will result in an overall reduction in clinically relevant adverse drug reactions (ADRs) and to evaluate the economic and quality of life impacts. Participants will be randomised to receive personalised guided prescribing of supportive care therapy (study arm) or standard of care (control arm) for a period of 12 weeks. The follow up period includes prospective patient reporting of symptoms and quality of life through electronically delivered surveys, for a maximum of 12 months.
详细描述
One of the main areas of precision medicine that is easily implementable is pharmacogenomic testing. Germline testing of genes predisposing to drug toxicity or inefficacy can inform drug selection and dosing. This steers away from the historical 'trial and error' approach, avoids unnecessary adverse drug reactions (ADRs) and can potentially impact on health economic savings, through reduction in readmissions and admissions with ADRs.
This study will be a prospective, open, randomised implementation study in paediatric and adolescent patients with a new diagnosis of cancer or who are proceeding to first haematopoietic stem cell transplantation (HSCT). The current standard of care for paediatrics in Australia involves pharmacogenomic testing for TPMT and NUD15, for patients with acute lymphoblastic leukaemia. Participants of the study will receive pharmacogenomic testing across a range of clinically relevant variants. Participants will be randomised to either the control arm or the study arm. Test results for participants in the study arm will be used to guide the dose and drug selection of 27 drugs commonly used in supportive care. The pharmacogenomic test results will be released to the study arm at week 4 and to the control arm at week 13, after the 12 week intervention period.
To determine whether pre-emptive pharmacogenomic testing does reduce clinically relevant adverse drug reactions, the Paediatric Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (Ped-PRO-CTCAE) survey will be delivered at 3 time points within a 12 week period. This survey is a patient reported outcome measurement tool developed to evaluate symptomatic toxicity in participants receiving cancer therapy. After survey completion, semi-structured interviews will be conducted by an academic pharmacist with the aim of generating a CTCAE grade of severity for each of the symptoms defined in the Ped-PRO-CTCAE and assessing the causality of an adverse drug reaction using the Liverpool Adverse Drug Reaction Causality Assessment Tool (Liverpool ADR-CAT). These mechanisms will support the assessment of both severity and causality of any adverse drug reactions.
To evaluate the economic and Quality of Life impacts (QoL), participants will also complete The Child Health Utility 9D (CHU9D) QoL surveys specific to children and young adults at 3 timepoints over the 12-month period and consent to a Health Economics Analysis. This includes collection of Medicare Benefits Schedule (MBS)/ Pharmaceutical Benefits Scheme (PBS) data from Services Australia and Victorian Data Linkage Group to compare the costs of management of both the control and study arm.
Data from the study will be securely stored on the REDCap database. Patients will be allocated a unique patient identifier prior to their de-identified data being added to the database.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Supportive Care
- 盲法
- None
入排标准
- 年龄范围
- — 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age < 18 years
- •New cancer diagnosis or patient receiving HSCT or patient has a relapsed cancer diagnosis and is starting treatment after more than 6 months without.
- •Starting treatment with a chemotherapeutic agent that is not single agent oral targeted therapy.
- •Must also be taking a medication for which there is an established CPIC guideline available.
- •Parent or patient is able and willing to give consent for patient to take part and be followed up for at least 12 weeks.
- •Patient is amenable to venepuncture and blood draw (5mL ideally with an absolute minimum requirement of 2.5 mL) or has Whole Genome Sequencing available (WGS).
- •Patient and/or parent is able and willing to sign an informed consent form.
- •Patient and/or parent is able to complete Ped-PRO-CTCAE survey in English, Italian or Chinese.
- •Study enrolment limit has not been reached.
排除标准
- •Age > 18 years.
- •Patient has a life expectancy estimated to be less than three months by the treating clinical team.
- •Duration of the drug of inclusion total treatment length is planned to be less than one week.
- •Patient and/or parent is unable to consent to the study.
- •Patient and/or parent is unwilling to take part in the study.
- •Patient and/or parent is able unable to complete Ped-PRO-CTCAE survey in English, Italian or Chinese.
- •Patient has existing impaired hepatic or renal function for which a lower dose or alternate drug selection are already part of current routine care.
- •Patient has a glomerular filtration rate of less than 15 mL/min per 1.73m
- •Patient has advanced liver failure.
研究组 & 干预措施
Standard of Care
Standard of Care prescribing for period of 12 months. Participants will receive pharmacogenomic test results according to the current standard of care. The participants will be followed up for a minimum of 12 weeks, with maximal time-period being 12 months depending on time of enrolment.
干预措施: Release of Extended Pharmacogenomics Report at Week 13 (Diagnostic Test)
Experimental Arm
Extended Pharmacogenomic prescribing for a period of 12 months. Participants will receive pharmacogenomic testing across a range of clinically relevant variants, to guide the dose and drug selection of 27 drugs commonly used in supportive care. The participants will be followed up for a minimum of 12 weeks, with maximal time-period being 12 months depending on time of enrolment.
干预措施: Release of Extended Pharmacogenomics Report at Week 1 (Diagnostic Test)
Experimental Arm
Extended Pharmacogenomic prescribing for a period of 12 months. Participants will receive pharmacogenomic testing across a range of clinically relevant variants, to guide the dose and drug selection of 27 drugs commonly used in supportive care. The participants will be followed up for a minimum of 12 weeks, with maximal time-period being 12 months depending on time of enrolment.
干预措施: Release of Extended Pharmacogenomics Report at Week 13 (Diagnostic Test)
结局指标
主要结局
Reduction in the number of adverse drug reactions (ADRs)
时间窗: 12 weeks
The primary outcome is a reduction in adverse drug reactions among patients with actionable pharmacogenomic variants. An adverse drug reaction will be considered as any CTCAE grade 2 and above for non-haematological toxicities or CTCAE grade 3 and above for haematological toxicities. CTCAE grades are defined as 1,2,3,4 or 5, with 5 indicating the most severe.
次要结局
- Therapeutic drug monitoring(12 months)
- Physician and Pharmacist adherence to the CPIC guidelines(12 months)
- Change in quality of life outcomes using CHU9D(Baseline, Week 12, 12 months)
- Occurrence of at least one ADR which contributes to primary endpoint(12 weeks)
- Incidence of drug cessation due to lack of efficacy(12 months)
- Incidence of drug cessation due to ADR(12 months)
- Number of self-reported ADRs(12 weeks)
- Number of dose adjustments(12 weeks)
- Occurrence of at least one causal, clinically relevant, drug-genotype specific ADR, attributable to the index drug.(12 weeks)
- Number of serious self-reported ADRs(12 weeks)
- Health care expenditure related to adverse events using MBS/PBS data(12 months)