It is known that individuals respond differently to the same medicine with some people benefitting, some experiencing no effect and others suffering side-effects or even coming to harm. Some of the differences in response to medications can be explained by our genes. Genes are short sections of DNA. Each individual has over 20,000 different genes. Genes carry instructions for making the proteins needed to build things within the body including the sites where medicines act. Pharmacogenomics is the study of how our genes affect the way our body responds to medications.
Doctors can test for gene variations that might put an individual at risk of severe side-effects or mean that they are likely to receive no benefit from a specific medicine. Though not widely available in the NHS, testing allows doctors and patients to chose a different dose or avoid the medicine completely. It is estimated that almost everyone in the population (\>95%) carries at least one gene variation that affects our response to medicines.
The PHOENIX study will recruit 4,000 participants who are admitted to hospital or attend an outpatient clinic who require a new drug prescription. The new drug prescription will be one who known pharmacogenomic implications. A cheek (buccal) swab will be taken which can be used to test a large number of genes known to alter the response to medicines. Around half of the participants will be tested immediately whilst the other half will have the test after three months. The results of the test relevant to each patients new prescription will enable the doctor prescribing to determine if any changes to that medicine would be beneficial. Information will be collected about participants quality of life, subsequent admissions to hospital, medication changes and side-effects. An assessment of cost saving to the NHS will also be made.
Capable of giving informed consent directly or via a legal representative (e.g., next of kin, welfare guardian, health care power of attorney).
Participants who are newly prescribed one of the trial-eligible index drugs during their hospital stay may be approached for consent. Consent should be obtained within 3 days of the first dose of the index drug being administered. If there is a clear clinical plan documented on HEPMA indicating that the patient will be started on an eligible drug (but has not yet received the first dose), consent may be obtained in anticipation. However, formal trial enrolment will only occur once the first dose of the index drug has been administered.
Participant is able to provide a cheek swab
Participant is able to take part and be followed-up for at least 12 weeks.
Inability to give informed consent directly or via a legal representative.
Non-English speakers without translation support.
Participants co-enrolled in other trials where a medication is one of the index drug is part of the trial protocol.
Inability to give informed consent directly or via a legal representative.
Parallel
Pharmacogenomic testing
Diagnostic testThe PGx testing will analyse genetic variants across 16 key pharmacogenes in each given DNA sample, all of which focus on variants with established implications for drug response as recommended by published Clinical Pharmacogenetics Implementation Consortium (CPIC) and the Dutch Pharmacogenetics Working Group (DPWG) guidelines Testing will be performed immediately in the intervention arm or at three months in the standard of care arm.
Composite of ADRs and/or treatment failures
Composite of ADRS (CTCAE ≥2) and/or treatment failures (applies to specific drugs where treatment failure is captured by hospital admissions with the condition for which the index drug was commenced).
5-level EQ-5D version (EQ-5D-5L) EuroQol
Assess changes in quality of life using the EQ-5D-5L questionnaire administered monthly over three months to explore the impact of PGx-guided care on participants' overall well-being. The EQ-5D-5L questionnaire will comprise of ive dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems and extreme problems. The patient is asked to indicate his/her health state by ticking the box next to the most appropriate statement in each of the five dimensions. This decision results in a 1-digit number that expresses the level selected for that dimension. The digits for the five dimensions can be combined into a 5-digit number that describes the patient's health state. The EQ VAS records the patient's self-rated health on a vertical visual analogue scale where the endpoints are labelled 'The best health you can imagine' and 'The worst health you can imagine'. The VAS
PGx Result Utilisation in Intervention Arm
Measure the proportion of participants in the intervention arm who receive at least one drug/dose selection or modification based on PGx test results, offering insight into clinical application.
PGx Result Utilisation in Standard Care Arm (Post-Delayed Genotyping)
For participants in the standard care arm, determine the proportion who receive at least one drug/dose modification after delayed genotyping, highlighting the potential impact if PGx results were available at baseline.
Frequency of Actionable Genotypes at Baseline
Report the frequency of actionable genotypes that lead to drug/dose selection or modification of all drugs, including the index drug, at baseline.
Sub-group analysis- Age
Intervention effects on the primary and selected secondary outcomes will be compared between subgroups using interactions within regression models. Subgroups defined by the age of participants.
Sub-group analysis - Sex
Intervention effects on the primary and selected secondary outcomes will be compared between subgroups using interactions within regression models. Subgroups defined by the sex of participants.
Sub-group analysis- Scottish Index of Multiple Deprivation (SIMD)
Intervention effects on the primary and selected secondary outcomes will be compared between subgroups using interactions within regression models. Subgroups defined by the SIMD of participants.
Sub-group analysis- Ethnicity
Intervention effects on the primary and selected secondary outcomes will be compared between subgroups using interactions within regression models. Subgroups defined by the ethnicity of participants.
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NHS Greater Glasgow and Clyde
Lead sponsor
University of Glasgow
Collaborator
