A study to assess the usefulness of using genetics to improve prescribing
| ISRCTN | ISRCTN14050335 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN14050335 |
| IRAS number | 305751 |
| Secondary identifying numbers | NIHR301748, IRAS 305751, CPMS 51741 |
- Submission date
- 14/06/2022
- Registration date
- 23/06/2022
- Last edited
- 08/05/2025
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Other
Plain English summary of protocol
Background and study aims
There is a growing understanding that the effectiveness and safety of many regularly prescribed medications can be influenced by common genetic changes. This is a concept known as pharmacogenetics (PGx). Despite this awareness, testing for these genetic changes is rarely done in the UK prior to prescribing. One reason for this is that it is not well understood what proportion of patients who have these genetic changes, also take the related medicines. This study aims to resolve this issue. By linking individuals' historical prescribing records with genetic data, this study will aim to better understand the clinical usefulness of genetic testing before prescribing and help to determine whether this should be done on a routine basis in the NHS.
Who can participate?
People aged over 18 years admitted to the Manchester University NHS Foundation Trust or attending an outpatient appointment, as a patient or relative, at the Manchester University NHS Foundation Trust.
What does the study involve?
Participants complete a short consent form and a sample of blood (3 ml) will be taken on the same day by a trained member of the research team. This will occur during their stay in MRI or during their outpatient appointment (if applicable). Basic demographic details will be collected during this time. This consent and sample/data collection process should take no more than 30 minutes. Beyond this, participants won’t be asked to do anything further for the study or attend any future study visits.
DNA will be extracted from the blood sample and stored in the Manchester Centre for Genomic Medicine, a specialist NHS genetics laboratory which performs genetic testing for the North West of England. The DNA sample will then be tested for about 75 genetic changes which are thought to be related to how well medicines work. All participants will have details about their past medical and drug history collected from the Greater Manchester Care Record (GMCR). Their medication data and genetic data will then be linked in a secure database. This data will be pseudo-anonymised, meaning that the researcher analysing the data will not know whose data they are looking at. Analysis of this final database will help researchers to understand the usefulness of pharmacogenetic testing.
What are the possible benefits and risks of participating?
Taking part in this study will help academics and clinicians understand whether this type of service should be rolled out in clinical practice. No genetic data will be reported to patients, as this type of pharmacogenetic information has not yet been approved for clinical use. Participants will not receive payment for taking part in the project.
Where is the study run from?
University of Manchester (UK)
When is the study starting and how long is it expected to run for?
October 2021 to October 2024
Who is funding the study?
National Institute for Health Research (UK)
Who is the main contact?
Dr John McDermott, john.mcdermott@mft.nhs.uk
Contact information
Principal Investigator
Manchester Centre for Genomic Medicine
Manchester University Hospitals NHS Foundation Trust
Oxford Road
Manchester
M13 9WL
United Kingdom
 ORCID ID |
0000-0002-5220-8837 |
|---|---|
| Phone | +44 (0)161 701 4912 |
| john.mcdermott@mft.nhs.uk |
Study information
| Study design | Cross-sectional trial |
|---|---|
| Primary study design | Observational |
| Secondary study design | Cross sectional study |
| Study setting(s) | Hospital |
| Study type | Screening |
| Participant information sheet | Not available in web format, please use the contact details to request a participant information sheet |
| Scientific title | A cross-sectional trial assessing the clinical utility of pre-emptive pharmacogenetic testing in primary and secondary care: the Implementing Pharmacogenetics to Improve Prescribing (IPTIP) trial |
| Study acronym | IPTIP |
| Study objectives | If a pre-emptive pharmacogenetic test were implemented, what proportion of patients would have their prescriptions adjusted based on the results? |
| Ethics approval(s) | Approved 25/02/2019, HRA and Health and Care Wales (HCRW, Castlebridge 4, 15 - 19 Cowbridge Rd E, Cardiff, CF11 9AB, UK; Tel: not available; approvals@hra.nhs.uk), ref: 22/PR/0012 |
| Health condition(s) or problem(s) studied | Pre-emptive pharmacogenetic testing |
| Intervention | This is an observational study recruiting across two study arms, inpatient (IPTIP-I) and outpatient (IPTIP-O). The information gathered at recruitment will be sufficient for the electronic platform to generate a study ID, allowing 3 ml of EDTA blood to be taken and labelled with the IPTIP study ID only. EDTA blood samples will then be transported to the Manchester Centre for Genomic Medicine via existing and secure clinical pathways for internal specimen transport. There, DNA will be extracted and quantified by the North West Genomic Laboratory Hub (NW-GLH), an NHS ISO15189 accredited laboratory. DNA samples will be labelled with the Study ID and stored at -20°C until genotyping. Genotyping will be undertaken using the AgenaTM iPLEX PGx 74 assay. This pre-designed assay targets frequent and clinically relevant variants across 20 pharmacogenes. Following source data collection, with participant consent, study ID, identifiable demographic, and inpatient prescribing data will be shared with Graphnet CareCentric who operate the Greater Manchester Care Record (GMCR). These records will then be linked with outpatient prescribing data from within the GMCR and deposited as a pseudonymised dataset (labeled with study ID only) available for analysis by the research team within Graphnet’s secure data analysis environment. Participant genotype will then be added to the final dataset within the secure research environment, linked by the Study ID. The final pseudonymised dataset will contain the study ID, medicine history, participant genotype and metabolizer status. This will allow an assessment of the primary and secondary outcomes for the trial. The proportion of patients with a genotype related to a medicine they are currently, or have previously been, prescribed. Genotype-phenotype relationships will be assigned where there is high-level PharmGKB evidence for clinical actionability (Levels 1A or 1B). Rates for the whole cohort will be presented but will be split by recruiting site and by age. These measures will be used to quantify the potential clinical utility of pre-emptive PGx testing in different settings, directly informing policy decisions around the implementation of PGx nationally. In addition to the primary outcome, baseline characteristics will be presented. Medicine exposure by British National Formulary (BNF) class will be presented with sub-analysis by age group, sex, and the presence of recorded co-morbidities. Analysis will be presented for the whole cohort, and separately for inpatient and outpatient arms. Genotype and metaboliser frequencies, derived using Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines, will be presented for the whole cohort. These frequencies will then be analysed by age, sex, and ethnicity. Analysis will be presented for the whole cohort, and separately for inpatient and outpatient arms. Statistical differences in genotype based on demography, or recruiting site, will be tested via ANOVA or independent t-test. Genotype frequencies will be compared against an independent control cohort, generated as part of an ongoing trial, genotyping 1500 patients from the TARDIS Trial. This will allow for comparison as to whether the dataset generated in this fellowship is consistent with others around the country, so clarifying generalizability. Finally, the predictive value of patient variables, such as age, co-morbid status, or ethnicity, for exposure to medicines where pharmacogenetic guidelines exist will be determined. This will be used to assess whether these variables, either in isolation or in combination, could be used to define a targeted screening approach for pharmacogenetics. |
| Intervention type | Genetic |
| Primary outcome measure | The proportion of patients with an actionable genotype related to a medicine they are currently, or have previously been, prescribed. Genotype-phenotype relationships will be assigned where there is high-level PharmGKB evidence for clinical actionability (Levels 1A or 1B). This will be expressed as a percentage of the whole study cohort (i.e. number of individuals with an actionable variant receiving a corresponding medicine/the total study cohort). Sub analyses will be undertaken by age and comorbid state. For the inpatient cohort (IPTIP-I) hospital prescriptions will be assessed at a single timepoint during the admission following recruitment. For both cohorts (IPTIP-I and IPTIP-O), Historical GP medicine records will be accessed at a single timepoint after recruitment has closed. Genetic data will be generated for all participants once recruitment has closed. |
| Secondary outcome measures | Current secondary outcome measures as of 16/10/2023: 1. Medicine exposure by British National Formulary (BNF) class will be presented with sub-analysis by age group, sex, and the presence of recorded co-morbidities. Analysis will be presented for the whole cohort, and separately for inpatient and outpatient arms. This will be presented as a percentage of individuals within the whole cohort, or given sub-group, exposed to a particular medicine class. 2. Genotype and metaboliser frequencies, derived using CPIC guidelines, will be presented for the whole cohort. These frequencies, presented as percentages, will then be analysed by age, sex, and ethnicity. 3. Clinical outcomes based on the presence of clinically relevant variants (primary outcome measure) measured using analysis of the patient's healthcare record. For the inpatient cohort (IPTIP-I) hospital prescriptions will be assessed at a single timepoint during the admission following recruitment. For both cohorts (IPTIP-I and IPTIP-O), Historical GP medicine records will be accessed at a single timepoint after recruitment has closed. Genetic data will be generated for all participants once recruitment has closed. Previous secondary outcome measures: 1. Medicine exposure by British National Formulary (BNF) class will be presented with sub-analysis by age group, sex, and the presence of recorded co-morbidities. Analysis will be presented for the whole cohort, and separately for inpatient and outpatient arms. This will be presented as a percentage of individuals within the whole cohort, or given sub-group, exposed to a particular medicine class. 2. Genotype and metaboliser frequencies, derived using CPIC guidelines, will be presented for the whole cohort. These frequencies, presented as percentages, will then be analysed by age, sex, and ethnicity. For the inpatient cohort (IPTIP-I) hospital prescriptions will be assessed at a single timepoint during the admission following recruitment. For both cohorts (IPTIP-I and IPTIP-O), Historical GP medicine records will be accessed at a single timepoint after recruitment has closed. Genetic data will be generated for all participants once recruitment has closed. |
| Overall study start date | 01/10/2021 |
| Completion date | 04/10/2024 |
Eligibility
| Participant type(s) | Mixed |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | 646 |
| Key inclusion criteria | 1. Participants must be admitted to the Manchester University NHS Foundation Trust or attend an outpatient appointment, as a patient or relative, at the Manchester University NHS Foundation Trust 2. Participants must have the capacity to independently consent 3. Patients must be over the age of 18 years |
| Key exclusion criteria | 1. Patients unable to independently consent 2. Patients under the age of 18 years |
| Date of first enrolment | 04/07/2022 |
| Date of final enrolment | 03/10/2024 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centres
Oxford Road
Manchester
M13 9WL
United Kingdom
Manchester
M13 9WL
United Kingdom
Sponsor information
University/education
Oxford Road
Manchester
M13 9PL
England
United Kingdom
| Phone | +44 (0)161 306 6000 |
|---|---|
| doctoralacademy@manchester.ac.uk | |
| Website | https://www.manchester.ac.uk |
"ROR" |
https://ror.org/027m9bs27 |
Funders
Funder type
Government
Government organisation / National government
- Alternative name(s)
- National Institute for Health Research, NIHR Research, NIHRresearch, NIHR - National Institute for Health Research, NIHR (The National Institute for Health and Care Research), NIHR
- Location
- United Kingdom
Results and Publications
| Intention to publish date | 01/10/2024 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Stored in publicly available repository |
| Publication and dissemination plan | Findings, positive or negative, will be published in open access peer reviewed journals and presented at international conferences. A dedicated PPIE dissemination strategy will be developed with the PPIE VOCAL team at the Manchester University NHS Foundation Trust. |
| IPD sharing plan | An anonymised version of the genetic dataset will be stored in a data repository with no limitations on access or use. Genotype data will be deposited in the Figshare repository (https://figshare.com/) at the end of the study following publication. Data will be open access and will be entirely anonymised, with no study ID. There are no restrictions on access to the data. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| HRA research summary | 28/06/2023 | No | No | ||
| Protocol file | version 5.3 | 21/09/2023 | 16/10/2023 | No | No |
| Statistical Analysis Plan | version 5.3 | 21/09/2023 | 16/10/2023 | No | No |
| Interim results article | 17/10/2024 | 12/12/2024 | Yes | No | |
| Protocol article | 06/05/2025 | 08/05/2025 | Yes | No |
Additional files
Editorial Notes
08/05/2025: Publication reference added.
12/12/2024: Publication reference added.
09/04/2024: The intention to publish date was changed from 01/04/2024 to 01/10/2024.
16/10/2023: The following changes were made:
1. Protocol (not peer reviewed) and statistical analysis plan (SAP) uploaded.
2. The overall study end date was changed from 04/01/2024 to 04/10/2024.
3. The secondary outcome measures were changed.
4. The recruitment end date was changed from 03/07/2023 to 03/10/2024.
04/07/2022: Internal review.
16/06/2022: Trial's existence confirmed by the HRA.
