Study to assess the rollout of a genetic-guided prescribing service in UK General Practice

ISRCTN	ISRCTN15390784
DOI	https://doi.org/10.1186/ISRCTN15390784
ClinicalTrials.gov (NCT)	Nil known
Clinical Trials Information System (CTIS)	Nil known
Integrated Research Application System (IRAS)	319800
Protocol serial number	CPMS 55532, IRAS 319800
Sponsor	Manchester University NHS Foundation Trust
Funders	National Institute for Health and Care Research, NHS England

Submission date: 14/02/2023
Registration date: 19/04/2023
Last edited: 18/10/2024

Recruitment status: Recruiting
Overall study status: Ongoing
Condition category: Other

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

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. Although there are guidelines in place for genotype-guided prescribing for many gene-drug pairs, very few are used in practice as previously, genetic testing could not be turned around in a clinically relevant timeframe.

The PROGRESS trial is part of a programme of work to introduce pharmacogenetic testing in general practice and to assess the implementation of this new service. A panel of genes with known implications for a range of commonly prescribed medicines has been selected and an informatic solution to help guide prescribing has been developed called the Genomic Prescribing Advisory System (GPAS). This pharmacogenetic testing and advisory system will be implemented at a number of GP practices to establish whether genetic testing can be delivered to support genotype-guided prescribing in a clinically relevant timeframe.

Who can participate?
The study is recruiting over two phases. In phase one (months 1-6), five “early-adopter” sites will invite patients who are being considered for 4 classes of medicine as part of their routine appointment. These medicines include Statins, Proton Pump Inhibitors, Selective Serotonin Reuptake Inhibitors, and Tricyclic Antidepressants.

What does the study involve?
Participants would be required to donate a blood or saliva sample for genetic testing, with the aim to return results to the GP within 7-10 days. Patients will be alerted by their GP once results are available and a prescription can be issued. In the second phase (months 7-18), additional sites across the country will be included. The study is designed to identify any challenges in implementing this service as well as collect information on patient and health care professional’s attitudes to using the service.

What are the possible benefits and risks of participating?
Participants will benefit from having access to a new clinical service which is under consideration by the NHS, which allows medicines to be optimized for an individual based on their unique genetic information. By taking part, information will be generated which may inform safer, more effective prescribing for the current problem but also remain in the participant's health record to inform any future prescribing decisions. The intervention is low risk, with a single blood or saliva sample required for DNA testing.

Where is the study run from?
The study is run by Clinical Geneticists based at Manchester University NHS Foundation Trust, in partnership with the North West Genomic Medicine Service Alliance (GMSA). Recruiting sites will be a selection of GP practices, initially in the North West of England (Phase I) and later rolled out to GP practices across the UK (Phase II).

When is the study starting and how long is it expected to run for?
April 2022 to April 2026

Who is funding the study?
The study is funded by NHS England with support from the National Institute for Health Research (NIHR) (UK)

Who is the main contact?
Professor William Newman (Chief Investigator)
william.newman@manchester.ac.uk

Contact information

Prof William Newman
Principal investigator

Manchester Centre for Genomic Medicine
6th Floor, St Mary's Hospital
Oxford Road
Manchester
M13 9WL
United Kingdom

ORCID ID	0000-0002-6382-4678
Phone	+44 1612766276
Email	william.newman@manchester.ac.uk

Prof William Newman
Scientific

Manchester Centre for Genomic Medicine
6th Floor, St Mary's Hospital
Oxford Road
Manchester
M13 9WL
United Kingdom

Phone	+44 1612766276
Email	william.newman@manchester.ac.uk

Ms Amy Ingham
Public

Manchester Centre for Genomic Medicine
6th Floor, St Mary's Hospital
Oxford Road
Manchester
M13 9WL
United Kingdom

Phone	+44 1617019140
Email	amy.ingham@mft.nhs.uk

Dr John McDermott
Scientific

NIHR Doctoral Fellow
Manchester Centre for Genomic Medicine
University of Manchester
Manchester
M13 9WL
United Kingdom

ORCID ID	0000-0002-5220-8837
Phone	+44 (0)1612765606
Email	john.mcdermott@mft.nhs.uk

Study information

Primary study design	Interventional
Study design	Pragmatic interventional implementation study
Secondary study design	Non randomised study
Study type	Participant information sheet
Scientific title	Pharmacogenetics Roll Out – Gauging Response to Service
Study acronym	PROGRESS
Study objectives	To assess the implementation of a pharmacogenetic guided prescribing service in UK primary care.
Ethics approval(s)	Approved 20/03/2023, London - Surrey Research Ethics Committee (Level 3, Block B, Whitefriars, Lewins Mead, Bristol, BS1 2NT, UK; +44 2071048388; surrey.rec@hra.nhs.uk), ref: 23/LO/0201
Health condition(s) or problem(s) studied	Assessment of pharmacogenetic guided prescribing across a range of commonly prescribed medicine classes, initiated in primary care.
Intervention	The PROGRESS trial is designed to assess the viability and utility of a pharmacogenetic-guided prescribing service in Primary Care. Potential participants attending their GP practice for a routine appointment, who are being considered for a pre-defined list of commonly prescribed agents, will be offered testing for a panel of genes with known implications for this range of medicines. Genetic results will be fed back to the referring clinician via a novel informatic solution developed as part of this programme, known as the Genomic Prescribing Advisory System (GPAS). Data will be collected around the proportion of participants with actionable pharmacogenetic information and service performance-related outcomes such as turnaround times for testing and metrics related to how results were used.
Intervention type	Genetic
Primary outcome measure(s)	The Pharmacogenetic Clinical Utility Metric (Defined as the proportion of patients across the study cohort with a CPIC Level 1A variant related to the medicine which triggered recruitment to the study) – determined through genetic testing as part of study
Key secondary outcome measure(s)	1. The proportion of patients recruited to the study who had their pharmacogenetic results returned within 10 working days (Monday – Friday) of enrolment. The day of enrolment represents day 0. Collected from patient records. 2. Average turnaround time from enrolment to PGx results being available on GPAS. Collected from patient records. 3. The proportion of enrolled patients whose GPAS system record was accessed by a member of the clinical team. Collected from patient records. 4. The proportion of participants who had a prescription issued before the pharmacogenetic results were available. Collected from patient records. 5. Average time from recruitment to prescription. Collected from patient records. 6. The proportion of patients who had at least one prescription amended over the course of the study based on the pharmacogenetic data. Collected from patient records. 7. Average turnaround time from enrolment to results being integrated into the Electronic Health Record (EHR). Collected from patient records. 8. Proportion of participants who have a delay (more than 10 working days) in results being integrated into the EHR. Collected from patient records. 9. The proportion of enrolled participants for whom a clinical decision support notification was triggered. Collected from patient records. 10. The average number of clinical decision support notifications which triggered over the course of the study (expressed as per month/visit/prescription). Collected from patient records. 11. The proportion of participants who had a prescription issued before the pharmacogenetic results were available. Collected from patient records. 12. The proportion of patients on a given class of medicine who had their index medicine (i.e., the medicine which precipitated recruitment) changed at 1 and 6 months following prescription. This outcome will be compared against anonymized historical (non-genotyped) comparators, matched for demographics, from the Greater Manchester Care Record (GMCR). Collected from patient records.
Completion date	01/04/2026

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	All
Target sample size at registration	1450
Key inclusion criteria	1. Participants must be a registered patient at one of the recruiting GP practices. 2. Participants must have capacity to independently consent. 3. Participants must be 18 years of age or over. 4. Participants must be being considered for a new prescription of one of four medicines classes, or participants being considered for an agent change within one of the four medicine classes. The eligible medicine classes (and specific medicines) are: 4.1. Selective Serotonin Reuptake Inhibitors [citalopram, escitalopram, fluvoxamine, paroxetine, sertraline] 4.2. Tricyclic Antidepressants (prescribed for pain or depression) [amitriptyline, clomipramine, doxepin, imipramine, nortriptyline, trimipramine] 4.3. Statin Therapy [atorvastatin, fluvastatin, pravastatin, rosuvastatin, simvastatin] 4.4. Proton Pump Inhibitors [esomeprazole, lansoprazole, omeprazole, pantoprazole, rabeprazole]
Key exclusion criteria	1. Patients unable to independently consent. 2. Patients under the age of 18 years.
Date of first enrolment	19/06/2023
Date of final enrolment	31/12/2025

Locations

Countries of recruitment

United Kingdom
England

Study participating centre

Manchester University NHS Foundation Trust

Manchester Centre for Genomic Medicine
6th Floor, St Mary's Hospital
Oxford Road
Manchester
M13 9WL
United Kingdom

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Data sharing statement to be made available at a later date
IPD sharing plan	The data sharing plans for the current study are unknown and will be made available at a later date.

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
HRA research summary			26/07/2023	No	No
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes
Protocol file	version 6.0	25/07/2024	18/10/2024	No	No

Additional files

ISRCTN15390784 PROGRESS Protocol V6.0 25.07.2024.pdf: Protocol file

Editorial Notes

18/10/2024: The following changes were made to the trial record:
1. Uploaded protocol (not peer-reviewed) as an additional file.
2. The recruitment end date was changed from 01/10/2024 to 31/12/2025.
02/06/2023: The recruitment start date has been changed from 05/06/2023 to 19/06/2023.
03/05/2023: The following changes have been made:
1. A scientific contact was added.
2. The recruitment start date has been changed from 01/05/2023 to 05/06/2023.
19/04/2023: Trial's existence confirmed by National Institute for Health and Care Research (NIHR) (UK).