An EQA Scheme for TPMT Activity and Thiopurine Metabolites

Collection of Blood Samples for Use in an External Quality Assurance (EQA) Scheme for Thiopurine S-methyl Transferase (TPMT) Activity and Thiopurine Metabolites, 6-thioguanine Nucleotides (6TGN) and 6-methyl Mercaptopurine Nucleotides (6MMPN).

Participation in EQA schemes, where available, is mandatory for the United Kingdom Accreditation Service (UKAS). No EQA scheme currently exists for TPMT and thiopurine metabolites, which is a potential shortcoming of these tests. A pilot of this project has been awarded funding by Clinical Pathology Accreditation (CPA).

The purpose of this work is to collect samples for an EQA scheme for whole blood TPMT (activity and genotype) and thiopurine metabolites, which will be run in collaboration with UK NEQAS (United Kingdom National External Quality Assessment Service), and facilitate a comprehensive world-wide service that enables laboratories providing these tests to fulfil quality goals and ultimately provide optimal patient care.

Study Overview

• Status: Unknown
• Conditions: External Quality Control; Thiopurine S-methyl Transferase (TPMT)
• Intervention / Treatment: Diagnostic test: Quality control - enzyme activity

Detailed Description

The thiopurine S-methyl transferase (TPMT) enzyme is involved in the breakdown of thiopurine drugs (such as azathioprine), which are commonly used to treat inflammatory bowel disease and autoimmune diseases. Different individuals in the population have different, genetically determined, levels of TPMT. An individual with absent TPMT activity has a high risk of serious side effects from thiopurine drug treatment. In routine practice, TPMT activity in the blood is measured before starting patients on thiopurine drugs to determine an effective and safe starting dose.

Thiopurine metabolites are the breakdown products of thiopurine drugs and are monitored in the blood of patients on thiopurine drugs to optimise their drug dose.

These tests are performed by laboratories across Britain and around the world. It is important for patient care that the results are of high quality and consistent across different centres. One way of assessing this is through an EQA scheme. No EQA scheme currently exists for TPMT/thiopurine metabolites, which is a potential shortcoming of the tests.

Venous blood collected from NHS staff volunteers and SWBH outpatients, who have had TPMT measured as part of their routine care, will be distributed to participating laboratories every two months. Where it is not possible to find suitable blood donors, pooled surplus blood samples from the laboratory will be used instead. The laboratories will test the samples and return results to UK NEQAS for comparison. A report will be compiled allowing them to compare themselves with other centres and make changes where necessary.

• Study Type: Observational
• Enrollment (Anticipated): 40

Contacts and Locations

Study Locations

• United Kingdom
  • West Midlands
    • Birmingham, West Midlands, United Kingdom
      • Recruiting
      • Department of Biochemistry, City Hospital
      • Contact: Jenna Waldron, FRCPath; Phone Number: 01215075025; Email: jenna.waldron@nhs.net
      • Contact: Jonathan Berg, FRCPath; Phone Number: 01215075345; Email: jonathanberg@nhs.net

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Interested staff working within the Pathology Department at SWBH NHS Trust

A list of SWBH NHS Trust patient TPMT results will be gathered from the Pathology computer system. Those with a TPMT activity of interest, measured in the past five years, will be contacted with the agreement of their hospital consultant.

Description

Inclusion Criteria:

• Pathology staff member - able to donate 60 mL of venous blood.
• SWBH NHS Trust outpatients - have had TPMT activity measured within last 5 years. Consultant happy for them to be contacted. Able to consent and donate 60 mL of blood.

No known Hep B or C, HIV, syphilis or cytomegalovirus infection.

Exclusion Criteria:

• Donors for each distribution will be under no obligation to participate if they are no longer willing to. Only volunteers able to give informed consent themselves will be recruited (i.e. no children or adults lacking the capacity to consent themselves).

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Other

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
NHS staff volunteer donors; Interested staff working within the Pathology Department at SWBH NHS Trust will be provided with written information regarding the proposed EQA scheme and the sample collection procedure. A consent form will be given to staff members, who will be asked to return the signed form within 1 week if they wish to participate. Each participating staff member will be assigned a unique patient identifier to allow for sample results to be anonymised.	Diagnostic test: Quality control - enzyme activity; A blood sample will be collected from patients and staff donors, no more than twice per year.
SWBH outpatient donors; A list of SWBH NHS Trust patient TPMT results will be gathered from the Pathology computer system (Telepath). Those with a TPMT activity of interest, measured in the past five years, will be contacted with the agreement of their hospital consultant. Information and consent forms will be sent to the patient either through the post or via their hospital consultant. Each participating patient will be assigned a unique patient identifier to allow for sample results to be anonymised.	Diagnostic test: Quality control - enzyme activity; A blood sample will be collected from patients and staff donors, no more than twice per year.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
TPMT activity	TPMT activity will be determined by participating laboratories	5 years EQA scheme

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Thiopurine metabolites	Thiopurine metabolites will be determined by participating laboratories	5 years EQA scheme

Collaborators and Investigators

• Sponsor: Sandwell & West Birmingham Hospitals NHS Trust
• Collaborators: Birmingham Quality
• Investigators: Study Director: Jonathan Berg, FRCPath, MBA, SWBH, Pathology director

Publications and helpful links

Helpful Links

• Birmingham quality UK NEQAS
• SWBH Pathology laboratory

Study record dates

Study Major Dates

• Study Start (Actual): February 24, 2017
• Primary Completion (Anticipated): February 24, 2022
• Study Completion (Anticipated): February 24, 2022

Study Registration Dates

• First Submitted: November 5, 2015
• First Submitted That Met QC Criteria: November 5, 2015
• First Posted (Estimate): November 6, 2015

Study Record Updates

• Last Update Posted (Actual): April 25, 2017
• Last Update Submitted That Met QC Criteria: April 24, 2017
• Last Verified: April 1, 2017

More Information

Terms related to this study

• Other Study ID Numbers: IRAS 194310

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: Not applicable. Results will be analysed anonymised.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No