dru cymru central laboratory · 2019-05-22 · dru cymru laboratory originally based in cardiff in...

DRU Cymru Central Laboratory

Dr Gareth Dunseath, Manager – Accredited Central Laboratory


DRU Cymru Laboratory

Originally based in Cardiff in Llandough Hospital then UHW before relocating to Swansea University in 2010

Currently housed in the Grove Building, Swansea University, Singleton Campus since mid-2017


The Lab team- who are we?

Lab Director Prof Steve Luzio

Lab Manager Dr Gareth Dunseath

Quality Facilitator Dr Charlotte Jones

Lab Project Manager Dominic Bright

Molecular Biology Dr Sarah Prior / Dr Rachel Churm


Our aim

to provide a high quality service specialising in tests relevant to diabetes and endocrinology research. In addition tothis analysis service, we are able to support the development and testing (including validation) of new devices.

What we can provide:

• Setup advice

• Provision of sample collection kits with sample labels

• Sample collection / Lab manuals

• Sample transport arrangement (ambient / chilled / frozen)

• Sample analysis using a variety of methods

• Customised results reporting

• Sample storage at -20 / -80°C in freezers linked to temperature loggers and alarms

• Biobanking


Good Clinical and Laboratory Practice (GCLP) Accreditation

• Demonstrates that the DRU Cymru Lab complies with Good Clinical andLaboratory Practice (a quality system for laboratories analysing samples fromClinical Trials) and operates to a standard that maintains patient confidentialityand ensures their rights while also demonstrating the reliability, quality andintegrity of the data that we produce.

• GCLP Accreditation first achieved in 2007 following a 2 day external audit

• Successfully re-accredited in 2008/9 2011, 2012, 2014, 2016 and early 2019


What does GCLP cover?

• Samples

• Equipment

• Analysis

• Quality control

• Results reporting

• Project management

• Staff training

• Audits

• Logistics

• Contracts/agreements


Facilities- Technology available

• Clinical Chemistry analyser • Fully automated• Semi automated

• HPLC Laboratory HbA1c analyser

• Glucose/lactate analyser (‘Gold Standard’ method)

• Automated ELISA workstations

• ELISA photometric plate reader

• Chemiluminescence plate reader

• Point of Care Analysers (PoCT)• Hba1c• Urinalysis

• Fridges/Freezers (-20 and -80°C)

• 24/7 external temperature monitoring with alarms (via text /email)• Sample tracking and barcoding software



• Sample tracking/logging software with barcoding

• Exact location and details of individual samples recorded- allows us to comply with HTA regulations



External temperature monitoring

Results constantly uploaded to a websiteallowing a ‘live’ view of the temperatures



External temperature monitoring

When things go wrong:

When temperatures are outsidepre-set limits, text and email alertsare sent to all lab users


Lab manuals

Customised lab manuals with instructions/details for study teams (including e.g. sample collection details, storage, sample shipping, stock ordering etc.)


Results reporting

• Customised to suit the needs of the client:

• Single, signed results sheets through to large spreadsheets

• All results are verified by a second lab member before submission

Participant

ID

Visit

number

Sample

timepoint

Glucose Insulin C-

peptide

Cortisol NEFA D-

Hydroxybutyrate

mmol/L pmol/L pmol/L ng/ml mmol/l mmol/l


Who do we work with?

Collaborations with / support to:

• Universities

• NHS

• Pharmaceutical companies

• Diagnostics and Device manufacturers

• Other SMEs


Study support

Currently we are providing laboratory support to around 15 diverse studies, both in set-up and ongoing:

• 2 large multicentre studies in T1DM (UK wide)

• 1 study with 2 study sites (Cardiff/Sweden)

• Nutritional study (Sri Lanka)

• Technology development/validation study with Welsh SME

• 2 studies leading to PhD

• Biomarker study in Gestational Diabetes Mellitus

• Development of a novel treatment for managing T2DM using faecal microbiota transplantation

• Cardiovascular health in prison population


Studies supported – Clinical Trials

Closed Loop from Onset in type 1 Diabetes - ‘CLOuD’

Assessing the effect of closed loop insulin delivery from onset of T1DM in youth on residual beta-cell function versus standard insulin therapy

• NIHR EME funded study

• Multicentre study aiming to recruit approximately 100 participants

• Newly diagnosed with T1DM and aged less than 18

• Each participant in study for 2 years (plus 1 year extension)

• DRU Cymru Lab providing sample collection equipment (tubes, labels, lab manuals etc)

• Organising periodic frozen sample collection from sites using courier service

• Analysing HbA1c (every 3 months) and C-peptide and glucose from MMTT (every 6 months)

• So far analysis on over 1200 glucose and C-peptide samples and almost 500 HbA1c samples


Studies supported – Clinical Trials

USTEKID study

Phase II multi-centre, double-blind, randomised trial of Ustekinumab in adolescents with new-onset type 1 diabetesto determine the efficacy of Ustekinumab for preserving Mixed Meal Tolerance Test (MMTT) stimulated 2-hour insulin C-peptide area under the curve (AUC) at week 52 as compared to placebo.

• NIHR EME funded study

• Multicentre study aiming to recruit approximately 72 participants

• Newly diagnosed with T1DM and aged less than 18

• Dosed within first 100 days of diagnosis

• DRU Cymru Lab measuring eligibility screening samples for beta-cell autoantibodies and MMTT C-peptide levels

• Batch analysing additional autoantibody samples, HbA1c, MMTT samples and dried blood spot C-peptide levels

• As of 2nd May, 6 participants randomised


Studies supported – Device Trials

Study of the Accuracy of the SmartSensor telemed (SSt) Oral Glucose Tolerance Test (OGTT) Device

Single use, disposable OGTT device, offering the potential for an OGTT to be performed at home / community setting

• All instructions provided

• Device has 2 glucose dehydrogenase strips (0 hour and 2 hour)

• User activated buttons

• Procedure driven by internal clock/timer with audible and visible prompts

• Results not displayed but stored on a detachable data record

Long term relationship with manufacturer, have worked on several previous version of the device


Study of the Accuracy of the SmartSensor telemed (SSt) Oral Glucose Tolerance Test (OGTT) Device

to determine the accuracy of the SSt OGTT Device in comparison to two laboratory reference methods using blood samples obtained during an OGTT

• 100 participants (with and without glucose intolerance)

• Attended Joint Clinical Research Facility (JCRF) having fasted overnight

• At time 0, a fingerprick blood sample was taken and applied to the 0 hour glucose strip

• A corresponding venous glucose sample taken for reference laboratory glucose measurement (2 analysers)

• A 75 gram glucose drink was consumed

• Process repeated after 2 hours

• Data record removed, scanned and results uploaded to a database

• Results and diagnosis compared to reference laboratory


Published in Diabetic Medicine April 2019

Results

• Easy to use with 98% success rate

• Excellent agreement between device and reference laboratory analyser

glucose concentrations

• Excellent agreement between device and reference laboratory diagnosis

Glucose

intolerant by:

Device

N Sensitivity Specificity

FPG

(≥6.1mmol/l)

98 1.000 0.988

2 hour PG

(≥7.8mmol/l)

96 0.900 0.987


Studies supported – Device Trials

Glucose meter studies to International Organisation for Standardisation (ISO) guidelines

When used properly glucose monitoring may allow the user to take action to control the amount of glucose present in the blood


Glucose meter studies to ISO guidelines

e.g. • Menarini• GlucoRx• Agamatrix• Mendor

Why is this needed?

New ISO guidelines (ISO15197) have been introduced to establish acceptable performance

95% of individual glucose meter results should fall within ± 15% of the ‘gold standard’ measurement procedure at glucose concentrations ≥5.55 mmol/L

and/or 95% with ± 0.83 mmol/L of the ‘gold standard’ measurement procedure at glucose concentration <5.55 mmol/L


To determine the system accuracy of blood glucose meters in comparison to the laboratory reference method

What is done for the study?

1. Approximately 100 volunteers recruited to allow glucose concentrations to cover a wide concentration range

2. Fingerprick performed using a lancet

3. Capillary blood collected into a capillary collection tube

• Centrifuge

• Measure glucose on reference laboratory analyser

4. Multiple measurements made on study glucose meters

5. Repeat step 3

6. Accept results if the 2 reference laboratory glucose results are within 0.22mmol/L (at glucose concentrations

<5.55mmol/L) or within 4% (glucose concentrations ≥5.55mmol/L)

7. Data assessed by ‘bias’ and in ‘error grids’


Example results


Alternative sampling techniques

Finding ways to increase the convenience and comfort of collecting samples from patients and study participants, especially when samples are required at multiple visits over an extended period of time

• Typically many tests require a venous blood sample

• Require trained staff for sample collection

• Participant needs to attend a clinical site for each sample collection

Currently DRU Cymru Lab are investigating alternative methods of sample collection for some of our more common biological markers, including different sample types (e.g. capillary blood and urine) and also ‘microsampling’ methods, where very small ‘fingerprick’ capillary blood samples are collected onto specialised collection devices.

• Can these samples be collected easily by participants from home?

• Can these samples be sent to DRU Cymru Lab through the postal system without any stability issues?

• What new markers can be measured from samples collected in this way?


Alternative sampling techniques

‘Fingerprick’ capillary blood

• Dried Blood spots (DBS)

• Volumetric Absorptive Microsampling (VAMS™) - Mitra®


Contact details:

Diabetes Research Unit Cymru Laboratory Ground floor, Grove buildingSwansea UniversitySingleton ParkSwanseaSA2 8PP

[email protected]

www.diabeteswales.org.uk/en/lab


mailto:[email protected]

http://www.diabeteswales.org.uk/en/lab

dru cymru central laboratory · 2019-05-22 · dru cymru laboratory originally based in cardiff in...

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