NHS Digital Reform:Enabling Clinical Trials?

Presented by Jason Wakelin-SmithSenior GCP & GLP Inspector, MHRA

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NHS IT – Back on the Agenda

Common message:“The ability to collect, aggregate and analyse the data generated by the NHS is not only critical to delivering the triple aims of healthcare, but also underpins the NHS and wider life sciences research strategies”

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Moving with the Times?

eSystems

eTMF

eRX

eHR

eSource

eCRF

ePRO

• Organisation’s own systems

• Sponsor provided systems

• Equipment and associated software

• Supporting systems

*

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Bring Your Own Device / Wearables

• Data collection / compliance assessment

• Metadata supporting primary data

• Data protection concerns?• Source data? • Investigator – control of

data?• Archiving and retention?

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Primary Objective

To ensure that whichever solutions are chosen by each organisation include the capabilities to support the conduct of clinical trials in terms of:• Operational requirements• Regulatory requirements• Data integrity expectations• Realistic processes

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Worst Case Scenario?

That data generated using the electronic systems could not be used to support clinical trials

That the electronic systems had not been designed to meet the requirements of clinical research and work-arounds are required

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“If it’s not good enough for clinical trials…”

• Joint MHRA / DH Position statement on EHR (Sep 15)

• Sent to Trust CEOs• DH considered that if the

EHR was not fit for purpose for clinical trials then it would not be fit for purpose for routine clinical care

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An electronic parallel? eTMF

Similar idea to that of the eHR– an electronic repository of trial data & documents

• Critical findings• Return visits• Significant amount of

work to resolve issues

“Where provision of the Trial Master File (TMF) does not

comply with Regulation 31A 1-3, as the TMF is not readily

available or accessible, or the TMF is incomplete to such an extent that it cannot form the

basis of inspection and therefore impedes or obstructs

inspectors carrying out their duties in verifying compliance

with the Regulations”

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R&D Involvement?

• User requirements specification?• User acceptance testing?• Ways of working• Tailored requirements specific for CTIMPs?• Regulatory requirements and expectations• Risks?

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Considerations: Standard Requirements

• Physical security• Restricted access• Managed permissions• Data protection• Back-up & recovery

Consider from CTIMP point of view!

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Considerations: CTIMPs

• System to include CTIMPs• Audit trails to exist, be useful &

user-friendly• Amendments & additions to entries

to be obvious and require appropriate sign-off

• Investigator oversight / review of entries and data (e.g. labs, imaging)?

• Blinding• Archiving & retention

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Process Design

ALCOA

Proportionate risk-based controls Ease of data

recording

Enables event reconstruction

Source data review

Principles equally applicable to paper and electronic systems

AttributableLegibleContemporaneousOriginalAccurate

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Considerations: Live System

• Trust oversight of CTIMP requirements and processes inc.data integrity

• Processes & procedures

• Training

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Multiple Systems• How do they fit together?• Touch points?• Dependencies & data

transfers• Access• Can you answer – “what

constitutes the patient’s medical record and where can the components be found”?

• System maps

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Considerations: External Requirements

• External access:• Monitoring / audit• Inspection

• Exports of data?• Blinding & QC of

exports

“The printouts present in the investigator files for trial subjects were not always an accurate reflection of the

database content and the audit trails are not systematically printed and made available”

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Patient Confidentiality

• Trial specific access• Read-only access• Appropriate

permission set• Access to audit trails• Across systems /

links?

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Patient Confidentiality

• Trial specific access• Read-only access• Appropriate

permission set• Access to audit trails• Across systems /

links?

Current Work-around:• CRA provided with a

site access to EHR• Agreement to only view

trial patients• Site review of patient

records accessed• Company disciplinary

process• à Trust based

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Audit trail example02 July 2014 ‘Inclusion criteria = COPD diagnosed > 3 months ago. FEV1 48% (PRE-bronchodilator).mMRC score >1. No exacerbations in last 12/12’

Visit 110 July 2014 ‘‘Inclusion criteria = COPD diagnosed > 3 months ago. FEV1 48% (PRE-bronchodilator).mMRC score >1. No exacerbations in last 12/12. Current COPD Rx = nil’

Post monitoring visit when eligibility queried03 October 2014 ‘Inclusion criteria = COPD diagnosed > 3 months ago. FEV1 48% (PRE-bronchodilator).mMRC score >1. No exacerbations in last 12/12. Current COPD Rx = Ventolin PRN’

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Example: Scanning• Queries & concerns raised

about Trusts who were digitising medical records and then destroying the originals

• MHRA/DH Expectations: • Creation of certified copies• Mapping of content• Audit trails of creation,

amendment and deletion• Continuing access

• Advise original records retained. Could destroy originals (but at risk)

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Scanning Issues

• Lack of robust QC process

• Scan order / missing sections

• Scan resolution / image capture

• Metadata / colour• Outsourcing & oversight• Search (image vs OCR)

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Data Integrity

The extent to which all data are complete, consistent and accurate throughout the data lifecycle*

* from initial data generation and recording, through processing (including transformation or migration), use, retention, archiving and retrieval.

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Risk Reduction Strategies

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Summary

• The digital age is here and is to be embraced• We already work within a semi-digital CT world• Imperative that research/CTIMPs are considered early

in the design and procurement phase• You cannot ignore CT requirements• You will need to provide the necessary inputs and be

able to influence the direction of travel• You need to understand and be able to explain the

systems in use• Its not just about obtaining and commissioning the

system – it will need oversight and maintenance• Increased focus on data integrity

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ReferencesICH E6 (R2)http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2009/09/WC500002874.pdf

E-Source Reflection Paperhttp://www.ema.europa.eu/docs/en_GB/document_library/Regulatory_and_procedural_guideline/2010/08/WC500095754.pdf

MHRA Electronic Health Records Position Statementfile:///H:/Electronic%20Health%20Records_MHRA%20Position%20Statement_Final%20(1).pdf

MHRA Data Integrity Guidance Documenthttps://www.gov.uk/government/news/mhra-gxp-data-integrity-definitions-and-guidance-for-industry

MHRA Inspectorate Blog https://mhrainspectorate.blog.gov.uk/https://mhrainspectorate.blog.gov.uk/2017/04/20/computer-system-validation-gcp/

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MHRA Sources of Information

GCP Guide Inspectorate Blog GCP Forum

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