. 2019 Oct 2;121(9):738–743. doi: 10.1038/s41416-019-0588-1

Table 1.

Challenges to the development and implementation of new molecular diagnostic tests and possible solutions to these

Challenge	Solutions
1. NHS commissioning and standardisation of testing
-Limited pathology budgets and current funding structures mean that tests that could improve patient outcomes (and even save money in the long term) may not be funded -Many different tests available (including for the same biomarker), leading to regional variation in testing -The timing of investigations within diagnostic/management pathways can influence the choice of the testing method -When a new therapy has been recommended by NICE, the NHS should commission funding for the companion diagnostic test, but this has not always been the case -Innovative tests that may have a disruptive effect on the local NHS pathways may be less likely to be adopted -Variation in how tissue samples are collected and processed and in how tests are performed and interpreted	-Lobbying for alternative funding sources and changes to how tariffs are allocated -Rigorous assessment of different tests, leading to greater understanding of their strengths and weaknesses, with the aim of uniform adoption of the optimal test -Within reason, flexibility should be encouraged in the new national testing system to ensure that patients have access to the most appropriate test at each point in their care pathway -Ensure that NICE and the NHS are aligned so that when a new therapy is recommended by NICE, there is timely uptake of any companion diagnostic test -Centralised commissioning of testing (as with the recent reconfiguration of genomic testing within the NHS) -Development of SOPs and regular participation in EQA schemes
2. Ethical and regulatory issues
-Requirement for ethical approval and consenting procedures during test development/clinical trials -Uncertainty about the necessary regulatory requirements (e.g. clinical trial authorisation, EU IVDR and US FDA approval) for new molecular diagnostic tests and accreditation of laboratories performing them (uncertainty greater within academia and NHS than within industry) -Uncertainty about how ‘Brexit’ will affect regulation of in vitro diagnostics in the UK (the IVDR, an EU regulation, came into effect in May 2017 and gave manufacturers 5 years to prepare for a new legislation that will require more rigorous assessment of in vitro diagnostic medical devices—it is currently unknown how ‘Brexit’ will affect this)	-Greater clarity with regard to when ethical approval and consent are and are not required (e.g. test development/validation vs. performance assessment of an already-validated test) -Encourage researchers to seek ethical approval at an early stage in test development -Encourage researchers, clinicians and NHS managers to interact with regulators at an early stage in test development and implementation (e.g. through MHRA’s innovation office)³² -Promotion of both UK²⁷ and European²⁸ regulatory guidelines -Lobbying for clarification of legislative/regulatory impact of ‘Brexit’ and possible exemptions from new EU regulations, when appropriate
3. Information technology
-Development of standardised, robust IT infrastructures -Data storage and sharing -Volume and complexity of data	-Investment in IT infrastructure, ensuring new software is compatible with existing ones -Consideration of technical, legal and ethical issues to ensure that data can be safely stored and shared for clinical and research purposes -Development of novel computational approaches (e.g. AI) to facilitate automated analyses
4. NHS culture
-Staff must be aware of emerging technologies and willing to adopt them -Patients should be educated and empowered to ensure that they receive appropriate molecular testing	-Improved nationwide dissemination of information about established/emerging tests and funding sources -Greater communication between specialties (such as at the MDT meeting), to encourage reflex testing by pathologists, when appropriate -RCPath to include NICE recommendations in their best-practice guidelines and datasets -Sharing of case studies demonstrating clinical benefit and cost-effectiveness -A national workshop involving clinical staff, laboratory scientists and NHS managers -Education and mentoring of patients and enhanced communication between patients, clinicians and pathologists (e.g. through the NCRI Consumer Forum)
5. Education/training
-Urgent need to upskill the NHS workforce in molecular diagnostics	-Inclusion of molecular diagnostics in UG medical curricula and increased prominence in PG training, including training of senior staff (CM-Path is actively working to develop training opportunities in molecular pathology)^19,20 -Cross-discipline and cross-sector training to include clinicians, pathologists, nurses, managers and industry -Identify best-practice examples in molecular diagnostic training from other countries
6. Monitoring of uptake/response
-Lack of systematic monitoring of molecular diagnostic testing in the NHS, leading to a knowledge gap regarding current practices across the UK -Lack of data regarding the clinical impact of test adoption	-NHS genomic reconfiguration to introduce a new molecular diagnostic test directory and commissioning system -Inclusion of molecular diagnostics in quarterly NHS England Innovation Scorecard produced by HSCIC -Mandatory recording of how new tests have influenced patient care (e.g. treatment allocation)

Challenge

Solutions

1. NHS commissioning and standardisation of testing

-Limited pathology budgets and current funding structures mean that tests that could improve patient outcomes (and even save money in the long term) may not be funded

-Many different tests available (including for the same biomarker), leading to regional variation in testing

-The timing of investigations within diagnostic/management pathways can influence the choice of the testing method

-When a new therapy has been recommended by NICE, the NHS should commission funding for the companion diagnostic test, but this has not always been the case

-Innovative tests that may have a disruptive effect on the local NHS pathways may be less likely to be adopted

-Variation in how tissue samples are collected and processed and in how tests are performed and interpreted

-Lobbying for alternative funding sources and changes to how tariffs are allocated

-Rigorous assessment of different tests, leading to greater understanding of their strengths and weaknesses, with the aim of uniform adoption of the optimal test

-Within reason, flexibility should be encouraged in the new national testing system to ensure that patients have access to the most appropriate test at each point in their care pathway

-Ensure that NICE and the NHS are aligned so that when a new therapy is recommended by NICE, there is timely uptake of any companion diagnostic test

-Centralised commissioning of testing (as with the recent reconfiguration of genomic testing within the NHS)

-Development of SOPs and regular participation in EQA schemes

2. Ethical and regulatory issues

-Requirement for ethical approval and consenting procedures during test development/clinical trials

-Uncertainty about the necessary regulatory requirements (e.g. clinical trial authorisation, EU IVDR and US FDA approval) for new molecular diagnostic tests and accreditation of laboratories performing them (uncertainty greater within academia and NHS than within industry)

-Uncertainty about how ‘Brexit’ will affect regulation of in vitro diagnostics in the UK (the IVDR, an EU regulation, came into effect in May 2017 and gave manufacturers 5 years to prepare for a new legislation that will require more rigorous assessment of in vitro diagnostic medical devices—it is currently unknown how ‘Brexit’ will affect this)

-Greater clarity with regard to when ethical approval and consent are and are not required (e.g. test development/validation vs. performance assessment of an already-validated test)

-Encourage researchers to seek ethical approval at an early stage in test development

-Encourage researchers, clinicians and NHS managers to interact with regulators at an early stage in test development and implementation (e.g. through MHRA’s innovation office)³²

-Promotion of both UK²⁷ and European²⁸ regulatory guidelines

-Lobbying for clarification of legislative/regulatory impact of ‘Brexit’ and possible exemptions from new EU regulations, when appropriate

3. Information technology

-Development of standardised, robust IT infrastructures

-Data storage and sharing

-Volume and complexity of data

-Investment in IT infrastructure, ensuring new software is compatible with existing ones

-Consideration of technical, legal and ethical issues to ensure that data can be safely stored and shared for clinical and research purposes

-Development of novel computational approaches (e.g. AI) to facilitate automated analyses

4. NHS culture

-Staff must be aware of emerging technologies and willing to adopt them

-Patients should be educated and empowered to ensure that they receive appropriate molecular testing

-Improved nationwide dissemination of information about established/emerging tests and funding sources

-Greater communication between specialties (such as at the MDT meeting), to encourage reflex testing by pathologists, when appropriate

-RCPath to include NICE recommendations in their best-practice guidelines and datasets

-Sharing of case studies demonstrating clinical benefit and cost-effectiveness

-A national workshop involving clinical staff, laboratory scientists and NHS managers

-Education and mentoring of patients and enhanced communication between patients, clinicians and pathologists (e.g. through the NCRI Consumer Forum)

5. Education/training

-Urgent need to upskill the NHS workforce in molecular diagnostics

-Inclusion of molecular diagnostics in UG medical curricula and increased prominence in PG training, including training of senior staff

(CM-Path is actively working to develop training opportunities in molecular pathology)^19,20

-Cross-discipline and cross-sector training to include clinicians, pathologists, nurses, managers and industry

-Identify best-practice examples in molecular diagnostic training from other countries

6. Monitoring of uptake/response

-Lack of systematic monitoring of molecular diagnostic testing in the NHS, leading to a knowledge gap regarding current practices across the UK

-Lack of data regarding the clinical impact of test adoption

-NHS genomic reconfiguration to introduce a new molecular diagnostic test directory and commissioning system

-Inclusion of molecular diagnostics in quarterly NHS England Innovation Scorecard produced by HSCIC

-Mandatory recording of how new tests have influenced patient care (e.g. treatment allocation)

AI artificial intelligence, EQA external quality assessment, EU European Union, HSCIC Health and Social Care Information Centre, IT information technology, IVDR In Vitro Diagnostic Regulation, MDT multidisciplinary team, MHRA Medicines and Healthcare products Regulatory Agency, NICE National Institute for Health and Care Excellence, NCRI National Cancer Research Institute, NHS National Health Service, PG postgraduate, RCPath The Royal College of Pathologists, SOPs standard operating procedures, UG undergraduate, UK United Kingdom, USFDA United States Food and Drug Administration