Robust, fair and sustainable:Our vision for the future access and provision of molecular diagnostics in England

Diagnostics; making a difference

Early adoption of new tests

National-level commissioning

Clinical leadership overseeing the

implementation of the framework

Flexibility and horizon scanning

Joined-up decision-making

Supporting the NHS’s research

capacity

Integrated assessment and access

Reform of funding arrangements for

molecular diagnostics

Monitoring of uptake

1. Executive summary

Rapid advances in medical science and technology are transforming the way we identify, treat and prevent health problems. The potential benefits to patients and the NHS of a thriving life sciences sector are vast.

However, in the area of molecular diagnostics, further reform is needed to ensure patients can realise the benefits of these tests and receive equity in care and improved clinical outcomes. In this paper BIVDA has laid out its vision for the future of molecular diagnostics in England.

The focus of our vision looks at the usage of molecular diagnostics in oncology. This is because the majority of the current usage is in cancer. However, there are also many tests on the market in other therapy areas and, over the coming years, patients with a variety of diseases, such as autoimmune, inflammatory and neurodegenerative illnesses, can expect to benefit from access to molecular diagnostic testing. Establishing a sustainable framework for cancer today will benefit other patients tomorrow.

At the heart of this vision is the establishment of a new national framework for commissioning and funding molecular diagnostics tests. This system should be aligned to the principles of:

In our vision, we are calling for the following actions:

• NHS England to develop a national framework for the commissioning of molecular diagnostics which is implemented at the earliest opportunity, and is in line with the recommendations of the Independent Cancer Taskforce

• Molecular diagnostics are embedded at every stage of the cancer treatment pathway – from assessing which is the best type of treatment to monitoring its effectiveness

• Commissioning and policy decisions relating to the provision and access to molecular diagnostics are joined up to ensure equal patient access

• Molecular diagnostics are used to enhance and support the NHS’s research and development capabilities

• Decisions about which tests are made available on the NHS are aligned to decisions about which treatments are made available. For instance, where a precision medicine can benefit patients with a certain biomarker, NICE should recommend patients are tested for this

• Mechanisms are put in place to monitor access to and uptake of molecular diagnostics

Over the coming months we look forward to working with colleagues and interested parties to take this vision forward, to ensure molecular diagnostics are able to play their part in delivering world-class outcomes.

2. Introduction

Advances in stratified medicines have helped to transform the way we understand and treat health conditions in the UK today. An improved knowledge of the genetic and biochemical markers that sit behind diseases such as cancer means there is a growing number of medicines available that can be targeted at specific patient groups, to deliver the best possible outcomes.

Patient access to these treatments is reliant on the availability of appropriate molecular diagnostic tests. Diagnostic tests form an important – and growing – part of high quality care in England, helping to guide clinicians towards the right treatment option for a patient, as well as ensuring that NHS resources are used effectively.

Molecular diagnostic tests have been available on the NHS for a number of years, with the vast majority being utilised in oncology. However, there is widespread recognition that a fragmented commissioning system for these tests has led to varied access, with some patients missing out on appropriate treatment options.

Fixing the current system has been a long-standing commitment:

• The Department of Health’s 2011 Cancer Strategy pledged to “develop a commissioning and funding structure to enable the efficient delivery of high quality molecular diagnostic testing through centres of excellence”i

• The Department of Health’s Cancer Policy Team published proposals in December 2012 for ensuring equitable access to complex molecular diagnostic testing for cancer patientsii

• Draft clinical commissioning policy for molecular diagnostic testing is currently under development by NHS England Implementation of these commitments has been slow or has stalled. The coming six months present a number of opportunities for Government and NHS England to tackle this issue head on through:

• Accelerated Access Review, which aims to make recommendations for how the NHS can speed up access to innovative treatments, devices and diagnostic tests

• Consultation on future reform of the Cancer Drugs Fund (CDF)

• Implementation plan from NHS England in response to the Independent Cancer Taskforce’s cancer strategy for England

• NICE’s consultation on developing service guidance to provide and delivery diagnostic services

• Implementation of work with Monitor and NICE on commissioning intentions for prescribed specialised services, including the prioritisation of new cost effective tests

BIVDA is the national industry association for the manufacturers and distributors of in vitro diagnostic (IVD) products in the UK and we currently represent more than 95% of the industry and over a hundred organisations ranging from British start up companies to UK subsidiaries of multinational corporations. BIVDA members currently employ over 8,000 people in the UK, with a total industry turnover of approximately £900 million.

This paper sets out BIVDA’s vision for future provision and access of molecular diagnostics in England.

3. How molecular diagnostics are contributing towards achieving world-class outcomes

Significant advances in our knowledge and understanding of the genetic characteristics sitting behind health problems has led to an increase in the number of targeted therapies available to treat diseases. The use of targeted medicines has been widely recognised as an important step forward in the fight against diseases such as cancer by:

• Ensuring treatment is focused on those patients who will derive a benefit

• Minimising exposure to side effects associated with ineffective treatment

• Focusing NHS expenditure on treatment which is likely to deliver a benefit and release savings through more accurate dosing

However, targeted treatments only work if the clinician knows which patients to target. In cancer, the availability of molecular diagnostics is an essential part of the treatment pathway, by allowing healthcare professionals to determine whether a patient is suitable for an appropriate therapy or not. Routine use of these tests is recognised as an important enabler of safe, effective and affordable care. Examples of such tests include analysis of the KRAS gene to help oncologists determine whether a bowel cancer patient will respond to cetuximab. Testing for the HER2 gene has also become routine practice in the treatment of breast cancer patients when determining which treatment the woman will respond to most effectively.

Advances in the development and use of molecular diagnostics mean that such tests can also be used at different stages of the treatment pathway to fulfill different functions. As well as informing initial decisions about which medicine to use, appropriate testing can help to guide decisions to switch treatments or amend the regimen.

Targeted breast cancer treatment

Around 20% of women with breast cancer are positive when tested for the HER2 gene, which is associated with aggressive cancer cell growth. Herceptin is a treatment designed specifically to target the HER2 protein.

Before beginning treatment, patients are required to be tested for their HER2 status. Clinical trials have shown that HER2 positive individuals receiving Herceptin as a treatment experience substantial improvements in survival and quality of life compared to treatment, with conventional chemotherapy alone.

The highly targeted nature of the treatment means that response rates are good, and wastage is minimised. HER2-negative tumours will not derive any benefit from Herceptin. It is therefore vitally important that patients who are positive for the protein are identified accurately to ensure that they will benefit from the treatment, and that those who are negative do not receive the treatment unnecessarily.

For example, in a similar way to how patients with HIV have their CD4 cell count (blood cells which help the body fight off the disease) regularly tested, it is possible to monitor tumour activity in cancer. BIVDA members are investing in developing tests to enable this to become a reality in routine clinical practice and are hopeful that these will be available within the next five years.

Samples collected from patients for molecular diagnostic testing also have significant research value to the NHS and to the UK’s life sciences sector. With patient consent, collection of these samples can allow researchers to carry out further investigations into the genetic biomarkers and factors that sit behind health conditions. This in turn can help to further improve our health knowledge and help us to discover the next generation of treatments.

4. Current provision and access to molecular diagnostics

We have set out in this paper the benefits that improved access to molecular diagnostics can make to the NHS, both in relation to improved patient outcomes but also in making treatment more cost effective. And yet, despite advances in targeted medicines (particularly for cancer), a number of system barriers within the NHS have compounded equitable access and uptake of molecular diagnostics.

Figures released by Cancer Research UK in July 2015 revealed that between 2011 and 2014 there has been a 51% increase in the volume of molecular diagnostic tests carried out through the NHS.iii However, the analysis has also uncovered a large proportion of the patient population that is missing out on these important tests.

Cancer Research UK’s figures found that in 2014 approximately 16,000 patients with lung and bowel cancer missed out on a test which could have helped to explore potential treatment options.iv Around 3,500 of these patients could have been eligible for a targeted drug that may have helped them.v

Figure 1: Cancer Research UK’s data on testing of melanoma, lung and bowel cancer patients in England during 2014vi

BIVDA is concerned about these findings, although they do not surprise us. They are the symptom of a system that is not properly funded, not properly commissioned and not properly evaluated.

35,600 patients needed a test

19,600 received a test

16,000 did not receive a test

3,500 missed out on targeted therapies

Under current arrangements, molecular diagnostics are commissioned through many different channels:

This inconsistency in commissioning has been compounded by ad hoc funding arrangements reached with pharmaceutical companies relating to specific tests. For example, the manufacturer of Herceptin initially funded Her2 testing when it launched the drug for breast cancer. Although these arrangements are to be welcomed in that they have facilitated earlier access to effective treatment for patients, they have resulted in further fragmentation and placed no incentive on the NHS to address this problem. Now that pharmaceutical manufacturers are withdrawing initial funding of tests, the problem of inequitable access to tests is growing.

Routine access to molecular diagnostic tests has also been hindered by:

• Confusion over the extent to which molecular diagnostics can and will be funded through the CDF

• Uncertainty about the future of the CDF and how future reforms of the fund will or will not affect access to certain diagnostics tests

• Financial pressures on NHS England’s specialised commissioning programme, which have limited the willingness to pay for services which could be seen as additional

• Wider issues within pathology, which have made some centres wary of any initiative that could be seen as paving the way for centralisation or reconfiguration

• Overlap with the 100,000 Genomes Project

• Lack of clarity around proposals to re-procure Genomic Laboratory Services

• Absence of a systematic way to assess, validate and update molecular tests for clinical use

• The presence of budget silos, with molecular diagnostic being funded from one budget and corresponding treatment being funded from another

Advances in technology mean that future tests could be delivered outside of traditional laboratories and in different care settings. Any future framework must therefore be flexible to these advances.

For too long the system has relied on piecemeal arrangements rather than introduced fundamental reform. But, the size of the pipeline for new targeted drugs and companion diagnostics means it is now becoming unsustainable.

Case study – Oncotype DX

The Oncotype DX breast cancer test (the Onotype DX test) is a validated multi-gene diagnostic assay that predicts the likelihood of adjuvant chemotherapy benefit in a subset of breast cancer patients.

The Oncotype DX test has been available within the NHS since 1 April 2015 on a limited basis through a confidential access scheme, with Trusts participating on an individual basis.

This access scheme is not intended to be a permanent commissioning solution within the NHS. Therefore, an alternative method of access and funding, such as inclusion of the test within NHS Best Practice Tariffs, will need to be established.

On a test-by-test basis

Through a block contract agreement

with a specialist testing centre

Within the agreed procedure

tariff price

Following an individual funding

request by a laboratory

Funding of molecular

diagnostics

5. Opportunities to fix the system

Significant amounts of time and energy have been invested by industry, charities, the Department of Health and NHS England to find a workable solution to reform the way molecular diagnostics are funded through the NHS. Although we have been frustrated with the delays to implement the necessary changes, we have welcomed these contributions and the commitment of those that have been involved in leading them.The learnings from this work should be considered as part of the three immediate opportunities we believe exist to fix the current system. These are the:

• Accelerated Access Review

• Reform of the CDF

• Implementation plan of the Independent Cancer Taskforce’s strategy

Accelerated Access Review

The Accelerated Access Review will make recommendations for how the life sciences industry, government and the NHS can work together to speed up access to innovative drugs, devices and diagnostics for NHS patients. This is an important review and has the potential to play a significant role in setting the future of the life sciences sector in the UK.

We welcome the fact that the interim report, published in October 2015, from the Review includes reference to:

• Current challenges around approval of companion diagnostics

• No funding requirement for medtech/diagnostics

• Exploring how the current tariff system can best respond to the new way of devices, diagnostics and digital health products

The vision of the UK being the best place in the world to design, develop and deploy these products is welcome – and realistic. But to be achieved we cannot see the barriers to access in isolation. Uptake of new treatments and tests will not always be a reimbursement issue nor will it always be a regulatory issue. Access issues exist at different ‘flashpoints’ across the care pathway. It is for this reason that we have welcomed the Accelerated Access Review taking a whole system approach. The role of diagnostic tests should be considered at every stage of the Review – from research and developmentthrough to uptake and access.

Reform of the CDF

Since it was established in 2010, the CDF has given patients access to cancer treatments that have not been approved by NICE and are not yet routinely available on the NHS in England. A number of the treatments availablethrough the fund have an associated companion diagnostic test. For example, Dasatinib and a BCR-ABL1 test and Cetuximab and a KRAS test.

However, since its inception, there has been confusion amongst interested stakeholders about whether companion diagnostics are eligible for funding through the CDF or not.

In July 2015, NHS England confirmed plans to consult on the future operating model of the CDF. At the time of writing, the details of that new operating model are unclear, but NHS England did confirm that it intends to consult on plans for the CDF to “become a ‘managed access’ fund for new cancer drugs, with clear entry and exit criteria”.vii We recognise the Fund is aperiod of evolution and does not represent a long-term solution to the funding of molecular diagnostics. But, the Fund is one of the mechanisms through which tests are made available, so any new operating model should provide clarity about how companion diagnostics are to be funded through any future managed access fund. However, future reform of the CDF should not distract from wider efforts within NHS England to introduce a robust and coherent system for long-term funding of molecular diagnostics.

Implementation plan of the independent cancer taskforce’s strategy

In July 2015, the Independent Cancer Taskforce published its cancer strategy for England. Achieving World-Class Cancer Outcomes: A Strategy for the NHS 2015-2020 made almost 100 recommendations, which are now being considered by NHS England as part of the next spending review negotiations.

In its final report, the independent taskforce noted the fragmentation of access and provision to molecular diagnostics. It recommended therefore that:viii

• NHS England should transform access to molecular diagnostics to guide treatment for cancer:

– NHS England should nationally commission access to molecular diagnostic tests to guide treatment, starting with the following cancer types in 2016: melanoma, lung, colorectal, breast and all paediatric cancers. This would be in addition to haematological cancers, with a further broadening out to all cancer types where treatments are already subject to a molecular diagnostic test by 2020

– Use of molecular diagnostic tests by providers should be added to the Cancer Outcomes and Services Dataset (COSD)

– NHS England should undertake a year by year review of molecular diagnostics capacity given the pace of scientific and technological advance

As we have noted earlier, proper investment in molecular diagnostics has the potential to avert costs to the NHS by helping healthcare professionals to prescribe treatments that will be more effective and reduce the possibility ofside effects.

NHS England intends to publish a detailed implementation plan in response to the Taskforce’s recommendations during the second half of 2015/16.ix

However, we recommend NHS England introduce interim arrangements for the funding and commissioning of molecular diagnostic tests during 2015/16 to avoid any further unnecessary delays to patients access to tests and treatments. We would recommend NHS England consider using a proportion of the £25 million reserve currently being held for the commissioning of new treatments to fund this.x

6. The principles of future reform

We believe there are two aspects to the future reform of the system for making molecular diagnostics available on the NHS:

1. Establishing a robust, fair and sustainable service which supports research and development of new diagnostics and treatments

2. Agreeing the standards and criteria by which tests are to be commissioned and funded for clinical purposes

Establishing a robust, fair and sustainable service

We believe a future service for providing molecular diagnostics should be developed on the principles of:

Integrated assessment and access

Early adoption of new tests

Clinical leadership overseeing the implementation of the framework

Joined-up decision-making

Monitoring of uptake

National-level commissioning

Flexibility and horizon scanning

Supporting the NHS’s research capacity

Reform of funding arrangements for molecular diagnostics

In practice, this means:

• Early adoption of new tests, with nationally agreed criteria for provision and regulation of tests throughout the pathway

• Flexibility and horizon scanning, with new tests being available through the NHS as and when additional evidence emerges

• Integrated assessment and access, with diagnostic tests. Those related to a new drug should be appraised together with the drug and mandatory funding for NICE-recommended treatments explicitly stating whether and when molecular testing should be carried out

• National-level commissioning, with NHS England coordinating close working between industry, patient representatives, NICE and the Cancer Drugs Fund panel

• Joined-up decision-making, with collaboration and consistency in what tests are being made available through the NHS across different policy initiatives (eg the Cancer Drugs Fund, routine commissioning, Genomic Laboratory Services)

• Reform of funding arrangements for molecular diagnostics, with clarity over the level of reimbursement for different tests and funding routes

• Clinical leadership overseeing the implementation of the framework, with partnership arrangements in place with industry, commissioners and providers (both NHS and from the independent sector)

• Supporting the NHS’s research capacity, with commissioners being encouraged to incorporate research into the standard care pathway, so further investigations and trials can be carried out on leftover tissue samples

• Monitoring of uptake, with routine collection and publication of data on the levels of uptake of molecular diagnostics by commissioner and provider

Agreeing the standards and criteria for tests to be made available

Diagnostic and genomic testing is a rapidly evolving field, with new tests being developed all of the time. Any future system for delivery of molecular diagnostic testing should therefore be flexible to support clinical leadership and early adoption of new tests.

There must be arrangements in place to make additional tests available as and when new evidence emerges and to decommission tests if and when they are superseded by more accurate or clinically useful alternatives. It is also important to have a system in place that can fund a multiplex panel approach to molecular testing.

If there is a move towards an increased use of multiplex panels, then mechanisms need to be put in place to ensure there is consistency in how tests are provided.

However, there are some overarching criteria that should be followed when determining what tests should be commissioned, funded and made available on the NHS. We believe therefore that any future framework should fund diagnostic testing in line with the following service standards:

• National commissioning guidance or policy statements

• NICE guidance and recommendations

• The European Commission’s In Vitro Diagnostic Medical Devices Directive

• The requirements set out in NHS England’s Pathology Quality Assurance Review

• Accreditation of service laboratories to ISO 15189, requirements for quality and competence

We are also calling for decisions about which tests are made available on the NHS to be aligned to decisions about which treatments are made available. For instance, where a precision medicine can benefit patients with a certain biomarker NICE should recommend patients are tested for this as part of the technology appraisal.

7. Monitoring uptake and adherence to standards

Realising our vision for the future of molecular diagnostic testing in England means improving our understanding of current activity, coverage and funding of molecular diagnostics across the NHS.

We have welcomed Cancer Research UK’s recent report, which makes a useful contribution to this area. However, we would propose a broader sharing of intelligence on current activity that covers the full range of testing. In particular, it would be useful to draw on intelligence provided by:

• Relevant Clinical Reference Groups, who should be sighted on patterns of delivery

• Cancer Research UK as part of its review into molecular diagnostic provision

• Diagnostics manufacturers, who will have an understanding of levels of usage of their own particular tests

• Pharmaceutical companies, who will have intelligence about levels of testing for their particular medicines

By utilising these information sources, we should be able to develop a more detailed analysis of the requirements moving forward. BIVDA would be happy to support NHS England in undertaking such a review, including requesting information from our members about testing activity.

We also support recommendations of the Independent Cancer Taskforce and others to improve the level of data available on quality, activity and performance of diagnostic testing services in England. We would recommend establishing a nationally agreed dataset (or scorecard) for monitoring purposes. Indicators for inclusion could include:

It is important that diagnostic testing activity is linked with other national datasets, including disease registries and Hospital Episode Statistics. This will help to track the contribution of diagnostic testing in improving patient outcomes and informing the results of clinical trials.

Provider adherance to quality assurance

schemes

Length of wait (actual and average) for a patient between

sample being taken and results being available

Number of test referred by

individual providers

Patient participation research studies

Number of tests carried out

Number of research studies undertaken

Devonshire House (2nd Floor)164-168 Westminster Bridge Road · London · SE1 7RW Tel 0845 6188224 · Email enquiries@bivda.co.uk

Diagnostics; making a difference

Referencesi Department of Health, Improving outcomes: a strategy for cancer, January 2011ii Department of Health, Ensuring equitable access to complex molecular diagnostic testing for cancer patients, June 2012iii Cancer Research UK, Molecular diagnostic provision in England: for targeted cancer medicines (solid tumours) in the NHS, July 2015iv Cancer Research UK, Molecular diagnostic provision in England: for targeted cancer medicines (solid tumours) in the NHS, July 2015v Cancer Research UK, Molecular diagnostic provision in England: for targeted cancer medicines (solid tumours) in the NHS, July 2015vi Cancer Research UK, Molecular diagnostic provision in England: for targeted cancer medicines (solid tumours) in the NHS, July 2015vii NHS England, Board paper – Future delivery of the Cancer Drugs Fund (CDF), July 2015viii Cancer Taskforce, Achieving world-class cancer outcomes: A strategy for England 2015-2020, July 2015ix NHS England, Board paper – Report of the Independent Cancer Taskforce - ‘Achieving World-Class Cancer Outcomes: A Strategy for the NHS 2015-2020’,

July 2015x NHS England, Report of Specialised Services Commissioning Committee to the Board, July 2015

8. Taking our vision forward

BIVDA looks forward to discussing the ideas contained within this paper with interested parties over the coming months. We will continue to work with stakeholders to examine further ways to ensure equitable access for patients to molecular diagnostics and to support the NHS to deliver world-class outcomes.

For further information please contact Doris-Ann Williams, Chief Executive of BIVDA, on 0207 921 9592 or doris-ann@bivda.co.uk.

BIVDA, November 2015