Genomic Medicine - Science and Technology Committee Contents


The framework for translational research in the UK

3.1.  "Translational research" is the research which bridges the gap between basic or clinical research and the application of innovations in a healthcare setting. It is vital to realising the potential of genomic medicine. Examples include developing diagnostic tests to a marketable product and research to assess their clinical utility (that is, their benefit to patients).


3.2.  In a White Paper published in 2003, Our inheritance, our future: realising the potential of genetics in the NHS (Cm 5791) ("the 2003 Genetics White Paper"), the Government outlined their vision for the NHS in the context of genetic science. It was:

    "… to lead the world in taking maximum advantage of the safe, effective and ethical application of the new genetic knowledge and technologies as soon as they become available".

3.3.  But Sir David Cooksey, in his 2006 Review of UK Health Research Funding ("the Cooksey Review"), identified translational research as an area of weakness and warned that the UK was at risk of failing to reap the full economic, health and social benefits that public investment in health research should generate. Two key gaps were identified: first, the translation of ideas from basic or clinical research into development of new products and new approaches to treatment of disease and illness; and, second, the use of those new products and approaches in clinical practice. In this chapter we focus on the first of these gaps.

3.4.  The Cooksey Review identified a range of cultural, institutional and financial barriers to the translation of publicly-funded research into clinical practice and made a number of recommendations to overcome them. They included:

  • better co-ordination of health research and coherent funding arrangements to support translation through the establishment of an Office for the Strategic Co-ordination of Health Research (OSCHR) to co-ordinate research between the National Institute for Health Research (NIHR) and the Medical Research Council (MRC) and to monitor progress; and
  • the inclusion of additional funding streams in ring-fenced funding for Department of Health (DoH) research, and additional funding in key areas including Health Technology Assessments (HTAs) to support the uptake of new ideas and technologies.

In 2007, the Government set up OSCHR in accordance with the review recommendation.

3.5.  Since its creation, OSCHR has been responsible for the co-ordination of public sector health research in the UK, estimated to be worth £1.7 billion a year by 2010-11. Its partners, the NIHR and MRC, have jointly developed a new approach to translational research, including a more coherent funding arrangement which involves each organisation taking the lead on funding for core activities (the MRC for early development of new opportunities from discovery research and development to early-stage clinical trials and the NIHR for large-scale clinical trials). The recent injection of funding through OSCHR for translational research has, according to Professor Peter Donnelly, Director of the Wellcome Trust Centre for Human Genetics at the University of Oxford, "had an extremely positive impact" on translational research (p 79). We commend this strategic and co-ordinated approach to translational research and the work of OSCHR in achieving this co-ordination.

3.6.  None the less, OSCHR's first progress report, published in November 2008, indicated that significant challenges remain; and the recent report by the Bioscience Innovation and Growth Team, The Review and Refresh of Bioscience 2015, published in January 2009, confirmed this: "despite all of the activity [to improve the translation of health research into clinical applications] …, the adoption of new therapies, drugs and procedures in the NHS remains painfully slow … and the translation of these improvements into patient benefit has not yet materialised".[8] As for genomic medicine in particular, the Foundation for Genomics and Population Health ("the PHG Foundation") told us that although genomic science was in a "robust state", "progress is dramatically slower in evaluating the clinical and public health relevance of these scientific advances and in developing systems for effective translation of validated tests and interventions into clinical practice" (p 134). Oxford Nanopore expressed a similar view (p 325).

Funding and translational research in genomic medicine

3.7.  In the 2003 Genetics White Paper, the Government made a commitment to provide £50 million to help the NHS make better use of advances in genetic science. This included investing £18 million capital on upgrading NHS genetics laboratory facilities, £2 million "start-up" funding over three years for initiatives to bring the benefits of genetics into mainstream practice, £15 million to support the development of five genetics knowledge parks over five years, and £2.5 million for pharmacogenetic research into existing medicines. The Government also made a commitment to ensure that the necessary infrastructure (such as informatics and laboratory services) was in place and that training was available to support translational research. In April 2008, the Government published a review of the 2003 White Paper—Genetics White Paper Review 2008 ("the 2008 Review"). (The White Paper and Review are considered further in Chapter 4.)

3.8.  Although the Government has now fulfilled many of the objectives set out in the 2003 White Paper, a number of witnesses expressed concern about whether the funding commitments were sufficiently long-term. The Research Councils UK (RCUK), for example, warned that the "high level of investment [set out in the White Paper] … will need to be maintained to ensure that the developing understanding feeds through into benefits for clinical care and public health" (p 1). According to Oxford Nanopore: "It is essential that the investment in genetics is part of a long-term strategy to support innovation in the field and not a one-off event" (p 325); and the Wellcome Trust Sanger Institute referred to the importance of having a "strategic vision and sustained investment" (p 328). It is perhaps reassuring therefore that the need for sustained funding was acknowledged in the 2008 Review that genetics is still a relatively new area of work, and the review recognises that developments need to be considered over a longer timeframe, and will require sustained support.[9]

3.9.  When asked about the Government's plans to extend the programmes set out in the 2003 Genetics White Paper, the Minister of State for Public Health, Dawn Primarolo MP, said:

    "Both the MRC and NIHR have new funding streams supporting … translational research … We have also invested more money in the NIHR's health technology investment programme, and that programme has recently put out a themed call for the evaluation of diagnostic tests, and on top of that the Department of Health, with the Wellcome Trust, has the Health Innovation Challenge Fund, which will have a big part to play … [we have] recently appointed Professor John Burn from the Newcastle Centre for Life as Chair of the National Clinical Genetics Specialty Group … responsible for facilitating and encouraging timely development and, building on this, we plan to award £100,000 a year to the University of Newcastle under the direction of Professor Burn to enable clinical geneticists to come together and to identify current research activity and new funding opportunities" (Q 857).

3.10.  Although we welcome these initiatives, we question whether they amount to a sufficiently strategic, long-term approach to funding translational research into genomic science. Recognising this deficiency, Professor Sir Alex Markham, Chair of OSCHR Translation Medicine Board, suggested that OSCHR had a role to play in remedying it:

    "OSCHR should be charged to make sure that there is some strategic thinking going on constantly about genetics and its place in the health system. The structures that have been built over the last 12-18 months in and around OSCHR are well designed to do that … I think we have an oversight capacity now that we have never had in this country before to take the hot science into the clinic when appropriate" (Q 474).

3.11.  On 4 November 2008, the Prime Minister, Gordon Brown MP, asked OSCHR to work with the Department of Health (DoH) and the Department for Innovation, Universities and Skills (DIUS), through the MRC, NIHR and the research community, to identify a set of National Ambitions for Translational Health Research, with a view to developing an overarching set of national objectives to encourage the translation of major research breakthroughs into new NHS treatments and services within a decade. As part of this initiative, we recommend that OSCHR should take the lead in developing a strategic vision for genomic medicine in the UK with a view to ensuring the effective translation of basic and clinical genomic research into clinical practice.

3.12.  This strategic vision should form the basis of a new Government White Paper on genomic medicine which should outline:

  • the measures the Department of Health will take in order to facilitate the translation of advances in genomic science into clinical practice;
  • a roadmap for how such developments will be incorporated into the NHS; and
  • proposals for a programme of sustained long-term funding to support such measures.

Strategies to facilitate translational research in the NHS


3.13.  In his Foreword to OSCHR's first progress report, Professor Sir John Bell suggested that real commitment to research was still lacking in most NHS trusts, something that had to change if a culture of innovation in the NHS were to develop. The final report of Lord Darzi of Denham's NHS Next Stage Review, High Quality Care for All ("the final report"), published in June 2008, proposed placing a legal duty on Strategic Health Authorities (SHAs) to foster and promote innovation which, in addition to other initiatives to encourage translation in the NHS, was intended to encourage cultural change. Commenting on that report, Professor Sir John Bell told us that although it was helpful that the NHS constitution was going to have within it a commitment with regard to research, "there needs to be central management to make sure that it is a main pillar of the whole organisation" (Q 453). Whilst acknowledging this caution, we are encouraged by recent developments with regard to cultural change within the NHS.


3.14.  The UK Clinical Research Collaboration was established in 2004 to streamline applications for clinical trials. It has led to significant improvements in the applications process. These include setting up an infrastructure to conduct clinical research in the NHS through the national clinical research networks and the provision of an advisory service and model agreements for clinical trials. The establishment of the Integrated Research Application System in 2008, in conjunction with the National Research Ethics Service, which provides for one data entry point for applications, has also received positive feedback from the research community.

3.15.  However, it appears that the process for the establishment of clinical trials in the NHS remains burdensome, in particular because of the way in which the EU Clinical Trials Directive has been applied in the UK, and also because of the complexities surrounding confidentiality and consent in the sharing of medical data for research purposes (see Chapter 6). The Review and Refresh of Bioscience 2015 report noted that the proportion of UK patients in global trials fell from six per cent in 2002 to two per cent in 2006, and suggested that, although the EU Clinical Trials Directive aimed to simplify and harmonise the rules governing clinical trials in the EU, the opposite had in fact been achieved; and, it was further suggested, differences amongst member states in applying the Directive had made the UK an increasingly unattractive location for biotechnology businesses to conduct research.[10]

3.16.  The Association of the British Pharmaceutical Industry (ABPI) also referred to difficulties with the clinical trials process, including the "slow start-up of trials and recruitment of patients." (p 369); and Professor Collins told us:

    "The regulatory obstacles to the use of medical records, and the regulatory burden for clinical trials as a consequence of the EU Directive on clinical trials and its implementation into UK law, have pushed research and research funding out of the UK … The consequence of these, and also of NHS research governance, is that our ability to do this kind of research has been made increasingly difficult and costly, and research is being slowed substantially" (Q 527).

3.17.  We recommend that the Government revises the UK implementation of the EU Clinical Trials Directive, in consultation with the research community, to make it less burdensome for researchers.

3.18.  The European Commission is currently considering whether the EU Clinical Trials Directive should be reviewed in 2010. The Review and Refresh of Bioscience 2015 report urges the UK to take a leadership role in any revision of the Directive to ensure consistency and to prevent the UK continuing to be an unattractive place, for both regulatory and financial reasons, to conduct research.[11] If the European Commission decides in favour of a review of the EU Clinical Trials Directive in 2010, we urge the Government to participate fully in discussions in order to ensure that the revised Directive is less burdensome for researchers.


3.19.  According to a recent ABPI survey, "the volume of collaborations declined between 2003 and 2007". From the industry's perspective, the ABPI cited "escalating cost, increasing international competition for research funds, difficulty in contract negotiation and lack of incentives available for academics to collaborate more closely with industry" as barriers to collaborative research and noted that "if the UK is to have the best chance to lead in genomic medicine, these issues should be addressed" (p 367).

3.20.  With regard to the involvement of academia, the Human Genetics Commission (HGC) noted that "certain conditions—such as the cost of postdoctoral funding in the UK and level of incentive for academics to collaborate with industry on research projects under the proposed Research Excellence Framework—are not currently optimised for collaboration between the pharmaceutical industry and academia" (p 161). This view was echoed in a recent Nature article in which the University of Oxford stated that "it is not financially viable" to participate in the Innovative Medicines Initiative, a major new initiative to fund European public-private partnerships, due to the funding terms of the initiative.[12]

3.21.  Professor Pirmohamed agreed that escalating costs inhibited collaboration with industry. He suggested that recent changes in funding mechanisms were part of the problem. The move to Full Economic Costing in April 2006 has meant that industry has had to pay for 100 per cent of the direct costs (for example, laboratory supplies for a project or the salary of a scientist to run it) and the indirect costs (for example, a proportion of the maintenance cost for university facilities) for each individual project, or their proportionate share of the direct and indirect costs of a collaborative project. According to Professor Pirmohamed, "it has made a difference to us in terms of full economic costing in that certain companies have walked away because of the additional costs" (Q 746).

3.22.  There is also a lack of incentive for the NHS to take part in research collaboration. The Institute of Medical Genetics (IMG) told us:

    "Co-operation between industry and the NHS is essential, but NHS resources to collaborate with industry are at best miniscule, if only because actual and perceived rules, such as commissioners not being allowed to fund 'R&D', create huge barriers to progress. If R&D were regarded more as R, D & S, indicating 'Research, Development and Service', that might help break down this barrier. Research then would be thought more of the remit of research funding bodies, and D&S rightly the remit of the NHS" (p 247).

3.23.  The charitable sector is also discouraged from collaborating. We were told by the Breast Cancer Campaign that "there is presently no initiative to involve all funders of research in collaboration, and we believe that this will continue to slow down advancement across all areas of research" (p 500).

3.24.  Although there seem to be so many practical disincentives to collaboration, the industry and others acknowledge its significance in principle. For example, the pharmaceutical company, Astrazeneca, said:

    "Progress in genomic medicine and translation to clinical practice will require an integrated approach between stakeholders; including scientists to discover and develop biomarkers, diagnostic companies to develop enabling technology to test the biomarkers, pharmaceutical companies to conduct clinical trials demonstrating the clinical utility of the diagnostics and the healthcare system to translate the linked drugs and diagnostics to clinical practice" (p 477).

The Academy of Medical Sciences (AMS) endorsed this view:

    "Extensive collaboration is required between pharmaceutical companies, academia and the regulatory authorities to validate new technologies [for genomic medicine]. This will require companies to share safety data and to engage in new pre-competitive joint research in the UK and internationally" (p 467).

3.25.  The DoH and the ABPI have worked closely to develop the concept of "joint working" between the NHS and the pharmaceutical industry, and have issued best practice guidelines for NHS staff and a supporting best practice "toolkit". The Royal College of Physicians is also preparing a report on promoting collaborative working; and the Minister for Science and Innovation, Lord Drayson, told us:

    "[It is] central to the effect and development of innovative medicines and … in particular in the case of developments from the field of genomics is the vital importance of this public/private partnership and the relationship between the academic research base, the NHS and the early stage development into the large pharmaceutical industry … The MRC … just this week … is launching a new collaborative scheme".

But, he concluded, "we need to do more'" (Q 903).

3.26.  Whilst we welcome the new MRC collaborative scheme, we are aware that the 2006 Cooksey Review recommended that OSCHR should also encourage greater collaboration to facilitate the translation of scientific advances into clinical applications. We recommend that the proposed White Paper on genomic medicine (see paragraph 3.12 above) and the Strategic Vision of the Office for the Strategic Co-ordination of Health Research should identify barriers to collaborative working between academia and the pharmaceutical and biotechnology industries, and ways of removing them and also address the need for incentives for collaboration so as to promote translational research in the UK.

Assessment, evaluation and regulation of diagnostic tests


3.27.  Genetic tests are essential for the diagnosis of single-gene disorders and genomic tests are becoming increasingly useful for differentiating treatments of particular groups of patients in common diseases. The development and assessment of such tests require research to prove their clinical utility and validity. But whereas clinical validity is tested as part of any assessment of the risks and benefits of new diagnostic tests—partly for funding reasons, clinical utility, which looks at the benefit to the patient, tends not to be. As a result, there is currently little data on which to assess the clinical utility of genetic and genomic tests in the NHS (pp 108, 136-7 and 395). The Royal College of Pathologists further suggested that research into clinical utility was inadequate because of "the organisational difficulty of conducting this type of research; its relative lack of 'prestige' amongst the scientific community; and a traditional reluctance of the major grant-giving bodies to fund 'mundane' research into such practical matters" (p 108).

3.28.  Other than tests for single-gene disorders, genetic tests (such as pharmacogenetic tests and gene expression profiling) are entering the NHS on an ad hoc basis, often without a proper assessment of their clinical utility or validity. As a result, there is a risk that some tests may be used without good evidence of their clinical utility, and others with clinical utility may fail to get through the process due to funding difficulties. Dr Christine Patch, Genetic Counsellor Manager of the Clinical Genetics Department of Guy's and St Thomas' NHS Foundation Trust, referred to there being "a sort of technology creep" and commented that tests were being introduced "prior to really detailed evaluation". She suggested that these problems arose because "at the moment there is a funding and policy gap in that area" (Q 292). The HGC made a similar comment:

    "There is a need to assess clinical validity and utility in specific clinical pathways, as a recent PHG Foundation/Royal College of Pathologists report has recommended. However, proper evaluation of clinical utility takes time and may require large-scale studies; the provision of government funding for this sort of work would help to ensure that the benefits that could derive from further development of some types of genetic testing might be realised" (p 163).

3.29.  The IMG also said that, as part of the assessment of clinical utility and validity, "an individual accredited service laboratory has to do a considerable amount of work in, often, completely redesigning an analytical method used in research to suit it for patient diagnostics. This is a crucial area of activity for which the NHS makes minimal provision in support and funding" (p 247). The Joint Committee on Medical Genetics (JCMG) told us that "the exclusion of research proposals including novel laboratory testing from the current funding calls of the NHS National Institute for Health Research (NIHR) is significantly exacerbating this problem" of developing such tests, and that other sources of funding were not bridging the gap (p 550). Dr John Crolla, Chairman of the JCMG, told us (in June 2008) that the Joint Committee had tried to have discussions with the NIHR "because several members have reported that there is a funding gap"—and the "NIHR would be the place that we would look to create specific funding streams" (Q 192).

3.30.  Although many other funding organisations cover the assessment of innovations generally (such as the National Horizon Scanning Centre and the Centre for Evidence-based Purchasing), none of them have a specific remit to fund development research into the utility and validity of genomic tests. The Royal College of Pathologists noted that "all these agencies are selective in the topics they will address, and many new innovations are not covered by the remit of any of them" (p 109). Under the current system, the development of genomic tests is often funded through the Primary Care Trust itself, through charitable grants or the MRC, rather than through the NIHR. The arrangements are informal and usually developed through the interest of individuals or patient groups. In the view of the IMG, "clear direction needs to be given that funding for the development of diagnostics is included in the remit of governmental research-granting bodies" (p 247).

3.31.  Given the evidence we received of a funding gap, it was in some respects reassuring to hear from the NIHR Chief Scientific Adviser, Professor Dame Sally Davies (in January 2009) that NIHR's Health Technology Assessment programme (HTA) and the Health Services Research Network did have a responsibility for the assessment of genetic tests and their translation into clinical practice, and that the DoH were "putting vastly more money into the Health Technology Assessment programme so that people can apply for grants to look at … clinical utility" (Q 858). However, we remain concerned. The HTA programme does not cover genetic or genomic diagnostic tests alone, but all diagnostic tests. We are also aware that research proposals on genomic tests have been declined. The UK Genetic Testing Network (UKGTN) expressed concern that genetics was not a high enough priority for research within the HTA, and they noted with disappointment that the "HTA did not take up a proposal to examine microarrays and their introduction into clinical practice" (p 212).

3.32.  Professor Sir John Bell suggested that a specific HTA programme for diagnostics was "essential" as the problems associated with diagnostics were very different from those associated with therapeutics and "such a programme would provide information … for the regulatory decision as to whether or not to license such technologies in the NHS" (p 226). We agree. We recommend that the National Institute for Health Research ring-fence funding, through a specific Health Technology Assessment programme, for research into the clinical utility and validity of genetic and genomic tests within the NHS.


3.33.  At present, genetic tests for single-gene disorders which are developed within the NHS are evaluated by the UKGTN. The UKGTN is a collaborative group of NHS laboratory scientists, clinical geneticists, NHS commissioners and patient representatives. Tests that pass the UKGTN evaluation process, the "Gene Dossier Process", are recommended to commissioners for funding within the NHS.

3.34.  The UKGTN system works well for tests for single-gene disorders. In contrast, it is unclear how genomic tests for common diseases, including pharmacogenetic and microarray-based tests, are evaluated. The Medicines and Healthcare products Regulatory Agency (MHRA) is responsible for assessing the safety of new "in vitro diagnostic devices" including genomic tests, but this task is largely limited to ensuring compliance with EU regulations. It does not address the clinical validity or utility of tests. NICE and NHS QIS (Quality Improvement Scotland) have a remit to evaluate innovations in laboratory diagnostic techniques but in practice, according to the Royal College of Pathologists, "they have evaluated only a very small number" (p 109). It appears, therefore, that there is no body at present with a specific remit to evaluate pharmacogenetic tests or genomic tests for common diseases.

3.35.  Professor Peter Furness, President of the Royal College of Pathologists, suggested that the UKGTN Gene Dossier Process could be adapted to evaluate genetic tests for multifactorial disorders, but believed that the UKGTN was "vastly too small" to take on the task of running the process (Q 193). Professor Sir John Bell took a similar view: "I am not persuaded that the structure [of UKGTN] … is necessarily transferable into this rather more complicated, complex world where clinical utility testing will have to be done on thousands of patients in large prospective cohorts" (Q 448).

3.36.  The position with regard to the evaluation of genomic tests contrasts with the evaluation system for new drugs which, after clinical trials, have to pass through a rigorous independent evaluation within the National Institute for Health and Clinical Excellence (NICE) to assess their utility, validity and cost-effectiveness. According to Roche Applied Sciences, "the pathway for approval of new drugs in the UK is well-established …, but there is no NICE equivalent for diagnostics. The lack of clarity regarding both the regulatory and commissioning pathways presents a serious barrier to making novel molecular diagnostics available for clinical evaluation and use" (p 565).

3.37.  We note that Lord Darzi of Denham's final report included a commitment to creating a single evaluation pathway for new clinical technologies; and we were told by the Minister for Public Health, Ms Primarolo MP, that the DoH were already working closely with NICE to develop a new evaluation pathway which would include genetic testing. She also noted that the Ministerial Technology Strategy Group was considering the establishment of a diagnostic evaluation programme, due to start in June 2011 (Q 882).

3.38.  We welcome DoH's consideration of a diagnostic evaluation programme within NICE—but more needs to be done now. We note Professor Sir John Bell's view that there is a "need to identify a new agency that can handle the clinical utility evaluation of diagnostics" and that the NHS should "utilise NICE for this purpose" (p 226). We agree. We therefore recommend that the Department of Health extends the remit of the National Institute for Health and Clinical Excellence to include a programme for evaluating the validity, utility and cost-benefits of all new genomic tests for common diseases, including pharmacogenetic tests.


3.39.  Tests are developed both within the NHS and by independent laboratories (including tests for single-gene disorders, genetically complex diseases and pharmacogenetic tests). Those developed by independent laboratories are used within the NHS, in private healthcare services and directly by the consumer. Although these tests are regulated through the EU In Vitro Diagnostics Directive, the Directive does not require their clinical utility to be proved and nor are they subject to evaluation by an independent body (Q 299). Under the Directive most genetic tests are classified as "low risk", which means that the manufacturer of the test is responsible for ensuring that the test fulfils the requirements of the Directive rather than a regulatory body such as NICE or UKGTN.

3.40.  Ms Primarolo told us that the MHRA had acknowledged the concerns raised by Member States, including the UK, over the classification of genetic tests and that there was overwhelming support for moving genetic tests to the second highest risk category. This would require them to be subject to a more stringent assessment than they are at present. Ms Primarolo told us: "The Commission are currently assessing the results of the public consultation and I hope that this will produce some sort of proposal on the way forward as quickly as possible" (Q 879).

3.41.  We recommend that the Government support the re-classification of genetic tests to "medium risk" in the current review of the EU In Vitro Diagnostic Medical Devices Directive so as to ensure that all genomic tests on the market have been subject to pre-market review before their use either by the consumer directly or by the NHS and private healthcare services.

The development of stratified or personalised uses of medicines

3.42.  Stratified or personalised use of medicines entails matching therapies to specific patient groups using clinical biomarkers to target more effective treatments, for example by taking account of patient susceptibility to particular drugs or to adverse drug reactions. The stratification of patient groups for the purposes of prescribing involves using tests—often genetic tests—to separate patient groups according to their likely response to a particular therapy. Such tests are required for certain treatments under NICE guidelines. The number of drugs for which such tests are recommended is currently small but is likely to increase in the future. In its 2007 report, Optimizing stratified medicines, the Academy of Medical Sciences noted a consensus amongst researchers, economists, healthcare providers and the pharmaceutical industry that "stratification is desirable for patients, healthcare systems and companies".

3.43.  Stratified use of medicines is the area of genomic medicine which is predicted to hold the greatest potential for the healthcare sector in the near-term. It has the potential to cut the cost of ineffective drug treatments within the NHS and also reduce life-threatening adverse reactions. However it also presents one of the biggest translational challenges—not only because of the complexities of developing and assessing a medicine and a genetic test at the same time but also because of the lack of incentives within the pharmaceutical and biotechnology industries to develop stratified medicines.

3.44.  Given that the current blockbuster model for drug development is not considered to be sustainable in the longer term and that the industry is under pressure due to the economic downturn, there is a pressing need for the industry to develop new business models for personalised medicines and it is vital to ensure that Government provides industry with incentives to do so.


Flexible pricing

3.45.  At present there is little incentive for the pharmaceutical industry to develop the genomic tests necessary for the application of stratified medicines. Under existing business models for drug development, drugs are targeted at a large number of patients. This ensures a return on the substantial research and development investment needed to bring the drugs to market. But stratified use of medicines is targeted at much smaller patient groups, and also requires the development of an accompanying test. For stratified medicines therefore the return on investment and the cost for treatment will have to be higher for each patient.

3.46.  Professor Sir John Bell suggested that "the delivery of a new set of genetic tools into the clinic has proved really difficult in every jurisdiction". One reason for this was that diagnostic companies could not be relied on "to do what is done in therapeutics, which is to demonstrate clinical utility" and this was "because the cost of a clinical utility programme is such that, at the prices paid for diagnostics, they would never get the money back" (Q 444).

3.47.  Pricing of medicines for use within the NHS is governed by the Pharmaceutical Price Regulation Scheme (PPRS). It is a non-contractual scheme aimed at ensuring that safe and effective medicines are available on reasonable terms to the NHS, in the context of a strong, efficient and profitable pharmaceutical industry. Despite this recognition of the needs of the industry, the pharmaceutical companies, Roche and Astrazeneca, were critical of PPRS. They told us that it failed to reflect the therapeutic value of the drugs that companies were supplying to the NHS (thereby endorsing the findings of an Office of Fair Trading market study of the PPRS in 2007)—"a situation" they warned "that is likely to become even more acute as personalised medicine develops" (p 360).

3.48.  Roche suggested that "a new model" was required "consisting of flexible pricing for personalised medicines and intellectual property protection and value-based reimbursement for both targeted drugs and companion diagnostics" (p 360). This would allow the price of a medicine to be amended retrospectively if the value of the medicine to patient care had proved to be higher than first anticipated. In November 2008, the PPRS was revised to introduce a more flexible pricing scheme which took into account the possibility of retrospective price change. According to the report, The Review and Refresh of Bioscience 2015, this development was welcomed by industry.[13]

3.49.  Whilst, as Professor Dame Sally Davies told us, value-based or flexible pricing was now an option under the new PPRS and therefore medicines targeted at a stratified group of patients could be submitted for consideration under the scheme (Q 906), problems remain. We recommend that the Government continue to work with the pharmaceutical industry to extend value-based pricing for the stratified use of medicines under the PPRS to reflect the value of drugs sold for stratified use and the increasing use of genetic tests to accompany such treatments.

3.50.  In light of the evidence we received about existing medicines (Q 719 and pp 360-61), we recommend further that, with regard to medicines for common diseases which are already in use in the NHS, the National Institute for Health Research should target funding to encourage the development of pharmacogenetic tests to stratify use of these medicines in order to improve their efficacy and to reduce the frequency of adverse reactions.


3.51.  Whereas the 2003 Genetics White paper acknowledged the importance of protection of intellectual property (IP) to encourage innovation and to ensure that innovations are transferred into clinical practice, the 2008 Review made no mention of how IP could be managed in the development of the stratified use of medicines and their accompanying diagnostics. We are aware that recent reports on IP—by the Department of Trade and Industry (DTI) in 2004 and the Gowers Review of Intellectual Property in 2006—concluded that the current law on IP was appropriate, but we believe that more work needs to be done on the management of intellectual property rights and the development of stratified medicines.

3.52.  We were told by the UK Intellectual Property Office (UK IPO) that the 2004 DTI report "supported the view that the current law and practice in the UK met the needs of researchers" and that "while the Gowers Review highlighted some historical concerns about the patenting of genes", it had "indicated that current policies for the scope of patents in this area were set at the right level and recommended that these should be maintained" (p 581). However, the UK IPO noted also that, although the UK has a strong IP track record in the academic sector, "there appears to be very little patent filing activity from the hospital sector", and that "given the importance of clinical research in developing and understanding disease conditions, it would be worth considering why this situation arises" (p 592).

3.53.  Dr Stuart Hogarth, member of the Society for Genomics Policy and Population Health, also questioned whether the current IP arrangements met the needs of researchers involved in stratified medicines. He told us that "it has been quite clear in our research [on the regulatory framework for genetic tests] … that because the industry's traditional business model is that it has intellectual property in testing platforms, not in biomarkers, it is poorly incentivised to do clinical studies that develop the evidence base for the clinical validity" or utility of new biomarkers. He explained this was because a company "that puts the investment into such a study", unless it has intellectual property in the biomarker, "will immediately have multiple other companies riding on that investment" (Q 338).

3.54.  We recommend that the Department for Innovation, Universities and Skills[14] address the issues relating to the management of intellectual property rights within the healthcare sector to improve incentives for stratifying uses of new and existing medicines and for development of pharmacogenetic tests necessary for stratification.


3.55.  A further disincentive to the stratified use of medicines arises from the separate development and authorisation processes for therapies and diagnostic tests. We received evidence, for example, that the health technology assessment for new diagnostics happens too late in the drug development process. According to the Bioindustry Association (BIA), "it is widely accepted by drug developers that, as long as the disease and response biomarkers are known, the earlier they are integrated and analysed in the clinical development programme, the better. Integration of biomarkers as early as in Phase I studies gives the opportunity to build the necessary knowledge to allow personalised medicine to be implemented at a later stage in clinical practice" (p 487). The BIA also commented that "timescales for the approval of genetic tests should not exceed those for drug approval, and medicines which employ pharmacogenetic information during prescribing must be assessed in a timely and appropriate manner during reimbursement decisions by NICE" (p 483).

3.56.  The ABPI suggested that "an integrated regulatory framework for the co-development of a medicine with a diagnostic or predictive test should be a priority" for the future. They suggested further that "OSCHR should take leadership in developing a UK national strategy on stratified medicines", taking into account "emerging science in drug discovery and diagnostics; e-Health; clinical application; regulatory environment; and health economics" (p 368). The Review and Refresh Bioscience 2015 report also called for the Government to develop a stratified disease strategy, involving industry, academia and a wide-range of relevant organisations.[15]

3.57.  We share the view that there should be a national strategy on stratified medicines to promote the development and use of such medicines. We therefore recommend that the Department of Health set out a national strategy on stratified uses of medicines (as part of the proposed White Paper on genomic medicine recommended in paragraph 3.12 of this report). The purpose underlying this strategy should be to streamline the co-development of stratified uses of medicines and of pharmacogenetic (or other) tests. This should achieve better value for money through effective targeting of pharmaceuticals by removing the current barriers to translation and encouraging the development and uptake of stratified uses of medicines.

Encouraging innovation in the biotechnology and healthcare sectors

3.58.  As we have said (see paragraph 2.5 above) the UK is well placed to capitalise on the huge potential market for genomic medicine because of the leading role played by UK scientists in the field, the availability of charitable and Government funding, and the ability to conduct genome-related clinical trials and research within the NHS. However, innovation in the sector is currently poor, with little uptake by the NHS of innovative medicines. The BIA told us that "currently the UK is one of the lowest adopters of innovative medicines in the EU" (p 486). To address this issue, the ABPI suggested the creation of an Innovation Platform by the Technology Strategy Board (TSB),[16] co-sponsored by DoH and DIUS.

3.59.  The Minister for Science and Innovation, Lord Drayson, explained: "The Technology Strategy Board is the mechanism within Government which identifies those areas where it is regarded that the UK has strategic competitive advantage in the scientific area and where there is both significant growth potential but also meeting what is regarded as the key demand facing the country" (Q 857). With regard to genomic science, in particular, he said "as yet the Technology Strategy Board has not identified genomics as a key platform and it could be argued that it should, and this is something which I am interested in looking into." (Q 857). He continued:

    "… [genomic medicine is] clearly an area where the United Kingdom has real global leadership; it is an area where the United Kingdom also has this unique advantage of the assets of the NHS and the structures which we have in the Department of Health. The question is: can we find better ways to support the development of innovative medicines and wealth in this country through the exploitation of those assets and that is certainly something into which I am urging the Technology Strategy Board to look further" (Q 907).

3.60.  We recommend that genomic science is adopted as a key technology platform by the Technology Strategy Board, to drive forward commercial development and clinical application in this area over the next five years and to maintain the UK lead in genomic medicine.

8   A Report to Government by the Bioscience Innovation and Growth Team, The Review and Refresh of Bioscience, January 2009, p 2. Back

9   The 2008 Review, p 26. Back

10   See footnote 8 above, pp 1-2. Back

11   Ibid, p 14 (recommendation 5). Back

12   Natasha Gilbert, "European finding plan 'unviable'", Nature, vol 456, 4 December 2008, p 551. Back

13   See footnote 8 above, p 4. Back

14   We are aware that on 5 June 2009, after this report was ordered to be printed by the House, the Department for Innovation, Universities and Skills (DIUS) and the Department for Business, Enterprise and Regulatory Reform (BERR) were merged to form the Department for Business, Innovation and Skills (BIS). Back

15   See footnote 8 above, p 48 (recommendation 15). Back

16   The Technology Strategy Board invests in and manages a range of delivery mechanisms and programmes to drive technology-enabled innovation. To guide their work, technology areas are identified, with Innovation Platforms targeting specific areas of challenge. Back

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