Regenerative medicine Contents

3Adoption in the NHS

36.In this chapter, we look at the adoption of regenerative medicine in the NHS, examining the current infrastructure, the role of the National Institute for Health and Care Excellence and NHS England in taking regenerative medicine forward. We also examine the opportunities for regenerative medicine following the Accelerated Access Review and the Government’s Industrial Strategy.

NHS infrastructure

37.According to REGenerableMED (an ESRC-funded regenerative medicine project) the wider adoption of regenerative medicine therapies will require major, long-term infrastructure commitment alongside a responsive clinical demand-dependent product supply.66 At present, adoption by the NHS has been most rapid for clinician-led surgical procedures whose development may require only minor adjustments to existing clinical practices, such as limbal stem cell transplantation67 to restore corneal function. A key determinant has been how well the administration of particular cell therapies aligns with existing clinical treatment pathways.

38.The Scottish National Blood Transfusion Service voiced similar concerns: “No matter how good the science and manufacturing, if these products do not complement current clinical practice and harness existing infrastructure, implementation will be tortuous”.68 REGenerableMed explained that the emergence of potential complex advanced therapies and products (including medical devices and diagnostics) which do not have a clear regulatory and commercial route to their clinical use, highlights a need for regulation that can evolve in tandem with emerging scientific knowledge and new technologies.69 Professor Paul Whiting from the Medical Research Council’s Regenerative Medicine Research Committee explained the particular benefits of the NHS facilitating such an approach:

The UK is uniquely positioned to do long-term follow up, because of the NHS, where everybody has their identifier and people can get tracked through the system and monitored for a long time. That is not necessarily true, or largely not true, in many other places. That is an opportunity for us. […] The earlier you are getting the NHS familiar with these types of treatments, how they are dealt with, how they are processed at pharmacy and how they are then delivered to patients, the better, because that is what the NHS is going to have to square up to as these treatments get closer to market anyway, and the earlier we can promote that innovation in the NHS at a clinical trial level, the easier it is going to be further down the line when these treatments start to get approved […] and adopted in the NHS for patient benefit. The NHS is a resource that we have that is not replicated anywhere else in the world, so why don’t we use it for that purpose?70

39.The expansion of regenerative medicine as a scientific discipline—with its core principles of rejuvenation, regeneration and replacement (‘the 3Rs’)—is helping to drive a shift in healthcare from symptomatic to curative treatments. This is seen in an increase in clinical trials of regenerative medicine therapies.71 Our witnesses, nevertheless, described difficulties they have experienced in doing clinical research within the NHS. There were concerns about the current infrastructure and capacity of the NHS that does not lend itself to doing regenerative medicine clinical trials research. Parkinson’s UK told us that:

The research culture in the NHS needs to improve to embrace research. Capacity needs to be increased across the NHS to allow health professionals time to carry out research and develop their skills […] Many clinicians’ workloads do not allow them to have capacity to carry out research.72

40.The University of Bristol believed that “the system is not clear to the majority of researchers in regenerative medicine”. It wanted “a formal national regenerative medicine network” to be created, comprising researchers, industry, NHS and regulatory bodies, “to enhance synergy, sharing and cross-fertilisation across an area of science that is highly interdisciplinary”.73

41.The Academy of Medical Sciences also expressed concerns about the preparedness of the current healthcare system to adopt regenerative medicine therapies:

We need to consider the preparedness of the UK healthcare system, in terms of technical and clinical capacity as well as capability for the complexity of such therapies (including when running clinical trials) taking into account the cost implications. The technologies required for regenerative medicine are not current available through NHS laboratories and there will be significant training needs for all healthcare staff […] To maximise cost-effectiveness and appropriately manage demand in the shorter term, there may be a case for accreditation of centres that wish to deliver regenerative medicine therapies, so that the appropriate infrastructure is in place.74

42.REGenerableMED highlighted that although NHS England has policy responsibility for healthcare ‘innovation’, regenerative medicine has not been explicitly mentioned in any its recent strategies such as the NHS Five Year Forward View or ‘sustainability and transformation plans’75 Adoption of regenerative medicine varies by individual NHS Trusts.76 Nevertheless, one of our NHS England witnesses reassured us that:

Regenerative medicine links very much to our strategy […].That has been developed, and now we are going into implementation. We feel it meets our approach to the health and wellbeing gap and the link to the Five Year Forward View around precision and personalisation. For that […] we need clear clinically-led decision making about making the right products available and put into practice for our patients; that we work with industry in general to ensure we can get the best innovative pricing around; […] that we make sure that, where they are commissioned, we get the uniformity of access across England that we would expect our patients to want; and importantly that we continue to collate the data we need to make sure that the treatments are delivering in the way they are expected to.77

43.Dr Sven Kili, head of Gene Therapy development from GlaxoSmithKline, voiced concerns regarding the NHS’s capacity to take forward regenerative medicine:

Very often, you approach an NHS hospital, they are under staffed. The nursing staff who are working to support are so busy just taking care of patients that they do not often have the time to look after a study […] We need a mechanism to make them better to be able to do clinical trial work.78

Professor Paul Whiting from the Medical Research Council’s Regenerative Medicine Research Committee similarly told us that:

It is not easy to interact with the NHS very often. It is not obvious where the portal is, the entry point, for some things you want to do, and people are enormously conscious of the perceived or otherwise ‘stress’ that the NHS is under. That is, if we are not careful, going to build a reluctance to interact with the NHS.79

44.In July 2016, NHS England announced the results of its “clinical prioritisation process”, and confirmed that funding would not be allocated for the routine commissioning of stem cell transplants.80 While providing second stem cell transplants was recognised by NHS England as being clinically effective, the treatment was considered unaffordable relative to other treatments. According to the Anthony Nolan, “this decision represents a backwards step for the health service as second stem cell transplants were routinely available to patients prior to 2013”.81

NICE Heath Technology Appraisals and NHS Specialised Commissioning

45.Regenerative medicine presents particular difficulties for the National Institute for Health and Care Excellence’s (NICE’s) technology appraisal process because while such therapies potentially confer substantial health gains, they can also be expensive on a per-patient basis and be supported by a weak evidence base. In response to recommendations set out by the Regenerative Medicine Expert Group, NICE published in March 2016 the findings of an independent appraisal of regenerative medicines and cell therapies.82 It included a ‘mock’ appraisal of a hypothetical product83 based on new, unlicensed cell therapies for treating a type of leukaemia in children.84 Their report concluded that NICE’s health technology appraisal methods could be applied to regenerative medicine and cell therapies,85 but Advanced Therapy Medicinal Products (ATMP) developers still had some concerns:

Some cell and gene therapies will not meet NICE’s criteria for appraisal because of NICE’s cost threshold or the challenges of managing ‘immature data’;
Some cell and gene therapies will be for rare conditions with patient populations that are very small, in which case they will not be assessed by NICE. In these cases, therapies would have to be considered under specialised commissioning routes rather than through NHS commissioning, and their adoption will be determined at local rather than national NHS levels; and
There is a perception that NICE’s data requirements to tackle the uncertainty around novel cell and gene therapies may be disproportionately burdensome compared to traditional small-molecule or biological medicines.86

46.Subsequently, NICE and NHS England consulted on proposals in January 2017 to change the arrangements for evaluating drugs and other health technologies through NICE’s ‘technology appraisal’ and ‘highly specialised technologies’ programmes.87 The proposals include introducing a ‘budget impact threshold’ of £20 million, linking NICE and NHS England processes for evaluating highly specialised technologies and the introduction of a new ‘fast track’ appraisal. Michael Hunt of ReNuron told us that “companies like us spend a lot of time thinking or worrying about the ability of payers to pay for these treatments: how are they going to be paid for, are the existing mechanisms appropriate, in terms of NICE evaluation, health technology appraisals and so on”.88

Payment and reimbursement

47.In the England and Wales NHS, new healthcare therapies may be paid for (or ‘reimbursed’) in accordance with decisions at a local level via individual NHS Foundation Trusts and regional Clinical Commissioning Groups, or at a national level through a NICE Technology Appraisal.89 In addition, NHS England is able to commission ‘specialised services’.

48.Securing reimbursement in these ways was identified by our witnesses as a major challenge. Michael Hunt from ReNuron told us that manufacturers of regenerative medicine therapies have struggled to obtain reimbursement consistently across EU countries.90 There remains substantial inconsistency in the uptake of the Health Technology Assessment (HTA) across the EU, despite proposals to improve coordination.91 Questions raised about the suitability of existing HTA methodologies led NICE to undertake a review of the technology appraisal of a regenerative medicine therapy on the NHS. REGenerableMED saw a need to extend this analysis to a wider range of regenerative medicine therapies. It recommended that priority should be given to gathering information on Clinical Commissioning Groups’ position on regenerative medicine in service contracts and for further support to be given for coordination between the MHRA, NICE’s Office for Market Access and NHS England.92

49.Michael Hunt from ReNuron told us that:

The biggest challenge that now remains, beyond garnering clinical data for proof-of-concept in man is getting these treatments adopted in the UK through the NHS in routine practice and, of course, paid for—’reimbursed’. How are we going to pay for treatments, especially where there is the potential for very significant long-term healthcare savings, quite apart from patient benefits in the long term that may come at a considerable up-front cost compared with more conventional treatments? That is the difficult equation that the field now needs to tackle and solve.93

50.Keith Thompson, Chief Executive from the Cell and Gene Therapy Catapult, emphasised that:

The next step in the deconstruction of all the barriers is to get more rapid access to the NHS and to join up the reimbursement challenge. Compared with Japan as a for instance, Japan’s regulatory regime changed, it’s fairly complex, but they gave earlier conditional licensing plus reimbursement. They get early access to patients and they get paid for it. Although global pharmaceutical firms probably take a more global view, certainly SMEs are very attracted to that and it is SMEs that come in, do the early work and put their roots down into complex supply chains that simply cannot be uprooted and moved elsewhere.94

51.Having a universal NHS for all patients provides a receptive environment for the development and adoption of innovative and scientific advances in regenerative medicine. The next Government should nevertheless work with NHS England and Clinical Commissioning Groups to create the appropriate financial incentives to stimulate regenerative medicine research and innovation within the NHS, which will encourage more clinicians to become more involved in research. The next Government should also support work by NHS England and NICE to deliver a ‘fast track’ appraisal system for emerging regenerative medicine therapies.

52.The next Government should also work with the biotech sector and with NHS England and NICE to agree new reimbursement payment models which take greater account of the value of regenerative medicine therapies that offer cures, reduce healthcare costs and make treatments available earlier to patients.

A strategy for regenerative medicine

53.The Accelerated Access Review was commissioned by the Department of Health and the former Department for Business Innovation and Skills in November 2014.95 It made recommendations in October 2016 to make it easier for NHS patients to access innovative medicines, medical technologies, diagnostics and digital products, to improve patient outcomes.96 The review recommended the creation of a new ‘accelerated access partnership’ to speed up and simplify the process for getting the most promising new treatments and diagnostics safely from pre-clinical development to patients.97 The review concluded that accessing innovation in the NHS had become increasingly challenging. Through the proposed new partnership of NHS England, NHS Improvement, NICE and the MHRA, innovators would be able to access joined- up help for clinical development, regulation and assessment of cost-effectiveness.98

54.Innovate UK hoped that the review would make further recommendations that would speed up the adoption of ATMPs (paragraph 30) so that patients will benefit from these treatments earlier.99 We are still awaiting the Government’s response to the recommendations set out in the Accelerated Access Review.

55.There is no explicit mention of regenerative medicine in NHS England’s recently updated Five Year Forward View,100 although there was a focus on innovation and the likely opportunities in the life sciences in the Government’s Industrial Strategy.101 NHS England published its Personalised Medicine strategy in September 2016, in which personalised medicine was defined as “a move away from ‘one size fits all’ approach to the treatment and care of patients with a particular condition, to one which uses new approaches to better manage patients’ health and targets therapies to achieve the best outcomes in the management of patients’ disease or predisposition to disease”.102 This strategy had a strong focus on informatics and genomics, but there was no mention of regenerative medicine. Dr James Palmer told us that regenerative medicine was “so interlinked [with personalised medicine] that it is right that the NHS has focused on the genomics side first, because the regenerative medicine side is still a way away from those big transformative curative treatments; they are not coming through thick and fast”.103

56.The Regenerative Medicine Expert Group provided recommendations to Government to develop an NHS regenerative medicine strategy to deliver innovative treatments. While the Government has responded and made progress through investment in further research and in setting up the Cell and Gene Therapy Catapult, there is still more work to be done. A strategy is needed that covers the entire value chain—academic research, commercial development and clinical application—if the UK is to respond to the challenges of our healthcare system as well as facilitate economic growth.

57.NHS England needs to take a lead on regenerative medicine by including it explicitly in its Personalised Medicine strategy. This would send a strong signal to the sector of the NHS’s commitment and willingness to adopt new and emerging therapies.

58.The next Government should work with UK Research & Innovation, industry, academic researchers and the health sector to develop a strategy for Advanced Therapies, which should include regenerative medicine and cell therapies. The strategy should be aligned to the Government’s response to the Accelerated Access Review and the strategic objectives outlined in the Government’s Industrial Strategy Green Paper.

66 REGenerableMED (REG0004)

67 Limbal stem cell transplantation involves the grafting of stem cells that have been taken from donor eyes and grown in tissue culture, with the aim of improving vision and other symptoms such as eye irritation and dryness.

68 Scottish National Blood Transfusion Service (REG0015)

69 REGenerableMED (REG0004)

70 Q114

71 Caplan A.I, Mason C., Reeve B, “The 3Rs of Cell Therapy”, Stem Cells Translational Medicine, vol 6 issue 1 (2016)

72 Parkinson’s UK (REG0005)

73 University of Bristol (REG0002)-

74 Academy of Medical Sciences (REG0014)

75 REGenerableMED (REG0004)

76 REGenerableMED (REG0004)

77 Q192 [Dr Jonathan Fielden] (see also NHS England, Board Paper - Strategic Framework for Specialised Services, May 2016)

78 Q103

79 Q117