House of Commons - After the storm? UK blood safety and the risk of variant Creutzfeldt-Jakob Disease

After the storm? UK blood safety and the risk of variant Creutzfeldt-Jakob Disease - Science and Technology Committee Contents

3 Technology evaluation and the role of the scientific gatekeeper

30. Given the risk posed by prion transmission and the inability of existing measures to fully mitigate this risk, efforts are continuing, both in the public and private sectors, to develop new technologies for prion detection, inactivation and removal. The primary customers for these technologies are UK Blood Services and the NHS, access to both of which is typically mediated by one of several scientific bodies responsible for assessing the evidence to support technology adoption. Through the discussion of three case studies, this chapter examines the Government's approach to the evaluation of vCJD risk mitigation technologies, with particular focus on the role played by these scientific gatekeepers.

Case study 1: decontamination of surgical instruments

THE TECHNOLOGY: DUPONT'S RELY+ON PRION INACTIVATOR

31. According to the Department of Health's Decontamination Science Working Group, the risk to public health posed by surgical prion transmission is "not thought to be great".[92] However, "as it is known that a substantial number of people in the UK are carrying the abnormal prion protein that is responsible for the transmission of vCJD […], it cannot be assumed that there is no risk".[93] In response to this threat, the Government has dedicated significant funds to the field of decontamination science, valuing its current programme of research into this area at approximately £3.4 million.[94] This includes work focused on the development of new coatings for surgical instruments and "novel decontamination processes such as plasma technology", as well as "a substantial research project" looking at "novel ways to detect protein on surgical instruments".[95]

32. According to Professor John Collinge, Director of the MRC Prion Unit, this investment follows on from a similar "directed programme" of decontamination research, worth "I think […] over £10 million", initiated in the mid-2000s.[96] This was intended to encourage research groups to develop novel ways of removing prions from the surface of surgical instruments and resulted in the creation of "several solutions and products", one of which was based on a technology developed by the (publicly-funded) MRC Prion Unit itself. This technology was later commercialised by DuPont.[97] Dr Kelly Board, a Technical Specialist at DuPont, explained how this partnership came about:

According to Dr Board, the resulting product, the Rely+On Prion Inactivator, "rapidly reduces the potential risk of prion transmission in biosurgical instruments through use of a manual pre-soak product prior to the usual decontamination methods".[99] Dr Board added that the product's performance had been validated multiple times and had been shown to reduce the risk of infection "by greater than 1 million fold".[100] Rely+On was launched in May 2007 and was subsequently evaluated by the Government's Rapid Review Panel during 2008 and 2009.[101]

THE GATEKEEPER: THE RAPID REVIEW PANEL

33. The Rapid Review Panel (RRP) is an "independent arms-length" scientific advisory committee hosted by Public Health England (PHE).[102] It is responsible for providing "a prompt assessment of new and novel equipment, materials and other products or protocols that may be of value to the NHS in improving hospital infection control and reducing hospital acquired infections", including those caused by prions.[103] According to Dr Paul Cosford, PHE Medical Director, the RRP was set up "in the early 2000s at the specific request of UK chief medical officers" as "a specific means of rapidly reviewing new technologies and new ways of providing for hospital infection control".[104] The Government stressed that, despite its mandate to assess and make recommendations about the potential value of new technologies, it was not within the RRP's remit to "influence procurement and the 'uptake' of products into the NHS".[105]

34. Following assessment by the RRP, a new technology can receive one of eight recommendations. To obtain recommendation 1, the highest level of endorsement, the RRP must conclude that scientific evaluation of the product has "shown benefits that should be available to NHS bodies to include as appropriate in their cleaning, hygiene or infection control protocols".[106] In 2008, DuPont's Rely+On Prion Inactivator received the second highest level of recommendation, recommendation 2, which recognised that "basic research and development" had been completed and that "the product may have potential value", but recommended that further "in-use evaluations/trials" take place "in an NHS clinical setting".[107]

35. Despite receiving this recommendation, DuPont put further development of its product "on hold" in 2010.[108] It gave two main reasons for this decision:

· Difficulties trialling the product in an NHS setting: DuPont stated that it experienced difficulty in fulfilling the RRP's recommendation that it conduct further evaluation of its product in an NHS setting, as arranging "meaningful NHS trials" proved to be "incredibly challenging".[109] According to Dr Board, "it was very difficult for us to obtain approval to trial the product in healthcare settings" and, although the company made "several attempts" to conduct such trials, "only one materialised".[110] (Dr Board stated that this trial was "successful".[111]) The obstacles involved in initiating a UK clinical trial were well-documented in our own 2013 report on the subject.[112]

· Poor likelihood of NHS uptake: According to DuPont, while acknowledging that Rely+On "may have potential value", the RRP nevertheless "indicated that a pre-soak decontamination method would not obtain widespread use [in the NHS] while the prevalence of vCJD in the population remained unclear".[113] This was partly a result of the product's incompatibility with existing processes: as a pre-soak product, use of Rely+On would involve introduction of "an additional step to the decontamination process".[114] An Infection Prevention Product Specialist assigned by the Government to work with RRP applicants advised DuPont that "unless a much higher risk to the public" became apparent, such a change in procedure was "unlikely to be recommended in authoritative guidance" and DuPont's product was "therefore unlikely to be widely used".[115] Dr Board stated that this lack of a regulatory driver for product use was the "primary" barrier to further investment and development.[116]

Professor Collinge stated that it was "perhaps not surprising" that DuPont's product had not been adopted by hospitals, as the NHS was "notoriously resistant to change".[117] Nevertheless, he said that he considered it "quite extraordinary" that a product which was the result of research directly funded by the Government, and which successfully tackled a problem acknowledged by the Department of Health, had not been put to use.[118] DuPont stated that it had not received any return on the investment that it made in this product and that there would need to be "significant justification" for it to re-start development.[119]

36. The Minister stated that she was aware of Professor Collinge's criticism of the Government's handling of this issue but that there was "nothing to stop" DuPont from "taking matters further [by] going back to the rapid review panel and doing further development and further tests".[120] She added:

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Dame Sally repeated the RRP's view that "in-use evaluation trials" were now needed "in an NHS clinical setting" and stated that it was "for the company to do that".[122]

37. Given the NHS's resistance to change and the well-documented challenges associated with initiating a UK clinical trial, the Minister's assessment that "no barriers" were put in the way of DuPont's prion inactivation product does not reflect the reality of the situation. Where technologies are developed in direct response to Government need—and on the back of Government funding—the Government must be prepared to take steps to help companies overcome barriers to adoption. We ask the Government to set out how, in future, it will ensure that the directed research that it funds is better supported through the technology readiness pathway. In particular, we ask the Government to set out how it will ensure that promising clinical technologies are promptly trialled in an NHS setting, so that potential adoption challenges can be quickly identified and resolved.

38. We also question the value of a scientific review panel which has no mandate or power to ensure that the products that it recommends can be tested in, and eventually adopted by, the NHS. We see this as further evidence of the Government's passive approach to technology uptake. We propose that the Rapid Review Panel (RRP) be given stronger powers to ensure that its recommendations open the door to in-use evaluation and stimulate NHS uptake.

The Code of Practice for Scientific Advisory Committees

39. As a Scientific Advisory Committee (SAC), the RRP falls within the scope of both the Government Office for Science's 2011 Code of Practice for Scientific Advisory Committees ("the Code") and its 2010 Principles of scientific advice to government ("the Principles").[123] The Principles, which set out the "rules of engagement" for the relationship between the Government and its scientific advisers, highlight the need for "transparency and openness" and state that "scientific advice to government should be made publicly available unless there are over-riding reasons[124] […] for not doing so".[125] The Code likewise states that "SACs should operate from a presumption of openness" and sets out several measures to achieve this.[126] These include publishing, "as a minimum, programmes of work, meeting agendas, minutes, final advice (where appropriate) and an annual report".[127] The Code also stipulates that "Chairs and members should declare any interests they have that are relevant to the remit of the SAC" and that these should be published as part of the annual report.[128] With the exception of brief statements communicating the results of individual technology assessments, none of this information currently appears to be available for the RRP.[129] In particular, there was no evidence of any annual report having been prepared or published and no declaration of interests from the RRP's Chair or members. (We did not receive evidence from the RRP as part of this inquiry.)

40. In our view, all Scientific Advisory Committees should adhere to both the 2010 'Principles of Scientific Advice to Government' and the 2011 'Code of Practice for Scientific Advisory Committees'. We were disappointed to find that the Rapid Review Panel (RRP) failed to do so. We recommend that the Chief Medical Officer takes action to rectify current weaknesses. We request a progress report be sent to us well before the dissolution of Parliament.

Case study 2: prion filtration

THE TECHNOLOGY: PROMETIC'S P-CAPT PRION FILTER

41. Prion filtration is a process through which prions are physically removed from blood through the use of highly specific resin ligands, in order to "provide increased protection against the transmission of vCJD via blood and blood-derived products".[130] One group heavily involved in the development of this technology is the UK-based company ProMetic BioSciences ("ProMetic"). In 2002, ProMetic established a joint venture with the American Red Cross aimed at developing materials "with the ability to capture and remove prion proteins from a wide variety of biological source materials including blood, red cells, plasma and plasma proteins".[131] Four years later, following what ProMetic termed "extensive performance and safety testing", the P-Capt prion filtration device obtained its CE mark,[132] making it "the world's first prion-filtration product acknowledged to increase the safety of red blood cell concentrate".[133] At this point, the product became subject to further scientific evaluation, led by the Advisory Committee on the Safety of Blood, Tissues and Organs (SaBTO).

THE GATEKEEPER: THE ADVISORY COMMITTEE ON THE SAFETY OF BLOOD, TISSUES AND ORGANS

42. SaBTO is an independent scientific advisory committee responsible for advising "UK ministers and health departments" on "the most appropriate ways to ensure the safety of blood, cells, tissues and organs for transfusion/transplantation".[134] As part of its remit, SaBTO is specifically tasked with considering the "cost-effectiveness of interventions, including the introduction of new safety measures" such as prion filtration.[135]

43. In 2006, SaBTO initiated its evaluation of ProMetic's P-Capt device.[136] This consisted of three stages:

i) UK Blood Service studies. According to Professor Marc Turner, SaBTO, in 2006 UK Blood Services were asked to "commission and carry out a number of independent studies" to demonstrate the P-Capt filter's safety and efficacy "in the real word".[137] This included a series of laboratory studies and the PRISM A trial, which was intended to detect any adverse effects from use of prion-filtered red blood cells in a clinical setting.[138] Professor Turner stated that these studies "broadly showed that the filters were safe and were not causing any adverse impact to patients".[139]

ii) First set of efficacy evaluations. An initial set of efficacy evaluations, conducted by the Health Protection Agency (HPA, now Public Health England) and completed in 2009, showed that the P-Capt filter "removed infectivity" from test samples, "though not to the same extent as in the studies reported by the manufacturer".[140] Nevertheless, SaBTO concluded that the study supported the hypothesis that "prion infectivity" could "be removed by the filter" at levels high enough to confer protection on transfusion recipients.[141]

iii) Second set of efficacy evaluations. The second set of efficacy evaluations consisted of two studies; one, in hamsters, conducted by the HPA and one, in sheep, conducted by the Roslin Institute. Interim results were reported to SaBTO in March 2012;[142] to our knowledge, final results have not yet been published in a peer-reviewed journal.

Following completion of the first set of efficacy evaluations in 2009, SaBTO concluded that there was "sufficient evidence" to suggest that the P-Capt filter was effective in reducing prion infectivity and recommended that "filtered red cells be provided to those born since 1 January 1996, subject to satisfactory completion of the PRISM clinical trial".[143] The PRISM study was completed and reported positive results in March 2012;[144] however, at this time SaBTO received interim results from the second set of efficacy evaluations and decided that "no final decision" should be made until "further data on efficacy is available with respect to both the ongoing hamster and sheep studies and the final result of the current human appendix prevalence study".[145] In its evaluation of ProMetic's P-Capt device, SaBTO also drew on a cost-effectiveness analysis conducted on its behalf by the Department of Health's Health Protection Analytical Team.[146] In December 2012, having reviewed all of the available data, SaBTO decided to rescind its initial recommendation.[147] Prion filtration has therefore not been adopted by UK Blood Services and ProMetic has, to date, received no return on its $50 million (approximately £30 million) investment in this technology.[148] According to the UK Blood Services Prion Working Group, research conducted as part of this evaluation process cost upwards of £5.2 million.[149]

44. ProMetic criticised several aspects of this evaluation process and stated that it "strongly believed" SaBTO's 2012 reversal of its provisional recommendation "to be motivated by considerations other than filter efficacy".[150] ProMetic was particularly critical of the length of time taken to complete the PRISM A study (approximately 5 years), a technical issue in one of the hamster studies which it claimed compromised the filter's performance and the decision to test the filter in sheep, which it had previously demonstrated was "not an appropriate model" for determining the efficacy of the filter when used on human blood.[151] However, Dr Lorna Williamson, Medical and Research Director at NHS Blood and Transplant (and also a member of SaBTO), stated that these results had been "considered in the round" alongside other evidence and that she was "happy" with SaBTO's recommendation.[152]

45. We do not wish to question the scientific decision-making of the Advisory Committee on the Safety of Blood, Tissues and Organs (SaBTO) and we respect its decision not to recommend adoption of prion filtration at present. However, we feel that the time taken to reach this decision was excessive and that the process, particularly in its latter stages, entailed an unnecessary level of uncertainty for the commercial developer. We have some sympathy for SaBTO's desire to wait until more evidence was available before making a decision; however, if industry is to continue to develop innovative blood safety products for the UK market, SaBTO must introduce greater speed and predictability into its evaluation process. We recommend that, in future, when assessing a new technology, SaBTO agree with stakeholders at the outset what the evaluation will consist of, together with key dates, milestones and decision-points. This 'evaluation roadmap', and any subsequent amendments, should be made publicly available to ensure maximum transparency and accountability.

46. We also consider it important that the health technology appraisals conducted by SaBTO—and all other SACs—use the same methodology and meet the same high standards as those undertaken by the UK's centre of excellence for this activity: NICE. We therefore recommend that the Government Office for Science work with NICE over the next 12 months to develop and publish a standard methodology for all SACs tasked with conducting health technology appraisal. Until this guidance is published, we recommend that a NICE representative review and, where necessary, provide input to all such appraisals undertaken by, and on behalf of, SACs.

SaBTO's relationship with Government

47. The Government Office for Science's 2011 Code of Practice for Scientific Advisory Committees ("the Code") and its 2010 Principles of scientific advice to government ("the Principles") both highlight the importance of scientific advisors maintaining a level of independence from Government.[153] The Code, in particular, states that Scientific Advisory Committees (SACs) such as SaBTO should "expect to operate free of influence from the sponsor department officials" and that members should be "professionally impartial in their activity" on behalf of the SAC.[154]

48. Under its terms of reference, SaBTO is responsible for providing advice to "Ministers of the UK Government and the Devolved Administrations as well as UK Health Departments".[155] It is not sponsored by, and its advice is not formally directed at, any of the four UK Blood Services. However, SaBTO's Code of Practice acknowledges that its advisory role extends to "UK Blood Services […] and to the NHS more widely" and many of its recommendations are implemented by these organisations.[156] At present, two members of SaBTO also hold senior management roles in UK Blood Services: Dr Lorna Williamson, Medical and Research Director of NHS Blood and Transplant (NHSBT), and Professor Marc Turner, Medical Director of the Scottish National Blood Transfusion Service (SNBTS). NHSBT is an NHS Special Health Authority and, as such, "can be subject to ministerial direction".[157] SNBTS is a division of NHS National Services Scotland, a non-departmental public body of the Scottish Government.[158]

49. As well as being members of SaBTO, Dr Williamson and Professor Turner are also members of UK Blood Services' Joint Professional Advisory Committee (JPAC), which is responsible for developing UK-wide operational policies, often drawing heavily on SaBTO's advice.[159] According to JPAC, this advisory relationship between SaBTO and UK Blood Services also operates in reverse, as "much of the detailed evidence on which SaBTO deliberates is the result of work by Blood Services staff" and other Blood Service advisory committees reporting in to JPAC.[160] During the period in which ProMetic's prion filtration device was being evaluated, Professor Turner was also Chair of both SaBTO's prion sub-group and the UK Blood Services Prion Working Group.

50. Scientific Advisory Committees should be—and be seen to be—independent of the bodies to which they are providing advice. At present, the Advisory Committee on the Safety of Blood, Tissues and Organs (SaBTO) comprises members who are both contributing to, and acting on, the advice that it formulates. We consider that this could be damaging to its perceived independence and a source of potential conflicts of interest. We recommend that SaBTO's terms of reference be amended to reflect the fact that it does, in effect, provide advice to UK Blood Services as well as the Government. We suggest that SaBTO's current membership be reviewed and potentially revised in light of this change.

Case study 3: vCJD blood testing

THE NEED FOR A VCJD BLOOD TEST

51. A key strand in UK Blood Services' strategy for preventing transfusion-transmitted infections is the use of blood tests to enable those donations carrying known pathogens to be identified and discarded.[161] Unfortunately, this is not currently a viable strategy for mitigating the risk of vCJD transmission because no suitable high-throughput test currently exists. Witnesses were unanimous in their support for the development of such a test. Professor Sheila Bird, MRC Biostatistics Unit, expressed concern that the absence of a vCJD blood test meant that we could not protect the blood supply from prions in the same way that we can protect it from other pathogens, such as hepatitis B and C and HIV, and stated that development of a validated test should "undoubtedly" be a research priority.[162] Professor Richard Knight, Director of the National CJD Research and Surveillance Unit ('the surveillance unit'), agreed that development of a test was "extraordinarily important" and "would be a great boon in all sorts of ways".[163] In addition to its potential screening applications, witnesses highlighted the role that a blood test could play in providing certainty to patients thought to be at risk of vCJD. Joseph Peaty, TaintedBlood, told us that, some years ago, it had "looked very much" as though he was suffering from the early signs of vCJD.[164] He explained:

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The Government did not explicitly state its support for the development of this technology but acknowledged that a test "may be advantageous".[166]

52. The number of research groups working to develop a vCJD blood test has fallen in recent years. According to Professor Marc Turner, Advisory Committee on the Safety of Blood, Tissues and Organs (SaBTO), "looking back a decade or so ago, there were probably […] a dozen or more different research groups and commercial companies working" in this area. Now, however, "there are really only two or three".[167] Professor Turner stated that the "most advanced test by far" was the one currently being developed by the MRC Prion Unit, a publicly-funded research group led by Professor John Collinge.[168] In addition, Prionics AG, a Swiss company, has continued to conduct work in this area, as has the Scottish National Blood Transfusion Service, working in partnership with the national surveillance unit.[169]

THE TECHNOLOGY: THE PRIONICS BLOOD TEST

53. Prionics AG is a developer of diagnostic tests for major livestock diseases.[170] In 2001, when surveillance programs for BSE became mandatory in the European Union, Prionics "pioneered" the use of in-situ rapid diagnostic tests and, today, the company continues to develop diagnostic tools for prion diseases such as vCJD.[171] According to Prionics, it has made a "significant investment" in this area, spending "€5 million to €10 million" on the development of prototype vCJD blood tests since 2002.[172] In 2009, NHS Blood and Transplant (NHSBT) issued a tender for the development of a diagnostic test for use in vCJD blood screening. Following a successful bid, Prionics was awarded a framework contract pending further evaluation of its test by the National Institute of Biological Standards and Controls (NIBSC), the body tasked with maintaining and managing the distribution of rare vCJD blood samples.[173]

THE GATEKEEPER: THE NATIONAL INSTITUTE OF BIOLOGICAL STANDARDS AND CONTROLS

54. The National Institute of Biological Standards and Controls (NIBSC) is a body of the Medicines and Healthcare Products Regulatory Agency, an Executive Agency of the Department of Health.[174] It hosts the CJD Resource Centre, which exists to "help research scientists obtain characterised materials for studying and developing diagnostic tests" for all forms of CJD.[175]

55. In order to develop a diagnostic blood test, it is necessary for researchers to have access to blood samples from people who have suffered from the target infection. In the case of common blood-borne pathogens such as hepatitis B and HIV, such samples can be easily obtained. However, because vCJD is such a rare disease, patient samples are extremely scarce.[176] In the UK, the majority of samples from confirmed vCJD cases are initially collected and stored at either the surveillance unit or the MRC Prion Unit.[177] According to the NIBSC, following requests for access to these samples from several test developers in the mid-2000s, the Government concluded that access should be "controlled" and only granted to those developers whose tests were most likely to be successful.[178] In 2007, an Oversight Committee was established within the CJD Resource Centre to "perform evaluations" of prototype tests and "manage the distribution of samples" according to a standard protocol.[179] According to Dame Sally Davies, Chief Medical Officer, the NIBSC currently holds samples from 16 individual vCJD patients: equivalent to approximately "one and a half tablespoons" of blood.[180]

56. In order to gain access to these samples, test developers require NIBSC approval. However, according to the NIBSC, "it was agreed at the start of the [CJD Resource] Centre's existence" that the two primary centres of UK prion research—the national surveillance unit and the MRC Prion Unit—should be exempt from this process in order to avoid "unreasonably" restricting their research work.[181] Additional samples are therefore currently held and used by these units and, on occasion, are provided directly to other test developers without recourse to the NIBSC evaluation process.[182]

57. Several witnesses expressed concern about the way in which access to vCJD samples was controlled in the UK. Christine Lord, mother of vCJD victim Andrew Black, pointed out that the Government held "all the keys" to vCJD test development and claimed that a "few select scientists and Government officials" held "a monopoly" over this research area.[183] Mrs Lord added that relatives of victims had been "thwarted and blocked" in their attempts to share blood samples with foreign research groups.[184] Dr Alex Raeber, Head of Research and Development at Prionics AG, agreed that, "as a foreign company", Prionics was "not treated in the same way as other stakeholders" and had faced "big challenges" in obtaining access to samples.[185] According to Dr Raeber, while the NIBSC had done "an excellent job" in setting up the test validation process, the number of samples made available through this process was "very limited".[186] Prionics' test was evaluated on the basis of two samples from known vCJD patients and, on the basis of this evaluation, was deemed "not sufficiently fit for purpose".[187] The test was never used by UK Blood Services.

58. Dr Raeber criticised this evaluation process, stating that it was "really not adequate" for the NIBSC to validate the efficacy of his company's test on the basis of only two samples[188], particularly given that there was no guarantee that prions were present in these particular samples.[189] Professor Sheila Bird, MRC Biostatistics Unit, agreed that the statistical significance of this evaluation was questionable and pointed out that "provision of fewer than five or six vCJD samples within a blind panel of 500" was an "inadequate—or very harsh" statistical assessment to which to submit a prototype test.[190] In contrast, the test developed by the MRC Prion Unit (discussed below) has so far been validated on the basis of 21 samples from known vCJD cases, all sourced directly from its own collection of patient samples.[191] In response to these criticisms, the NIBSC stated that its process was "open to all" and that, in fact, "most interactions" had been with non-UK developers rather than UK companies.[192] It acknowledged that it was "not ideal that only two samples were made available" to Prionics, but stressed that this decision was made only after "substantial discussion in the Oversight Committee".[193]

59. We understand the need to carefully control access to rare vCJD samples and commend the National Institute of Biological Standards and Controls (NIBSC) for putting in place a standard protocol for test validation. However, we are disappointed that so few samples are currently held by the NIBSC and consider its process to be undermined by the fact that the two major centres of UK prion research—the National CJD Research and Surveillance Unit and the MRC Prion Unit—can each use and distribute samples independent of NIBSC evaluation. All test developers should be given equal opportunity to gain access to the available samples and these should be distributed on the basis of merit alone. We recommend that access to all vCJD patient samples—including those currently held elsewhere in the UK—be managed through the NIBSC, according to a consistent set of test validation protocols.

60. We were also concerned by the apparent statistical weakness of past NIBSC evaluations. We recommend that the CJD Resource Centre Oversight Committee add to its membership an individual with expertise in biostatistics, who can provide it with expert advice on this matter during future deliberations.

THE TECHNOLOGY: THE MRC PRION UNIT BLOOD TEST

61. The MRC Prion Unit was established in 1998 and is located at the UCL Institute of Neurology.[194] It was formed "to provide a national centre of excellence with all necessary facilities to pursue a major long-term research strategy in prion and related diseases".[195] The Unit undertakes research across a wide-range of topics and aims to "seamlessly combine basic (laboratory) and clinical (patient-based) research" in order to enable "better early diagnosis, prevention, and effective treatment" of prion disease.[196] It receives approximately £6 million per year from the Medical Research Council and is led by John Collinge, Professor of Neurology and Head of the Department of Neurodegenerative Disease at the UCL Institute of Neurology.[197]

62. In February 2011, the Unit announced that it had developed a prototype blood test capable of detecting "blood spiked with a dilution of vCJD to within one part per ten billion—100,000 times more sensitive than any other method developed so far".[198] In this study, the prototype test returned no false positives from 100 control samples and accurately identified 15 of 21 samples taken from known vCJD patients as positive, indicating that the test was 100% specific and approximately 70% sensitive.[199] In a larger follow-up study published in early 2014, the prototype was tested on 5,000 control samples (from US citizens considered not to have been exposed to BSE) and a subset of the vCJD samples previously used in the 2011 study. It again demonstrated 100% specificity and 70% sensitivity.[200]

63. Professor Collinge stated that the next logical step in the test's development would be to carry out a larger 'population prevalence' study in which the prototype would be used to test 20,000 UK blood samples and 20,000 US blood samples, at an estimated cost of £750,000.[201] According to Professor Collinge, if, during this study, the test returned positive results only from UK samples, two things could be concluded:

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A proposal for this study was considered by the MRC in March 2013, but was rejected, in part because of the test's "low level of sensitivity".[203] According to the MRC:

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Professor Collinge disputed the MRC's decision, claiming that the recommended steps constituted "test development work" which lay outside of his unit's area of expertise.[205] He added that, in the view of his Unit's "statistical advisers", the test's sensitivity was "perfectly adequate to do the study that we propose to do" and that it may not be possible to further increase sensitivity because "it could be that only 70% of people with vCJD have prions in their blood".[206] Professor Collinge also highlighted that feedback from diagnostics companies was "very much" that they wanted to see the results of a larger study "before thinking about whether they would help us to take [the test] any further"—a view confirmed by several industry representatives.[207]

64. Expert witnesses strongly supported Professor Collinge's proposal for a UK blood prevalence study; indeed, Dr Simon Mead, Association of British Neurologists, stated that there now appeared to be "scientific consensus" on this matter.[208] Professor Marc Turner, SaBTO, agreed with Professor Collinge that the test's sensitivity was "pretty good" and considered a blood prevalence study to be "the next logical step" in its development, while Dr Roland Salmon, Acting Chair of the Advisory Committee on Dangerous Pathogens, considered there to be "a great deal of scope" for the test to be used for research purposes in its current state.[209] Dr Lorna Williamson, NHS Blood and Transplant (NHSBT), took a similar view:

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The Government, however, stated that there were "currently no tests suitable" for this purpose and was non-committal in its support for further test development work.[211] Dame Sally Davies, Chief Medical Officer, stressed that the Government had "limited budgets for healthcare, public health and research" and that it had previously "given a lot of money to this area of prion research, particularly to Professor Collinge".[212] The Minister said that she was "open-minded to receiving advice" on this matter, but added that she was "pretty satisfied that, proportionate particularly to the number of cases and deaths over the last 10 years or so, there is a good body of work going on at the moment".[213]

65. The incubation period of prion diseases such as vCJD can extend to several decades and it is therefore possible that individuals infected in the 1990s might not yet have developed symptoms. We do not follow the Minister's logic that there should be a link between the number of cases seen in the last ten years and the level of resource dedicated to prion research. We simply do not know, at present, how many people have been exposed to prions and what the implications of this might be for the blood donor pool. There is an urgent need to reduce this uncertainty.

66. Based on the testimony that we have heard, we consider that a vCJD blood prevalence study utilising a version of the prototype test developed by the MRC Prion Unit would be of considerable value, both for test development and research purposes. We recognise that significant public funds have already been directed towards the development of this test; we view this as even more reason to ensure that a return on this investment is realised. To cut off support now would be a false economy. We recommend that the Government ensures that a large-scale vCJD blood prevalence study be initiated in the UK within the next 12 months.

92 BTO20 para 3 [DH DSWG] Back

93 BTO20 para 3 [DH DSWG] Back

94 BTO55 [Government supplementary] Back

95 BTO20 paras 7-9 [DH DSWG]. See also BTO55 [Government supplementary] Back

96 Oral evidence taken on 27 November 2013, HC (2013-14) 846, Q43 Back

97 Oral evidence taken on 27 November 2013, HC (2013-14) 846, Q43 Back

98 Q67 Back

99 Q67 Back

100 Q67 Back

101 Q67 Back

102 Public Health England, 'Rapid Review Panel', hpa.org.uk, accessed 30 June 2014 Back

103 Public Health England, 'About the Rapid Review Panel', hpa.org.uk, accessed 30 June 2014; BTO31 para 53 [Government] Back