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

4 CJD risk management and surveillance

CJD risk management and 'at risk' individuals

67. Both classical and variant forms of CJD[214] are relatively rare and precautions are in place to prevent those known to be suffering from the disease from passing it on to others. However, CJD's long incubation period—that is, the time between infection and the onset of symptoms—means that people could unknowingly carry the disease for many years before symptoms appear. During this time, they could participate in procedures which risk exposing others.[215] To date, in the UK, over 6,000 people have been identified as being at increased risk of CJD as a result of this type of retrospectively recognised secondary exposure.[216] Public Health England (PHE) divides these people into two groups:

· "individuals with a known link to a clinical case of vCJD (through donation or receipt of blood or blood products, receipt of certain pooled plasma products or following surgical exposure); and

· groups of individuals, not linked directly to a clinical case but who, on the basis of a risk assessment, are defined as likely to have been exposed to a high enough risk of exposure through their treatment with blood or plasma products to inform them about this risk, where possible, and to recommend that public health precautions concerning blood, tissues, organs and surgery are followed".[217] (These precautions are detailed in box 1.)

Incidents leading to further additions to the 'at risk' list continue to occur and, until its dissolution in March 2013, were managed under the advice of the CJD Incidents Panel, a scientific advisory committee with expertise in CJD risk management.[218] According to PHE, between January 2010 and March 2013, the CJD Incidents Panel was notified of 43 'CJD incidents' and 70 lower-risk 'CJD reports'.[219]
Box 1: Public health advice for those notified that they are 'at risk' of having contracted CJD[220]

You have been identified as being at increased risk of CJD. You can reduce the risk of spreading CJD to other people by following this advice.
·  Don't donate blood. No-one who is at increased risk of CJD or who has received blood donated in the United Kingdom since 1980 should donate blood.
·  Don't donate organs or tissues, including bone marrow, sperm, eggs or breast milk.
·  If you are going to have any medical or surgical procedures, you should tell whoever is treating you beforehand so that they can make special arrangements for the instruments used to treat you.
·  You are advised to tell your family about your increased risk. Your family can tell the people who are treating you about your risk of CJD if you need medical or surgical procedures in the future and are unable to tell them yourself.

NOTIFICATION OF 'AT RISK' INDIVIDUALS

68. Historically, cases of potential CJD transmission were managed by the CJD Incidents Panel in collaboration with several bodies.[221] These included the Health Protection Agency, now PHE, which maintains a CJD Section to provide "national advice and support to prevent the potential spread of CJD in healthcare settings",[222] and the UK Haemophilia Centre Doctors' Organisation, an association of medical practitioners working within UK haemophilia centres.[223] Since the dissolution of the Panel last year, "responsibility for actions on individual CJD incidents"—including patient notification—has passed to local teams.[224] Dr Katy Sinka, PHE CJD Section, stated that when notifying an individual of their 'at risk' status, the aim was "to provide as much information and support as possible".[225] She added that "a whole suite of written information" had been produced to achieve this and that notification usually involved the person's GP or clinical specialist, "so there is someone who is able to support them and explain the risks".[226] The written information referred to by Dr Sinka consists of two six-page leaflets which detail the reasons for a person having been designated as 'at risk' and the potential implications of this status.[227] Website details are provided for those who wish to obtain further information.

69. Several witnesses highlighted issues with this process. Liz Carroll, Chief Executive of the Haemophilia Society, stated many of the people with bleeding disorders who were thought to be at risk had been written to, "but that was the extent of what happened really".[228] Mark Ward, TaintedBlood, confirmed that he had received such a letter but agreed that there had been little further support.[229] According to the CJD Support Network, a UK charity supporting those affected by CJD:

230

Nevertheless, the Government's Chief Medical Officer, Dame Sally Davies, indicated that she was "confident" that local CJD management and reporting structures were robust and that 'at risk' individuals were receiving the necessary support.[231]

70. People who are notified that they may have been exposed to CJD will inevitably be alarmed by this information and will likely have questions that cannot be answered in the leaflets currently provided by Public Health England. We consider it totally inappropriate for this news to be communicated solely in writing. We recommend that the Government put robust measures in place to ensure that all individuals assigned this designation receive the news verbally, either from a healthcare provider or from a CJD specialist with experience in patient communication.

The impact of 'at risk' notification

71. Several witnesses stressed to us the negative impact that 'at risk' notification could have on a person's life: Christine Lord, mother of vCJD victim Andrew Black, described the designation as "a sword of Damocles hanging over these people's heads".[232] Mark Ward, TaintedBlood, who has himself been notified that he is 'at risk' of CJD, agreed that the experience was like "walking around with a loaded gun pointing to your head",[233] adding:

234

Dr Simon Mead, Association of British Neurologists, described notification as a "concrete harm" because individuals were notified of their risk "with no opportunity for a blood test to confirm or not whether that risk is real, and with an indefinite prospect of a potentially incurable disease".[235] Dr Cosford, PHE, agreed that the "actual benefit" of telling a person that they were at risk was "very limited" and that notification was therefore "a very delicate area".[236]

72. Witnesses highlighted the potential for a vCJD blood test to minimise the harm caused by notification. Joseph Peaty, TaintedBlood, who is also 'at risk', highlighted that a blood test such as the one developed by Professor Collinge's group at the MRC Prion Unit could "possibly offer an element of comfort to some people—an element of reassurance", even if the results were not 100% reliable.[237] Liz Carroll, the Haemophilia Society, agreed that she "absolutely" thought that people should have the opportunity to utilise the existing test.[238] According to Professor Collinge:

239

Professor Collinge stated that the MRC Prion Unit had not, to date, made its test available to 'at risk' individuals because he did not think enough was known about infection risk for it to be useful.[240] However, he added that if more information was gathered "it may be that we could offer the test and provide some predictive value" for people impacted by their 'at risk' designation.[241] Professor Collinge stated that the test was already "in clinical use at the National Prion Clinic", where it was used for "diagnosing variant CJD".[242]

73. It is clear that the prototype vCJD blood test developed by the MRC Prion Unit cannot yet be relied upon for universal screening purposes. However, it could be of significant value to those people who have been notified that they are at increased risk of carrying the disease. Until the implications of a negative test result can be more firmly established, current precautions must remain in place for those considered to be 'at risk' of vCJD. However, the results of an imperfect test may provide comfort to some. We therefore recommend that 'at risk' individuals be given the opportunity to participate in the blood prevalence study recommended in paragraph 66.

CJD surveillance

74. The Government described national surveillance as "the cornerstone" of its policy "to monitor and control the spread of vCJD".[243] At present, this system consists of two main strands:

i) 'enhanced surveillance' of those considered to be 'at risk' of CJD, led by Public Health England (PHE); and

ii) national monitoring and investigation of suspected and confirmed cases of CJD, led by the National CJD Research and Surveillance Unit (NCJDRSU).

ENHANCED SURVEILLANCE OF 'AT RISK' INDIVIDUALS

In-life surveillance

75. According to PHE, individuals designated 'at risk' of CJD are "followed-up" in order to ascertain whether their potential exposure eventually leads to signs of clinical infection. It states that:

244

These "enhanced surveillance" activities are coordinated by PHE but rely on data held by several other organisations which are individually responsible for monitoring different 'at risk' cohorts (see table 2). Of particular note is the UK Haemophilia Centre Doctors' Organisation (UKHCDO), which is responsible for the surveillance of 3,875 bleeding disorder patients identified as having received plasma products between 1990 and 2001—the largest single 'at risk' group.[245]

Table 2: Summary of groups 'at risk' of CJD[246]

'At risk' group Organisation responsible Individuals designated 'at risk' Individuals notified of their 'at risk' status
All (alive)
CJD cases and asymptomatic infections

Recipients of blood from donors who later developed Vcjd Public Health England 67 27 (15) 4

Blood donors to individuals who later developed vCJD 112 107 (104) 0

Other recipients of blood components from these donors 34 32 (19) 0

Plasma product recipients (non-bleeding disorders) who received UK sourced plasma products 1980-2001 11 10 (4) 0

Certain surgical contacts of patients diagnosed with CJD 154 129 (113) 0

Highly transfused recipients 11 10 (6) 0

Total for 'at risk' groups where PHE holds data 389 315 (261) 4

Patients with bleeding disorders who received UK sourced plasma products 1980-2001 UK Haemophilia Centre Doctors' Organisation 3,875 National information incomplete 0

Recipients of human derived growth hormone Institute of Child Health 1,883 1,883 (1,504) 75

Total for all 'at risk' groups 6,147 >2,198 (>1,765) 79

76. When questioned about its enhanced surveillance scheme, Dr Katy Sinka, Head of PHE's CJD section, stated that there were long-term processes in place to identify "any development of neurological symptoms or CJD in people who have been told that they are at increased risk".[247] However, PHE acknowledges that it only holds data on 389 of the 6,147 individuals identified as being 'at risk' of CJD and that not all patients in this larger group have necessarily been notified of their status (see table 2).[248] In particular, PHE explains that:

249

Evidence from the cohort of patients managed by the UKHCDO indicated that, in contrast to the picture offered by PHE, little follow-up or support had been offered. TaintedBlood, a national advocacy organisation for haemophiliacs and others with bleeding disorders, stated that there had been a "breakdown in communication" following patients' notification of their 'at risk' status and that there had been no opportunity for patients to "discuss any concerns or fears".[250] Liz Carroll, the Haemophilia Society, agreed that there was no protocol in place to ensure that these patients were followed up, so it was impossible to "know for sure" that all patients had been notified or "what happened to everybody after that".[251] According to Mark Ward, TaintedBlood: "nobody is prepared to talk to you; nobody will give you any information, and I actually have nobody looking after me".[252] However, the Government's Chief Medical Officer, Dame Sally Davies, stated that she believed that clinicians were "giving good support" to those 'at risk' of CJD and were following those at highest risk "very carefully".[253]

77. The Government claims to be undertaking close surveillance of those it considers to be 'at risk' of CJD. Yet it cannot provide reliable data either on the total number of people designated 'at risk' or the number who have been notified of this fact. This is unacceptable. We recommend that the Government conduct an immediate audit of the entire 'at risk' cohort to establish whether any notifications remain outstanding and to ensure that appropriate support and follow-up is in place for all those affected. We also propose that the Government commission an independent review of the transfusion data pathway to ensure that, in the event of any future blood contamination incident, it can promptly trace, notify and provide support to affected recipients.

78. We were disappointed by the evident lack of support provided to those designated 'at risk' of CJD. We consider it inappropriate for the Government to have effectively delegated responsibility for the care and surveillance of a large proportion of these individuals to external bodies such as the UK Haemophilia Centre Doctors' Organisation—a charitable organisation with no formal relationship with the Executive. We recommend that the Government, through its public health agencies, assume direct responsibility for the surveillance and support of all those considered to be 'at risk' of CJD, with input from other specialist organisations as required.

Participation in research

79. PHE states that its follow-up of individuals 'at risk' of CJD includes the collection of blood and tissue samples and post-mortem investigation.[254] However, evidence suggests that only a small subset of individuals have been asked to provide consent for such research. Dr Katy Sinka, PHE, stated that, of the "small cohort [of 'at risk' individuals] that Public Health England follows up", "twenty-seven people were asked" for their consent for post-mortem investigation, "eleven of whom said yes".[255] These twenty-seven individuals included several patients who had received blood or blood products from donors who later developed vCJD and were therefore at particularly high risk of carrying the infection.[256] (Three of the eight patients examined from this cohort died of vCJD and the fourth showed signs of infection.[257]) According to Professor Knight, Director of the National CJD Research and Surveillance Unit, "in 2013 there were eleven deaths in the enhanced surveillance cohort"—"as far as we know, no post-mortems were done".[258]

80. Witnesses broadly agreed that data collected after death would be helpful in increasing our understanding of CJD, but disagreed about whether this justified compulsory post-mortem examination. Professor Bird stated that it was "regrettable" that "valuable evidence" from potential carriers of CJD was being destroyed and argued that those considered to be at high risk "should be subject to mandatory post-mortem" in the public interest.[259] She continued:

260

The majority of witnesses, however, shared the view of Joseph Peaty, TaintedBlood, who stated that "the mandatory route" was not "the right way to go".[261] For example, Professor Knight stated that he "would be very opposed to mandatory autopsy" and Dr Roland Salmon, Advisory Committee on Dangerous Pathogens, did not consider this to be "a terribly practical suggestion because I do think people expect a degree of autonomy about how they dispose of their bodies".[262] Professor Marc Turner, Advisory Committee on the Safety of Blood, Tissues and Organs (SaBTO), agreed that mandatory post-mortem would be "a step too far".[263]

81. In our view, the decision to participate in research should always rest with the individual or, in exceptional circumstances, their loved ones. Nevertheless, samples contributed by those potentially exposed to CJD are of immense scientific value and we are disappointed that more has not been done to obtain consent from those willing to participate in research. We recommend that the Government consider ways to increase the number of 'at risk' individuals giving consent for research participation, particularly post-mortem. We ask that the Government summarise its plans for achieving this in its response to this Report.

THE NATIONAL CJD RESEARCH AND SURVEILLANCE UNIT

82. The National CJD Research and Surveillance Unit ('the surveillance unit') was established in 1990 in response to a recommendation made by the Southwood Working Party.[264] Based at the Western General Hospital in Edinburgh, the unit was initially tasked with identifying any changes in the pattern of CJD cases which could be traced back to the BSE epidemic. It recognised such a change in 1996 and its work led to the characterisation of a new form of the disease: variant CJD (vCJD).[265] Figures for UK deaths from CJD—including both classical and variant forms—continue to be updated and published by the surveillance unit on a monthly basis and it also works on "a significant number of research projects", including studies focused on evaluating the risk of blood-borne transmission of vCJD.[266] It is supported primarily by public funds and the Government confirmed to us during our inquiry that it would continue funding the surveillance unit until "at least" 2017.[267]

Classification and reporting

83. National CJD surveillance is currently based on a "passive" system of bottom-up reporting.[268] Clinicians (most often neurologists) with someone under their care who they think may be suffering from CJD are asked to refer the case to the surveillance unit, which then investigates further.[269] If there is evidence to support a diagnosis of CJD, specialists from the unit classify that patient as either a 'definite', 'probable' or 'possible' case. Only cases receiving a final classification of 'definite ' or 'probable' are included in official statistics, which, to date, state that there have been 177 UK deaths from vCJD, most recently in 2013.[270]

84. One witness challenged the veracity of these official figures. Christine Lord, mother Andrew Black, who died of vCJD in 2007, stated that there had been a "definite under-reporting of vCJD cases" and provided the Committee with several examples of deaths which she alleges to have been misclassified by the surveillance unit.[271] According to Mrs Lord, "many flexible protocols" are used to diagnose vCJD "and this means that victims can disappear from official stats".[272] Professor Richard Knight, unit director, acknowledged that there was likely to be some accidental under-reporting but denied that cases had been deliberately misclassified, as suggested by Mrs Lord.[273] He explained:

274

Professor Knight stated that the surveillance unit had done "various things" to try to ascertain that it had "not missed cases" of CJD, including conducting retrospective reviews of death certificates to identify potential instances of disease.[275] He added that CJD cases were classified on the basis of a "diagnostic classification protocol" which had been "published in peer review journals", "presented at a wide variety of scientific meetings" and "discussed endlessly with international colleagues".[276] Thus, while acknowledging that he could not be "absolutely confident" that no cases had been missed, Professor Knight considered it unlikely that there was significant under-reporting and stated that the UK had "as good a surveillance system" as was "practically possible".[277]

85. Other witnesses agreed that deliberate under-reporting was unlikely.[278] However, there was evidence to suggest that some cases might be accidentally overlooked due to misdiagnosis, particularly given the similarities between CJD and other more common forms of dementia. According to Professor Collinge, MRC Prion Unit, "diagnosis of dementia in the elderly is not done well in this country" and, "given the way these people are investigated", a case of either classical or variant CJD could well be misdiagnosed as Alzheimer's disease.[279] Dr Simon Mead, Association of British Neurologists[280], agreed that poor diagnosis of dementia could give rise to "massive under-ascertainment" of CJD in the elderly.[281] Professor Knight stated that the surveillance unit was also interested in whether it was "missing cases in the elderly", particularly of classical forms of CJD, and that it had submitted a proposal to the Department of Health for a study to investigate this matter in more detail.[282] Dame Sally Davies, the Government's Chief Medical Officer, confirmed that there was "some discussion at the moment" as to whether the Government "could and should" fund this proposal.[283]

86. Evidence of potential under-reporting is also provided by the so-called "calibration problem"—that is, the discrepancy between the number of transfusion-transmitted cases of vCJD predicted by the available scientific evidence and the actual number of cases recorded in official statistics. In 2011, an analysis conducted by the Department of Health presented a model which attempted to solve the calibration problem.[284] Under this model, assumptions about the likely infectivity of blood and susceptibility to infection of transfusion recipients were varied in order to match the actual number of transfusion-transmitted cases reported by the surveillance unit. The amended assumptions generated by this model were used in the cost-effectiveness analysis performed on ProMetic's prion filtration device. However, according to ProMetic, "making the model fit the observed number of cases could result in a serious under-estimate of the possible future extent" of transfusion-transmitted vCJD.[285] ProMetic added that if the assumed prevalence of prions across the UK population were adjusted to 1 in 2000, as per the recent appendix study findings, then "the number of cases predicted by the model would significantly exceed the actual number of cases reported to date".[286] According to ProMetic, "this raises the question of whether a significant number of vCJD cases are currently being missed".[287]

87. We are confident in the integrity of the National CJD Research and Surveillance Unit and have not seen any evidence to corroborate claims of deliberate under-reporting or misclassification. However, we share our witnesses' concerns that cases could be missed due to misdiagnosis, particularly in the elderly. We recommend that the Government lend its support to research intended to give greater clarity over the causes of atypical dementia in the elderly and, through this, the potential rate of undiagnosed CJD.

214 In this Chapter, the term 'CJD' refers to both classical and variant CJD unless otherwise indicated. Back

215 Parliamentary Office of Science and Technology, vCJD in the future, POSTnote number 171, January 2002 Back

216 Public Health England, 'Creutzfeldt-Jakob Disease (CJD) biannual update (February 2014) with briefing on novel human prion disease', 14 February 2014, hpa.org.uk, accessed 30 June 2014 Back

217 BTO34 [PHE] Back

218 Health Protection Agency, 'CJD Incidents Panel', hpa.org.uk, accessed 30 June 2014 Back

219 Public Health England, Health Protection Report: weekly report, Volume 7, Number 33, 16 August 2013, hpa.org.uk, accessed 30 June 2014 Back

220 Public Health England, 'Information for people who have an increased risk of CJD', May 2013, hpa.org.uk, accessed 30 June 2014 Back

221 Health Protection Agency, 'CJD Incidents Panel', hpa.org.uk, accessed 30 June 2014 Back

222 Public Health England, 'Creutzfeldt-Jakob disease: General information', hpa.org.uk, accessed 30 June 2014 Back

223 UK Haemophilia Centre Doctors' Organisation, 'Introduction to UKHCDO', ukhcdo.org, accessed 30 June 2014 Back

224 BTO31 para 57 [Government] Back

225 Q266 Back