Science in emergencies: UK lessons from Ebola Contents

2Increasing the UK’s preparedness for major disease outbreaks

10.This chapter considers measures that the UK could instigate, or develop further, to improve our capacity to withstand global disease outbreaks. Increasing the UK’s emergency preparedness involves taking steps to ensure that, as a country, we are better able to anticipate, absorb, and accommodate ‘shocks’ to the system, such as extreme events, while also recovering rapidly, and continuing to develop.

Disease surveillance

11.Disease surveillance and early diagnosis are vital components of controlling the spread of diseases. Public Health England (PHE), which manages the UK’s national and international systems for detecting disease threats, was praised by witnesses for the strength, quality and effectiveness of its surveillance capacity.9 There was also a consensus across the evidence we received that the Government must work to strengthen surveillance capacity and capability globally, especially in emerging infection ‘hot spots’ that tend to be located in less economically developed countries.10 The Government appeared to have taken a similar view, announcing in March 2015 a £195 million investment in the Fleming Fund “to build laboratory capacity, surveillance networks and response capacity in low- and middle-income countries”.11

12.Surveillance data loses its value, however, if it fails to reach those who have the ability to act upon it. As Dr Jeremy Farrar from the Wellcome Trust explained, “surveillance on its own without the capacity, willingness and leadership that allow you to respond is not stamp-collecting, but it is not far from it”.12 We raised concerns with PHE that while it was publishing the information gleaned from its disease surveillance capabilities in a “whole range of different reports”, that information was not making its way into the hands of those who had the power to escalate the situation and intervene.13 When asked if, rather than circulating published papers, PHE communicated directly with the Government it was hard to get a clear answer. Professor Paul Cosford could not categorically confirm that Ministers had been alerted, instead concluding that:

The specific answer to your question about whether we talked to advisers to the Secretary of State is that I am sure we must have done, but it was not flagged as being a major problem for the UK at that point.14

13.Similar concerns were raised at the international level about the ability to share surveillance data and ensure that it was effectively communicated. The Medical Research Council stressed that “monitoring spread of disease [and its] transmission dynamics […] can only be properly investigated using real time data collection, sharing and analytics”.15 Yet, as a report of the Harvard-LSHTM Independent Panel on the Global Response to Ebola highlighted, “reliable systems for rapid transmission of epidemiological, genomic, and clinical data were not established during the Ebola epidemic”.16

14.Witnesses were clear that the slow communication of, and action upon, real-time data comes at the cost of thousands of lives in outbreaks of this ferocity. A study by researchers at the London School of Hygiene and Tropical Medicine, for example, recently calculated that while setting up nearly 3000 treatment beds in Sierra Leone by the UK and Sierra Leonean Governments saved 56,000 lives, an estimated 12,500 more cases could have been averted had this intervention occurred only a month earlier.17 The Wellcome Trust confirmed that a “lack of real time data of infection rates […] significantly impacted on both the ability to make decisions regarding treatment and prevention of spread of the disease.”18 The Chief Medical Officer (CMO), Professor Dame Sally Davies, was more explicit, stating that delays by the international community in responding “probably meant that lives were lost”.19 The Medical Research Council and the Academy of Medical Sciences indicated that the CMO was now working with the WHO “to develop a new, more advanced system to share data on a disease with health agencies and doctors and nurses on the frontline”.20

15.The rapid transmission of disease surveillance data to those with the ability to interpret and act upon it is a vital component of disease control. In its absence, we have seen, in the case of Ebola, how quickly an outbreak can spread and the devastation it can cause. The lines of reporting of surveillance data must, therefore, be clear and well-understood by those involved to ensure a co-ordinated and timely escalation. We are not convinced that the systems in place for interpreting, sharing and escalating disease surveillance data across the Government operated effectively during the early stages of the Ebola outbreak. We discuss later in this report how a lack of clarity about which diseases, or types of diseases, are covered in the National Risk Register, may have contributed to this situation.

16.We recommend that the Government sets out, in its response to this report, how surveillance data is escalated, both within Public Health England and across Government, and identify the triggers that would prompt warnings to reach ministers and senior officials with the capacity to act. We also ask for an update on the Chief Medical Officer’s work with the World Health Organization to develop systems to share disease data.

Financing vaccine, treatment and diagnostic developments

17.In the absence of rapid diagnostic tests for Ebola, or any licenced drugs and vaccines, health workers in affected West African countries struggled to diagnose patients and provide effective care. Dr Jeremy Farrar from the Wellcome Trust expressed his frustration that, nearly four decades after the virus was first discovered, we still understand very little about how to treat Ebola patients effectively.21 This situation is not unique to Ebola, nor is it indicative of a general poverty of ambition to do more. Witnesses repeatedly explained that the slow progress in tackling emerging infectious diseases related, in large part, to the funding mechanisms for drug and vaccine development globally.

18.The majority of funding for drug and vaccine research and development originates from private sector bodies, particularly pharmaceutical companies. However, as Professor Adrian Hill from the Jenner Institute explained, “the business case for large pharma becoming involved in marketing or developing vaccines [for Ebola and other outbreak pathogens] is very weak”.22 Typically, outbreaks of emerging infectious diseases tend to be both small and rare. As a result, the market for interventions targeting these diseases has been considered too limited for pharmaceutical companies to justify the costs of shifting their resources “away from more commercially viable projects to work on tools for epidemics that may not happen”.23

19.This lack of “commercial viability”,24 alongside a scarcity of alternative funding mechanisms, were identified as key reasons for a repeated failure to take promising vaccines and treatments for Ebola through ‘Phase 1’ clinical trials.25 As a result, when an Ebola epidemic did materialise, vaccines were not even ‘on the shelf’, ready to be tested further in humans who were at risk of becoming ill. Dr Jeremy Farrar from the Wellcome Trust described this as a “fundamental error”.26

20.To avoid a similar situation occurring when the next outbreak strikes, Professor Hill advocated establishing an alternative model of funding. He stressed that a system was needed “whereby public and foundation money is used to work with academics and industry to develop Ebola vaccines and other vaccines for which the business case is weak”.27 The British Society of Immunology made a similar recommendation, adding that this type of public-private collaboration would be “best achieved […] under a common programme and following a nationally agreed framework”.28

21.During last six months, the Government has made several announcements that suggest such a shift towards more public investment in ‘neglected diseases’. In June 2015, the Prime Minister announced the creation of the UK Vaccine Research and Development Network with the aim of bringing together “the best expertise across the country […] to focus on the most threatening diseases including Ebola, Lassa, Marburg and Crimean-Congo Fever”.29 The Network “will invest £20m over the next 5 years to develop new vaccines” with additional investment anticipated from the private and research sector.30 Two additional funds were outlined in the Spending Review: a £1 billion ‘Ross Fund’, in partnership with the Bill and Melinda Gates Foundation, to support “the global fight against malaria and other infectious diseases.”31 A further £1.5 billion over the next 5 years was committed by the Chancellor to establish a ‘Global Challenges research fund’ to ensure “UK science takes a leading role in addressing the problems faced by developing countries”. 32 We welcome the Business Secretary’s reassurance that the Global Challenges fund will include support for health research programmes “including vaccines and emerging and current viral threats”.33

22.Part of the suffering seen throughout the Ebola outbreak resulted from a long-term market failure to invest in interventions for rare, but potentially catastrophic, disease epidemics. Through a combination of public and private investment, the UK now has the opportunity to capitalise on its world-class strengths in the field of tropical medicine, and reverse decades of underfunding in vaccine, treatment and diagnostic R&D in emerging infectious diseases. We welcome the Government’s recent announcements of much needed research funds in this area.

23.To maximise the effectiveness of these funds, we recommend that the Government works with leading experts to publish an ‘emerging infectious disease strategy’. This should set out a long-term plan identifying the ‘priority threats’ the UK wishes to address, how much funding will be directed to each threat, as well as how action will be delivered and outcomes evaluated. The strategy should outline how coordination across funding streams will be achieved, so that there is no unnecessary duplication of research. Open knowledge and data sharing should be set as default conditions for those receiving public funds.

A diagnostic test for Ebola

24.The need for a much more strategic approach to research and development funding was demonstrated by Dr Oliver Johnson of the King’s Sierra Leone Partnership in his account of the events surrounding the trial of a new diagnostic test for Ebola early in 2015. Diagnosing Ebola quickly was highlighted as important for “protecting health workers and allowing […] patients either to get Ebola treatment or move on and get other care” but existing tests required a blood sample to be sent to a specialist lab. Dr Johnson told us that “at some stages it was taking up to a week to get results”.34

25.Working in partnership with Public Health England, a new diagnostic test for Ebola—the ‘rapid diagnostic antigen test’ (RDT)—was subsequently trialled in Sierra Leone by the King’s Sierra Leone Partnership and others. Developed by the Government’s Defence Science and Technology Laboratory (DSTL), and its industry partner BBI Detection, the RDT enabled a result to be obtained at the ‘point of care’ within 20 minutes.35. Data from the study were “very positive”36: the test was found to be “highly sensitive, specific and [performed] well in an operational setting”.37 Though an additional, confirmatory blood test was “probably” still required, Dr Johnson considered that DSTL’s test “would be very useful overall in bringing outbreaks under control”.38 He saw it as a “real success” and something that “Britain [could] be proud of”.39

26.Notwithstanding the promising results, and the production of “about 10,000” of these rapid diagnostic tests, Dr Johnson stated that he had “not been able to operationalise them”.40 Despite our questioning, we did not receive clear answers as to why this failed to occur. Initially, when we asked PHE and the Defence Medical Service to clarify what had happened, both were unable to shed light on the situation.41 Subsequently, both PHE and the Ministry of Defence informed us that for a test of this type to be made available, the following would need to be in place:

a)The device in question to have received the necessary clearance for emergency use by the World Health Organization.

b)International consensus on how best to deploy antigen RDTs.

c)The approval of the relevant health body in the country where the test will be used.42

27.PHE stated that these requirements had not yet been met: “This particular antigen RDT does not have regulatory clearance for emergency use and has not been through the [Emergency Use Assessment and Listing Procedure] process which is, de facto, a prerequisite for wider deployment”. It added that there was also “a lack of [international] consensus about where and how [antigen rapid tests] should be used”.43 None of these requirements, however, were referred to by the Department for International Development in its response to a question, tabled in June 2015, about when the rapid diagnostic test would be made available:

The device has been evaluated in Sierra Leone by PHE to determine its utility in the outbreak setting, and the decision on whether to proceed with production now rests with the manufacturer.44

28.Different reasons for not deploying the test were subsequently heard by the International Development Committee (IDC). Giving evidence to the IDC, Dr Johnson speculated that the reason lay in wrangling and disagreements across the UK Government about funding.45 This speculation was not confirmed by Justine Greening MP, Secretary of State for International Development, when she appeared before the IDC. Instead, she raised concerns about the accuracy of the test, and the potential for disruption to arise from re-training health care workers to use the new testing process.46

29.The rapid diagnostic antigen test is an example of the innovations that can be achieved in Government research and development facilities, working in conjunction with private partners and clinicians. The UK should be proud of the efforts made by all of those involved. We were therefore disappointed to learn that, despite the promise shown by the test, and the production of 10,000 test kits, it has not been operationalised. The different explanations advanced for not deploying the test suggest a worrying lack of co-ordination across the key Government departments and agencies that were at the forefront of delivering the UK’s response to Ebola. Along with other evidence we received, we are concerned that this is indicative of more systemic co-ordination problems, and an accountability deficit, for key aspects of the UK Ebola response.

30.The Government must clarify, it its response to this report, why the rapid diagnostic antigen test was not released for use during the Ebola outbreak, distinguishing any technical, commercial and budgetary factors involved. We ask that the Government also sets out what steps it will take to ensure a joined-up, cross-departmental approach, with clear lines of accountability, to address future outbreaks.

Vaccine manufacturing capacity

31.Throughout our inquiry, we heard about the UK’s strengths and expertise in emerging infectious disease research and treatment. Both Professor Chris Whitty of the London School of Hygiene and Tropical Medicine, and former Chief Scientific Advisor at DFID, and Dr Jeremy Farrar from the Wellcome Trust stressed that the UK is “world-leading” in vaccinology, that “the academic base for understanding immunology [...] is as strong in the UK as it is anywhere in the world” and that “our tropical epidemiology and tropical public health is among the best in the world, if not the best, in many diseases”.47 Yet both witnesses, and others who gave evidence, highlighted that we lack the capacity to go further and manufacture vaccines. Professor Adrian Hill from the Jenner Institute described this capacity gap as a “national security issue”48 while Dr Farrar stated that “if something dreadful happened on a regional or global scale, getting vaccines from other countries would be incredibly difficult”. The UK, he added, would “be on [its] own. That is a very worrying situation to be in”.49

32.The Chief Medical Officer, Dame Sally Davies, told us that the UK has some vaccine “manufacturing capability” but that “it is degraded and we are looking at how we can try and attract companies back [to the UK] to do some manufacturing”.50 The Vaccine Research and Development Network, for example, is seeking to identify the vaccine “manufacturing […] gaps”.51 Professor Hill suggested that another way to tackle this problem was through establishing “investigational stockpiles”—storing tens of thousands, rather than millions, of doses of vaccines that have not been fully licenced, so that:

once there is an outbreak, not only do you have the opportunity to control it when it is tens of people, not thousands, but you also get a chance to test your vaccine and show that it is efficacious.52

33.Professor Hill cautioned, however, that even small stockpiles cannot be created in the UK “in weeks” since “you need years to build manufacturing plant”.53 Dame Sally disagreed with this approach, emphasising that “we do not stockpile vaccines” on the grounds that we would need to have the right vaccine for the right strain which, she told us, was “quite difficult”.54 The Minister highlighted that while any stockpiling decision would need to be made in collaboration with the WHO, it does not currently consider there to be a strong national or international consensus on the effectiveness of investigational stockpiles.55

34.The lack of capacity to manufacture vaccines places the UK in a vulnerable position when the next epidemic strikes, whether for use overseas or at home. We urge the Government not simply to encourage private sector investment in vaccine manufacturing capacity, but to negotiate with vaccine manufacturers to establish pre-agreed access to capabilities that can be called upon quickly when the next epidemic emerges. In the longer-term, this may not be sufficient. We recommend that the Government commissions the UK Vaccine Research and Development Network to:

a)identify the actions required to address the UK’s deficiency in manufacturing capacity and;

b)investigate the public health, economic and regulatory feasibility of establishing investigational stockpiles of vaccines that would be ready for Phase 2 trials during an outbreak.

9 Q57; Wellcome Trust (EME015)

10 Wellcome Trust (EME015) para 13; Medical Research Council (EME014); Microbiology Society and the Society for Applied Microbiology (EME013) para 12; The Academy of Medical Sciences and The Royal Society (EME011) para 6; Department of Health (EME008) para 31

12 Q100

13 Q124

14 Q127

15 Medical Research Council (EME014)

16 Suerie Moon et al, “Will Ebola change the game? Ten essential reforms before the next pandemic. The report on the Harvard-LSHTM Independent Panel on the Global Response to Ebola”, The Lancet, volume 368, (2015), pp 2117-2226

17 Adam J. Kucharski et al., “Measuring the impact of Ebola control measures in Sierra Leone”, Proceedings of the National Academy of Sciences of the United States of America, vol 112 (2015), pp 14366-14371

18 Wellcome Trust (EME015) para 8

19 Q167 [Dame Sally Davies]

20 Medical Research Council (EME014); The Academy of Medical Sciences and The Royal Society (EME011)

22 Q50

23 Bill Gates, “The Next Epidemic — Lessons from Ebola”, New England Journal of Medicine, vol 372 (2015), pp 1381-1384

24 Q51

25 Phase one trials aim to test the safety and efficacy of a new drug or vaccine. A small number of people, usually healthy volunteers, are given a small dose of the drug or vaccine and are monitored for side effects. This is normally the first time that the intervention has been tested on humans.

26 Q99

27 Q50

28 British Society for Immunology (EME004) para 2.3

29 Prime Minister calls for ‘wake-up to the threat from disease outbreak’, Prime Minister’s Office News Story, 7 June 2015

30 Medical Research Council (EME014)

32 HM Treasury, Spending Review and Autumn Statement 2015, Cm 9162, November 2015, p 29

33 Correspondence from Sajid Javid MP to Nicola Blackwood MP on The Science Budget and the Spending Review, 7 January 2016

34 Q110

35 Defence scientists support efforts to defeat Ebola, Press release, Ministry of Defence and Defence Science and Technology Laboratory, 21 May 2015; N F Walker et al, “Evaluation of a point-of-care blood test for identification of Ebola virus disease at Ebola holding units, western area, Sierra Leone, January to February 2015”, Eurosurveillance, vol 20 (2015)

36 Q110

37 N F Walker et al, “Evaluation of a point-of-care blood test for identification of Ebola virus disease at Ebola holding units, western area, Sierra Leone, January to February 2015”, Eurosurveillance, vol 20 (2015)

38 Q110

39 Q110

40 Q110

41 Q116; Q162

42 Supplementary written evidence Public Health England (EME019); Supplementary written evidence from the Ministry of Defence (EME020)

43 Supplementary written evidence Public Health England (EME019)

44 HL Deb, 22 June 2015, HL288 [Lords written answer]

45 Oral evidence taken before the International Development Committee on 10 November 2015, HC (2015-16) 338, Q46 [Dr Johnson]

46 Oral evidence taken before the International Development Committee on 30 November 2015, HC (2015-16) 338, Q137 [Secretary of State]

47 Q96

48 Q75

49 Q92

50 Q183

51 Supplementary written evidence submitted by Jane Ellison MP, Parliamentary Under Secretary of State for Public Health (EME021)

52 Q55 [Professor Hill]

53 Q75

54 Q182

55 Supplementary written evidence submitted by Jane Ellison MP, Parliamentary Under Secretary of State for Public Health (EME021)

© Parliamentary copyright 2015

Prepared 21 January 2016