A d v ic e Pa p er (11-09)

JUNE 2011

Influenza Pandemic Preparedness Strategy:

a response to the UK Government and the Devolved Administrations

The UK Government and Devolved Administrations are developing a UK-wide strategy for planning for and responding to an influenza pandemic, taking account of the experiences and lessons learned in the 2009 (H1N1) influenza pandemic.The RSE believes that the strategy document is appropriately wide-ranging and the topics covered and the analyses of the different phases of a potential pandemic are comprehensive.The document successfully aligns the pandemic preparedness strategy with the available scientific evidence. In terms of maximising the utility and cost-effectiveness of the strategy, we recommend that it should have a broader focus and in addition to influenza pandemics it should also include epidemics. It is also important that it is developed with reference to the expertise and experience that exists internationally.The key challenge will be ensuring that once developed, the strategy can be rolled-out in practice. A key part of this will include the establishment of an effective surveillance programme. The sharing of scientific information is a vital part of the process, but this is often not seen as a priority.This needs to be addressed. Clarity and openness in communicating with the public should be a central part of the strategy, and will require a coordinated response from government, its agencies and the media.

Summary
The key challenge will be in preparing the ground to enable the practical implementation of the strategy. It is far from clear that the position on the ground today is any different from 2009 and we envisage that considerable work will be required to improve matters. A key focus of the strategy should be on the gathering of intelligence that would monitor the spread and severity of an influenza outbreak.This requires accurate and detailed surveillance data to be gathered at an early stage. There is a requirement for access to rapid diagnostic testing to inform an effective surveillance programme. Unnecessary delay was caused in 2009 by the intergovernmental arrangements that required the diagnosis results from theWest of Scotland Virology Centre to be confirmed by theVirus Reference Laboratory at Colindale before they could be announced. Our understanding is that the Glasgow laboratory offers the complete range of respiratory virus diagnostics and we are concerned that it has no formal Scottish status in the relationship with Colindale.We strongly recommend that a Scottish Respiratory Virus Surveillance Unit should be established at the earliest opportunity. But it remains important that Scottish Ministers work with their counterparts in other parts of the UK to ensure that the unit works as part of a network. We suggest that the UK Governments consider establishing a cohort of volunteers for sampling for the influenza virus. As well as being activated during a pandemic, the cohort should be on stand-by all year so that it can be activated during the influenza season.This would help provide for year-on-year improvements in clinical and epidemiological information. Whilst use of antiviral drugs will both reduce the symptoms and reduce the spread of the infection, the disease can only be prevented by widespread vaccination.Appropriate planning for a public health programme needs a reliable indication of when a vaccine will be available. Modelling work 1 has suggested that vaccination could be very important in terms of limiting prophylactic absenteeism within the population. It also suggests that the cost of vaccinations is likely to be less than the economic savings gained from vaccination.

1 The economy-wide impact of pandemic influenza on the UK: a computable general equilibrium modelling experiment; Richard D Smith, Marcus R Keogh-Brown,Tony Barnett and Joyce Tait; BMJ 2009; 339:b4571

A d v ic e Pa p er (11- 09)

Summary (continued)
We agree that the sharing of scientific information is a vital part of the process of managing a pandemic. In practice, however, this is very poorly implemented. Many of the relevant agencies and laboratories do not regard data sharing as a priority; indeed they are often not properly resourced for this key activity.As a result, valuable information is routinely lost in the system. These issues need to be addressed at the earliest opportunity to ensure the practicable implementation of the strategy. Improving communication is key. Good coordination between the government and its agencies and the media is vital to ensure that mixed and confusing messages are not given, and to ensure that all public pronouncements are given responsibly. It is important that public communication is led by a person who not only has the authoritative technical competence, but also the ability to synthesise complex information and communicate it to the public in an understandable form. Coordination of international efforts and communications is vital. In this regard the alignment of the announcements made by theWHO and the advice given by the Chief Medical Officers in the UK is important. We are surprised that the strategy does not refer to the US Centers for Disease Control and Prevention (CDC). Given its expertise and resource base, in preparing the strategy for the UK, we would expect our planners to be aware of the CDCs recommendations and developments, as well as those emanating from the European Centre for Disease Prevention and Control (ECDC). We recommend that there should be a general principle that the strategy should have wider applicability rather than focussing solely on pandemic influenza. For example, the strategys surveillance programme should not only be targeted at virology, but must encompass bacterial infections.Wider applicability would also make sense in terms of maximising the cost-effectiveness of implementing the strategy. We understand that the intention is to close the Health Protection Agency (HPA) as part of the UK Governments public bodies reform programme. It is crucial that the functions and scientific independence of the HPA are fully protected when transferred to the new Public Health Service. It is also of critical importance that the strategy is fully costed and that the necessary financial resources for implementation are in place.

Introduction
1 The Royal Society of Edinburgh (RSE), Scotlands National Academy, commends the intention of the UK Governments to develop an Influenza Pandemic Preparedness Strategy. In 2009, the RSE produced a briefing paper 2 for the Scottish Parliament in which we recognised that there would need to be an independent review of the science and the governmental response to the H1N1 outbreak. We were pleased, therefore, that Dame Deirdre Hine chaired an independent review of the appropriateness and effectiveness of the UK Strategy for responding to the H1N1 pandemic.We welcome the current proposals for an updated, UK-wide strategic approach to planning for and responding to the demands of an influenza pandemic, taking account of the experiences and lessons learned in the recent H1N1 outbreak. We are pleased to respond to the consultation on the strategy.The RSE is well placed to do so because of the multi-disciplinary breadth of its Fellowship which permits it to draw upon advice from experts across the fields of epidemiology, virology, infection and immunology as well as social sciences and public health. We would be pleased to discuss further any of the issues raised in our response with the Pandemic Influenza Preparedness Team.

Opening remarks
3 In general terms, we believe that the strategy document is appropriately wide-ranging and the topics covered and the analyses of the different phases of a potential pandemic are comprehensive.The document effectively aligns the pandemic preparedness strategy with the available scientific evidence. In particular, the document is evidence-based with input from relevant experts; it has drawn upon and learned from previous experiences of influenza pandemics; it provides a detailed consideration of the socio-economic and media-relevant aspects of a pandemic; and it recognises the importance of having a flexible set of responses that will enable the relevant authorities to adapt optimally to rapidly changing circumstances.

Centers for Disease Control and Prevention 4 Whilst we recognise that theWorld Health Organisation (WHO) is responsible for identifying and declaring an influenza pandemic based on the global situation, we are surprised that the strategy does not refer to the US Centers for Disease Control and Prevention (CDC). Given their expertise and resource base and the fact that they were among the first responders for the H1N1 (2009) pandemic, our planners need to be aware in preparing the strategy for the UK of the CDCs recommendations and developments, as well as those emanating from the European Centre for Disease Prevention and Control (ECDC).

http://www.royalsoced.org.uk/cms/files/advice-papers/2009/H1N1_briefing.pdf

A d v ic e Pa p er (11- 09)
The need for a broader strategic approach 5 We are concerned that pandemic preparedness gives too narrow a focus for influenza preparedness.We are aware of influenza epidemics that have had more severe health effects than pandemics.We believe that the strategy would benefit from having wider applicability and we would urge government to ensure that epidemics are factored into the plans. Indeed, we recommend that there should be a general principle that the strategy should have wider applicability than a sole focus on pandemic influenza. In the sections which follow, we highlight a number of areas where the strategy would benefit from a broader approach. The need for greater precision 6 Whilst we recognise that there is still a great deal of uncertainty over many issues related to influenza, we believe that the strategy would benefit from greater precision in places. For example, on p.15, it states that, roughly one half of all people will display symptoms of some kind (ranging from mild to severe).This is too vague and should be clarified. On p.16, it goes on to say that,between 1% and 4% of symptomatic patients will require hospital care, depending on how severe the illness caused by the virus is.This wording needs to be made more precise as it raises a number of questions. Does this anticipate that only 1% to 4% of people will have severe illness? Furthermore, how many people with severe illness may not be ill enough to be admitted to hospital, and how do they actually define severe illness? 7 We would add that careful consideration should be given to the words used in the strategy, particularly those that could influence public perceptions and behaviour. For example, whilst an influenza pandemic could legitimately be described as having only mild or moderate impact, it needs to be remembered that such impacts will inevitably result in deaths. 10 It is important that the expectations embedded in the strategy are realistic and allow for pragmatic decisionmaking. It is critical, therefore, that the focus of the strategy is on the gathering of intelligence that would assist in monitoring the spread and severity of an influenza outbreak. Detection, surveillance and diagnostics programme 11 It will be important to detect an incipient pandemic originating elsewhere if the UK is to be optimally prepared. It will only be feasible to produce a meaningful projection of a pandemic if good data are available at an early stage.This requires early, accurate and detailed surveillance data to be gathered as a priority. Surveillance is crucially important in monitoring virulence and transmission patterns.The analysis of surveillance data with a view to early detection and estimating rates of spread requires that the data are shared immediately with the wider scientific community. 12 The strategys surveillance programme should not only target virology, it must also encompass bacterial infections, as people who have had a viral infection are more susceptible to secondary bacterial infections. Notwithstanding the understandable public pressure for planning a strategy for pandemic influenza, in practice morbidity is dependent upon secondary bacteria so it is important to include them in the surveillance programme. 13 There is a requirement for access to rapid diagnostic testing to inform an effective surveillance programme so that individuals with flu symptoms can be investigated at an early stage to ascertain whether they have succumbed to a new variant of the virus. Diagnosis based on realtime reverse transcriptase PCR (RT-PCR) technology offers important advantages in high sensitivity and specificity as well as speed and suitability for use in regional laboratories because it uses inactivated virus. 14 In our view, unnecessary delay was caused in 2009 by the intergovernmental arrangements that required the diagnosis results from theWest of ScotlandVirology Centre to be confirmed by theVirus Reference Laboratory at Colindale before they could be announced. Our understanding is that the Glasgow laboratory offers the complete range of respiratory virus diagnostics and we are concerned that it has no formal Scottish status in the relationship with Colindale. We strongly recommend that a Scottish Respiratory Virus Surveillance Unit that makes use of modern technology and methods should be established at the earliest opportunity. Such a facility would have great merit in enabling earlier diagnosis and action to be taken expeditiously, but it remains important that Scottish Ministers work with their counterparts in other parts of the UK to ensure that the unit works as part of a network, which would also ensure provision of quality assurance and reference material.

Resourcing the response 8 We understand that the intention is to close the Health Protection Agency (HPA) in 2012 as part of the UK Governments public bodies reform programme. In order to ensure that there is no disruption to planning for and responding to future pandemics or epidemics, including specifically, the lines of communication between the responsible agencies in devolved regions of the UK, it is crucial that the functions and scientific independence of the HPA are fully protected when transferred to the new Public Health Service. It is also of critical importance that the strategy is fully costed and that the necessary financial resources for implementation are put in place.

Implementation of the Strategy

9 In our view, the key challenge will be in preparing the ground for practical implementation of the strategy. It is far from clear that the position on the ground today is any different from 2009 and we envisage that considerable work will be required to improve matters.

A d v ic e Pa p er (11- 09)
Proactive sampling and establishing a cohort of volunteers 15 It is important that sufficient resources are available for intensive, proactive virological sampling in outbreak areas irrespective of known actual contact.We believe that this is more efficient than contact tracing as a means of gathering real-time information on virulence and transmission patterns in the initial stages of an outbreak. Given that reporting structures are not comprehensive and their application can be highly subjective, as they depend upon public perceptions and health department messages, we would not want the strategy to place too much reliance on contact tracing.We understand that this was one of the criticisms that arose from the H1N1 (2009) outbreak. 16 We suggest that the UK Governments consider establishing a cohort of volunteers for sampling for the influenza virus.The cohort should be made up of a range of participants from different ethnic backgrounds, age groups (which should include children) and regions. As well as being activated during a pandemic, the cohort should be on stand-by all year so that it can be activated during the influenza season.This would help provide for year-on-year improvements in clinical and epidemiological information.We would draw attention to Generation Scotland 3, an ambitious medical genetics research programme which involves a number of complementary projects and sample collections, as a model that could usefully be looked at for the purposes of the current strategy. 17 As we have suggested that there should be a general principle that the strategy would have wider applicability than pandemic influenza, the cohort could also be applied for other clinical and epidemiological matters. This would be a positive contribution in terms of maximising the cost-effectiveness of maintaining the cohort. Sero-surveillance 18 In parallel with rapid diagnostic testing, sero-surveillance should be embedded in the strategy.Whilst it is widely recognised as the gold standard epidemiological tool for tracking levels of infection from epidemic or pandemic influenza, this is not recognised in the strategy. If any reliance is to be placed on real-time modelling during a pandemic then sero-surveillance data will be a key input. Preparation on making sero-surveillance an explicit component of the strategy should take place now to ensure that it can be utilised during an epidemic or pandemic. Research capacity and capability 19 In view of the uncertainty about the potential behaviour of a new viral strain, especially the possibility to cross species barriers, we must not simply depend on the investigation of severe or unusual human cases as has been the case in the past.We must maintain a strong virology science base so that we continue to be well positioned to combat new strains of influenza as well as the emergence of other zoonotic diseases of viral origin. 20 In this context, it is essential that the capacity to innovate is built into the Reference Laboratories and hospitals, and that funding is provided specifically for this purpose. It is important to ensure that they are able to use the latest techniques and state-of-the-art methods. Otherwise, they will be unable to deliver what is expected of them. Detect, Evaluate,Treat, Escalate and Recover (DETER) phases 21 We believe the new approach to the indicators for action in a future pandemic response in the form of the five phases (DETER) is sensible.As recognised in the strategy, the phases are not linear. In our view, it may be difficult to determine when one phase has changed to another. It is likely that there will be regional variation in the epidemic and there will be difficulties in acquiring sufficiently accurate information in all subject and geographical areas simultaneously.This reinforces the need for rapid and reliable diagnostic testing to inform a response to a new virus. 22 Whilst it might not be possible to halt the global spread of a new virus, we believe that greater emphasis should be given to minimising exposure and transmission of the virus.The current version of the Evaluate phase would otherwise be pointless.

Sharing Scientific Data and Information

23 Section 3.1 of the strategy refers to the importance of sharing scientific information to minimise the potential health impact of a future influenza pandemic.We agree that this is a vital part of the process of managing a pandemic, but it is very poorly implemented in current practice. Many of the relevant agencies and laboratories do not regard data sharing as a priority; indeed they are often not properly resourced for this key activity.As a result, valuable information is routinely lost in the system.These issues need to be addressed at the earliest opportunity to ensure the practicable implementation of the strategy. 24 Data sharing is a high profile topic at present and the Royal Society of London (RSL) is beginning a new, major policy study on the use of scientific information as it affects scientists and society 4.The inquiry will examine the benefits and risks of openly sharing scientific data and include a consideration of the responsibility of scientists, their institutions and the funders of research for open data.We would urge those involved in the preparation and implementation of the current strategy to engage with the RSL study. It is essential that the discussion embraces data produced with public money by government and its agencies.

3 http://www.generationscotland.org/ 4 Science as a public enterprise: opening up scientific information; http://royalsociety.org/policy/sape/ See also, Geoffrey Boulton, Michael Rawlins, Patrick Vallance, and Mark Walport (2011). Science as a public enterprise: the case for open data, The Lancet, 377(9778), 1633-1635

A d v ic e Pa p er (11- 09)
Ethical constraints 25 Ethical constraints on access to and use of data, collection and analysis of samples, and reporting of the results are key issues. Samples from children and the use of their data pose particular difficulties.These issues are highlighted in a recent review by the Academy of Medical Sciences 5 of the regulation and governance of UK health research involving human participants, their tissue or their data.We would urge the Government to adopt the reports recommendations. Communication of data 26 Sections 5.15 to 5.16 deal with the communication of data in a pandemic, where it is stated that the principles and practices of the Code of Practice for Official Statistics for the release of data will be followed wherever possible. We very much agree with this approach, but it should be more than lip service. For example, principle 4 of the Code states that statistics are produced to a level of quality that meet users needs.This is crucial, but open-ended: for example, what may be required for a Minister will not be adequate as input into mathematical models. Users needs and the uses to which the data will be put need to be better anticipated.We believe that this is achievable by a process of consultation with modellers and others. between the government and its agencies and the media is vital to ensure that mixed and confusing messages are not given, and to ensure that all public pronouncements are given responsibly. Difficulties arise when there are significant discrepancies. Lack of information or conflicting information in this problematic area increases the risk of panic reactions. 30 We would support more work to improve the publics general understanding of epidemics and pandemics and to make them more aware of the unpredictability of influenza which limits the extent to which the scientific information can be certain.

School Closures
31 Sections 4.23 to 4.25 of the strategy consider the policy on school closures.We believe that this would benefit from greater clarity and could usefully be informed by modelling work6 which suggests that school closures and prophylactic absenteeism could greatly increase the economic impact of a pandemic.This work indicates that in the event of a mild pandemic, prolonged periods of school closures will not be necessary and could greatly increase the economic impacts and should therefore not be primary focus of schools planning. The severity of the pandemic should be taken into account when developing this policy.

Public Communication
27 Improving communication is key. It is often said that public information needs to be controlled to avoid panic. On the contrary, the evidence is that provision of clear information is an antidote to panic. It is important that public communication is led by a person who not only has the authoritative technical competence, but also the ability to synthesise complex information and communicate it to the public in an understandable form.These attributes are crucial to ensure the trust and confidence of the public and to ensure that the public reaction is commensurate to the risk.The excellent contribution of Rear Admiral Anne Schuchat at the CDC during the 2009 pandemic is worthy of note in this regard. 28 Coordination of international efforts and national communication is vital. In this regard the alignment of the announcements made by the WHO and the advice given by the Chief Medical Officers in the UK is important. 29 For many citizens, the media are the primary source of knowledge and understanding on scientific issues. We recognise that media relations are particularly difficult, as the UK media tends to court dissenting views rather than raise public awareness of the issues. Frequent sensationalist reporting is unhelpful, and inhibits informed dialogue between the scientific community and the public. Good coordination

Use of antiviral medicines

32 Within the UK, the measures being taken in preparation for a pandemic include stockpiling of antiviral drugs and facemasks.The adequacy of these measures is kept under constant review but, until a pandemic occurs, there is no way of knowing exactly what will be required. 33 Targeted antiviral prophylaxis (TAP) has been used to manage previous epidemics.Two antiviral drugs, Tamiflu and Relenza, are available and many countries have large stocks available.Whilst use of antiviral drugs will both reduce the symptoms and reduce the spread of the infection, the disease can only be prevented by widespread vaccination.The role of TAP needs to be fully assessed. 34 The influenza virus is an RNA virus that can mutate rapidly and antiviral drug-resistant strains would be expected to emerge.Whilst we recognise that novel methods for overcoming drug-resistance are being developed, for the foreseeable future consideration should continue to be given to restricting use of these drugs to seriously ill patients and not to use them for general prophylaxis even in the early stages of the pandemic. Individuals who have been given a course of antiviral drugs, but do not complete the course, probably contribute to the emergence of circulating drug-resistance strains.

5 A new pathway for the regulation and governance of health research (January 2011) http://www.acmedsci.ac.uk/p47prid88.html 6 The economy-wide impact of pandemic influenza on the UK: a computable general equilibrium modelling experiment; Richard D Smith, Marcus R Keogh-Brown, Tony Barnett and Joyce Tait; BMJ 2009; 339:b4571

A d v ic e Pa p er (11- 09)
It will be important to monitor for drug-resistance throughout a pandemic and to be prepared to alter the administration of these drugs in the light of the frequency of circulating drug-resistant strains. Plans should be drawn up for the scenario that the pandemic virus is resistant to all antiviral medicines. Reduction of transmission by practising good hygiene will become even more important.

Additional Information and References

Advice Papers are produced on behalf of RSE Council by an appropriately diverse working group in whose expertise and judgement the Council has confidence.This Advice Paper has been signed off by the General Secretary. In responding to this call for evidence the Society would like to draw attention to the following Royal Society of Edinburgh publications which are relevant to this subject: The Royal Society of Edinburgh Briefing Paper on, The H1N1 Outbreak and theThreat of Pandemic Influenza (May 2009) The Royal Society of Edinburgh Report on, Avian Influenza:An Assessment of theThreat to Scotland (December 2007)

Vaccination
35 We recognise that it is unlikely that a vaccine effective against a new strain of pandemic influenza virus could be produced before the disease affects the UK.Appropriate planning for a public health programme needs a reliable indication of when a vaccine will be available. During the 2009 outbreak, vaccination did not start until the epidemic was waning, and many of those vaccinated are likely to have already been infected.Whilst the population-level benefits of vaccination may have been minimal at this stage, it would likely prove significant in the face of subsequent waves of influenza. The economics of vaccination 36 Economic modelling7 suggests that the overall mortality rate is the driver of behavioural change, and vaccinations, whether pre-pandemic or pandemicspecific, could be extremely important in preventing mortality rates from reaching the point at which the severity of the pandemic provokes sufficient fear to invoke a sudden increase in prophylactic absenteeism within the population.The modelling also suggests that the cost of vaccinations is likely to be less than the economic savings gained from vaccination.

Any enquiries about this Advice Paper should be addressed to the RSEs Consultations Officer, Mr William Hardie (Email: evidenceadvice@royalsoced.org.uk) Responses are published on the RSE website (www.royalsoced.org.uk).
Advice Paper (Royal Society of Edinburgh) ISSN 2040-2694

7 Ibid. 6

The Royal Society of Edinburgh (RSE) is Scotlands National Academy. It is an independent body with a multidisciplinary fellowship of men and women of international standing which makes it uniquely placed to offer informed, independent comment on matters of national interest.
The Royal Society of Edinburgh, Scotlands National Academy, is Scottish Charity No. SC000470