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Professor drh. Wiku Adisasmito, MSc, PhD.
XIII International Symposium on Respiratory Viral Infections, Rome, Italy, 13–16 March 2011
Conclusions
O The registry provides a scalable, multi-lingual repository that provides information critical to the understanding of influenza A/H5N1 in humans in preparation for any possible future pandemic. The protocol also allows for the future capture of information relevant to other influenza strains.
O The Avian Flu registry is a prime example of a successful public-private collaborative research effort that has proven to be an effective means of aggregating, analysing and disseminating information on the clinical course and effective treatments for influenza A/H5N1.
O Key ingredients to the success of these long-term partnerships have been:
(1) adoption of bilateral confidence-building measures, including a long-term commitment and follow-up; (2) maintenance of a pragmatic approach to research while maintaining scientific rigor; (3) participation of collaborators reflecting a broad array of medical, scientific and public health interests; (4) the ability to communicate and accept data in many languages; (5) responsiveness to collaborators’ analytic needs; and (6) delivery of country-specific and aggregate information.
O To find out more about the Avian Flu registry project, please visit http://www.
avianfluregistry.org or contact Nancy Dreyer (lead investigator; ndreyer@outcome.
com).
Acknowledgement
Support for third-party writing assistance for this poster was provided by F. Hoffmann-La Roche Ltd.
Abstract
Background: The spectre of a devastating pandemic of H5N1 raises many questions about disease detection and control. While the World Health Organization’s reporting systems provide valuable information about outbreaks and mortality, questions remain about the natural history of the disease and what treatments, if any, can reduce the risk of mortality from this highly pathogenic disease. Despite the availability of some country-specific data and meta-analyses, there has been an absence of detailed global data that would provide enough cases for meaningful analyses and generalisable inferences.
Methods: In 2006, Roche provided funding for a global avian influenza patient registry, through an arms-length agreement with Outcome Sciences, Inc., an independent research firm. The objective of the registry was to find and pool structured patient data to characterise clinical presentation and disease course, including information on the treatments used. A protocol was created and reviewed by appropriate ethics committees. Unique features of this registry include its structured data collection, which supports extracting information from a wide variety of existing data sources from many countries and in many languages, its web-based technology for data collection and information sharing, its success in partnership building and communication, and its approach to governance and reporting.
Results: A registry was created that facilitates the ongoing collection of demographic, exposure, viral testing and clinical data on retrospective and newly occurring cases of avian influenza through a web-based data entry interface. Patient data comes from medical records, administrative data sources, and detailed case studies from the published literature or reputable sources on the internet. Collaboration was established between treating physicians, ministries of health, and academics. As of 1 February 2011, this collaborative research programme has assembled detailed information on 387 laboratory-confirmed and 234 likely or possible cases from 12 countries. Of the laboratory-confirmed cases, 17% are from medical records in six countries, 60% are from clinical and administrative records in two countries, and 23% are from published case series in five countries. Abstracts of registry results have been presented at six conferences, and the first aggregate manuscript of registry results was published in October 2010. Overviews of real-time aggregate registry data and analytical reports are also available to registry contributors on a secure website. Information on the content of conference presentations is available to the public through the registry website (www.avianfluregistry.org).
Conclusions: Public-private collaborative research efforts like this can be an efficient means to aggregate, analyse and disseminate information about the clinical course and effective treatments for emerging infectious diseases like H5N1, and other rare diseases.
Introduction
O Pandemic influenza outbreaks take place when a novel strain, to which humans are immunologically naïve, emerges and develops efficient human-to-human transmission.
O Several novel strains of influenza have been circulating in bird populations for some years. Influenza A/H5N1 in particular is endemic in poultry in parts of Asia and Egypt.1 While this strain has not yet developed mechanisms for efficient human transmission, its high virulence and wide geographic spread2 give it strong pandemic potential.1
O The virulence of influenza A/H5N1 is illustrated by its high mortality: as of 9 February 2011, of the 520 cases reported, 307 had resulted in death.2 This corresponds to a mortality rate of ~59%.
O The World Health Organization’s (WHO) reporting systems provide valuable information about outbreaks and mortality, but questions remain about the natural history of the disease and treatment effectiveness. Much information on the presentation, prognosis, treatment efficacy and outcomes of influenza A/H5N1 is in the form of case reports and is often country- or region-specific.
O To help address the need for a detailed global resource that would collect sufficient cases for meaningful analyses and inferences, Roche has provided funding for a global avian influenza patient registry – the Avian Flu Registry – via an arms-length agreement with an independent research firm (Outcome Sciences, Inc., Cambridge, MA, USA and St. Prex, Switzerland).
O The registry is intended primarily to be used to (i) collect and pool structured patient data to characterise clinical presentation and disease course in patients with influenza A/H5N1, together with details of therapeutic management and clinical status at discharge, and (ii) enhance communication via dissemination of data and analyses. Findings from the database have recently been released in the literature for the first time.3
O The protocol for the registry has been reviewed and approved by ethical review committees in study countries as required.
Governance and reporting
O A structure has been formalised by a charter that governs certain aspects of the registry via a steering committee known as the Data Access and Publication Committee (DAPC).
The charter clarifies the interactions of the DAPC with the CIG.
O The DAPC is responsible for facilitating efficient dissemination of results from the registry through high quality, ethical presentations and publications designed to maintain the integrity and good reputation of the registry. Data are reported as aggregates, and may be shared with competent regulatory authorities and international public health organisations, such as the WHO.
Figure 1. The Avian Flu Registry in action.
Figure 2. Members of the Contributing Investigators’ Group at a recent meeting.
Table 1. Avian Flu Registry case classifications and definitions.
Classification Registry definition WHO equivalent
Laboratory-supported case Positive laboratory test for H5N1 Confirmed case
Likely case Definition 1
Epidemiologically linked by time, place and exposure to a likely or confirmed human or avian H5N1 case AND equivocal test or positive laboratory confirmation of an influenza A infection, but insufficient evidence for H5N1 infection AND clinical symptoms consistent with disease (regardless of severity), fever AND/OR flu-like symptoms AND/OR gastroenteric symptoms Definition 2
Epidemiologically linked by time, place and exposure to a likely or confirmed human or avian H5N1 case AND death due to unexplained acute respiratory illness AND test not performed
Probable case
Possible case Epidemiologically linked by time, place and exposure to a likely or confirmed human or avian H5N1 case AND test not performed or negative AND clinical symptoms consistent with disease (regardless of severity), fever AND/OR flu-like symptoms AND/OR gastroenteric symptoms
Suspected case
Methods
O The registry was launched in May 2007, and is an observational database of patients with suspected or confirmed avian influenza A/H5N1. Cases are classified as: possible (similar to WHO ‘suspected’ case); likely (similar to WHO ‘probable’ status); or laboratory-supported (similar to WHO ‘confirmed’ status; Table 1).
O All cases are laboratory-confirmed or epidemiologically linked by time, place and exposure to a probable or confirmed avian influenza case (in either humans or animals). Patients with no or mild symptoms, but with seroconversion, are also eligible for inclusion.
References
1. Van Kerkhove MD, et al. PloS One 2011;6(1):e14582.
2. World Health Organization. Cumulative number of confirmed human cases of avian influenza A/(H5N1) reported to WHO. 9 February 2011. Available at: http://www.who.int/csr/disease/avian_influenza/country/cases_table_2011_02_09/en/index.html (accessed 10 February 2011).
3. Adisasmito W, et al. J Infect Dis 2010;202:1154–60.
4. Dreyer NA, Garner S. JAMA 2009;302:790–1.
Stephen Toovey
Royal Free and University College Medical School
Royal Free Campus London, UK
Email: [email protected]
Global patient registry for A/H5N1: a modest success story
Nancy A Dreyer,
1Stephen Toovey,
2Anna Swenson,
1Wiku Adisasmito,
3Ebun Bamgboye,
4Paul KS Chan,
5Richard Coker,
6Nazim Dogan,
7Viktor Gasimov,
8Wanna Hanshaoworakul,
9Nelson Lee,
5Ahmet Faik Oner,
10Mukhtiar Zaman
111
Outcome Sciences, Inc., Cambridge, MA, USA;
2Royal Free and University College Medical School, London, UK;
3University of Indonesia, Jakarta, Indonesia;
4St. Nicholas Hospital, Lagos, Nigeria;
5
Chinese University of Hong Kong, Hong Kong SAR, China;
6London School of Hygiene and Tropical Medicine, London, UK;
7Atatürk University Medical School, Erzurum, Turkey;
8Azerbaijan Ministry of Health, Baku, Azerbaijan;
9
Ministry of Public Health, Nonthaburi, Thailand;
10Yuzuncu Yil University, Van, Turkey;
11Khyber Teaching Hospital, Peshawar, Pakistan
Data collection and collaborator involvement
O The process of establishing effective collaborations included a substantial amount of field work (Figure 1). The Contributing Investigators’ Group (CIG) comprises investigators who actively contribute clinical or epidemiologic data, or who contribute substantially to the acquisition of data (Figure 2).
O Data collection is by abstraction from a variety of data sources (Figure 1). Data are supplied as follows: directly from in-country reporters who help to abstract clinical data;
through clinical records and reports from governmental health institutions at national, regional and district levels; from published case series and other publically available data. Published case reports have been included only if they include details of age, sex, country, symptoms, exposure or viral testing, and outcome.
O Core data elements include demographic information, details of exposure, clinical signs and symptoms, and any antiviral, antimicrobial or concomitant treatment; follow-up details may include laboratory confirmation, viral phenotyping/genotyping and patient outcome wherever possible.
O Reporters can enter data directly using an web-based secure information platform (http://www.avianfluregistry.org) that conforms to current guidelines for high-quality registries4 (Figure 3), can use paper report forms, or can send case data in for abstraction by the registry administrator.
a) Case-finding in Turkey
b) Abstracting records
c) Building collaboration
Figure 3. Welcome screen for online users of the Avian Flu Registry.
Results
O As of 1 February 2011, this collaborative research programme has assembled detailed information on 387 laboratory-confirmed and 234 likely or possible cases from 12 countries. Of the laboratory-confirmed cases, 17% are from medical records in six countries, 60% are from clinical and administrative records in two countries, and 23% are from published case series in five countries. The confirmed cases collected to date include 74% of the WHO reported cases and have substantial data available on clinical characteristics and treatments.
O Abstracts of results have been presented at six conferences (see https://www.
avianfluregistry.org/publications-presentations.html), and the first aggregate manuscript of registry results was published in October 2010.3 Overviews of real-time aggregate registry data and analytical reports are also available to registry contributors on the registry website.
O Importantly, the registry involves no therapeutic or behavioural interventions, and poses no risk to patients. Individual informed consent is not necessary because the registry is an observational resource derived from existing data, with no direct contact with patients.
