The Role of Public-Private Partnerships in Patient Registries

There are many reasons that healthcare stakeholders – including government agencies, providers, academics and industry – are interested in working together on registries. These include the mutual benefit of improved data availability in areas that can be used to inform safety monitoring, comparative effectiveness, and disease incidence. Registries can also be used to shape clinical trial design and, in some situations, to help identify clinical trial participants.

A public-private partnership (PPP) is funded and operated through a contractual agreement between a public agency-at the federal, state or local level-and one or more private-sector entities. Some effective public-private partnerships for registries are in place, including state-level immunization registries and bioterrorism surveillance systems, but potential for expansion of this approach remains.[i]

In addition, several legislative actions have proposed a role for PPPs in registry development.[ii] Possibilities for new and useful PPPs include registries that can be used for systematic monitoring of populations of interest for which substantial evidence gaps remain after product launch; for example, new treatments used by children. These joint ventures are also useful for following treatments for delayed risk and benefits, such as long-term follow-up of hip implants and artificial knees. 

The Avian/Pandemic Flu Registry: A case study

Emerging infectious diseases-with their potential to cross international borders and pose a large-scale threat to public health-are well suited for PPP-based registries. An example is the Avian/Pandemic Flu Registry (www.avianfluregistry.org), a collaborative, observational study involving members of the international scientific and medical communities who are interested in better understanding the clinical course and effectiveness of current treatments for avian influenza in humans. The registry, which was financially supported by the pharmaceutical manufacturer Hoffmann-La Roche and involved collaboration among five countries’ government health agencies, aimed to study influenza A, with a focus on subtype H5N1, which continues to cause infections and possesses pandemic potential.[iii]

From the outset, this registry was designed to conform to principles of good practice for registry science, having a research contract for funding, a memorandum of understanding with country reporters, a steering committee for stakeholders, a data access and publications committee, and various other governance structures.[iv] The registry research contract gave the scientific team permission to publish results without funder control of content, authorship, or journal selection.

Findings of broad public health interest

Data have been collected from many countries on symptoms, presentation, treatment, clinical course, and survival, and the registry now houses the world’s largest collection of clinical data on human avian influenza cases. The registry has produced real-world data about how H5N1 has been treated, and which treatments have worked best. A recent paper described 308 cases from 12 countries, and showed that H5N1 causes high mortality, especially when untreated.[v]

Registry data also were used to describe which treatments were being used. The predominant treatment at that time was oseltamivir, an anti-influenza antiviral. Analysis showed that early initiation of treatment substantially enhances the chance of survival.[vi] Other work showed that even delayed treatment was effective, and treatment was largely beneficial for all age groups. An analysis of registry data from 215 patients in 10 countries showed that oseltamivir was especially effective for treating H5N1 infection when given early and before onset of respiratory failure.[vii]

Another paper reported that the presence of rhinorrhea (runny nose) seemed to indicate a better prognosis for children with H5N1, with most patients who reported rhinorrhea surviving regardless of age, country, or treatment. Still another paper described differences between confirmed and possible cases of infection with H5N1 among those who presented for medical attention during known H5N1 outbreaks between 2005-2011 in Azerbaijan, Indonesia, Pakistan and Turkey.[viii] Demography, exposure to poultry, and presenting symptoms were compared, but only the common symptoms of fever and headache presented significantly more frequently in confirmed H5N1 cases than in possible cases. Reported exposure to infected humans was also more common in confirmed cases. In contrast, unexplained respiratory illness, sore throat, excess sputum production, and rhinorrhea were more frequent in possible cases.

Taken together, the registry data consistently show that prompt treatment with antivirals confers a strong survival benefit for H5N1 cases, providing support for presumptive antiviral treatment as a potentially life-saving measure for all possible cases presenting during an outbreak of H5N1. 

Overall, the avian flu patient registry was a nimble and responsive approach that was less expensive than investments in fixed capacity, and compiled practically all the accessible data on then-known cases of H5N1. Over the five-year period from June 2007, through April 2012, the registry collected detailed exposure, clinical and treatment information on 648 cases of confirmed and suspected H5N1 avian influenza from 13 of 16 countries reporting avian influenza,[ix] including cases from Azerbaijan, Bangladesh, Cambodia, China, Egypt, Hong Kong, Indonesia, Laos, Nigeria, Pakistan, Thailand, Turkey and Vietnam. Known cases were missing from three countries that are remote and were difficult to access at that time (Djibouti, Myanmar, and Iraq).

All in all, the PPP aspect of this registry contributed to the registry’s success by forcing a workable governance structure. Not only that, the diverse mix of investigators helped shape findings of broad public health interest, and all collaborators benefited from the sharing of information. This success shows the benefit of providing mobile expertise to rapidly amplify local capacity and to generate rigorous, locally relevant, and globally generalizable evidence.

Lessons: Key success factors for PPPs

Key factors to the success of PPPs in setting up and operating successful registries center around the interactions between the partners, and the design employed. Among the partners, the operating practices of biopharma companies-designed to ensure high standards of quality and safety reporting- make this industry well suited to work with public institutions with related interests. However, private funding can be difficult to obtain for public-private partnerships due to the uncertain return on investment and substantial competition for post-approval funding from more commercially-focused projects. It can also be difficult to secure private sector funding for a project that was not required by any regulatory authority and which may ultimately reveal a previously undetected harm in a vulnerable subgroup.

The avian flu registry is a nice example of the benefits that can accrue. Inclusion of public partners such as high-quality academic institutions can broaden the relevance of data that are collected. For example, bird flu registry contributors who maintained active medical practices wanted information that would help guide others when faced with similar situations. The fundamental principle of making the partnership rewarding to all contributors will guarantee the success of future efforts of this kind.  

The infrastructure of a registry needs to be suited to the sustainability and clinical and population impact of the research question. A mobile team may not be the best approach to answer to questions of more sustained interest. For example, registries for large subgroups of concern, such as pregnant women, would provide systematic data about the effects of new treatments. A standing pregnancy registry could continuously recruit pregnant women for study and follow them through delivery. A multi-sponsored registry would be a particularly useful application here. 

Overall, important factors in determining a PPP registry’s success include:[x]

• Availability of funding;

• A pragmatic research approach that maintains scientific rigor;

• An ability to operate in a broad range of cultures and to work with data in many languages;

• Involvement of stakeholders with diverse interests in medicine, science and public health;

• A workable governance structure to support scientific, operational and financial decision-making;

• Patience from all participants in allowing the time needed to establish geographically diverse collaborations; and

• Responsiveness to each stakeholder’s analytic needs, including the ability to provide both country-specific and aggregate data.

Looking ahead, PPPs have particular promise not only as a response to emerging infectious diseases, but also as a systematic approach for monitoring the risks and benefits of new treatments for common conditions and therapies used by a different type of patient than was studied in pre-launch clinical trials. While critics may view the objectives of patient registries as being too broad, examples such as the avian flu patient registry illustrate that there is scope to provide valuable insights, particularly in areas where no other data exist. Shared funding mechanisms for generating timely and relevant population-based information can have a tremendous public health impact, and is likely to become more common.

[i] Registries for Evaluating Patient Outcomes: A User’s Guide. Second Edition. AHRQ Effective Healthcare Program. http://www.effectivehealthcare.ahrq.gov/ehc/products/74/531/Registries%202nd%20ed%20final%20to%20Eisenberg%209-15-10.pdf

[ii] Food and Drug Administration Amendments Act of 2007. [Accessed July 7, 2009]. Available at: http://frwebgate .access .gpo.gov/cgi-bin/getdoc .cgi?dbname=110_cong_public_laws&docid =f:publ085.110

[iii]Adisasmito W, Chan PK, Lee N, Oner AF, Gasimov V, Aghayev F, Zaman M, Bamgboye E, Dogan N, Coker R, Starzyk K, Dreyer NA, Toovey S. Effectiveness of antiviral treatment in human influenza A(H5N1) infections: analysis of a Global Patient Registry. J Infect Dis. 2010 Oct 15;202(8):1154-60. doi: 10.1086/656316.

[iv] Dreyer NA, Toovey S, Oner AF, Bamgboye E, Dogan N, Zaman M, Gasimov V, Adisasmito W, Coker R, Chan PKS, Lee N, Tsang O, Hanshaoworakul W, Phommasack B, Touch S, Swenson A, Reddy D. Investigating outbreaks of novel infectious disease: an international case study. Journal for Clinical Studies. 2013; 5(2): 52-53. [full text]

[v]Adisasmito W, Chan PK, Lee N, Oner AF, Gasimov V, Aghayev F, Zaman M, Bamgboye E, Dogan N, Coker R, Starzyk K, Dreyer NA, Toovey S. Effectiveness of antiviral treatment in human influenza A(H5N1) infections: analysis of a Global Patient Registry. J Infect Dis. 2010 Oct 15;202(8):1154-60. doi: 10.1086/656316.

[vi] Oner AF, Dogan N, Gasimov V, Adisasmito W, Coker R, Chan PKS, Lee N, Tsang O, Hanshaoworakul W, Zaman M, Bamgboye E, Swenson A, Toovey S, Dreyer NA. H5N1 Avian Influenza in Children. CID 2012:55 (1 July 2012) •

[vii] Chan PKS, Lee N, Zaman M, Adisasmito W, Coker R, Hanshaoworakul W, Gasimov V, Oner AF, Dogan N, Tsang O, Phommasack B, Touch S, Bamgboye E, Swenson A, Toovey S, Dreyer N. Determinants of antiviral effectiveness in influenza virus A subtype H5N1. J Infect Dis. 2012 Nov; 206(9): 1359-66.

[viii] Zaman M, Gasimov V, Oner AF, Dogan N, Adisasmito W, Coker R, Bamgboye EL, Chan PKS, Hanshaoworakul W,  Lee N, Phommasack B,  Touch1 S, Tsang O, Swenson  A, Toovey S,  Dreyer NA.  Recognizing true H5N1 infections in humans during confirmed outbreaks.  The Journal of Infection in Developing Countries, in press.

[ix] Dreyer NA, Toovey S, Oner AF, Bamgboye E, Dogan N, Zaman M, Gasimov V, Adisasmito W, Coker R, Chan PKS, Lee N, Tsang O, Hanshaoworakul W, Phommasack B, Touch S, Swenson A, Reddy D. Investigating outbreaks of novel infectious disease: an international case study. Journal for Clinical Studies. 2013; 5(2): 52-53. [full text].

[x] Dreyer NA, Toovey S, Oner AF, Bamgboye E, Dogan N, Zaman M, Gasimov V, Adisasmito W, Coker R, Chan PKS, Lee N, Tsang O, Hanshaoworakul W, Phommasack B, Touch S, Swenson A, Reddy D. Investigating outbreaks of novel infectious disease: an international case study. Journal for Clinical Studies. 2013; 5(2): 52-53. [full text].