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Ensuring successful development and introduction of multipurpose prevention technologies through an innovative partnership approach

2014; Wiley; Volume: 121; Issue: s5 Linguagem: Inglês

10.1111/1471-0528.12911

1471-0528

Bethany Young Holt, Joe Romano, Judy Manning, Anke Hemmerling, Wayne C. Shields, L Vyda, Manjulaa Narasimhan,

Global Maternal and Child Health

Unintended pregnancies and the spread of sexually transmitted infections (STIs), including HIV, remain critical public health issues. Despite the apparent public health potential of comprehensive prevention methods, research and development for contraception and prevention of HIV and other STIs have historically remained separate because of different funding streams, policies and regulatory mechanisms.1, 2 The result has led to missed opportunities to effectively and adequately address these interconnected sexual and reproductive health (SRH) risks. One global collaborative partnership to advance the comprehensive SRH prevention field is the Initiative for Multipurpose Prevention Technologies (IMPT). Begun in 2009, the aim of this cross-sector initiative is to advance the development and eventual introduction of combination products for women that provide simultaneous protection from multiple SRH risks. To date, the IMPT has engaged product developers, scientific researchers, healthcare providers, funders and community-based advocates in China, India, the USA and across Africa and western Europe behind this common agenda. The IMPT defines multipurpose prevention technologies (MPTs) as products that combine protection against unintended pregnancy and STIs, including HIV.3-6 The vision for MPTs is a suite of accessible products that are woman-initiated, efficient and easy to use. MPTs currently in development include intravaginal rings that combine a contraceptive hormone with anti-viral drugs for HIV and herpes simplex virus type 2 prevention; on-demand products such as a diaphragm loaded with an anti-HIV drug; and co-administered or co-formulated multipurpose injectables. These products could represent a powerful means of achieving high public health impact in at-risk populations around the world. The IMPT is in its fifth year and is navigating the boundaries of collaborative decision-making around a complex product development agenda. This editorial describes the structured and innovative approach developed by the Initiative to facilitate MPT development, funding and introduction. The challenges and complexities of the MPT field call for a strategic approach that facilitates communication and coordination across three currently distinct SRH sectors: contraception, HIV and other STIs. It follows that a highly integrated and structured effort among stakeholders is necessary to ensure development and delivery efficiencies and to reduce long-term costs. There are numerous examples of successful global partnerships, and indeed, much of the success in public health and other areas is now being achieved through collaborative mechanisms. Examples of collaborations that have attempted to coordinate and accelerate efficient product development and access to public health goods are the Global HIV Vaccine Enterprise and the Global Meningococcal Initiative.7, 8 The IMPT's founding leaders acknowledged that standard coalition and collaboration mechanisms would be insufficient to align priorities and maintain coordination across such a broad swath of international actors in a long-term iterative engagement. They developed an organisational structure to ensure a high degree of commitment, communication and accountability among partners. The emerging collaboration approach is known as ‘collective impact collaborations’.9-11 Collective impact collaborations represent the commitment of a group of motivated, high-level and influential stakeholders from different sectors to a common agenda aimed at solving a specific social problem. They share five characteristics that distinguish them from other types of collaborations: (1) a common agenda; (2) shared measurement systems; (3) mutually reinforcing activities; (4) continuous communication; and (5) the presence of a backbone organisation. Although there are few examples of collective impact initiatives from the biomedical arena, such initiatives have been effective in areas including the environment, education and global health.9, 10 Part of this momentum is probably due to the recent economic recession and reductions in government and philanthropic funding, which has motivated the social sector to be more efficient with funding and other resources. For example, the Global Alliance for Improved Nutrition, a Swiss foundation based in Geneva, Switzerland, is an international alliance of organisations, government leaders, nongovernment organisations, universities and the private sector focused on reducing malnutrition by improving the health and nutrition of people in the developing world and has reached an estimated 667 million people in over 30 countries.12 To the extent possible, the IMPT is employing this type of collective impact strategy towards its overarching vision. The IMPT is still in its early stages, and its success as an innovative partnership will ultimately be measured by women's access to safe and effective MPT products—an outcome that is years in the future. However, many steps towards this goal are assessable now, such as increasing donor funding for the field; collectively assessing the MPT development pipeline and prioritising the most promising product candidates; and fostering collaborations between developers, socio-behavioural scientists, and market researchers around the need for specific types of MPT products. Through this collective approach, the IMPT aims to ensure that MPTs developed will not only be safe and effective, but that they will be accessible and used by women who need them most. Figure 1 illustrates the iterative process of the IMPT and key milestones to date. The development and introduction of products as complex as MPTs, and for different at-risk populations, poses numerous challenges. Novel and high-impact strategies that are sufficiently informed and robust are critical to address these challenges. Below is a brief outline of issues confronting MPT product development and introduction and the efforts taken to date to address them. The multidisciplinary approach of the MPT field creates several challenges for ensuring sufficient support. Funding for MPT products comes primarily from government and foundation sources, and although this approach has advanced contraceptive research and HIV and STI prevention and treatments, funding agencies traditionally frame their funding around singular issues and often support activities carried out by individual organisations and researchers, rather than encouraging or requiring collaboration and information exchange.11 As a result, there can be duplications of efforts solving the same issues in different programmes, while important gap areas are underserved. This slows broader progress in the field and can delay target product availability. In addition, the short-term funding cycles and focused commitments of many funding agencies present a challenge to the long-term nature of MPT development, regulatory approval and product introduction processes. The successful development and utilisation of MPTs will necessitate a long-range, flexible commitment from multiple funding sources over decades.13 MPT funding is further challenged by different missions, priorities, review processes and other factors that exist at different supporting agencies. As described later in this article, the IMPT is facilitating the collaboration of key MPT donor agencies to help ensure that MPT investment strategies and priorities are informed by field-wide priorities and gaps. To make significant advancement in the MPT field, the changing SRH needs of women throughout their life cycles, and in different regions of the world, must be considered.14 Until recently, funding programmes for HIV prevention research, as well as contraceptive research, have not adequately considered the socio-behavioural and marketing aspects integral to the successful public health impact of such prevention products. As a result, opportunities to incorporate women's preferences early in the drug development process have been missed.15-17 Hence, MPT product development must focus not only on what is necessary for technical feasibility and regulatory licensure, but also on the target market perspective, which includes a complex array of opinions from product users, healthcare providers, government ministries and procurement organisations. As in the case of specific technical product parameters, it will also be necessary to define user preference and other commercialisation targets before phase 3 trials. These critical attributes of a product are referred to as the Target Product Profile (TPP).18 The TPP will ideally describe the product attributes and label claims. It can also help to identify MPT project goals and risk, guide investment decisions, and serve as the basis for discussions between various stakeholders including the funders, on clinical, development, drug safety, manufacturing, marketing, regulatory, research and quality from the candidate nomination stage through and after marketing approval.19, 20 Hence, guided by the IMPT's Scientific Agenda Working Group (SAWG) and Acceptability, Demand and Uptake Working Group (ADUWG), the IMPT intends to merge TPP attributes with a similar set of acceptability and other market/commercialisation parameters by mediating a coordinated process with relevant experts and stakeholders. This added dimension will help to expand the traditional US Food and Drug Administration format for TPPs. The IMPT approach recognises the inherent competition in product development and respect for intellectual property. For example, industry and other product development partners compete for drug development funding and, in some cases, commercialisation of products. While the MPT field is still in a relatively early stage, many similar products are currently in development.21 Approaches to identify lead MPT product candidates is critical given the resource-limited environment and urgent need to provide MPTs to women. The IMPT recently established the Supporting Agency Collaboration Committee (SACC), which brings MPT funders together on a regular basis to share information about respective priorities, discuss means of collaboration and clarify issues of technical relevance (described below). The TPPs described earlier were derived in a product agnostic manner, and can, therefore, serve as a guidance tool for evaluation of product options for both funders and developers. Given the inherent complexity of MPTs, it is likely that they will confront a number of challenges for regulatory approval.21-23 The potential combination of different drug substances and the possible inclusion of drug delivery devices in MPT products will contribute to the complexity of the regulatory review process. The combination of approved drugs with other experimental drugs, the implementation of bioequivalence strategies and the unique chemistry, manufacture and control (CMC) issues of a combination product will all present regulatory challenges. Although these issues will need to be addressed individually for specific MPT products, it may be possible to identify some common elements that can be addressed more globally with regulators. Furthermore, MPTs will need to meet regulatory requirements in different countries. Hence, frequent communication between MPT developers and funding organisations regarding their regulatory strategies and collaborative efforts between international regulatory agencies or health authorities will be critical given the intended global use of MPTs and may inform the broader field. Alternative strategic models will be necessary to effectively and efficiently deliver the highest impact MPTs to women most in need of these products. Drawing from the application of the collective impact collaborations applied in other fields, the IMPT has developed a base strategy to achieve the necessary coordination of the diverse stakeholders involved. A summary of the framework employed to advance the MPT initiative is outlined below. The IMPT founders chose to create a ‘backbone organisation’, or Secretariat, to helm the initiative. This leadership model is distinctly different from more common leadership models such as hired staff or coordinating committees designed to fulfil coordination and central leadership duties. A backbone organisation is an organisation that is already expert and well networked in the field, has no conflicts of interest (in this case in MPT product development), and can adopt as its primary activities the leadership and central coordination for the initiative. With no conflicts of interest related to advancing specific MPT products, CAMI Health functions as Secretariat and neutral organising body to the IMPT, providing central leadership and coordination. In this capacity, the Secretariat functions as the planning, outreach and resource ‘hub’ for the IMPT by facilitating the strategic planning process, promoting collaboration among a broad cross-section of high-calibre organisations, providing MPT-relevant resources through a website and other forums, and fostering productive communication between partners across disciplines and continents. Key activities facilitated by the IMPT Secretariat are described in Figure 1; an example of its coordinating role is the recent in-person convenings of the IMPT SACC (described above), and the Steering Committee. Figure 2 illustrates the relationship of the IMPT Secretariat to the SACC, Steering Committee, technical working groups and Network of Experts (NoE). To ensure progress toward the IMPT's shared agenda and goals, the Initiative has identified four priority aims relevant to the successful development and introduction of MPT products: The IMPT has attempted to address each of these priority aims through the formation of technical working groups comprised of relevant independent experts. These working groups adhere to common goals for the IMPT and provide the means to maintain focus across stakeholders. For example, efforts of the IMPT's Communication and Advocacy Working Group (CAWG) have helped nurture regional interests that are rooted in specific countries and that share IMPT goals. This regionally focused collaboration allows for in-depth engagement with SRH, STI and HIV prevention leaders working in China, Kenya, India, South Africa, the USA and other countries. Many of these partners engage directly with women in diverse settings within their respective countries, facilitating much-needed feedback and MPT leadership development. In addition to MPT communication strategies developed specifically for India, Kenya and South Africa, strategies have also been developed for US and European advocates and policy-makers, resulting in the introduction of MPT language in several US federal guidance documents. Other IMPT working groups, including the SAWG, ADUWG and SACC, have been described earlier (also see Figure 2). The IMPT recognises that shared measurement systems are critical for identifying MPT priorities and gaps, for developing TPPs, and for tracking MPT funding. Such systems can serve as the basis of coordinated product development investments through the collective identification of critical gaps and avoidance of duplicative efforts. For example, within the first year of convening the SAWG, an objective vetting process was developed and implemented for identifying MPT products with the highest public health impact potential. A regularly updated MPT pipeline evaluation process and a searchable online database have also been created for the purpose of defining specific MPT product priorities and identifying MPT technology gaps, which need to be addressed to develop optimal products. Through this formal and objective process, a set of MPT priority product recommendations and priority MPT gaps have been collectively identified.5 In addition, a general MPT TPP has been developed, and dosage-type specific TPPs for MPT intravaginal rings, on-demand MPT products and injectable MPTs are currently in a collective vetting process. These tools are shared with funders and developers to help inform MPT priorities and gaps, and guide harmonised investments. The IMPT does not require all participants to participate in the same processes, but rather encourages and supports members to undertake activities in areas relevant to their respective interests and that enhance the actions of others. The IMPT Secretariat facilitates communication and coordination of these different activities to ensure that stakeholders' efforts fit into a mutually reinforcing plan of action. IMPT members have agreed on a strategic plan that will advance the development and uptake of a range of MPTs and that involves different roles based on members' capabilities. As mentioned previously, the IMPT's scientific agenda includes priorities and gaps for MPT research and development that are informed by product developers, manufacturers and regulators as well as social scientists and marketing experts from around the world.4, 5 Funding agencies supporting MPT development, ranging across small family foundations, large foundations and government agencies (e.g. Department for International Development, Indian Council for Medical Research, National Institutes of Health, United States Agency for International Development and Wellcome Trust), are also working to develop and implement strategies for viable, long-term collaboration, recognising that the success of the MPT field will require support not just for product research and development, but also for communication, advocacy, market and demand assessments to inform product introduction. The IMPT also participates in other relevant activities and coalitions that have overlapping agendas to promote information exchange and maximise limited resources, including the Reproductive Health Supplies Coalition (RHSC), and SRH and HIV Linkages Working Group. On behalf of the IMPT, the Secretariat (i.e. CAMI) is part of the National Institutes of Health-funded STI Clinical Trials Group (STI-CTG), the purpose of which is to provide the Division of Microbiology and Infectious Diseases within the National Institute of Allergies and Infectious Diseases (DMID/NIAID) with the ability to select and develop scientifically rigorous and feasible concept proposals and clinical research studies in therapeutics, vaccines, microbicides and diagnostics for STIs. IMPT participation in this activity has facilitated submission of approximately a half dozen MPT-focused concepts in less than 12 months. Building the IMPT partnership has involved several years of ongoing communication and regular convenings, which have helped members to build trust and appreciate their shared goals and motivation for collaboration. Even the process of creating consistent messaging and shared vocabulary around MPTs has taken time and resources. Communication with stakeholders takes the form of regular in-person and virtual meetings with technical working group members, and large, multidisciplinary symposia aimed to raise awareness about MPTs, and shape the next steps for the initiative. For example, the 2012 MPT symposium held in New Delhi resulted in the launch of an India-led multidisciplinary MPT task force, through which the IMPT raises awareness about MPTs and engages key stakeholders in South and East Asia.24 The IMPT also identifies and facilitates technical convenings with experts such as regulators, product developers and funders. Each of these IMPT-organised convenings has focused objectives and agendas and a thoughtfully invited cadre of participants to inform the next steps and priorities for the Initiative (Figure 1). As a result of the complexities and uncertainties of product development (e.g. results from clinical trials can be unexpected and may impact next steps for product development and the field), this iterative process is critical to the advancement of MPTs and the Initiative. The MPT field, and the Initiative, are still in the early stages, and success will ultimately be measured by women's access to safe and effective MPT products—an outcome that is years in the future. However, many steps taken by the IMPT towards this goal are possible, such as increasing donor funding, collectively assessing and prioritising the MPT product development pipeline and fostering collaborations around the need for specific types of MPT products. Critical to the success of MPTs and improved SRH worldwide is the commitment of funding agencies to collaborate and support key aspects of the product development-to-introduction continuum. While large-scale clinical trials of MPT products will require significant levels of financial support, more modest funding and in-kind support can make significant contributions to basic science research, communication and advocacy efforts and to understanding the potential market and demand issues that will be critical for MPT success. Greater collaboration and a widening of funding frameworks from single issues to a more comprehensive SRH framework will invigorate scientifically innovative and successful approaches for MPT development. Ideally, this collective impact approach will help to address the complex factors related to the development, regulatory approval and uptake of MPTs as vital public health commodities. The authors would like to acknowledge the valuable contributions of all our IMPT partners in helping launch and grow this global initiative. We also thank CAMI staff members, Kathryn Stewart, Diane Royal, Marisa Cheung and Laura Dellplain for their contributions to this paper and the Initiative. Appreciation also goes to Malcolm Young for valuable discussions and contributions to this paper. The work of CAMI is made possible by the generous support of the American people through the United States Agency for International Development (USAID) under the terms of the HealthTech V Cooperative Agreement #AID-OAA-A-11-00051, managed by PATH. Support was also provided by the Bill & Melinda Gates Foundation, and the Mary Wohlford Foundation. The contents of this paper are the responsibility of CAMI, IMPT and the Public Health Institute and do not necessarily reflect the views of USAID, the Bill & Melinda Gates Foundation, or the US Government.