Solutions for Coordination
Given the rapid resurgence of malaria, the multiplicity of candidate vaccines (over 40 at the time of this writing), and the multiple steps involved in the complex sequence of events necessary to translate fundamental research knowledge into a field-applicable, efficacious, and effective malaria vaccine, workshop participants felt it imperative that the process proceed with maximum efficiency, both with respect to time and to resource constraints.
The following was therefore recommended:
A federal “Malaria Vaccine Development Board” should be established and given the responsibility, authority, and resources to carry out the strategy or strategies most likely to result in accelerated, successful development of malaria vaccines. The board should include representatives from academia, relevant federal government agencies, pharmaceutical and biotechnology companies, and foundations. A critical initial task of the board would be to identify a limited number of the most promising malaria vaccine candidates and to focus U.S. development efforts on these selections. The board should monitor progress in malaria vaccine development in both the public and private sectors; identify development needs, opportunities, and priorities and advise interested parties and funding agencies of these findings; provide financial and other support for high-priority development efforts; and encourage collaboration among academia and private and public sector entities.
To succeed, the board must:
have access to sufficient resources to fill gaps in the malaria vaccine development process in a timely manner;
have a sustained, long-term commitment to malaria vaccine development;
be able to access all phases of the malaria vaccine development process, through field implementation in immunization programs;
have the flexibility to address rapidly changing needs, technologies, and priorities in the field of malaria vaccine development;
be able to access, in a cost-effective manner, optimal technologies and development expertise, in either the private or public sector;
be able to provide the leadership in conducting U.S. malaria vaccine development efforts and in coordinating these with international academic researchers, corporations, and relevant organizations such as the World Health Organization, the World Bank, the United Nations Development Programme, and the Commission of the European Communities.
While there are historical precedents for aspects of the proposed Malaria Vaccine Development Board, none completely covers all of the facets described above. Some examples of precedents that may be examined for relevance to specific elements of the board's charge include the 1941 Commission on Influenza of the Armed Forces Epidemiology Board, the National Task Force on AIDS Drug Development, and the National Foundation for Infantile Paralysis.
The board's development strategy should incorporate the action steps required for accelerated, cost-effective production, evaluation, and field application of the two malaria vaccines. The estimated costs of such a program and the optimal mix of governmental, academic, industrial, and foundation participation and support required should also be determined. In these determinations the board must clearly document the scientific foundation for any recommendations. In addition, because a major incentive for industrial investment in vaccine development is the size of the potential market for the vaccine, it is recommended that the board immediately commission independent market analyses for each of the proposed vaccine types, and that this information be made widely available to the global vaccine industry.
As a first step, it is recommended that the board consider convening a meeting of members to develop an agreement to ensure access to reagents in both the public and the private sector that could be useful in developing and conducting assays required to assess vaccine candidates in animals and humans. Such reagents should include, but not be limited to, purified recombinant proteins, synthetic peptides, live recombinant viruses and bacteria, DNA plasmids, and monoclonal antibodies. Having established strategies for sharing reagents equitably and consistently, the board could then address the more difficult goal of establishing productive, consensual alliances among government, academia, the nongovernmental sector, and industry for the purpose of rapid malaria vaccine development.
PREREQUISITES FOR SUCCESS
In order for the proposed Malaria Vaccine Development Board to be successful, effective leadership is necessary, and each participating entity must agree on the accepted strategy for vaccine development. This requires that each party identify areas of interest within the overall process, as well as areas of comparative advantage. Each entity should have a vested interest in sharing information and resources, and must find an economical method of doing so.
MODELS FOR COORDINATION AND LEADERSHIP
There is ample precedent for coordination of vaccine research and development. Commissions established by military medical boards have successfully addressed similar problems with other diseases. The first polio vaccines were developed largely under the auspices of the National Foundation for Infantile Paralysis, which coordinated all aspects of the process, from initial production to clinical evaluation. A Polio Vaccine Committee, comprised of scientists, physicians, and other experts, provided ongoing commitment and advice, while the National Foundation provided necessary funding. Strong leadership was a major component of the success of the commissions and the National Foundation. Another precedent for coordination is the National Task Force on AIDS Drug Development, which was chartered from 1993 to 1995 to identify and remove obstacles to AIDS drug discovery and development efforts. The task force consisted of 15 members from academia, industry, and community constituency groups; the directors of the National Institutes of Health and Federal Drug Administration; and the assistant secretary for health, who acted as chair. The task force forwarded a series of recommendations to the secretary for health, DHHS, that focused on incentives for increased involvement of industry and academia in AIDS drug discovery and development efforts.
An important question is whether these models are useful paradigms for the malaria vaccine effort. By and large, past efforts represent attempts to deal with product development issues. In many of these cases, the issues were sufficiently defined, and a straightforward, but detailed, development plan could be developed and implemented. In the case of malaria vaccine development, however, there are multiple candidate vaccines, multiple production technologies, and many other complex issues that need to be considered. Thus, as will be discussed below, coordination of malaria vaccine R&D requires not only a perspective on product development, but also on the management of complex, multiorganizational endeavors.
Factors limiting coordination and collaboration derive from several sources. First, different agencies or groups have distinct missions. For example, the primary objective of the Department of Defense malaria vaccine development program is to develop vaccines that will protect U.S. military personnel deployed in endemic areas. In contrast, the primary objective of the Malaria Vaccine Development Program of the U.S. Agency for International Development (USAID) is to develop vaccines for populations permanently residing in endemic areas. Because these end objectives differ substantially
from one another, it is possible that the agencies may elect to develop different types of vaccines, thereby limiting the perceived need to cooperate. In this hypothetical instance, it is still possible that the number of shared steps in the development process for each vaccine candidate will provide sufficient impetus for the sharing of resources.
A second hindrance to coordination stems from insufficient internal resources. A paucity of funding for a given agency program will limit the ability of that agency to collaborate with other agencies in a useful manner without crippling its own program.
Finally, there are bureaucratic and institutional hurdles. For example, coordination requires that participants respond to requests for assistance in a timely manner. Regardless of the cause, failure to do so delays the development process and leads other participants to seek alternative, and perhaps less productive, partnerships or to go it alone. In contrast, specific expertise and resources may be vested in individual agencies, so that coordination and collaboration among these agencies can be seen as synergistic for the development process as a whole. For example, the Centers for Disease Control and Prevention (CDC) has a specific mandate and expertise in the epidemiology and field studies of malaria, while the National Institutes of Health (NIH) vigorously supports laboratory and clinical studies of malaria. In such instances, it is important that the individual agencies coordinate their efforts, capabilities, and resources within the larger context of vaccine R&D.
Prioritization, Product Development, and Process Management
At the simplest level, coordinated malaria vaccine R&D requires participants to distinguish more promising malaria vaccine candidates from those with less promise, and to guide the most promising candidates through the development process. There is thus a need to prioritize candidate vaccines based on desirable characteristics, as well as to judge the probability of successful development. The desirable characteristics should reflect not only scientific and public health considerations, but also technical considerations related to feasibility; economic concerns; and, ultimately, delivery.
The establishment of priorities and criteria is also important for determining go/no-go criteria for product development. Early identification of such criteria would permit investigators and agencies working on lower-priority candidates to know what technical issues need to be addressed in order to improve the standing of their candidates.
Procedures for the systematic setting of priorities and product development of the kind described above are well established in both the public and private sectors. They presuppose, however, relatively well-defined candidate vaccines, preferably few in number, so that the decision points in the development process are minimized and fall within a relatively short time frame.
Initial Efforts to Coordinate Malaria Vaccine R&D
Beginning in the mid-1980s a number of federal agencies recognized that malaria vaccine R&D was proceeding, often in a disjointed fashion, in a variety of agencies, and that sharing of information could be mutually beneficial. The number of interactions subsequently increased until the late 1980s, when they were formalized through the formation of an ad hoc group, the Federal Malaria Vaccine Coordinating Committee (FMVCC), which met on a regular basis under the auspices of the USAID Malaria Vaccine Development Program. In 1995 the venue for FMVCC was changed to the NIH. By consensus, participants began to focus on more proactive efforts to accelerate malaria vaccine R&D through increased collaboration and cooperation among the participants. Several task forces charged with development of selected malaria vaccine products were established and have begun to coordinate the steps in the development process. In addition, FMVCC began to exchange information, identify generic gaps in the development process, establish collaborations to evaluate new vaccine technologies, and consider how vaccines might be evaluated in clinical and field settings. It also recognized the important need to reach out to other entities in the private sector and the international community. FMVCC was crucial in beginning the transition from coordinating individual product development efforts to the more complex task of process management. This process should continue.
THE NEXT STEPS
While acknowledging the accomplishments of FMVCC, workshop participants recognized that an additional major step must be taken. Coordination of research and communication between managers of development programs is essential, but not sufficient to meet the challenge of malaria vaccine development. Workshop members agreed that a powerful and authoritative federal Malaria Vaccine Development Board is needed to forge the alliance among government agencies and to establish the necessary partnerships with both the academic community and the vaccine industry.