Industrial strength research
AIDS vaccine field adopts more characteristics of industry
Like any great scientific challenge, the search for an AIDS vaccine requires money, minds, and collaboration. These first two requirements are closely related, and as new streams of funding flow into the field more interest is being focused on this pursuit. But as the research field broadens, global health leaders are emphasizing the need for cooperation and collaboration among research groups as an equally important component in the discovery process for an AIDS vaccine.
The emphasis on researchers working together more effectively and efficiently has inspired the emergence of several new collaborative efforts, many of which come in the shape of consortia or virtual institutes that are collectives of independent research groups willing to share ideas and resources. And this has inspired the adoption of a new research model, one which stresses coordination of efforts, rapid sharing of positive and negative results, structured decision making, accountability, and consideration of long-term goals. This model has much in common with the way research is done in large biopharmaceutical companies. But precisely how this model is fitted to the evolving field of AIDS vaccine research is currently a subject of discussion.
The idea of sharing data and results may seem to contradict the way research is done within biopharmaceutical companies. Generally speaking, industry is very protective of its research and closely guards its intellectual property. But within a given company research has long been a collaborative effort where a single product, like a drug or a vaccine, is passed through teams of scientists with different expertise until completion. A new medicine may start out with chemists but will go through teams of biologists, safety assessment specialists, clinical trial coordinators, as well as regulatory groups before it winds up in the hands of marketing professionals.
Conversely, academic scientific research has traditionally been a mostly solitary endeavor, heavily reliant on the specific expertise and interests of the principal investigator. Researchers at universities and institutes tend to work in small groups, sharing their results at conferences and through publication in scientific journals. This academic model means that research teams work on a specific aspect of a project, rather than seeing it through from start to finish.
While this investigator-driven model has thrown up fundamental findings in every scientific discipline, a mission as vast as developing an AIDS vaccine requires extensive coordination. "Focused development programs similar to those within industry are needed so that people can make informed decisions about what is working and what is not," says John Shiver, director of vaccine research at the US-based company Merck.
Over the last few years, support for an industry-like research environment for AIDS vaccines has gained momentum. In 2002 IAVI teamed with a number of academic and government research groups to establish one of the first such research programs, the Neutralizing Antibody Consortium. A collaborative effort involving investigators from across the US, the consortium members share standardized methods. Even more importantly, they share their ideas and discoveries freely and plan some of their experiments collectively.
In June 2003 a group of 24 scientists proposed the creation of a Global HIV Vaccine Enterprise, an "alliance of independent entities" that brings together many of the key players in AIDS vaccine research and calls for the coordination of efforts to improve vaccine discovery. The Enterprise has helped build consensus across the whole field and early last year published its scientific strategic plan that outlines the key unanswered questions in AIDS vaccine research.
Just last year the US National Institutes of Health (NIH) awarded funds to start the Center for HIV/AIDS Vaccine Immunology (CHAVI), a consortium of largely academic research groups. Additionally, the Bill & Melinda Gates Foundation will grant up to US$360 million over the next 5 years for the creation of a network of collaborating institutions. Part of the goal is to get people working across disciplines, says José Esparza, who is coordinating the effort. "We would like to bring together complementary expertise that otherwise would not be available."
The ability to bring together that expertise is just one of the strengths of the industrial approach. Other important aspects are the decision-making process, management, and oversight of a project. Instead of relying on decision making by consensus and committee, industry gives the authority to a project management team that guides vaccine candidates from research to development. A project manager is an asset to any research lab, says David Ho, scientific director of the Aaron Diamond AIDS Research Center, "we have come to appreciate how important that is to keep things on track."
For early stage research the project manager can help the investigator understand factors outside the researcher's area of expertise, such as whether a project has the potential to pass regulatory hurdles. This approach ensures that researchers are communicating and goals are being met. "The project manager provides the discipline to march the product through all the phases of its development," says Gary Nabel, director of the Vaccine Research Center (VRC) at the NIH.
Making it happen
Abandoning investigator-led academic research completely is not the solution, but this system has some shortcomings that make it less than ideal for AIDS vaccine development. Some research questions might simply be too difficult or too resource-expensive for a small research group to tackle alone. For example, studying mucosal immunity is prohibitively expensive due to the difficulty in collecting samples (see VAX December 2005 Primer onUnderstanding Mucosal Immunity). The lack of oversight in the academic environment may also mean that major questions can go unanswered, simply because nobody sought out that knowledge.
The new industrial-style collaborations are meant to sidestep pitfalls such as these. CHAVI contains some aspects of the industrial model but retains the committee-based approach common in academia. Their strategic plan includes both a discovery phase and a product development phase, each of which has a team leader, and the teams are organized according to the major unanswered scientific questions put forward by the Enterprise. "It is a grand experiment and the key is the interdisciplinary approach, using components of the corporate model, to focus the firepower to solve a very hard problem," says Barton Haynes, director of CHAVI.
This approach will put the focus on successful projects and allow prioritization of vaccine candidates before moving to full-scale clinical trials. For candidates that are ready for further testing, vaccine developers are increasingly interested in the Phase IIb "test of concept" trial, an expanded Phase II trial to evaluate the vaccine candidate's efficacy (see VAX September 2005 Primer on Understanding Test-of-Concept Trials). Merck is taking this approach with a Phase IIb trial of its lead candidate. The goal of these trials is to get answers sooner on whether a vaccine has the potential to work.
IAVI has been active in maintaining that research must adhere to project guidelines in a timely fashion, often testing a vaccine candidate in several trials simultaneously so the candidate can be evaluated as quickly as possible.
"Products that don't pass the bar are terminated quickly without waste of resources so that funds are used efficiently," says Seth Berkley, president and chief executive officer of IAVI.
Some of the drawbacks in traditional academic research stem from researchers having to constantly compete for grant funding, whereas industrial researchers usually know their funding is secure as long at the project is continuing to make progress towards its end goal. One option for meshing the industrial and academic approaches is to fund quality academic researchers with a proven record of achievement for longer periods of time and alter the grant renewal requirements for principal investigators in academia.
A secure source of funding might have another desired effect: luring experienced researchers into the field of AIDS vaccine research. Especially needed are experts in basic immunology, says Bruce Walker, director of Harvard Medical School's Center for AIDS Research, who explains that few immunologists that helped to explain how the immune system works have transitioned to working on HIV research. "It is not easy to attract people who are successful in other areas to change focus and work on HIV," says Walker.
But changing the research model alone won't lead to a vaccine. "We shouldn't forget that no matter what research model is used, much basic research remains to be done," says Mitchell Warren, executive director of the AIDS Vaccine Advocacy Coalition. "I would hate to see people stuck debating about what is the correct model."
But most global leaders and funding organizations agree that working to harmonize research practices will help ensure that the search for an AIDS vaccine is efficient and takes as little time as possible.