We use Grand Challenges to seek new knowledge or new concepts that will lead to interventions that would not otherwise have occurred or that would not have occurred as quickly without our investment. Inherent in this is a willingness to take risks, to make mistakes and to learn from these mistakes. In the last decade, we and our partners have run numerous challenge calls ranging from very specific technical calls seeking new biomarkers for TB to new concepts for promoting health seeking behaviors. Each of these varied challenge calls can be viewed as an experiment and increasingly we aspire to evaluate these individual experiments to permit the lessons they hold be applied to and improve future challenge calls.
Given the long time horizons that many ideas require to demonstrate proof of concept and then the subsequent barriers to achieve scale and impact, we have developed a framework to permit an intermediate evaluation of Return on Investment (ROI) for Grand Challenges which we hope can serve as a proxy for lives saved and lives improved. Other Grand Challenges partners have developed alternative frameworks which like this ROI are intended to guide their work. We will describe each of the terms in the ROI below.
Projects Transitioned to Development: Our primary metric of success is identifying new investment opportunities that ultimately result in lives saved. As an intermediate measure we track Grand Challenge investments that have demonstrated sufficiently robust proof of concept that they have transitioned to development. For our development pipeline we aspire to select the best opportunities that have achieved proof-of-principle independent of provenance. When proof-of-principle is demonstrated, we make the increased investments (when possible in partnership with other funders) required to take the concept forward into development. Therefore projects selected for the development pipeline provide a reasonably independent intermediate metric of success of Grand Challenge initiatives. To this end, we can view each challenge call as an independent experiment to be evaluated. If we apply this analysis to the original GCGH call which supported 44 projects, nine are currently on a pathway towards development (GREEN projects, 20 percent) and ten contribute essential tools or knowledge to other development projects (YELLOW projects, 23 percent). The remaining 25 projects (RED projects, 57 percent) have not, though many nonetheless made solid scientific progress.
An example of a GREEN project is the Eliminate Dengue project (www.eliminatedengue.com) led by Scott O'Neil, which has developed a potentially transformative new approach to controlling the insect vector that transmits dengue and this new approach is currently being evaluated in field trials. An example of a YELLOW project is "Drugs for Treatment of Latent Tuberculosis Infection" which was led by Douglas Young of Imperial College. Although this project never produced the new drug candidates envisioned, it changed the scientific perspective on the pathogenesis of TB, which is no longer viewed as either active or latent, but is now understood as a disease with a wide spectrum of activity. This new knowledge, along with tools developed by the project team are now foundational to both drug and vaccine development efforts for TB. Finally, RED projects range from a company which failed financially and was unable to complete the proposed work to projects like Nobel laureate Dr. Ralph M. Steinman's project "Improved Vaccine Efficacy via Dendritic Cells and Flavivirus Vectors," which produced a wealth of new knowledge, but the insights are not yet currently included in a specific manner in the development of a new global health intervention. It is also worth specifically calling out another group of RED projects – those that looked to produce needle-free, thermostable vaccines. In this case, the formulation of the challenge focused only on the scientific barriers and did not take sufficient account of the regulatory and commercial barriers; thus, although much good scientific work was accomplished, few of these projects are on a pathway towards development – in other words, what we asked scientists to do as formulated in the challenge call had substantive weaknesses, not the work that they performed in response to the call.
Strategic Learning and Landscaping: Although mainly anecdotal, we believe that the process of crafting a Challenge, which typically requires an extensive consultation with experts inside and outside the Foundation, begins a rich strategic learning process, which is uniquely enhanced by the diverse submission of ideas from innovators across the globe. For example, when we ran the Diagnostics Grand Challenge in 2009, which was complemented by Grand Challenges Canada's call in 2010, we received over 1000 submissions. These submissions provided a snapshot of the current state of diagnostics in response to a specific problem statement, capturing data from academic work that had yet to be published as well as proprietary concepts from commercial sources. Collectively, this new information and perspective has shaped the foundation's thinking in this area and guided the design of a range of planned initiatives.
Increased funding for innovation: Grand Challenges continues to provide an attractive platform for building co-funding partnerships and providing new funders a mechanism to increase their portfolios of solution focused investments. Perhaps more interesting is the evidence we have gathered for the indirect increase in funding for innovations against challenge problem statements. Under Grand Challenges Explorations we fund approximately 3 percent of the ideas submitted - we assume that this leaves many good ideas unfunded. We hypothesize that posting a challenge statement inspires scientists to develop new ideas and in many cases pursue these ideas they even if they are not selected for funding by the foundation. To test this hypothesis, in one analysis we surveyed declined applicants with 43 percent responding that the idea that they submitted was a new idea formulated in response to the challenge topic and 8 percent reported they were able to find funding for the work even though we did not provide funding. Although indirect, we believe this represents an important source of funding leverage for new ideas against challenge calls.
Increased Awareness of Global Health and Development: The Grand Challenges family of grant programs contributes to an increased awareness of the issues embodied in the challenge goals through at least three avenues: (1) challenge calls provide an opportunity for new entrants to directly explore how they can contribute to our issues; (2) in order to increase the pool of applicants to our open calls, we engage in a variety of marketing and outreach and, (3) in a many cases, both the initial publication of the challenge calls and the awards that are subsequently made provide a steady and diverse stream of media stories that capture in a particularly tangible way the potential for innovation to solve some of the world's most pressing health and development problems.
For an additional perspective on Grand Challenges, read this companion piece by Dr. Peter Singer, CEO of Grand Challenges Canada.