This post was originally featured on path.org on January 27, 2013 and was written by PATH’s Drug Development program. The post is the first in a three-part series. To see future posts in this series, check out path.org. In December, PATH hosted a Transformative Innovations event in Palo Alto, CA with a panel discussion on ways that public and private sectors can work together to save lives. In three installments, we’ll bring you excerpts of the discussion from our panelists Ponni Subbiah and Anurag Mairal, program leaders of PATH’s Drug Development and Technology Solutions programs, respectively, and Joel Segre, an independent strategy consultant focused on product development and distribution challenges in global health. In our first post, Ponni shares her insights into what makes a partnership successful and reflects on the potential for innovation coming from nontraditional sources. Q: One of the shifting paradigms of the future is that innovation will be multidirectional and come from anywhere in the world. What impacts do you see this having on solving global health challenges? PS: It’s quite exciting because it makes our work truly global, not a pushed-down approach to solving global health problems. We’re transitioning from a world where interventions were done to and for countries to a world where innovation happens with countries. Every sector is realizing that you’re missing opportunities by not tapping into local talent. Even though many of our end users lack access to education, their insights, experiences, and knowledge are invaluable to creating a successful end product. The playing field is becoming more even, and partnerships are now happening at the local level. The younger generation, especially, is much more global and informed in outlook than previous generations, and they’re all about innovation and creativity. The question is, how do we capitalize on that energy and harness it to accomplish global health goals? Traditionally, especially in the private sector, many local affiliate leaders of international companies were from high-income countries. This is changing with the recognition that developing a talent pipeline at the local level is critical for long-term success within a region or country. Similarly, one of PATH’s goals is to identify leaders on the ground to build a stronger presence in countries. We need strong leaders who are well connected and influential so we can build strong and fruitful relationships with governments and civil-society organizations.   Dr. Ponni Subbiah with Wolfgang Laux from Sanofi, PATH's manufacturing partner on the project to create semisynthetic artemisinin. Photo: PATH Q: PATH has pioneered the idea that innovation is not just about technology but about the way in which you engage with partners, the business models you deploy, and the way you think about creating markets. What lessons have you learned about how to do this effectively, how to make sure that partnerships result in real impact, rather than more talk and transaction costs? PS: One of the most critical lessons we’ve learned is that for a partnership to be successful, we have to do the due diligence at the beginning when we’re selecting partners. We need to make sure that the organization we partner with has not only the technical capabilities and areas of expertise needed for the project’s success but also institutional support for the nonprofit aims of the project, especially from senior leadership. It’s important to have those senior leaders on board to be champions for the humanitarian side of an endeavor and to help us drive the project forward. Once a partner is selected, sitting down from the get-go and having a clear discussion about what each organization hopes to get from the project, what the incentives are, deliverables, etc. is key. These kinds of big-picture discussions, aside from the day-to-day communications that take place, should occur at set intervals, at least every six months, because these variables may change over the course of the project. If the goals of a project change, it will require some course correction to get back on track. Another critical element of a successful partnership is building trust and transparency. Though we’re all very connected technologically speaking, I find that it’s still important to have face-to-face meetings. Connecting in person and getting to know someone’s personality and work style changes the way we work together, usually for the better. I think it fosters more open interactions and makes people more willing to be flexible and cooperative. In this field especially, when our partners are all over the globe, we have to be cognizant of creating enough opportunities for face-to-face meetings. We try to provide time and support to make sure team members get this opportunity to connect. What goes hand in hand with building trust and transparency is the ability to have tough discussions. Teams that actually go through some tough discussions and overcome them are the great teams; teams that don’t challenge each other and avoid putting issues on the table never get to that great team level. Each partner brings a different strength and area of expertise to the partnership, and accordingly, each partner is under different institutional demands and pressures. We have to make choices about the battles we pick and where and how we can compromise to move projects forward, given that everyone is committed to a high-quality end result. As a nonprofit, some of the most important qualities we can bring to the table are expertise in global health, flexibility, and patience. We have to be accustomed to change. With the start and end of each phase of a project, new partners may come aboard and others may become less involved in day-to-day activities. Each project team has to do the same thing—understand where each partner is coming from, identify the critical areas that need further discussion, and then work together to problem solve. For more Innovation. Transformation. Inspiration., stay tuned to the Drug Development blog for the next two installment with Dr. Anurag Mairal and Joel Segre, and follow them on Twitter and Facebook. More information PATH’s Drug Development program PATH’s Technology Solutions program The NGO challenge: stay ahead of the curve Semisynthetic artemisinin achieves WHO prequalification

In this regular feature on Breakthroughs, we highlight some of the most interesting reads in global health research from the past week. The Guardian wrote about the importance of the World Health Organization’s prequalification of medicines program (PQP): “The PQP has been a fantastic success story, giving a stamp of approval to good quality generics and allowing the governments of developing countries to buy effective versions of essential drugs they can afford.” However, the article argues that if the program is to become more sustainable, it needs to diversify its funding. The Bill & Melinda Gates Foundation has entered into two partnerships with South African institutions to develop new drugs and vaccines against HIV and AIDS, tuberculosis, and malaria. The multi-year, multimillion-rand partnerships are with the Medical Research Council's Strategic Health Innovation Partnerships and the University of Cape Town's Drug Discovery and Development Centre. The Saving Lives at Birth: A Grand Challenge for Development program has submitted a fourth round of requests for applications. The challenge seeks to identify and develop transformative approaches that integrate new technologies, better service delivery models, and improved “demand side” innovations that empower pregnant women and their families. Bill and Melinda Gates dispel three myths that block progress for the poor in their 2014 annual letter. The co-founders of the Bill & Melinda Gates Foundation address why poor countries aren’t doomed to stay poor, why foreign aids isn’t a big waste, and that saving lives doesn’t lead to overpopulation.

In this regular feature on Breakthroughs, we highlight some of the most interesting reads in global health research from the past week. GHTC member the International Vaccine Institute and the Institute for Translational Vaccinology have agree to collaborate on vaccine research and development and to promote capacity building in low- and middle-income countries. The partnership will focus on improving available technologies, as well as regulatory processes. The House and Senate Committees on Appropriations have released a fiscal year (FY) 2014 omnibus appropriations bill . Funding for global health programs at the US Agency for International Development saw some increases, while the National Institutes of Health remains woefully underfunded—even with an increase of $1 billion over last year’s post-sequestration levels. Results of an early-stage clinical trial show that stem cells taken from patients’ own bone marrow could be used to treat multidrug-resistant and extensively drug-resistant tuberculosis (TB). More tests will be required before this treatment option is validated as a possible alternative to current TB drugs. New research from Washington University in St. Louis School of Medicine has found that a form of malaria attacks red blood cells by “clamping down on cells with a pair of proteins.” This finding may aid scientists in the design of better vaccines and drugs against malaria.

The US Agency for International Development (USAID) is the nation’s lead foreign assistance agency. Throughout its 50-year history, USAID has worked with other government agencies, the private sector, and nongovernmental organizations to support the development and introduction of affordable health products appropriate for addressing the diseases and health issues in developing countries. The GHTC has launched a new blog series to highlight the impact of USAID’s commitment to global health research and development (R&D). The series will showcase stories from individuals who have benefited from the agency’s support and investment in R&D—as well as people whose lives would vastly improve if USAID were to expand its support for health R&D into new areas. Our fourth and final post in the series is by Dr. Cynthia Gama, a principal investigator with MatCH and works with the International Partnership for Microbicides (IPM) in South Africa. Based on her experiences, Cynthia writes about the need for USAID to support R&D for microbicides to protect women from HIV. Q: As a microbicide researcher working in South Africa, you witness every day the impact of HIV on women. Can you tell us about the effect of HIV on women in your community? A: It is very difficult to not see the face of HIV and AIDS every single day when working in communities such as ours. The KwaZulu Natal province in South Africa has a high incidence of HIV and while we all know that women bear the brunt of the epidemic, the resulting impact can been seen not only in the women but also in the young children who have lost their parents; the old grandmothers who care for orphans; the daughters who often drop out of school to help them; and the impact that HIV has had on all aspects of people’s lives. What gives me hope is knowing that we are working toward a product—a microbicide for women— that may help to reverse this trend in our community and give women and their families a better future. Dr. Cynthia Gama of MatCH. Photo: IPM Q: Why are microbicides and other women-controlled prevention methods so important in the fight against HIV? Are currently available prevention methods, like male condoms, realistic options for women in your community and other parts of the world? A: We know that condoms work—both male and female condoms—and we know that South Africa has one of the largest and best-established public-sector male and female condom programs worldwide. Women in our community receive HIV prevention and contraception advice from various sources. While women may have access to these prevention products, the challenge is that women may not always have the ability to negotiate their use with their partners. This could explain the disproportionately high numbers of our women being infected with HIV. As a researcher, I know that women desire more options to protect themselves, hence my commitment to making sure that collectively we can deliver more options to our communities. Our research center and community is involved in The Ring Study, which is evaluating a unique product, a long-acting microbicide ring. Women who participate are shown how to insert the ring themselves, which is designed to stay in place for a month at a time and release an antiretroviral drug to prevent HIV. Q: How has USAID support helped advance your research and the microbicide field as a whole? A: The support that our study sponsor, IPM, receives from donors such as USAID ensures that new products for women are developed, and that we can do the much needed work and research that would one day turn the hope of a microbicide product into reality. Without funding, none of what has been achieved thus far could have been possible. Q: What other benefits of clinical research for microbicide development—such as capacity building and infrastructure development—has USAID support had in your community? A: HIV prevention research has most certainly strengthened the scientific and medical research sector overall. Expertise in conducting large clinical trials is now available and well-developed, and has offered more employment opportunities. USAID support has helped to bring communities closer to science, and helped communities appreciate the need for clinical research and understand its benefits. Q: When a safe and effective microbicide becomes available, what impact are you hoping to see for women in your community and around the world? What role will USAID have played in this effort? A: On that day of jubilation we would know that our sisters, daughters, and granddaughters have much to look forward to. I hope that once a product shows efficacy, that our policy makers will ensure that it is made available as soon as possible. Organizations such as USAID and others together are making it possible for this dream to become reality.

In this regular feature on Breakthroughs, we highlight some of the most interesting reads in global health research from the past week. Researchers at Rice University have developed a rapid malaria test that uses laser pulse—eliminating the need to draw blood. The test has been found safe in healthy humans and will soon be tested on humans with malaria symptoms. The White House has nominated Dr. Deborah Birx as the next Global AIDS Coordinator and to lead the President’s Emergency Plan for AIDS Relief (PEPFAR). Dr. Birx is currently the director of the Centers for Disease Control and Prevention’s Global AIDS Program and works on PEPFAR implementation at her agency. The US Agency for International Development and GHTC member Population Council have entered into an agreement to develop a non-antiretroviral-based microbicide to block HIV and other sexually transmitted infections. If successful, the partnership could offer a low-risk, easily accessible product for women in low- and middle-income countries. According to the results of an early-stage clinical trial, patients with multi-drug resistant (MDR) or extensively drug-resistant (XDR) tuberculosis (TB) could be treated by using stem cells taken from their own bone marrow. If successful, the treatment could be an alternative for patients with MDR- or XDR-TB who do not respond to conventional drug treatment options.

The US Agency for International Development (USAID) is the nation’s lead foreign assistance agency. Throughout its 50-year history, USAID has worked with other government agencies, the private sector, and nongovernmental organizations to support the development and introduction of affordable health products appropriate for addressing the diseases and health issues in developing countries. The GHTC has launched a new blog series to highlight the impact of USAID’s commitment to global health research and development (R&D). The series will showcase stories from individuals who have benefited from the agency’s support and investment in R&D—as well as people whose lives would vastly improve if USAID were to expand its support for health R&D into new areas. Our third post is by Brian D’Cruz, a volunteer physician who has worked with Médecins Sans Frontières (MSF) in Congo Brazzaville and Central African Republic. Based on his experience with MSF, Brian writes about the urgent need for USAID to support R&D for neglected tropical diseases (NTDs) like sleeping sickness. Q: As an MSF physician working in Congo Brazzaville and Central African Republic, you saw many patients affected by sleeping sickness—an NTD that primarily occurs in the poorest, most rural areas in Africa. Can you tell us about some of your experiences treating this disease during your time with MSF? A: In Central African Republic, I saw firsthand the suffering caused by sleeping sickness. I vividly remember an 11 year old girl named Natacha. She lived in an area where medical care and screening for sleeping sickness had not been available for years due to increasing violence in the area. Our team was the first to treat sleeping sickness there in several years. Several months before we arrived, Natacha started to experience the symptoms of sleeping sickness—including sleep disturbances, memory problems, spasms of her hands, pain all over her body, and seizures. A few weeks before we arrived, she stopped walking. By the time her family was able to get to us, she could no longer speak or feed herself. During this entire time, her family was powerless to help her. By the time they reached our team, we were able to diagnose Natacha and start treatment, but it was too late. She died a few days after reaching us. Brian D’Cruz (second from the left) and other panelists discuss NTDs at a congressional briefing in June 2013. Photo: Research!America Q: What impact does sleeping sickness have on communities and individuals in Congo and Central African Republic? A: Sleeping sickness is fatal if untreated, and what’s more, patients with this disease suffer enormously before their deaths. MSF has been treating patients with sleeping sickness for more than 25 years and we have seen the consequences of this forgotten deadly disease. Natacha’s death is a vivid and terrible example of the suffering that these patients and their families endure. The effort required to find, screen, diagnose, and treat these patients can be enormous, especially as the disease tends to spread in regions with limited access to appropriate care. Sometimes, as in Natacha’s case, the disease spreads because of surrounding violence; other populations are affected because of mass displacement or because they live in very remote locations. Q: As you mentioned, sleeping sickness is fatal if left untreated. As a physician, do you have adequate tools to detect and treat this disease? A: Tools exist to diagnose and treat the disease, but these techniques are cumbersome and require huge resources. To diagnose patients, you need centrifuges, microscopes, and very complex diagnostic tests along with specially trained technicians capable of interpreting the tests. To make a final diagnosis, every patient must have a lumbar puncture, an often very painful procedure which involves collecting spinal fluid from the patient’s back. These tests must often be performed in areas with very little infrastructure (such as lack of electricity) and poor sanitation. Patients in the first stage of the disease may be treated with seven days of daily injections, but treating the advanced stages of the disease is very difficult. Recently, new treatment protocols have been adopted which are safer and easier, but these treatments still have limitations. The current best treatment is a combination therapy, called NECT, developed by the Drugs for Neglected Diseases initiative. This treatment, although a dramatic step forward, still has significant side effects. It also cannot be emphasized enough that active screening and treatment is a constant need; while efforts into research and development for better diagnostic and treatment are essential, we must also ensure that there are people actively finding patients. Q: What kinds of new health tools and products do you think are necessary to help sleeping sickness patients in the Congo and around the world? A: We desperately need a rapid point of care diagnostic test, much like those used for malaria. We need an affordable test which does not require electricity or refrigeration, which could be read by staff with minimal training. This would dramatically increase our ability to screen for this disease. Also, while the disease is curable, current treatment requires intravenous medications administered under close supervision. As the disease tends to spread in areas with very limited medical care, it can be very difficult to give proper care to patients after they’re diagnosed. An oral pill treatment for both stages of the disease would revolutionize our ability to care for patients. New game-changing tools may be available in the near future. Two new oral drugs are now being tested in clinical trials. If they were found to be safe and effective, they could be given to patients who test positive with a rapid test. Just one test and one short-course oral treatment: this simplified protocol would make a huge difference in remote settings. On-going clinical trials with these new tools need to be fully-financed. Q: USAID currently does not invest in research to create new tools for sleeping sickness and other NTDs. How would support from USAID for NTD research help you as a physician? What difference would this support make in the lives of patients? We would save a lot of lives. We would prevent a significant amount of suffering. This disease causes excruciating pain, disability, psychosis, and ultimately death. Increased funding for programs to find patients and treat them, and for better and more patient-adapted diagnostic and treatment tools, would be game-changers. In addition to sleeping sickness, MSF/Doctors Without Borders works on several other of the most neglected of the neglected diseases, including Chagas, Buruli ulcer, and visceral leishmaniasis. These diseases affect very poor, marginalized people, often in some of the remote places. There is no lucrative potential market in developing medicines for people suffering from NTDs. As a result we have limited diagnostics and archaic, sometimes toxic treatments. If we really want to make a difference in the lives of people suffering from NTDs, we will not only need to increase funding for these specific diseases, we’ll have to seriously start looking at ways to create new types of incentives for research and development of new medicines .