Marissa Chmiola

An injectable HIV and AIDS treatment that could offer HIV-positive individuals an option other than taking daily pills is entering late-stage clinical-trials. In previous studies, the drug—PRO140—was shown to be successfully in suppressing viral loads to an undetectable level for at least one month in 98 percent of patients. Most HIV-positive patients take nearly 30 antiretroviral pills every week. In some patients, these pills cause kidney and liver damage as well as resistance to further treatment. The developers of this new treatment hope PRO140 could become available in once-a-week, two-dose treatments by 2017, pending success of clinical trials. Former US Treasury Secretary Lawrence Summers and Lancet Commission member Gavin Yamey write in a Huffington Post op-ed that the development of game-changing health technologies will be critical to reaching the health goal in the Sustainable Development Goals (SDGs). They argue that reaching the SDG health targets is not possible with today’s health tools and that new medicines, vaccines, diagnostics, and other innovations will be required. To spur such innovation, they call for increased investment in global health research and development from all nations. A new observational study suggests that taking daily pills to prevent HIV infection—known as pre-exposure prophylaxis (PrEP)—is working to prevent HIV infection in the real world. Kaiser Permanente of San Francisco announced last week that none of its 657 clients receiving PrEP have become infected over a period of more than two years. When PrEP was introduced, many critics predicted that it could decrease condom use, in turn leading to more HIV infections. Advocates of PrEP say this study shows that such concerns were unwarranted, as PrEP is proving effective in nonclinical settings. CNN reports in-depth on the global spread of Dengue and efforts to control and treat the disease. While Dengue fever was once a problem only in pockets of South America and Southeast Asia, today more than 100 countries harbor risk of infection. Currently, there is no treatment or vaccine against for the disease and no effective prevention options; because the mosquitoes that carry Dengue bite during the day, bed nets that have been critical in preventing malaria are not effective for Dengue prevention. New mosquito control interventions, drugs, and vaccines are needed to tackle the disease.

Many infants have difficulty breastfeeding and must rely on cup feeding. Photo: PATH/Amy MacIver Breast milk is the perfect first food for newborns; it provides nutrients and energy that infants need and contains substances that strengthen their immune systems. Ideally, newborns are breastfed within their first hour of life with breastfeeding continuing for their first several months of life. However, some babies are not able to breastfeed—preterm babies often do not have the fine motor skills and babies born with facial anomalies like cleft palates cannot breastfeed. And in some cases, babies who are orphaned or have mothers too sick to breastfeed who must be fed with donor milk. In high-resource settings, these infants could have breast milk fed to them through feeding tubes or specially-designed bottles, but in low-resource settings these solutions are impractical and often unsafe in areas where reliable clean water is not available. Tubes must be inserted by a trained medical professional and are often not available in low-resource settings; while bottles are expensive—particularly those that adapted for use by infants with cleft palates— and difficult for mothers to keep free of bacteria due to their crevices. For infants in low-resource settings who cannot breastfeed, the World Health Organization recommends hand expression of breast milk and use of a small cup to feed newborns. Cups are easier to clean so reduce the risk of infection, and cup feeding has been shown in some studies to improve the transition of preterm infants to exclusive breastfeeding. The problem? There is no cup designed specifically for the job, and the household cups many mothers use have some serious drawbacks that can put their baby’s health at risk. A solution? A group of innovators from the University of Washington, Seattle Children’s Hospital Craniofacial Center, and PATH have invented the NIFTY™ cup—a simple-to-use, easy-to-clean, inexpensive cup designed specifically for delivering breast milk to infants. Your average cup won’t do for breastfeeding Because there is no standard cup designed for the purpose, mothers who need to cup feed typically use whatever small cups or devices they have on hand. For example, in India mothers typically use a miniature gravy-boat like device called a paladai—originally used to burn oil during religious ceremonies—that have sharp-edged metal spouts and can cause oral cuts or injuries to an infant. A young infant being cup fed with a mug in Kenya. Photo: PATH/Evelyn Hockstein In other areas of the world, mothers use coffee mugs, shot glasses, medicines cups, or whatever small cups they can find. Unfortunately, the relatively wide rims of these cups can make it difficult for a mother to maintain a consistent flow of milk to her newborn which can be problematic and even dangerous. Too much milk too fast can cause a newborn to aspirate, while too little milk can mean the baby does not get sufficient nutrition. “These infants are getting an erratic, inconsistent, sometimes too rapid flow [of milk] or not enough access to milk while they are feeding,” explained Christy McKinney, PhD, MPH, a clinical assistant professor at the University of Washington who helped design the NIFTY™ cup, “So the infants don’t get enough nutrients within the short amount of time to grow and fight infection.” During lengthy cup feedings, an infant can actually expend more energy trying to feed than it takes in, which can lead to a rapid decline in health. Another problem with standard cups is spillage. “About a third of milk is spilled at each feeding, said McKinney, “If you are trying to feed and hand expressing your breast milk, it’s a pretty painful experience to have a third of that spilled and wasted every time you are feeding, which can be 12 times a day for a newborn.” The NIFTY™ cup: a game changer for cup feeding A demonstration of feeding using the NIFTY cup. Photo: Marissa Chmiola/GHTC McKinney and her collaborators kept these drawbacks in mind as they set out to create the perfect cup for cup feeding. The NIFTY™ cup was designed with a unique reservoir that can hold a bolus of milk at its end. McKinney called this reservoir a “game changer.” It reduces spillage and allows the milk to be constantly available to the infant. McKinney explained that unlike a spout which only allows milk to be poured into an infant’s mouth, the unique reservoir of the NIFTY™ cup enables cup feeding to become a two-way street just like traditional breastfeeding or bottle feeding. “The mother is making sure that the reservoir is filled and then the infant gets to help pace the feed,” said McKinney, “That pacing results in a much calmer infant. They don’t run the risk of aspirating from too much milk poured into their mouth; instead, they can get the milk they need at the rate they want it, which allows for a calmer, integrated feeding experience between mother and infant.” The NIFTY™ cup inventors also made the cup out of silicone, which offers several advantages: The cup is soft and easy to squeeze, it prevents mouth injuries, it’s durable, and it can be boiled, which makes it easy to sterilize. Because the NIFTY™ has a reservoir that controls the flow of milk, the cup can be sized much larger than other cups used for cup feeding. This allow mothers to directly hand express the milk into the NIFTY™ cup rather than using multiple cups which in turn reduces spillage and opportunities for contamination. In addition, the NIFTY™ cup contains tracking markers on the side to monitor milk intake, it’s ergonomically designed for comfort, and it can be affordably produced at less than $1.00 per cup. In short, the NIFTY™ cup offers more advantages for mothers and infants than any other available cup. The long road to innovation For McKinney it has been over a five-year odyssey to turn the NIFTY™ cup from idea to reality. Inspired by her time as a Peace Corp volunteer in Ethiopia and having just completed her PhD studying craniofacial anomalies and beginning her new post-doctoral position, McKinney was looking for ways she could help children in low-resource settings with oral clefts. She saw feeding as the most problematic area and an area most in need of innovation. “So I just thought it would be nice to come up with an idea to feed these infants with,” said McKinney. With this concept in mind, McKinney began searching for a partner who could help make such an idea possible. She discussed the idea with Dr. Michael Cunningham, the director of the Seattle Children’s Hospital Craniofacial Center, where she completed her PhD, and they approached GHTC member PATH, based in Seattle. “We reached out to PATH…and there was sufficient interest to say let’s try and make this work,” said McKinney. Together they developed a design team which included McKinney (an epidemiologist); Dr. Cunningham (a craniofacial pediatrician); a social scientist, engineer, and commercialization officer from PATH; and an occupational therapist/lactation consultant from Seattle Children’s Hospital. Together, with funding from PATH and the Seattle Children’s Hospital Craniofacial Center, the team designed their first prototype cup. A product can only have impact if it meets end-user needs and people are actually interested in obtaining it. To make sure both applied to the NIFTY™ cup prototype, the team set out to test drive the cup in low-resource settings. With support from a nonprofit Transforming Faces—which supports care for children with oral clefts in South India—and additional funding from the University of Washington CoMotion, McKinney and the team took the NIFTY™ cup to Sri Ramachandra University in South India to do formative design work in both the cleft center and the Neonatal Intensive Care Unit. They introduced the cup to mothers and health providers including lactation consultants, watched the product in use, and conducted surveys to gauge interest in the product and to inform design. The NIFTY™ cup was a big hit. “I was really excited that they liked it more than what they were using,” said McKinney, “I didn’t quite know what to expect on that, but they are really excited to get it commercialized.” Armed with valuable feedback from South India, McKinney and the team regrouped and are doing a minor redesign of the product which will be complete this summer. Last month, the team won a grant from the Saving Lives at Birth Challenge. With this funding, the NIFTY™ cup developers plan to conduct a clinical study in Ethiopia to evaluate the product’s effectiveness compared to standard cups being used, and also develop a market shaping strategy for introducing the product. While it could still be some time before the product is widely available to those who need it, McKinney and the rest of the team are energized by the NIFTY™ cup’s lifesaving potential and the support they are receiving to continue development and introduction. “I’m so excited. This little idea has percolated so long, and people have finally seen the value it can bring,” said McKinney.

In this guest post, the HIV Vaccines & Microbicides Resource Tracking Working Group—comprised of AVAC as secretariat, the International AIDS Vaccine Initiative , and UNAIDS—discusses its new report examining investment in research and development (R&D) for HIV prevention options. Investment in R&D for HIV prevention fell slightly, from US$1.26 billion to $1.25 billion, between 2013 and 2014 and has largely been stagnant for nearly a decade, according to a new report from the HIV Vaccines & Microbicides Resource Tracking Working Group which looks at year-over-year spending on HIV prevention R&D and trends spanning the last 15 years. The report, HIV Prevention Research & Development Funding Trends 2000–2014: Investment Priorities to Fund Innovation in an Evolving Global Health and Development Landscape, provides detailed information on funding for R&D on HIV prevention options—including preventive HIV and AIDS vaccines, microbicides, pre-exposure prophylaxis (PrEP), the use of AIDS treatment by people living with HIV to reduce transmission, the use of AIDS treatment to prevent infections in infants born to women living with HIV, voluntary medical male circumcision, and female condoms. In addition to funding information for R&D for HIV prevention options, the report also provides an update on investment in HIV cures, therapeutic vaccines, herpes (HSV-2) vaccines, and multipurpose prevention technology research. Despite the slight decline in funding, HIV prevention R&D is still delivering important advances. The 8th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention held in Vancouver from July 20-22, showcased results for a range of groundbreaking research that has been supported over the past several years, including the Strategic Timing of Antiretroviral Treatment (START) trial, the HPTN 052 antiretroviral (ARV) treatment as prevention trial, and several groundbreaking oral PrEP trials. Results from studies of a vaginal ring containing the ARV dapivirine are expected in the next 12 months. Several different HIV and AIDS vaccine candidates, neutralizing antibodies, and long-acting injectable ARVs are currently in studies that could lead to multiple efficacy trials starting over the next two years. Robust ongoing investment will be critical to advancing these promising products through the R&D process. Through their research and analysis, the Working Group identified four key findings about the state of funding for HIV prevention R&D which are highlighted in the report: R&D investment is expanding beyond research to rollout: Since the Working Group began tracking investments in HIV prevention, a number of options have moved through the pipeline from research to rollout. The importance of investing in products beyond bench science and clinical trials is shown through the recent rollout and scale-up of options such as voluntary medical male circumcision and female condoms, and—in the demonstration project phase—PrEP. Majority of investment is from several large funders: The United States remained the largest public-sector funder of HIV prevention R&D, spending a total of $868 million in 2014—66 percent of the total investment. Combined, the US government and the Bill & Melinda Gates Foundation accounted for 83 percent of all HIV prevention R&D funding. Expanding and diversifying this investment base could bring in new perspectives and capacity and better assure sustained and consistent funding, reducing the potential negative impact of reductions by one or two primary funders. Increasingly important to HIV prevention is research into how to deliver HIV prevention products and ensure that those products meet the needs of, and reach, end users. Early investment to ensure the uptake of products is a growing part of HIV prevention R&D. Decrease in number of philanthropic funders engaged: While the total amount of philanthropic funding increased in 2014, the number of philanthropic funders engaged in HIV prevention research has been steadily declining since 2010. In 2014, 16 philanthropic funders invested in HIV prevention research, down from 30 in 2010. Development funding priorities are changing: The Millennium Development Goals and the United Nations Declaration of Commitment on HIV and AIDS galvanized increased investment in HIV and AIDS. This in turn led to greater overall HIV prevention R&D investment—an increase of threefold between 2001 and 2014. With the new Sustainable Development Goals set to be decided in September and global financing and development also in a period of transition, it remains to be seen whether HIV prevention R&D, and global health R&D as a whole, will receive a prominent place in the new international development agenda. For further analysis of HIV prevention funding trends, visit the Working Group's website at www.hivresourcetracking.org to download HIV Prevention Research & Development Funding Trends 2000–2014: Investing in innovation in an evolving global health and development landscape and to view additional Working Group reports, as well as graphics and PowerPoint slides.

Wendy Taylor of USAID introducing the other event partners. Photo: Marissa Chmiola/GHTC Last Wednesday 53 teams of innovators gathered at the International Trade Center in Washington, DC, for the Saving Lives at Birth DevelopmentXChange—an event resembling a cross between a science fair and an episode of Shark Tank. There were no baking soda volcanoes or smiley sponges to be found, rather innovative ideas to advance the health of pregnant women and newborns in poor communities around the world. And at stake was not a blue ribbon or a chance to take home Mr. Wonderful’s money, but something much more important—the chance to save the lives of mothers and their babies. Saving lives at birth through innovation This DevelopmentXChange served as the final stage of competition in the 5th annual Saving Lives at Birth Grand Challenges Program, a contest sponsored by the US Agency for International Development (USAID), the government of Norway, Grand Challenges Canada, and the UK Department of International Development, which aims to identify and advance groundbreaking and cost-effective solutions to improve maternal and newborn health. Innovators from around the world compete for grants to develop, test, and bring their ideas to scale. The competition covers three areas—technology development, service delivery, and demand creation. The program started in 2011 as a way to “leapfrog” solutions in the underserved area of research. “We recognized that the area of maternal and neonatal health is an area that had really not seen the type of innovation we need to save the lives of mothers and newborn around the time of birth and in the hardest to reach areas,” said Wendy Taylor, director of the Center for Accelerating Innovation and Impact at USAID. “So we put together the Saving Lives at Birth Grand Challenge…and called on the brightest minds across the world, engineers and entrepreneurs, scientists and students, to come up with new, groundbreaking ideas, new ways to prevent and treat mothers and newborns and save their lives in the most risky time—the 48 hours around the time of birth.” The response to this call has been tremendous. Since 2011, the program has provided over US$47 million in funding to 81 innovative tools and approaches, and many of the program’s successes are already having an impact as they begin to scale. To date, Saving Lives at Birth–supported innovations have been delivered to over 1.5 million women and newborns, saving at least 4,000 lives. This year the Saving Lives at Birth competition received more than 750 submissions, over half of which came from low-and middle-income countries (LMICs). Fifty-three teams were chosen to compete as finalists at the DevelopmentXChange. At the conclusion of the event, 17 award nominees were selected with additional nominees in the transition-to-scale category to be announced later this year. GHTC member projects featured as finalists Among the 53 finalists were 10 projects from GHTC member organizations: Validation of low-cost, user-friendly strip test for preeclampsia/eclampsia screening PATH Brandon Troy Leader showcases his team's innovation. Photo: GHTC/Courtney Carson Dr. Brandon Troy Leader and his team at PATH are developing a low-cost, easy-to-use strip to test for proteinuria—a key indicator of preeclampsia/eclampsia—during pregnancy. Preeclampsia is a serious health risk to both mothers and infants and accounts for at least 16 percent of maternal deaths in low-resource settings. Current diagnostics are either time-consuming and expensive—requiring 24 hour urine analysis—or inaccurate—relying on analysis of protein levels in urine which can fluctuate with fluid intake. Both of these tools are impractical for use in secondary health centers, where most women in LMICs receive treatment. The team’s innovative dipstick promises to deliver a quick, low-cost, and highly accurate test that will allow more women in low-resource settings to be diagnosed and appropriately monitored for preeclampsia/eclampsia. The strip tests for a new protein-to-creatinine (PR/CR) marker and uses a product specifically designed for this single application. It is available at less than $0.10 a strip—the current cost of the inaccurate protein-urine analysis diagnostic. In lab tests, the PR/CR strips showed 85 percent sensitivity, indicating that with appropriate clinical trials, the product could be quickly rolled out to communities in need. The team was seeking a Saving Lives at Birth validation award to test the PR/CR strips in a clinical trial with over 20,000 women and accelerate the product’s introduction into low-resource settings. Advancing introduction of new screening test for preeclampsia PATH To address the unmet need for effective screening and treatment of preeclampsia in low-resource settings, PATH is preparing for a large-scale evaluation of its innovative glycosylated fibronectin (GlyFN) test. The test targets the GlyFN biomarker, which occurs at higher concentration in the blood than other preeclampsia biomarkers and offers excellent sensitivity and specificity. Small scale tests indicate that the GlyFN test predicts preeclampsia in the third trimester of pregnancy with a sensitivity of 97 percent and specificity of 93 percent. The GlyFN test is innovative not only for its use of an easier to detect biomarker, but also for its accuracy and sensitivity in diagnosis. The PATH team was seeking a Saving Lives at Birth award to perform the first operational evaluations of the GlyFN test, refine training materials with users in the field, and implement a prospective-cohort study in Karnataka, India. Developing a model for national scale-up of the Pratt Pouch to prevent mother-to-child HIV transmission Elizabeth Glaser Pediatric AIDS Foundation (EGPAF) A syringe typically used to measure ARV dosage and the Pratt Pouch which could replace it. Photo: GHTC/Marissa Chmiola Dr. Edward Bitarakwate and his team at EGPAF Uganda are seeking to develop a model for the national scale-up of an innovative product to prevent mother-to-child HIV transmission known as the Pratt Pouch. About 1.5 million HIV positive women give birth each year. It’s possible to prevent mother-to-child HIV transmission if antiretrovirals (ARVs) are administered during labor and for several weeks following delivery. Unfortunately, many mothers don’t give birth in health facilities so their infants fail to receive ARVs during this critical period, and those who do are currently sent home with bottles of liquid ARVs and a syringe to measure appropriate doses to administer to their child. Keeping these syringes clean can prove difficult for new moms in low-resource settings, and the viscosity of the liquid ARVs makes it challenging to measure accurate doses. The Pratt Pouch addresses these challenges—it’s an easy to tear open package containing a premeasured dose of ARVs which can be stored safely for up to 12 months at any temperature. Dr. Bitarakwate described the pouch as a “ketchup packet” for ARVs, noting that the pouch is an adaptation of technology used in the food industry to package ketchup. The pouch was developed by a team of engineers at Duke University with support from a previous Saving Lives at Birth grant. Small pilot tests of the product in individual health care settings have demonstrated promise, so Dr. Bitarakwate is seeking funding to work with the Ugandan government to integrate the product into the country’s health system and create an effective model for national scale-up of the product. Reducing birth complications by increasing access to noninvasive, cloud-connected anemia screening diagnostic device PATH Masimo's Pronto-7 anemia screening device. Photo: PATH/Patrick McKern Iron-deficiency anemia affects half of all pregnant women in LMICs and can lead to poor pregnancy outcomes including preterm births, low birth weight, and maternal mortality, contributing to one-fifth of maternal deaths. However, anemia often goes undetected, as methods commonly used throughout sub-Saharan Africa require a blood draw, which can be prohibitive to patients and must be administered by highly-trained health professionals. PATH consulted more than 100 nurses, doctors, and other health professionals in sub-Saharan Africa, hearing repeatedly “noninvasive is the future” of diagnostics. PATH has partnered with California-based diagnostic manufacturer Masimo to create a noninvasive, easy-to-use, cloud-connected diagnostic device, using the “FDA-approved guts” of Masimo’s Pronto-7 hemoglobin test. Rather than drawing blood, the health worker merely asks the patient to place their finger on the sensor (see photo) and the results are available within a minute. PATH will use Masimo’s equipment and technology, but will develop a device that is more durable and even easier to read—enabling use by lower-skilled professionals. Andy Beddoe, a product development officer at PATH, explained that diagnostics that require disposable parts are more dependent on a robust supply chain. This device, however, will require no such disposables, and will use cloud-enabled software, allowing the manufacturer to “sell tests like you would cell phone minutes,” troubleshoot, or calibrate it remotely. Beddoe believes each device could last three to four years, administering more than 50,000 tests. The software could also be used for data collection and could be adapted for use in other diagnostics. A pediatric-friendly ARV dosage form: validation of palatability, flexibility, and accurate dosing of LPV/r PATH “[We’re] targeting the most vulnerable population infected with HIV,” explains Dr. Manjari Lal, senior research officer in Vaccine and Pharmaceutical Technologies at PATH, in discussing her project. Less than a quarter of HIV-positive children in LMICs are receiving ARVs, and for most families, the current treatment method involves breaking adult doses into two, crushing up one half, and mixing it with food. Lal’s team is working to transform lopinavir/ritonavir (LPV/r)—the first-line treatment for pediatric HIV—into a product that is palatable, heat-stable, and that allows for flexible dosing. The team is developing a freeze-dried, fast-dissolving tablet, which allows a parent to mix the medicine with water—as children often struggle with pills that must be swallowed. According to Lal, palatability is a major consideration for pediatric treatments, as infants won’t hesitate to spit out bitter medicines. The treatment is currently in the preclinical phase, and must go through animal studies and clinical trials with human adults before it is ready for use in children. Scaling an Integrated Human Milk Bank and Breastfeeding promotion program in Kenya PATH Human milk provides important nutritional and disease-preventing properties for infants and is particularly critical for those who are born preterm or have low birth weight. Unfortunately, some mothers are unable to produce milk or do so in the quantity needed to feed their newborn. While it’s preferable for infants to receive their own mother’s fresh milk through breastfeeding or hand expression, in cases when that is not possible, the World Health Organization recommends the administration of human donor milk. The idea of milk banks were developed to meet this need. These banks accept donor milk, screen and process it for safety, and disseminate it to mothers in need. PATH was seeking a grant to scale-up and evaluate the impact of an innovative and integrated human milking banking approach known as Mother and Baby Friendly Initiative Plus (MBFI+). Unlike stand-alone milk banks, the MBFI+ approach creates “hubs” that provide both lactation support and milk banking at the same facility. Kimberly Amundson—program officer on PATH’s Maternal and Child Health and Nutrition Team which is leading the project—describes MBFI+ as a “self-reinforcing cycle of supporting breastfeeding for all infants.” Mothers come into the facilities for lactation support, and are then able to donate any excess milk they may produce to those who need it, and those infants who receive donor milk often go on to be able to breastfeed just fine with their own mother. The team hopes to introduce the approach at two hospitals in Kenya, evaluate its effectiveness and potential cost savings, and position the approach for national adoption. Clinical validation of a novel, affordable uterine balloon tamponade, developed in Africa, to reduce maternal deaths due to postpartum hemorrhage. PATH Postpartum hemorrhage, or severe bleeding after childbirth, is the leading cause of maternal mortality, resulting in 125,000 deaths annually. However, with just a condom and a catheter—materials readily found in health clinics—the risk can be drastically reduced. The condom—connected to the catheter—is inserted into the uterus and slowly filled with water, inducing uterine contractions and ultimately slowing or stopping the bleeding. While such a device, known as a uterine balloon tamponade, is readily available in high-income countries, it can be used just once and can cost as much as $400. PATH and partners have worked to develop a device—designed and manufactured in Sou Africa with input from health professionals—that costs just a few dollars. While condoms work well, they vary greatly and the thickness of  a condom can impact the pressure exerted by the device. This uterine balloon tamponade involves a reusable bag that is filled with water and held at a certain height—depending on how much pressure is needed—connected to a reusable catheter which is in turn connected to the disposable, standardized balloon. The device has been successfully tested and with widespread introduction, an estimated 169,000 deaths could be prevented over the next fifteen years. PATH was seeking funding to conduct a clinical validation study of the product and develop a commercialization strategy to increase access to the product in LMICs. Use of a low-cost simulation model to expand postpartum intrauterine device services Jhpiego The Mama-U simulator at the Jhpiego display. Photo: GHTC/Marissa Chmiola Over 90,000 maternal deaths can be prevented each year through family planning use. Yet, many women who have just given birth don’t receive access to long-acting family planning methods like intrauterine contraceptive devices (IUCDs) because there are not enough health providers trained to properly administer IUCDs to women with postpartum bodies; and many women incorrectly believe the product may not stay in place given the changes to their bodies resulting from birth. Under a previous grant, Jhpiego found that using a postpartum body simulator called the Mama-U was effective for training workers and improving service delivery. According to Dr. Fauzia Assad, a medical doctor working with Jhpiego Pakistan, the Mama-U offers benefits over existing approaches to training for postpartum IUCD training. “It’s cost-effective, just $50 versus $600 for the usual model, culturally appropriate, easy to take along, very portable, easy to understand, and it offers the same level of difficulty one would experience with an actual patient because it has a similar feel and tension.” In earlier testing, Jhpiego found the product was not only helpful in training providers, but counselors found it helpful in educating patients, dispelling patient concerns, and increasing client use of IUCDs. Jhpiego was seeking a grant to build on past learning and show that the Mama-U can improve quality of services and patient uptake and change the way postpartum IUCD training, counseling, and services are delivered. Projecting Health India PATH People typically find it easier to learn a process if they see it demonstrated, rather than just hearing or reading about it. This is why the Projecting Health India program is using video as a medium through which to promote health behaviors. Projecting Health India a community-based, video education project, which trains communities in India to create and produce videos addressing a variety of health topics—including birth preparedness, breastfeeding, and family planning—which are shown at community mothers’ groups and village health days. The videos feature local actors and health workers and aren’t distributed outside the district for which they were produced. Michelle Desmond, a monitoring and evaluation officer at PATH involved with the program, described the approach “as hyperlocal” which is key to the program’s effectiveness. “Literature on behavior change shows that if you can empathize with a person you see practicing a healthy behavior, you are more likely to practice it yourself,” said Desmond. “So in these videos women are seeing people who sound like them, who look like them, who are in the same situation as them practicing these health behaviors.” After realizing that the videos were so popular that women were finding ways to transfer them onto their mobile phones to rewatch and share, Projecting Health partnered with mobile phone vendors in India to allow the videos to be easily loaded onto phones, providing an additional way for these videos to be distributed to harder to reach mothers. PATH was seeking a Saving Lives at Birth grant to scale up this project in government systems throughout the state of Uttar Pradesh. NIFTY: A Neonatal Intuitive Feeding Technology for preterm infants who have difficulty breastfeeding PATH A demonstration of feeding using the NIFTY cup. Photo: GHTC/Marissa Chmiola In high-resource settings, infants who struggle with breastfeeding can be fed with breast milk through tubes or bottles, however such technologies can be expensive, difficult-to-use, or unsanitary in low-resource settings. In LMICs, the World Health Organization recommends the use of small cups for infants with feeding difficulties, including preterm infants, infants who have lost their mother due to complications in pregnancy or childbirth, and children with cleft palates. There is currently no product on the market specifically designed for this purpose, and the metal or glass cups that are often used can be inefficient, or can cause injury to the infant’s mouth including cuts. To address these limitations, PATH and its partners created the NIFTY™ cup which is made of silicone, making it soft and durable. The cup can also be boiled without causing any damage—making it easy to sterilize. The cup also has a reservoir on the lip of the cup, making it easy to control the amount of milk delivered and prevent waste. The NIFTY™ cup costs just $1.25 to produce. This innovation was chosen as one of the 17 competition award nominees. The team at PATH will use the funding to test the NIFTY™ cup in hospital settings in Ethiopia and work with private-sector partners throughout the sub-Saharan market to commercialize the cup. Innovation is happening around the world In visiting the DevelopmentXChange, it was clear that innovation is happening in all corners of the globe and lifesaving ideas can come from anywhere and anyone. Saving Lives at Birth demonstrates the power of bringing governments, foundations, academic institutions, and for-profit companies together to address our most pressing health challenges. GHTC congratulates both our members and the other teams who were selected as finalists and award nominees—your work continues to inspire us. Authored by Marissa Chmiola, GHTC’s communications officer with support from Courtney Carson, senior policy and advocacy associate, and Kat Kelley, senior program assistant.

This Independence Day, GHTC is taking a break from our cookouts and parades to celebrate America’s extraordinary contributions to advancing innovation to save lives around the world. The US government has long played a leading role in the development of new technologies to diagnose, treat, and prevent diseases and conditions impacting people living in the world’s poorest places. US leadership in global health research and development (R&D) is a testament to our nation’s character, our ingenuity and entrepreneurial spirit, and our dedication to improving human lives worldwide. Below GHTC takes a look at America’s contributions to global health innovation: The US government is the largest funder of global health R&D in the world. The US government is by far the largest funder of global health R&D—contributing around 45 percent of total investment and 70 percent of all government investment each year. Even when measured as a proportion of gross domestic product (GDP), the US government remains the largest funder of global health R&D. Between 2000-2013, the US government invested over US$18 billion in global health R&D. While this may sound like an extraordinary amount of money, annual US investment in global health R&D represents only a tiny fraction of overall US government spending—less than one-tenth of one percent of our GDP. While US investment in global health R&D nearly doubled between 2000 and 2009, funding has been largely stagnant, or on the decline, since then. A sustained and robust US investment in R&D by the United States is critical to delivering the next generation of health technologies to address both existing and emerging diseases and conditions. The US government contributes more than just funding to advance global health R&D. Five federal agencies that are engaged in global health R&D—the US Agency for International Development, National Institutes of Health, Centers for Disease Control and Prevention, Department of Defense, and the Food and Drug Administration—contribute much more than just funding. The US government has been involved in the development of many breakthrough technologies that are transforming global health. Between 2000 and 2010, the US government was involved in the development of over half (25) of the 45 global health products. The US government has been involved in the development of lifesaving innovations, including: Antiretroviral treatments, which have dramatically extended the lives of those living with HIV and AIDS. A vaccine that protects against meningitis A, costing less than $.50 per dose, which been delivered to more than 251 million people in Africa’s meningitis belt since its launch in 2010. A pediatric antimalarial drug, which has had 300 million treatments delivered to children suffering from malaria in 50 endemic countries since 2009. US investment is fueling a robust pipeline of global health products with the promise to save and improve lives. As of 2012, the US government was involved in the development of 200 of the 365 global health products in the development pipeline. Promising innovations under development receiving support from the US government include: A preventative HIV and AIDS vaccine that could dramatically reduce new infections. New tools to prevent and treat malaria, including medicines that will both protect against the disease and prevent its transmission. Vaccines to prevent tuberculosis (TB), which are in various phases of clinical trials. New cost-effective diagnostics for malaria, TB, and neglected tropical diseases (NTDs). New vaccines for NTDs—such as dengue fever, Chagas disease, and leishmaniasis. US contributions to global health R&D are having a ripple effect beyond saving and improving lives. US contributions to global health innovation not only saves lives, but also produce direct benefits for Americans by creating jobs, strengthening US competitiveness in research and technology, improving US relations abroad, and enhancing our health and national security. US investments also drive economic progress and reduce poverty in low- and middle-income countries (LMICs). Between 2000 and 2011, health improvements accounted for about 11 percent of economic growth in LMICs. The development of new health technologies will ultimately provide LMICs with the solutions they need to tackle their most pressing health challenges and chart a course for self-sustainment. So this Fourth of July, as you enjoy your burger and watch fireworks light up the sky, take a moment to celebrate America’s contributions to global health. While there is much more to be done, Americans should take pride in our nation’s efforts to advance innovation to save lives worldwide.

21st Century Cures.Last week, the House Energy and Commerce Committee unanimously voted to approve the 21st Century Cures Act—a bill that aims to speed the development, approval, and introduction of new health technologies.Clocking in at over 300-pages, the legislation is packed full of proposed changes to the way health products are developed by the US National Institutes of Health (NIH) and regulated by the US Food and Drug Administration (FDA). Below, GHTC breaks down a few of the proposed changes that could matter most to global health researchers, product developers, and advocates.NIH receives boost in funding The legislation would reauthorize the NIH for the next three fiscal years (FY) and boost funding over that period, starting with US$31.8 billion in FY 2015 and increasing to $33.3 billion and $34.8 billion in FY 2017 and 2018 respectively. (As a reference, current NIH funding is around $30.3 billion.) It is important to note this boost is in discretionary spending, rather than mandatory spending, so these increases could still be subject to spending caps and sequestration cuts which in the past have significantly reduced NIH’s budget.The legislation would also provide $10 billion in new NIH funding over the next five years through the establishment of a new “NIH Innovation Fund.” This pot of money is mandatory spending, and thus would NOT be subject to spending caps and sequestration. The legislation mandates that at least $500 million per year of the fund would go to a new Accelerating Advancement Program, which seeks to address unmet medical needs in the United States including infectious diseases and neglected tropical diseases and antibiotics.The legislation would also mandate that the NIH, and the centers and institutes within it, develop five-year strategic plans to guide research activities. The language defining how NIH must use portions of the funding is unlike current NIH funding allocations and has some concerned that Congress is being too prescriptive with scientific research.NCATS permitted to expand into later stage research Photo: National Institute of Allergy and Infectious DiseasesThe Cures Act would remove current restrictions that prohibit the National Center for Advancing Translational Sciences (NCATS) at NIH from supporting clinical trials beyond phase IIA—the first round of trials to test efficacy, rather than just safety of a treatment in humans.NCATS was created to help advance translational science, particularly for rare diseases in the United States. At the time it was created, Congress prohibited the center from conducting later stage clinical research out of fear that it would then be competing with and duplicating private-sector product development activities. This legislation lifts that prohibition, extending NCATS ability to conduct trials through stage III—the final pre-market stage where safety and efficacy of a treatment are tested in in large groups of individuals.Many global health conditions qualify as rare diseases under the program’s definition because they impact fewer than 200,000 people in the United States, meaning this legislation change could permit NCATS to support later stage clinical research for many neglected diseases and other global health conditions.Bill promotes pediatric research Under the legislation, NIH would be required to establish a national pediatric research network to pool resources and coordinate activities on pediatric diseases. This legislation also encourages the NIH and FDA to work with the European Union, industry, and other partners to establish a global pediatric clinical trials network.Drugs often react differently in children than they do in adults, and creating pediatric-specific treatments has proved challenging for researchers and product developers producing treatments to be used both domestically and globally. This legislation seeks to overcome some of these challenges by promoting development and testing of pediatric formulations of drugs.Congress acknowledges importance of agency participation in scientific conferences The act includes a sense of Congress acknowledging the importance of participation in scientific conferences and meetings for both NIH and FDA employees. While the legislation doesn’t go so far as to lift existing restrictions or provide funding for participation, Congress’s recognition of this importance is a critical step forward.A GHTC analysis found that many agency representatives cite a lack of funding for participation in scientific conferences as a serious hindrance to enhancing coordination and collaboration among agencies engaged in global health research and development (R&D).Increases use of biomarkers and surrogate endpoints as clinical evidence at FDA Photo: FDA/Michael J. ErmarthThe legislation paves the way for the FDA to rely on biomarkers and other surrogate endpoints to accelerate product approval for a broader category of products. Proving that a product or treatment can successfully produce the desired clinical endpoint—may not be feasible in certain circumstances or can often require clinical trials that are large, long, and costly. So in some cases, trial sponsors have proposed using biomarkers—or biological indicators—that are correlated with the clinical endpoint as a substitute to assess the efficacy of a treatment or product more easily. For example, to measure whether a treatment prolongs cancer survival—a clinical endpoint—one might assess a surrogate endpoint like whether the treatment succeeds in shrinking tumors.At the moment, the FDA permits use of surrogate endpoints for accelerated approval for drugs intended to treat a narrow category of patients with life-threatening illnesses and unmet needs. The bill calls on the FDA to establish guidance for use of qualifying biomarkers and work with sponsors to establish parameters that would allow for approval of a broader set of products using surrogate endpoints.Use of surrogate endpoints poses both benefits and challenges. It could lower R&D costs and reduce the length of time needed to conduct clinical trials, thereby accelerating the availability of treatments. However, at the same time, it can often prove difficult to determine if a surrogate endpoint or biomarker is a reliable indicator that the product has the intended clinical benefit. For example, elevated cholesterol levels are linked with heart disease, but at the same time, it is possible that a drug that reduces cholesterol will have no measurable impact in preventing deaths from heart disease.Spurring antibiotic drug development If enacted, the Cures Act would create a new expedited FDA review pathway for antibiotics intended to treat “a serious or life-threatening disease, condition, or indication” and intended for use in a limited target population. This new pathway could allow the FDA to approve a product based on earlier Phase II trials and surrogate endpoints, rather than larger, later-stage Phase III clinical trials.Some organizations support this new pathway, arguing that it would expedite patient access to new antibiotics and help tackle growing antibiotic drug resistance. Others argue that this new pathway would allow products to be approved based on lower FDA standards, which could in turn put patient health and safety at risk.The bill would also increase Medicare payments to hospitals who use certain new antibiotics as a way to financially incentivize private-sector development of critically-needed new antibiotics. However, some critics of this provision argue that it would be counterproductive to the intended goals and would instead encourage overuse of new antibiotics, which would in turn hasten the development of drug resistant strains and further exacerbate the problem of antibiotic resistance.Changing the way medical devices are reviewed and approved Photo: FDAUnder the legislation, medical devices would be eligible for “breakthrough” designation by the FDA, which allow them to receive priority, expedited review.This new priority review program for devices is modeled after the breakthrough therapies program for drugs and is intended for “breakthrough technologies” for either conditions “for which no approved alternatives exist” or that would offer “significant advantage over existing approved or cleared alternatives.”In addition to creating this priority review pathway for medical devices, the legislation would also direct the FDA to take steps to ensure clinical trial designs for medical devices are “as efficient as practicable,” by exploring options such as the adoption of shorter or smaller trials, use of surrogate endpoints, or adaptive trial design.In an effort to further accelerate approvals of medical devices, the legislation would significantly alter the type of evidence the FDA could consider when reviewing a device for approval. This bill would allow the FDA to consider as valid scientific evidence case histories, registry data, studies published in peer-reviewed journals, and data collected in countries other than the United States. While this change could help speed the testing and approval of critically needed devices, critics argue it could also undermine FDA’s ability to ensure medical device safety and efficacy— citing the fact that case histories are anecdotal and lack a control group, while journal articles can often leave out critical information or can include mistakes, misrepresentation, or fraud, which the FDA may not become aware of if it relies solely on the published articles.Expansion of market exclusivity, but less than originally anticipated The legislation would extend by six months market exclusivity for drugs approved for a new indication or use for a rare disease or condition, extending a drug’s exclusivity period not only for the new indication, but for all of the drug’s indications.The purpose of market exclusivity is to help companies recoup the investments they made into R&D for a product or therapy and encourage future private-sector investment in research and product development. However, critics also note that extending market exclusivity delays entry of generics into the marketplace which can lead to increased costs for patients and limit affordable access to lifesaving health technologies. Product price can pose a significant barrier to access particularly in low- and middle-income countries.Earlier versions of the legislation featured additional provisions extending market exclusivity that were taken out of the version approved by the Committee. These included provisions which would have permitted the sale of market exclusivity to other companies and extended exclusivity for follow-on drugs and first-to-file American-made generic drugs.FDA receives increased funding To ensure FDA has the capacity to carry out its programming, the legislation would increase FDA funding by $550 million over the next five years. The bill would also exempt FDA user fee programs from sequestration spending cuts.While passage of the legislation through the Committee is a critical milestone, the act still has a long journey before it can become law. The legislation is expected to be voted on by the full House of Representatives in June. Meanwhile, parallel legislation is under development in the Senate. If both pass their respective chambers, the two versions will eventually have to be reconciled by both chambers before the legislation can be passed and then sent to the President for consideration. GHTC will continue to monitor this legislation as it develops.