GlaxoSmithKline (GSK) CEO Andrew Witty is leading the front on modernizing pharmaceutical multinational companies (MNCs) with his recent announcement for a customized drug pricing scheme for emerging market economies like India. He outlined the new approach clearly in several interviews such as this one:

“Our strategy is to grow our business in middle-income countries by increasing the volume of products we sell,” Chief Executive Andrew Witty said in an e-mailed interview. Extending Glaxo’s flexible pricing program for such nations would “improve the affordability of our medicines, increase access for patients with lower income levels and be profitable for GSK,” he said. In December 2008, shortly after he took over as CEO,  Witty signaled his intention to make GSK a lead player in the global development business of increasing access to medicines: “I believe the pharmaceutical industry has a huge role to play. But we need to take much more of a leadership role. Historically we have always reacted to problems. In the future I want us to be proactive, genuinely finding new ways to increase research, increase access and eradicate disease.”

And proactive he has been.  See here for a chronological list of different policy announcements about GSK’s commitment to the developing world from the reduction of its prices for patented medicines in LDCs in 2009 to a recent announcement in January 2010, at the Council of Foreign Relations of an “open innovation” strategy to help deliver new and better medicines to the developing world especially for neglected tropical diseases.   In this excellent talk (and if you have time it is worth watching the video), Witty walks us through the three ways in which he is changing GSK business model around open innovation, in addition to offering customized pricing to countries.  These include  1) greater flexibility around intellectual property and knowledge sharing; 2) creating partnerships for researchers to have access to GSK’s industrial scale expertise, processes, facilities and infrastructure in addition to their knowledge and know-how; and 3) releasing access to new compounds for others to join GSK researchers and accelerate discovery.

So, what’s different about this model? 

It strikes me as a win-win approach-one where both GSK AND its country partners are likely to benefit. For GSK, it will create a space to compete in future markets with local firms.  For example, as the pharmaceutical sector grows in India, Witty is anticipating competition and jumping in now to ensure access to these markets and to information. For LDCs and emerging market partners, the GSK approach has the potential to increase access to medicines, to direct financial investment to pharmaceutical infrastructure development, and to increase access to knowledge and know-how for their scientists, encouraging them to actively participate in the discovery and development of products.  

How is GSK making this happen?

1. Tapping talent from other countries to accelerate the discovery process of new and better drugs.   GSK is smartly engaging the growing scientific and technical talent in countries like India. This will enhance their discovery and development processes for drugs by offering Indian scientists actual knowledge about different compounds that can be used in drug development, access to high tech labs, infrastructure and the ability to pursue research projects that they have identified. 
2. Forging early partnerships with pharmaceutical companies in the developing world by increasing GSK’s flexibility around intellectual property. As patents expire and emerging market pharmaceuticals ramp up their R & D efforts, GSK will perhaps be in a better position, relative to other pharmaceuticals MNC, to access this information. It recognizes the value of partnerships in a very real and productive way–generate knowledge, share it with others for their use, and others who generate knowledge will likely share it with you for your use.

Andrew Witty, the economist (yes, and apparently one of the only to head a pharmaceutical MNC!) CEO seems to be thinking well ahead of his peers; other pharmaceutical MNCs are silent on these issues; supposedly staying clear of these countries (LDCs and emerging) right now, still unsure of the potential return on their investments in high volume markets. Witty, on the other hand, seems to be anticipating serious market shifts and designing GSK’s current operations to maximize its profits while doing some greater good.  In his words he is building a company that is “constantly earning the trust of society, not just by meeting society’s expectation, but by striving to exceed them, because if you don’t have that trust of society — the society in which we all operate and the societies we strive to serve, then you really, in my view, don’t have a long-term, sustainable business model.” He is modernizing his company from within and in the way it deals with external partners so that the discovery and development of drugs is a more global and dynamic process that never stops.  It’s still too early to tell if GSK’s approach will lead to a “successful” model,  but certainly worth watching closely to see how it strikes the balance between making markets for itself and making drugs more accessible to the poor.

While key questions remain—i.e., How is the evaluation being conducted? Will new data be collected in the communities or will it be just a review of project reports and secondary data? What and how many countries will be studied?—the evaluation comes as welcomed news. Communities and community health workers have long played a critical role in primary health care systems, and in World Bank programs. The World Bank’s MAP program in particular has a strong community focus, with a sizable amount of their funds and resources going to Community-Based Organizations (CBOs). However, while so much is going IN to the community response, there is little coming OUT of the World Bank in regards to reporting, monitoring, and impact evaluation. Donors and others in the development community are left wondering how exactly this money is spent, what programs the money focuses on, and how effective these programs are in curbing the epidemic.

Two of the main focuses of the evaluation are 1) to track the flow of funds from national to community levels; and 2) to assess the effects of the community response on the course of the epidemic. These are both important steps in identifying the roles that communities have and can play in the HIV/AIDS response, and issues that the Monitor has already examined, particularly in the report Following the Funding—which analyzes the transparency and effectiveness of funding data and flows of top AIDS donors.

There is no doubt that the World Bank MAP is a leader in channeling significant sums of money to CBOs at the community level—so much so that that MAP funds tend to be designed and reported around types of implementing agencies, rather than programmatic activities. In order for a country to qualify for funding, the government must first identify CBOs to serve as implementing recipients of funds. Given this emphasis on communities, it is particularly surprising that we don’t yet know the returns of these investments.

Findings from the HIV/AIDS Monitor (here and in two forthcoming reports on Performance Based Funding and the Health Workforce) about the MAP program, raise several issues about the allocation of resources to community based organizations that could reduce the effectiveness of community interventions:

Funding Bottlenecks: While the MAP is quick to disburse funds to national governments, the flow faces several challenges and delays once in the hands of the National AIDS Councils (NAC). Because these funds must first travel through the government system and because they are accompanied by complex reporting requirements, bottlenecks in the system often create slow and unpredictable money flows to the community, constraining program implementation. It is critical that the evaluation examine these funding flows and provide solutions to reduce these bottleneck challenges. In our Following the Funding report, we suggest that aligning reporting with national systems and increasing individual disbursement amounts based on the achievement of programmatic results could help reduce administrative burdens and ease the flow of funding to communities. Hopefully the evaluation will be able to provide more insight into how the administration of World Bank grants effects project performance at the community level.

Lack of Program Data—collection and reporting: At the national level, the World Bank collects and releases financial commitments by country and by broad program area. At the country level, while the World Bank collects disbursements to recipient organizations, this data is not shared publicly. At the community level, while individual countries may collect comprehensive data on the amounts of money committed or disbursed to different types of recipient and sub-recipient organizations, it is not required by the World Bank, and it is therefore not released publicly. Yet, since the bulk of MAP funding goes to communities, it would be beneficial to see and understand how this money is actually spent at the local level. This data should be both collected AND released because the information is vital for not only tracking recipient spending in the community, but also for identifying and evaluating the cost-effectiveness of these programs.

In addition, programmatically, the current data collected and released by the World Bank does not allow us to truly understand the extent to which communities have assisted in the response or which types of community-level programs are most effective. For instance, in our report Moving Beyond Gender as Usual, we found that the MAP has introduced gender-capacity building activities for community initiatives, but it does not systematically report on programming that results from this capacity building. Also, because of the lack of financial data collected at the community level, there is no way to know how much funding actually went to gender programming at the community level. In order to understand the effectiveness of community interventions—like gender programming—programs must be consistently monitored and evaluated.

In their current forms, MAP supported community based programs may be hindering or enabling governments’ and other stakeholders’ efforts to use aid effectively. Learning from an evaluation will help countries make informed decisions to allocate precious resources to community based interventions that are working—those that are helping to prevent new HIV infections and reducing deaths due to AIDS.

The January 12th earthquake in Haiti is the most lethal natural disaster of the past 20 years. On February 12th, the Associated Press reported that official Haitian government estimates of the dead had been revised upwards, now reaching 230,000 dead. Furthermore, the number could be much higher, since the government admits they have not yet been able to count all the bodies and they have excluded those buried by families or in private cemeteries. As the figure below shows, this new total surpasses the 225,000 dead in the 2004 Indian Ocean tsunami, and dwarfs the death tolls from recent earthquakes in Pakistan-controlled Kashmir and Sichuan, China.

A catastrophe’s death toll can also be measured in relation to the total population. The bars in the next chart show the deaths as percentages of the total populations of each relevant area. For the 2004 Tsunami in the Indian Ocean, the largest death toll was in the Indonesian province of Aceh on the island of Sumatra, where three percent of the population died. The 80,000 deaths in the Pakistan earthquake represented .4 percent of the population Pakistan’s Northwest Frontier Province. The Chinese and Burmese catastrophes killed fewer than one percent of the populations of the surrounding areas. In contrast, the Haitian earthquake killed 11.5 percent of the approximately two million people living in the immediate area of Port-au-Prince, which comes to 2.5% of the entire national population.

So in relative terms also, Haiti’s earthquake surpasses any of these natural disasters which have occurred in other countries.

Finally one can compare the mortality from the earthquake to the mortality from other causes of death which afflict Haiti or have swept the world. The largest cause of mortality in Haiti for the last decade has been the HIV/AIDS epidemic. In 2007, the last year for which UNAIDS has published data, an estimated 7,500 people died of AIDS in Haiti. The earthquake killed 30 times that many Haitians in a few days.

Other notable worldwide epidemics have been the bubonic plague in 1350 and the 1918 influenza epidemic. The first killed somewhere between 30% and 60 % of the population of affected European countries and the second between 3% and 6% of the entire world population. Thus for Haiti as a whole, the earthquake has had a mortality impact comparable to the 1918 flu epidemic and for the most affected region around Port-au-Prince the impact is comparable in magnitude to that of the bubonic plague in a less affected country of Europe.

Students of the bubonic plague of 1350 believe that its longer term repercussions on society were profound, including a general loss of faith in religion, a loss of respect for hereditary authority in general and the state in particular, the empowerment of the middle class and increases in the ratios of capital and land to labor resulting in increased wages for the poorest. While parallels between that continent-spanning catastrophe and the much more focused event in Haiti are risky, it is not hard to believe that Haiti will be a very different place in ten years than it would have been without the earthquake. Let’s hope that it is a better place, not a worse one.

Last week, I participated in an event at the Center for Strategic and International Studies (CSIS) in which U.S. Food and Drug Administration (FDA) Commissioner Margaret Hamburg announced a remarkable shift in the FDA’s thinking on food and drug import safety. If adequately supported by Congress and translated into concrete action, this change in strategy on food and drug safety could have significant benefits for U.S. and global health and development.

As I have discussed in depth elsewhere, food and drug safety are now global health programs. Unsafe food and drugs exact a staggering human and economic toll in developed and developing countries alike. Contaminated and adulterated food and drug products sicken and kill millions of consumers in the U.S. and elsewhere each year, fuel protectionism, raise business costs, and undermine development.

In this context, the health of U.S. citizens is interdependent with the health of other states’ citizens. The unsafe products we consume domestically are often the same products we export to other nations; the same is true for our trading partners. Given the increasing complexity and volume of the global trade in these products, no one country or national regulator alone can ensure the safety of food and drugs used by its citizens.

Ensuring the safety of foods and drugs requires strategies and tools similar to those used to successfully address other global health threats, like infectious diseases, that cross borders with trade and travel. Sustainable progress with those tools and strategies depends on the cooperation of trading partners, industry, and the multitude of entities involved in the international commerce and regulation of food and drugs.

Commissioner Hamburg’s speech last week reflected a new, high-level recognition at the FDA of the global nature of the food and drug safety problem. In addition to announcing an important new risk-based assessment tool, the Commissioner argued that it is no longer appropriate to think of unsafe food and drugs as “international or domestic [issues], but as common problems in a dramatically fluid and interconnected world, and the same kinds of strategies that we need to apply internationally, we need to apply at home – the shift from a reactive mode to a preventive mode, the focus on really assuring the safety and security of the supply chain, the notion of working in critical partnership with both industry and, domestically, with state and local health authorities.” Maintaining that the FDA could no longer “inspect its way to safety” in an era of increasing global trade, complex products, and transnational food and drug supply chains, the Commissioner stated

Now is the time for FDA to fully engage bilaterally, multilaterally and through international and regional organizations to work with countries throughout the world to share scientific and technical expertise, to harmonize international standards for safe food, drugs and medical products, to work with industry to enhance compliance with standards and, very importantly, to help countries with less mature economies and regulatory systems build capacity so that they can produce food and commodities that are safe, wholesome and meet international safety standards – both for their own consumption and for export.

Achieving that vision will not be easy. To start, Congress must pass pending food and drug safety legislation and give FDA the tools and resources it needs to work with our trading partners, particularly developing countries, to improve inspection and quality control of food closer to its place of origin and coordinate food and drug safety efforts with trading partners and regional and multilateral health and economic institutions. More targeted, effective measures are needed to encourage U.S.-based retailers and manufacturers to adopt stronger prevention, surveillance, and control of their supply chains and supplier and producer partners. U.S. efforts on food and drug safety must leverage and support international and intergovernmental resources and tools, particularly on issues of regulator interoperability, information exchange, and cooperation.

The potential implications of this new thinking for global health and development would be profound. The U.S. market has significant influence on food production and drug manufacturing practices globally. Today, 20 percent of all foods consumed in the United States originate outside our borders. As much as 40 percent of the medicines that Americans take and roughly 80 percent of the active pharmaceutical ingredients in all drugs sold in the U.S. originate from foreign sources. The FDA regulates all U.S. drugs and 80 percent of the U.S. food supply. In all, the FDA regulates nearly 20 million shipments of food, devices, drugs and cosmetics imports from more than more than 150 countries, 130,000 registered importers, and 300,000 foreign facilities. Even beyond its market influence, FDA is widely admired internationally and its practices emulated by regulators worldwide.

One important caveat is that the U.S. must be careful to consider the legitimate expectations and needs of developing countries in formulating its approach. Agriculture is an important, and sometimes singular, area of comparative advantage for many developing countries. Congress and the FDA should consider funding appropriate mitigation strategies and initiatives to help reduce costs for small and medium-sized developing country producers to comply with stricter food standards.

In the end, Commissioner Hamburg’s vision on food and drug safety is the right one. There is a pressing need for the U.S. and its trading partners to engage on global food and drug safety; the mandate for doing so has become nothing short of enlightened self-interest.

Success does depend on “crowding in” other funders’ investments, but under some scenarios the $10 billion could actually “crowd out.” Bilateral donor agencies, who themselves are fighting a tough budget climate, might breathe a sigh of relief thinking that they can hold at historical spending levels or even pull back from GAVI, and Daddy Healthbucks will save the day. Governments in GAVI-eligible countries, which under current rules now provide a co-pay for every dose of vaccine, might drag their heels a bit on moving toward greater levels of financial self-sufficiency. “Why are we chipping in 10 cents for every jab,” a Minister might ask, “when Bill Gates can afford $10 billion?” Even industry might think that they can cut a more favorable deal on both prices and support for R&D through product development partnerships.

But I expect that the Gates Foundation will use the resources in ways specifically designed to leverage others’ investments, and to lower the costs of getting vaccines to market and then to kids and teens. Accomplishing this will require a combination of incentives and institutional improvements to make all the dollars for vaccines and immunization work as hard as possible. What follows is pure speculation, but maybe they will:

• Put up all new contributions to GAVI in the form of a match: For every dollar GAVI raises from other sources, Gates could match it 1:1. (Interesting research shows that matching strategies are effective, but there’s no benefit from higher matching levels.) If particular types of contributions – say, support from private individuals – merit greater emphasis by GAVI’s resource mobilization team, the match could be higher as a special motivator to the organization.
• Invest in strengthening and streamlining the regulatory infrastructure, both globally and – very importantly – within the countries that are home to emerging manufacturers (Indonesia, India, Brazil). Ditto for clinical trials capacity and platforms that can be used for the development of multiple vaccines as time goes by. Bringing down the costs of developing these products, which is not as significant an issue in the price-insensitive markets, is high priority.
• Create the Maurice Hilleman Global Vaccine Prize, named after the remarkable microbiologist who developed more than three dozen vaccines. The prize could recognize achievements of scientists who have made major contributions to the development of vaccines that specifically benefit low-income countries.
• Explore whether and how strategic investments or incentives can hasten the development of joint ventures and other collaborations between multinational research-based firms and capable emerging manufacturers. Over the long term, moving to a high-scale/low-cost model of production is the route to vaccine affordability, regardless of whether the payers are national governments or donors.
• Recognizing that the health of the vaccine market globally is essential to the continued and diversified supply of vaccines for the poorest, make a one-time contribution to the Pan American Health Organization’s Revolving Fund to manage the introduction of higher-priced vaccines to the middle-income countries of the region.
• Create a 10-year Global Health Policy Fellows program, modeled on the Robert Wood Johnson Foundation Health Policy Fellows, to place mid-career global health professionals within Congressional and Executive branch offices. No amount of advocacy from the outside for health aid can replace dedicated, value-adding expertise on the inside. And the eventual network of Policy Fellows would be the next generation of policy movers and shakers.
• Endow immunization advocacy organizations in key countries, like Nigeria, where voices outside of the government are essential to keep the pressure on for immunization performance, and to counter the proliferation of negative messages about vaccines. An endowment rather than a grant is particularly important, so that the organizations can credibly say they are independent of a particular outside agenda.
• Work with the leadership at the World Health Organization and UNICEF to reinforce capacity for processes like developing evidence-based recommendations about vaccination schedules, prequalifying vaccines, issuing tenders, forecasting demand and more. Look at all the bottlenecks and focus resources on eliminating them.
• Create an innovation prize not for a vaccine but for a technology that will make many vaccines more usable in developing country contexts, such as for needle-free administration.

Oops, I think I just spent $10 billion!

These are just a few of the possible ways that the generosity of a lead donor can be extended and amplified. I suspect that cleverer ideas are being cooked up out there on the shores of Lake Union – and by some of our blog readers. Please use our comments feature to offer up your own thoughts.

More on the FY11 Budget

• Development and Obama’s Budget; Interview with CGD’s Sarah Jane Staats
• Obama’s First Budget Request: Modest Increases but Strong Signaling for Development
• MCC Slated for $1.28 Billion in FY2011 Budget Request
• Todd Moss’ Expert Commentary on President Obama’s 2011 Budget Request

Yesterday’s release from the White House of the FY2011 budget  and a simultaneous release of a consultation draft of the Global Health Initiative (GHI) by the State Department signal a strong commitment and evolving action plan from the Obama administration for global health engagement in 2011 and beyond.

Funding commitment: Putting $9.6 billion in to perspective
With the $9.6 B requested for global health for 2011 the Obama administration is increasing its financial commitment for global health, despite the many competing domestic and global priorities in the 2011 budget.  That says something about this administration’s willingness to continue the very good trend that President Bush put in to place with PEPFAR in 2003.  A quick look at the graph (with a shout out to Jen Kates and her team at the Kaiser Family Foundation for providing this as it comes hot of their press!) below shows a greater than 5 fold increase in U.S. funding for global health from 2001 to 2011.

The bulk (almost $7B of which is PEPFAR, including $1B for the Global Fund) of the funding is for HIV (details of the budget for global health can be found here) but the GHI is setting for itself a broader set of global health goals, making it more ambitious than PEPFAR, and potentially more responsive to a range of global health priorities in countries of greatest need. 

Ambitious Targets
The draft strategy is ambitious, to use the administration’s own adjective for its targets:
“We have set out ambitious targets to inspire an intensive effort. While specific targets will be established at the country level, the GHI is expected to achieve the following aggregate goals by the time performance can be measured in 2015.”  Full details of these targets and their specific timelines may be found in Annex A of the draft strategy (Page 12 and 13) but a few highlights of the targets and goals from this strategy are listed below as a snapshot of the challenge ahead:

HIV/AIDS: PEPFAR will: (1) support the prevention of more than 12 million new HIV infections; (2) provide direct support for more than 4 million people on treatment; and (3) support care for more than 12 million people, including 5 million orphans and vulnerable children.
Malaria: Reduce the burden of malaria by 50 percent for 450 million people, representing 70 percent of the at-risk population in Africa. This effort will include the expansion of malaria efforts into Nigeria and the Democratic Republic of Congo.
Tuberculosis (TB): Save approximately 1.3 million lives by reducing TB prevalence by 50 percent. This will involve treating 2.6 million new TB cases and 57,200 multi-drug resistant (MDR) cases of TB.
Maternal Health: Save approximately 360,000 women’s lives by reducing maternal mortality by 30 percent across assisted countries.
Child Health: Save approximately 3 million children’s lives, including 1.5 million newborns, by reducing under-5 mortality rates by 35 percent across assisted countries.
Nutrition: Reduce child undernutrition by 30 percent across assisted food insecure countries in conjunction with the President’s Feed the Future Initiative.
Family Planning and Reproductive Health: Prevent 54 million unintended pregnancies. This will be accomplished by reaching a modern contraceptive prevalence rate of 35 percent across assisted countries, reflecting an average 2 percentage point increase annually, and reducing to 20 percent the number of first births by women under 18.
Neglected Tropical Diseases (NTDs): Reduce the prevalence of 7 NTDs by 50 percent among 70 percent of the affected population, contributing to: (1) the elimination of onchocerciasis in Latin America by 2016; (2) the elimination of lymphatic filariasis globally by 2017; and (3) the elimination of leprosy.

Your chance to influence a major U.S. foreign assistance initiative
This is a tall order and the administration needs your help to think through issues of implementation and measurement of results for success.  For example, are these targets the right metrics of success? Many of us criticized PEPFAR for focusing on counting numbers treated and numbers cared for rather than on a decrease in deaths due to HIV and a decrease in new infections in a given population. So, what’s different about these targets?  In a refreshingly participatory process,  this administration has called for your comments on the Global Health Initiative’s draft strategy.  My colleagues at CGD and I will comment on specifics about the GHI strategy as we digest its different components. Send your useful and practical comments (read as–best to stay away from pushing for more money in this economic climate!) to ghi_comments@state.gov by February 22^nd. Let’s see what and how well we can do with the billions we have for global health. It’s an opportunity to contribute to the making of a major US foreign assistance program, so let’s try to get it right—that is achieving the targets laid out (relative to need by country and available budget) and being able to measure these to demonstrate success.  And if you are inspired and want our readers from around the world to know what you have shared with the U.S. government,  feel free to post your comments here as well.

Two award-winning journalists spent the better part of 2009 taking a global tour of drug resistance. The sights they found were astonishing – and terrifying. I spoke to one of them, Margie Mason, shortly after their five-part series entitled “When Drugs Stop Working: An Emerging Threat to Global Public Health” ran in newspapers around the world—unfortunately, in my view—during the week between Christmas and New Year. CGD has been tracking Margie’s journey and providing background information to her since she set out. Margie explained,

I was surprised by some of the things we found: I had no idea antibiotics were sprayed on fruit trees, and injected into palm trees. We also found there are 700 antibacterial or antimicrobial products on the market. Do you really need antimicrobial slippers and chopsticks?

You’ve got to admire Margie, a recent recipient of a Nieman Journalism Fellowship at Harvard University, and her Pulitzer-prize winning co-author, Martha Mendoza. This topic doesn’t exactly lend itself to the 3 paragraphs, 1 column format of USA Today. It’s complex, it’s hard to find the victims since many of them don’t know they have a drug-resistant disease, and there’s no smoking gun. “Drug resistance is not immediate”, explains Margie.  “It’s a slow, silent moving problem with many different aspects…it’s a truly global problem, and one that everyone is contributing to.” She continued,

Drug resistance was a real challenge to report on. It’s such a big issue and we tried to simplify and make it interesting to read about. There have been piecemeal stories but no-one has pulled it together in a comprehensive package. Our task was how to find things that haven’t been reported.

Our star gumshoes succeeded at that. In their first article—a breaking story that had never been made public—Mason and Mendoza reveal the first case of highly drug-resistant tuberculosis (coined XXDR-TB) in the U.S. They describe 19-year old Oswaldo Juarez’s struggle with the highly contagious and aggressive disease during his visit to Florida from Peru. Although XXDR-TB had never before been seen in the U.S., Dr. David Ashkin, one of the nation’s leading experts on tuberculosis and the medical director at AG Holley, the quarantine hospital where Juarez lived for a year and a half, explains that the case of Mr. Juarez “Really is the future. XXDR tuberculosis is so rare that only a handful of other people in the world are thought to have had it.  This is the new class people are not talking about.”

The capacity for TB to evolve into more aggressive and resilient strains is, in the words of Dr. Masae Kawamura, who heads the Francis J. Curry National Tuberculosis Center in San Francisco, “a time bomb…a man-made problem that is costly, deadly, debilitating, and the biggest threat to our current TB control strategies.”

Margie’s take on it?

The story of the kid in Florida was an incredible tale from a journalistic standpoint. We were trying to find XDR-TB in the U.S. There are a handful of TB centers across the country. AG Holley [a former TB sanitarium in West Palm Beach, Florida] is like a museum with all the old equipment. There are dark corridors, now without patients lining the walls, but where you can close your eyes and imagine yourself in another century. There are incredible patients there from all over the world. We met an Indian woman who came to the AG Holley with resistant TB and was separated from her newborn for eight months.

The two reporters’ drug resistance world tour tells of similarly heart-stopping sights elsewhere with the freshness that comes from seeing the problem for the first time. Frankly, it’s a welcome change from the scientific journals that produce almost all of the available knowledge about resistance. The journalists’ labor poured out over five days in late December, starting with Oswaldo’s story.

• Day Two: The first evidence of resistance to artemisinin combination drugs for malaria in Thailand – the same corner of the world where resistance to earlier malaria drugs began, and then spread worldwide.
• Day Three: The use of antibiotics in agricultural practices – amounting to 245 million tons of antibiotics consumed by animals in the U.S. alone.
• Day Four: The emergence of drug-resistance strains of HIV in South Africa – new and more resilient strains of HIV are being detected in roughly 5 percent of new patients in Africa, with higher resistance rates found in the U.S. and Europe.
• Day Five: The link between reduced antibiotic use in hospitals and better health results in Norway – while more than 65,000 people die of hospital-acquired infections annually in the U.S. alone.

Throughout the series, Margie Mason and Martha Mendoza compile personal stories, statistics and expert opinion to describe the dangerous capacity for medicine use to go wrong and create highly-resistant strains of infectious diseases. They conclude, “Forty years ago, the world thought that it had conquered TB and any number of other diseases through the new wonder drugs: antibiotics.  Today, all the leading killer infectious diseases on the planet are mutating at an alarming rate, hitchhiking their way in and out of countries.”

Did they arrive at this conclusion because their reporter instincts lead them to invent a crisis? No, these conclusions come straight from sober scientists. Dr. Tom Frieden, director of the U.S. Centers for Disease Control and Prevention, and a veteran of the fight against resistant TB in the U.S. asserted, “If we’re not careful with antibiotics and programs to administer them, we’re going to be in a post antibiotic era”. Margie and Martha also quote Norway’s MRSA Control Director, Dr. Petter Elstrom, who is apprehensive about the multi-drug resistant strain of Staphylococcus aureus—commonly dubbed MRSA. “So far we’ve managed to contain it, but if we lose this, it will be a huge problem. To be very depressing about it, we might in some years be in a situation where MRSA is so endemic that we have to stop doing advanced surgeries, things like organ transplants, if we can’t prevent infections. In the worst case scenario we are back to 1913, before we had antibiotics.”

Margie’s first-hand assessment is down-to-earth.

These strains are even scarier in the developing world. They can’t get treated. You can talk about these things and make plans about prevention and treatment. But when you see the setting you realize how challenging it is to make things work. These people are moving around all the time, they are poor.

Margie explained also that she was overwhelmed by the sheer scale of the problem.

I’ve been having dreams about drug resistance, waking up thinking about it. We’ve read books, interviewed hundreds of people. There’s just so much. We tried to hit on as many of the big issues as we could, but there are many others. We didn’t get into advertising or talk much about all the incentives paid to doctors to prescribe drugs. I’ve heard all kinds of anecdotes about what people get for prescribing drugs. We’re very quick to blame poor countries but in this case it’s a truly global problem, and one that everyone is contributing to.

There are, however, some glimmers of hope. In her interview with me, Margie noted the example of a Japanese doctor, who, after realizing that the nation’s seemingly ultra-modern, sterile facilities revealed MRSA levels that were among the highest in the world, changed his practices to reduce the frequent use and dissemination of antibiotics—and got positive results. Margie and Martha finish the series with a story about hospitals using amplified precautions (including universal screening programs) to reduce hospital-acquired infections in Pittsburgh. “There are ways to control this; it’s not a doomsday scenario,” Margie reports, adding that “there is more awareness now than a long time ago.”

Awareness, such as that generated by the AP series and similar articles, will be crucial in stemming the spread of once curable drug-resistant diseases across the world. To learn more, sign up for our monthly newsletter on drug resistance. It will direct you to the consultation draft report of the CGD Working Group on Drug Resistance. This is a manageable problem if only we all are willing to take the world tour with Margie and Martha.

Wow!  A vaccine this efficacious would be cause for celebration.

But medical researchers distinguish between the efficacy and effectiveness of an intervention.  An intervention, they point out, can be wonderfully “efficacious” under the controlled conditions of a randomized controlled trial (RCT), but might fail miserably in the typical setting for which it is designed.

Last week I had the pleasure of participating in a workshop that gathered many of those involved in planning  or potentially evaluating the rollout of medical male circumcision in the countries of Botswana, Kenya, South Africa, Swaziland, Zambia and Zimbabwe.  Sponsored by the Bill and Melinda Gates Foundation, the workshop in Johannesburg was partly to expose all of these policymakers and researchers to the latest efficacy information – and to a new device for male circumcision called the ShangRing – and partly to consider how the planned rollout of male circumcision in each country should be evaluated.

One view, held by some of the researchers at the meeting, is that medical efficacy has already been evaluated by rigorous randomized design so there would be little benefit in further rigorous evaluation during scale up.  In particular there is no need, they felt, to use HIV incidence as the endpoint of any future evaluation activity.  All that is necessary is routine monitoring and operations research to determine how to deliver circumcision as efficiently as possible.  They came to this conclusion because (1) they think that the efficacy is now virtually a biological certainty and (2) they think that any problems with effectiveness could be picked up by simply counting the number of circumcisions performed and the frequency of adverse events, without checking HIV incidence.

The contrary view is that the range of possible reductions in vulnerability suggested by the three existing trials of 38 % – 66 % leaves room for substantial concern.  In actual practice, perhaps the benefits would be even smaller than a 38 % reduction in risk.  For example, maybe during the rollout only those whose sexual practices are already safe would choose the intervention.  If this is the case, then counting successful circumcisions without noting HIV infections would overestimate the national effectiveness of the program – and leave policy makers puzzled by the continuing momentum of the epidemic.

In a presentation on the application of the concept of statistical power to evaluating the effectiveness of interventions, Sergio Bautista and I proposed that the design of an evaluation of a program rollout can and should differ from the evaluation of the medical efficacy of the same intervention in several dimensions, each of which would inform an important policy question:

External validity

While a medical efficacy RCT, such as those done for male circumcision, is intended only to achieve internal validity, the evaluation of a large-scale rollout needs to establish internal validity and external validity. Internal validity is necessary to be sure that the outcomes can be attributed to the intervention. Getting information on the context and conditions under which the program is rolled out is necessary for judging the external validity of the findings, so that results can be applied to estimate the program’s effectiveness on the whole country.

Cost-effectiveness threshold

Since a medical efficacy RCT should and usually does ignore costs, it need only have the statistical power to reject the hypothesis that the intervention is no better than competing interventions.  However, given the costs of achieving and sustaining high coverage of adult male circumcision in African countries, policy makers need to know that its efficacy is large enough to render it cost-effective in relation to other interventions.  Application of the male circumcision planning model created by Lori Bollinger and colleagues of the Futures Institute calculates that through the year 2015 at 60 % effectiveness MC will cost $1,560 dollars per HIV infection averted, while at 20 % effectiveness MC will cost $4,917 per HIV infection averted.  The former figure is attractive, the latter not so much.  So instead of just rejecting a null hypothesis of no effect, policy makers might be interested in rejecting the hypothesis that MC is 20% effective or less.  This is a more difficult hurdle for MC to clear, but could potentially be answered with the large samples that are available in a full-scale rollout.

Standard of care is a more defensible counterfactual in a rollout

Because standard IRB ethical standards required that the MC efficacy trials provide other HIV prevention interventions to those who did not receive the MC, the RCTs may have underestimated the effectiveness that male circumcision would have in a real setting, where these other HIV prevention interventions are less accessible.  But an effectiveness evaluation of a rollout would typically compare the effect in those communities that first receive the intervention first to that in the communities that receive it later.  Until they later receive the rolled out MC, those in the comparison group will be getting no more than is typically available in the country.  So the measured impact of MC is likely to be larger in this setting than in the RCTs.

Determinants of effectiveness

Policymakers will want to know how they can maximize the effectiveness of MC.  In the course of a full-scale rollout, there will be natural variation in various factors that influence both the supply and demand side of MC.  A selected few of these factors can be singled out for experimental variation and the rest can be studied with non-experimental methods.  Lessons on the determinants of effectiveness will help those managing the MC program, but would rarely result from efficacy evaluation studies alone.

Secondary outcomes and their determinants

Among the most important potential “spillover” effects of MC are (1) compensating risk behavior that might offset the benefits of MC; (2) infection rates among the female partners of the circumcised; (3) the effect of massive numbers of male circumcisions on the availability of and access to other types of health care; (4) the variation in unit cost of MC as health facilities first become more efficient (due to increasing scale and learning by doing) and then less so (due to decreasing returns); (5) the reproductive rate of HIV in the whole community as MC coverage increases.  The efficacy trials found cause for alarm on the first of these indicators in one of the three studies, but were unable to consider the other four issues.  Effectiveness trials can hope to examine all five -  and with much greater external validity than could be achieved in a small RCT.

With all the benefits of rigorous evaluation of full-scale rollout, it would be unconscionable not to undertake such studies. Years ago, the feasibility of such studies might have been questioned on many grounds: financial, methodological, political, and ethical. But despite difficulties, these excuses can no longer be sustained. Bill Savedoff reminds me that public agencies and foundations are beginning to provide substantial sums of money to rigorous impact evaluations, including through the recently created International Initiative for Impact Evaluation (3ie).  Researchers have demonstrated the feasibility of evaluating large-scale programs, most dramatically with rollouts of national conditional cash transfer programs. Even the political and ethical dimensions of these evaluations have been confronted and worked out by researchers and policymakers, especially those who are native to the countries in question, who recognize that their need to know the answers to the above questions is sufficiently important to society as to justify the effort of explaining the studies to the public and protecting a rigorous evaluation design.

Since its release in December 2009, specific pieces of PEPFAR’s new strategy have triggered much discussion both in Washington, D.C. and abroad. In the spirit of sharing-while-doing, Ambassador Goosby spoke at a Center for Strategic and International Studies (CSIS) event on Tuesday on “Confronting the Tough Challenges in HIV Prevention,” focusing his remarks on HIV prevention in the strategy.

As outlined in the strategy and stressed in Goosby’s comments, PEPFAR’s main goal towards prevention is to match as aggressive of a response as was launched for treatment in its first phase. This includes working with governments to map the prevention needs of a country, using high-impact, evidence-based approaches—including biomedical, behavioral and structural interventions—that are also linked to care and treatment programs. The strategy lays out the steps for countries to develop a basic package of prevention, but Goosby’s remarks did not hide the fact that there is still much more to learn. Questions raised by Goosby and the audience centered on PEPFAR’s efforts to ensure that prevention interventions are effective and geared towards the right populations, actually work to reduce incidence rates, and are cost-effective in their scale-up.

This administration’s plan for a more sustainable and effective resource allocation for treatment, care and prevention is promising. To be successful PEPFAR must work with countries to tackle the challenges to prevention as they launch an aggressive prevention response. Three big challenges for the U.S. administration to think about as it enters the implementation phase of the new strategy:

1) Scale-up: How do you scale-up prevention efforts? What does a scale-up plan look like for a given country?

While the strategy is good in defining the approach to prevention, it does little in the way of defining the operational features needed to actually expand prevention efforts (i.e., roll-out, monitoring and evaluation, etc.). For example, many prevention interventions are initiated at the community level, especially to tackle risks related to individual behavior, so what is the process for expanding these interventions and approaches across a region or country in a way that will result in the reduction of new infections? Perhaps the evolving guidance and country operational plans (COPS) will be more specific about prevention scale-up by country?

2) Metrics: How to measure prevention success?

There has been a general lack of information on prevention metrics, both in PEPFAR’s past, as well as in this new strategy. However, if prevention is truly going to be a defining feature of the Obama administration’s approach towards global HIV, there need to be measures in place to identify and show—both to Congress and to its beneficiaries,—PEPFAR’s progress in averting infection.

I asked this question at Tuesday’s event, and Dr. Goosby realistically noted that measuring effects on incidence takes time. Given that it’s hard to measure something that does not happen, it was encouraging to learn that PEPFAR is developing “surrogate markers of incidence” with experts both at home and abroad on this topic. Dr. Goosby did not elaborate what these surrogate markers might be except for a quick reference to indicators from ante-natal care, but committed to vetting these more publicly once developed. Clearly, this is something to look out for in the near future.

3) Incentives to scale up prevention for success: What incentives, if any, will PEPFAR provide to countries to prioritize prevention?

Creating incentives for national governments to focus on prevention efforts is a must for them to succeed. In a forthcoming CGD working paper, CGD colleague Mead Over translates CGD’s concept of “Cash on Delivery”, to HIV prevention. In COD aid, donors commit to pay a specific amount of money for a specific measure of progress, in this case, infections averted. Incentivizing prevention in creative ways is an important step in scaling up efforts and should be a critical component of PEPFAR’s new approach with governments and other country stakeholders.

Courtesy U.S. State Department

When it comes to Secretary of State Hillary Clinton, no sliver of the international development community is more enamored than the sexual and reproductive health and rights (SRHR) crowd (yes, that’s their self-designation). Last Friday, Hillary returned the love. In a speech (see the full text here) in the regal Benjamin Franklin reception room at the State Department, Secretary of State Clinton and many of her top staff brought the international dimension of reproductive health and family planning in from the cold. It’s been a long winter.

The occasion of the speech was the 15th anniversary of the “Cairo Conference” – officially the International Conference on Population and Development (ICPD) – in 1994, at which then-first lady Clinton was a very prominent and passionate leader of the U.S. delegation. Last Friday she said,

There is no doubt in my mind that the work that was done and the commitments that were made in Cairo are still really the bulwark of what we intend to be doing and are expected to do on behalf of women and girls.

The ICPD was particularly ill-timed. Several months later, Republicans took control in the U.S. Congress and anything having to do with sex, rights, or Hillary became a political cudgel. The conditions for advancing the Cairo Plan of Action on SRHR became worse in 2000 when George W. Bush took office, the Mexico City policy (known by some as the global gag rule) first imposed by Ronald Reagan was reinstated, U.S. funding was pulled from the UN Population Fund (UNFPA)and replaced by Nordic and other European countries and the U.S. became a pariah in international circles concerned about women and their rights.

The SRHR crowd in the U.S. went into exile. They’ve been there for almost half the time that has elapsed since Cairo. As Margaret Pollack (newly appointed Senior Advisor on Population Issues at the U.S. State Department) said at a UN Foundation luncheon to celebrate Friday’s speech, a lot of time has been lost that could have been spent achieving the Cairo Plan of Action – and not incidentally, getting much closer to achieving MDG 5, the maternal health goal.

Secretary Clinton seems to be in a hurry to make up for lost time. She used the full arsenal of her top staff and emboldened them with strong words. Eric Schwartz, assistant secretary of state responsible for population issues, opened the event saying, “We recommit to the principles of ICPD and its Plan of Action.” Ambassador-at-Large for Global Women’s Issues, Melanne Verveer, in introducing the Secretary, called her a woman who has not wavered on the issues of SRHR and applauded the focus on girls and women in the Secretary’s “groundbreaking speech on development” two days earlier at CGD. (For those who missed it, you can read the text of the prepared remarks here – note the very nice reference to Start with a Girl in her sixth point.)

Maria Otero, the undersecretary of state for democracy and global affairs, drove home the point that the Secretary is dead serious about putting the needs and condition of girls and women at the center of U.S. foreign policy. And completing the all-star line-up, USAID Administrator Raj Shah, sworn in just the day before, assured the crowd that a newly energized and excited USAID is ready to live up to the core principles of SRHR and the full vision that the Secretary articulated in last Wednesday’s speech – a speech he called “the most important statement on development by a secretary of state in decades.”

So what did Secretary Clinton deliver in her tidings of comfort and joy? (this speech was originally scheduled to happen right before Christmas but a Washington DC blizzard delayed it.) Four points that pretty much capture the essence of what’s needed:

1. Girls and Women: The Secretary not only “Started with a Girl,” but she put girls in the center and at the end of her speech as well. After reciting some of the brutal statistics that describe the sorry state of women’s and girls’ health – including a woman dying every minute of every day from pregnancy and childbirth and 70 million women and girls worldwide with their genitals carved up – she declared the situation intolerable. (For a discussion of the available statistics on girls, see Ruth Levine’s blog here.) In addition to reinforcing on-going U.S. programs to prevent maternal mortality and female genital cutting, the Secretary is asking every program in the State Department and USAID to determine what its contribution is for the well-being of girls and women. That will require some careful searching, but it is the soul-searching that will accompany it that could most change the State Department.
2. U.S. as a global leader: I felt an undercurrent of last year’s inaugural mood in the Benjamin Franklin room as the Secretary and her cadre spoke of the future. They were wiping away 8 years of U.S. blockage and manipulation of international family planning programs and policy negotiations. There was a sense of pride and almost disbelief in the audience that the reversal could be so complete. The members of the diplomatic corps that I spoke with afterwards were perhaps the most gratified. One ambassador said to me, “Now, when the U.S. speaks, people will listen again.”
3. More money: Getting down to the important details, Secretary Clinton said, “We’ve pledged new funding, new programs, and new commitments to MDG5.” The Obama Administration has already renewed funding to UNFPA and “more is on the way,” according to the Secretary. She said there will be in increase in population funding within the U.S. budget (as we’ve seen already, by almost one-third), and reproductive health and family planning , in addition to maternal and child health, will be central to the Global Health Initiative being constructed by a constellation of USG agencies in time for the President’s budget speech in February.
4. Centrality of SRHR to development: Perhaps most challenging but key to it all is the connection between SRHR and so many other development goals. Secretary Clinton gets it in spades, and so she said, “We understand there is a direct line between a woman’s reproductive health and her ability to lead a productive, fulfilling life. And therefore, we believe investing in the potential of women and girls is the best investment we can make.” And some concrete actions: “We are integrating women, adolescents and girls into our Global Health Initiative and our Food Security Initiative. We will make sure the integration of family planning happens…all health programs will be designed to take into account women and girls.”

I daresay that not just the SRHR crowd – stalwarts all—were pleased when she said off-script,

“I know it can sometimes be hard to take, we might grow weary of the ups and downs in these things that seem so self-evident to the rest of us that this must be done. But work with us, and let’s create structural and institutional change that does not get wiped away with the political winds.”

For those of us in the development community who are immersed in questions of how to achieve better health in the developing world and/or issues of the empowerment of women, the renewed attention to the health of girls and women is very welcome. At the same time, it’s hard to quiet the inner questions about how to reconcile enthusiasm for SRHR within the “international community” with the much less positive view in many of the governments of developing countries. While it is certainly the case that in some countries receiving U.S. development assistance (for example, Ethiopia and Egypt) there appears to be genuine high-level support for family planning and good reproductive health care, this is far from a universal position. At best, countries that are not actively supportive will permit family planning services to be provided when donors pay – which is why there is a dramatic ebb and flow of access to services depending on the party affiliation of the President of the United States. At worst, the policies and practices of governments with which we do development business are retrograde with respect to the health-related rights of girls and women.

This puts us in a little bit of a bind when it comes to simultaneously insisting on the value of a women-centered approach in health and the principle of “country ownership” and engagement in true partnerships – a priority for development policy that Secretary Clinton articulated in her address earlier in the week. One way to manage that conundrum is to invoke the fact that the vast majority of the world’s nations are signatories to the Convention on the Elimination of All Forms of Discrimination Against Women and the Convention on the Rights of the Child, which include provisions that cover almost all of actions that SRHR advocates promote. Therefore, as signatories they have already endorsed access to quality health services, protection from gender-based violence, and many other important objectives. But, sadly, the bind becomes tighter if we attempt to use this rationale because the U.S. is among the very few countries that has ratified neither of those conventions – along with Iran and Sudan in the case of CEDAW, and Somalia in the case of the CRC. In this domain, we fall far short of being able to serve as a model or inspiration – and are significantly challenged even to highlight the disconnect between other countries’ rhetoric and practices.

In spite of these significant reasons for caution, we can all bask for a moment in the reflected warmth from the end of the SRHR community’s long winter in exile.