A once-a-day pill to help prevent HIV infection could significantly reduce the spread of AIDS, but only makes economic sense if used in select, high-risk groups, Stanford researchers conclude in a new study.

The researchers looked at the cost-effectiveness of the combination drug tenofovir-emtricitabine, which was found in a landmark 2010 trial to reduce an individual’s risk of HIV infection by 44 percent when taken daily. Patients who were particularly faithful about taking the drug reduced their risk to an even greater extent – by 73 percent.

The results generated so much interest that the Stanford researchers decided to see if it would be cost-effective to prescribe the pill daily in large populations, a prevention technique known as pre-exposure prophylaxis, or PrEP.

They created an economic model focused on gay men, as they account for more than half of the estimated 56,000 new infections annually in the United States, according to the Centers for Disease Control and Prevention.

“Promoting PrEP to all men who have sex with men could be prohibitively expensive,” said Jessie Juusola, a PhD candidate in management science and engineering in the School of Engineering and first author of the study. “Adopting it for men who have sex with men at high risk of acquiring HIV, however, is an investment with good value that does not break the bank.”

For instance, using the pill in the general population of gay men would cost $495 billion over 20 years, compared to $85 billion when targeted to those at particularly high risk, the researchers found. The study will be published in the April 17 issue of the Annals of Internal Medicine.

Senior author Eran Bendavid, an affiliate of Stanford Health Policy at the Freeman Spogli Institute, said the results are a departure from a previous study. Earlier research found PrEP was not cost-effective when compared with other commonly accepted prevention programs.

The new Stanford study differs in a few important respects, taking into consideration the decline in transmission rates over time as more individuals take the pill. The Stanford team also assumed individuals would stop taking PrEP after 20 years, not stay on the drug for life, as the previous study had assumed.

The pill combination, marketed under the brand name Truvada, is widely used for treating HIV infection. But it wasn’t until a landmark trial, published in the New England Journal of Medicine in November 2010, that individuals and their doctors began to seriously consider using the drug as a preventive therapy. The drug’s maker, Foster City, Calif.-based Gilead Sciences Inc., has filed a supplemental new drug application to market it for prevention purposes.

The CDC issued interim guidelines on the drug’s use in January 2011, suggesting that if practitioners prescribe it as a preventive measure, they regularly monitor patients for side effects and counsel them about adherence, condom use and other methods to reduce their risk of infection.

In developing their model, the Stanford researchers took into account the cost of the drug – about $26 a day, or almost $10,000 a year – as well as the expenses for physician visits, periodic monitoring of kidney function affected by the drug, and regular testing for HIV and sexually transmitted diseases.

“We’re talking about giving uninfected people a drug that has some toxicities, so it’s crucial to have them monitored regularly,” said Bendavid, who is an assistant professor of medicine in Stanford’s School of Medicine.

Without PrEP, the researchers calculated there would be more than 490,000 new infections among gay men in the United States in the next 20 years. If just 20 percent of these men took the pill daily, there would be nearly 63,000 fewer infections.

However, the costs are substantial. Use of the drug by 20 percent of gay men would cost $98 billion over 20 years; if every man in this group took PrEP for 20 years, the costs would be a staggering $495 billion.

Given these figures, the researchers looked at the option of giving PrEP only to men who are at high risk – those who have five or more sexual partners in a year. If just 20 percent of these high-risk individuals took the drug, 41,000 new infections would be prevented over 20 years at a cost of about $16.6 billion.

At less than $50,000 per quality-adjusted life year gained (a measure of how long people live and their quality of life), that strategy represents relatively good value, according to Juusola.

“However, even though it provides good value, it is still very expensive,” she said. “In the current health care climate, PrEP’s costs may become prohibitive, especially given the other competing priorities for HIV resources, such as providing treatment for infected individuals.”

She said the costs could be significantly reduced if the pill is found to be effective when used intermittently, rather than on a daily basis. Current trials are examining the effectiveness of the drug when used less often.

Other co-authors are Margaret L. Brandeau, the Coleman F. Fung Professor of Engineering, and Douglas K. Owens, the Henry J. Kaiser, Jr. Professor at Stanford and senior investigator at the Veterans Affairs Palo Alto Health Care System. Owens also is director of Stanford’s Center for Health Policy and Center for Primary Care and Outcomes Research.

The study was funded by the National Institutes of Health and the Department of Veterans Affairs and supported by Stanford’s departments of Medicine and Management Science and Engineering.

The cloud offers game-changing opportunities for start-ups to large enterprises, if entrepreneurs and enterprise leaders know how best to harness its power. A panel of cloud computing experts shared their wealth of experience to a full house at the special event on Innovation in the Cloud: How Cloud Computing is Changing the Landscape of Entrepreneurship and Innovation, organized by the Stanford Program on Regions of Innovation and Entrepreneurship (SPRIE) in partnership with China America Innovation Network (CHAIN).

In this featured panel discussion at the Stanford Graduate School of Business for Stanford's Entrepreneurship Week 2012, the panel shared insights on cloud computing technology changes, enterprise transformation, business model innovation, investor strategies, and market opportunities, with more than 200 Stanford students, faculty, entrepreneurs and Valley professionals.

The panel was composed of serial entrepreneur Jim Dai, CEO of CalmSea, IT expert Sam Ghods, vice president of technology at Box.com, marketing expert Ken Oestreich, senior director of cloud and virtualization marketing at EMC, and investor Cindy Padnos, founder and managing director of Illuminate Ventures. Robert Scoble, startup liaison officer at Rackspace and a technical evangelist, moderated the discussion.

The panelists acknowledged that users had grown to accept everything could be virtual, and cloud is radically changing the face of enterprise strategy, processes, and outcomes. Cloud computing can dramatically decrease timelines and investment costs which encourages flexible growth and experimentation by rapid iteration. This shift, together with cloud computing’s cost effectiveness, strongly favors the way start-ups work.

For entrepreneurs, one piece of good news is that cloud allows smaller firms to compete with big players in new ways. This trend has also prompted the rise of micro VCs, with typical investments of $100,000 to $500,000. While SMEs continue to embrace cloud-based services, how large enterprises adapt and evolve the cloud market will remain interesting.

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Stanford Entrepreneurship Week 2012 takes place February 27 through March 7. This collection of over 30 events is hosted by the Stanford Entrepreneurship Network (SEN), a federation of programs, student groups and organizations supporting entrepreneurship in the Stanford community.

The February 10 Liberation Technology seminar titled, Can ICT Improve Clean Water Delivery Systems in Slums? Lessons from Kibera was led by two Stanford students, Katherine Hoffman, M.A. Candidate in International Policy Studies and Global Health together with Sunny Jeon, PhD candidate in Political Science. Hoffman and Jeon presented on the topic of the M-Maji system, a start-up non-profit project that uses mobile phones to empower communities with better information about water availability, price, and quality. M-Maji emerged from the Designing Liberation Technologies course taught at the Stanford d.school, which is dedicated to using mobile phone technology for health improvement in Kibera.  

The M-Maji project was conceived to confront a specific need in one of Africa's largest informal settlements: Nairobi's Kibera slum. Kibera holds about one quarter of Nairobi's population, but lacks a formal water and sanitation system. In short, water in Kibera is scarce, costly, uncertain, and often contaminated. The cost of water can rise up to over $3 per square meter during a shortage, and often takes up 20% of residents' income. Water is uncertain because about 40% of vendors in Kibera do not have access to a constant supply of water, especially since many of the connections that they do use are illegal. Additionally, water is often contaminated because water pipes run through sewer areas and are often plastic, since metal pipes would be taken as scrap. The result of these conditions is that the average person spends about 55 minutes per day looking for water, and about 68% of residents use informal water kiosks to access water.

M-Maji is a mobile platform designed to address problems facing both the seller and buyer of water in Kibera. Sellers report information about water availability and price at their water kiosk, enabling them to attract customers. Meanwhile, buyers access the system to find information about where water is available, at what price and at what level of quality. A third feature of the platform enables complaints and feedback regarding water sources. By coordinating and centralizing water information from multiple sources, M-Maji is designed to empower residents with better information about water availability, price, and quality, which ultimately helps to improve access to clean water.

There are several key reasons why a mobile platform that tackles the information side of the problem may be effective in solving the water problem in Kibera:

1. The water market is distorted, but not coordinated. Also, there is significant variation between neighborhoods.
2. Information asymmetry exists that is not solved by other sources or tools.
3. M-maji is needs-driven.
4. Relative to other interventions, M-Maji is cost-sensitive and low tech.

Although fieldwork conducted by the M-Maji team has indicated great potential for the platform's success, the team has also faced many challenges in implementation. One example stems from the platform's use of USSD sessions. Like SMS, these sessions allow short messages (up to 182 characters) to be exchanged. Users must enter a short code to begin a session, which then lasts about 2 minutes. However, the team has faced significant difficulty in getting mobile operators to allow access to USSD (in Swahili), as well as to negotiate rate agreements with mobile operators. The involvement of gangs and government in the water market introduces another challenges. In some cases, gangs bribe utility people to restrict the supply to push up prices, which may hinder the eventual effectiveness of the M-Maji tool.

Following the formation of a partnership with an important local NGO in Kibera called Umande Trust, M-Maji is moving rapidly into the pilot stage. The team is currently working to carry out a randomized impact evaluation to obtain convincing estimates of M-Maji's cost-effectiveness and impact on water outcomes. With the help of the community partner, the team is running a six-month long pilot on the West side of Kibera. In addition to surveying 1000 households for the baseline survey, the team is also carrying out data collection on water prices and water quality. M-Maji will officially launch in May or June of 2011, and the team will continue to reassess the project to better meet user needs as the results of the pilot become available.

 

Advances in high-yield agriculture achieved during the so-called Green Revolution have not only helped feed the planet, but also have helped slow the pace of global warming by cutting the amount of biomass burned - and the resulting greenhouse gas emissions - when forests or grasslands are cleared for farming. Stanford researchers estimate those emissions have been trimmed by over half a trillion tons of carbon dioxide. The paper is being released this week in the Proceedings of the National Academy of Sciences.

Advances in high-yield agriculture over the latter part of the 20th century have prevented massive amounts of greenhouse gases from entering the atmosphere - the equivalent of 590 billion metric tons of carbon dioxide - according to a new study led by two Stanford Earth scientists.

The yield improvements reduced the need to convert forests to farmland, a process that typically involves burning of trees and other plants, which generates carbon dioxide and other greenhouse gases.

The researchers estimate that if not for increased yields, additional greenhouse gas emissions from clearing land for farming would have been equal to as much as a third of the world's total output of greenhouse gases since the dawn of the Industrial Revolution in 1850.

The researchers also calculated that for every dollar spent on agricultural research and development since 1961, emissions of the three principal greenhouse gases - methane, nitrous oxide and carbon dioxide - were reduced by the equivalent of about a quarter of a ton of carbon dioxide - a high rate of financial return compared to other approaches to reducing the gases.

"Our results dispel the notion that modern intensive agriculture is inherently worse for the environment than a more 'old-fashioned' way of doing things," said Jennifer Burney, lead author of a paper describing the study that will be published online by the Proceedings of the National Academy of Sciences.

Adding up the impact

The researchers calculated emissions of carbon dioxide, methane and nitrous oxide, converting the amounts of the latter two gases into the quantities of carbon dioxide that would have an equivalent impact on the atmosphere, to facilitate comparison of total greenhouse gas outputs.

Burney, a postdoctoral researcher with the Program on Food Security and the Environment at Stanford, said agriculture currently accounts for about 12 percent of human-caused greenhouse gas emissions. Although greenhouse gas emissions from the production and use of fertilizer have increased with agricultural intensification, those emissions are far outstripped by the emissions that would have been generated in converting additional forest and grassland to farmland.

"Every time forest or shrub land is cleared for farming, the carbon that was tied up in the biomass is released and rapidly makes its way into the atmosphere - usually by being burned," she said. "Yield intensification has lessened the pressure to clear land and reduced emissions by up to 13 billion tons of carbon dioxide a year."

"When we look at the costs of the research and development that went into these improvements, we find that funding agricultural research ranks among the cheapest ways to prevent greenhouse gas emissions," said Steven Davis, a co-author of the paper and a postdoctoral researcher at the Carnegie Institution at Stanford.

To evaluate the impact of yield intensification on climate change, the researchers compared actual agricultural production between 1961 and 2005 with hypothetical scenarios in which the world's increasing food needs were met by expanding the amount of farmland rather than by the boost in yields produced by the Green Revolution.

"Even without higher yields, population and food demand would likely have climbed to levels close to what they are today," said David Lobell, also a coauthor and assistant professor of environmental Earth system science at Stanford.

"Lower yields per acre would likely have meant more starvation and death, but the population would still have increased because of much higher birth rates," he said. "People tend to have more children when survival of those children is less certain."

Avoiding the need for more farmland

The researchers found that without the advances in high-yield agriculture, several billion additional acres of cropland would have been needed.

Comparing emissions in the theoretical scenarios with real-world emissions from 1961 to 2005, the researchers estimated that the actual improvements in crop yields probably kept greenhouse gas emissions equivalent to at least 317 billion tons of carbon dioxide out of the atmosphere, and perhaps as much as 590 billion tons.

Without the emission reductions from yield improvements, the total amount of greenhouse gas pumped into the atmosphere over the preceding 155 years would have been between 18 and 34 percent greater than it has been, they said.

To calculate how much money was spent on research for each ton of avoided emissions, the researchers calculated the total amount of agricultural research funding related to yield improvements since 1961 through 2005. That produced a price between approximately $4 and $7.50 for each ton of carbon dioxide that was not emitted.

"The size and cost-effectiveness of this carbon reduction is striking when compared with proposed mitigation options in other sectors," said Lobell. "For example, strategies proposed to reduce emissions related to construction would cut emissions by a little less than half the amount that we estimate has been achieved by yield improvements and would cost close to $20 per ton."

The authors also note that raising yields alone won't guarantee lower emissions from land use change.

"It has been shown in several contexts that yield gains alone do not necessarily stop expansion of cropland," Lobell said. "That suggests that intensification must be coupled with conservation and development efforts.

"In certain cases, when yields go up in an area, it increases the profitability of farming there and gives people more incentive to expand their farm. But in general, high yields keep prices low, which reduces the incentive to expand."

The researchers concluded that improvement of crop yields should be prominent among a portfolio of strategies to reduce global greenhouse gases emissions.

"The striking thing is that all of these climate benefits were not the explicit intention of historical investments in agriculture. This was simply a side benefit of efforts to feed the world," Burney noted. "If climate policy intentionally rewarded these kinds of efforts, that could make an even bigger difference. The question going forward is how climate policy might be designed to achieve that."

David Lobell is a Center Fellow at the Freeman Spogli Institute for International Studies and at the Woods Institute for the Environment. The Program on Food Security and the Environment is a joint project of the Woods Institute and the Freeman Spogli Institute. The Precourt Institute for Energy and FSE provided funding for Jennifer Burney's research on agriculture and energy.

Among hundreds of applicants, REAP was one of only 25 groups to secure a competitive grant from the International Initiative for Impact Evaluation, or 3ie, to assess the value of expanding vocational education training (VET) in China.

Read below for a summary of the proposed study.

Investment in Vocational vs. General Schooling: Evaluating China’s Expansion of Vocational Education and Laying the Foundation for Further Vocational Education Evaluation

A key policy question in developing countries, including China, is how to balance investments between vocational and general education in a way that supports economic growth and reduces social inequality. There is no definitive study in any developing country on the returns to vocational education and training (VET). In the absence of information on how VET might affect the earnings of workers, it is unclear if recent efforts of the Chinese government to expand VET are sound. If the returns are negligible, the government might consider slowing the expansion or improving the quality of VET.

Additionally, it is estimated that only about 40% of the students that graduate from junior high school in poor, rural areas continue with their studies; the rest enter the unskilled labour force. Why are these rates so low? Surprisingly, little is known about the factors that keep students out of school. There is no systematic study of what is working in VET and what is not. Despite the rapid expansion of VET, China has set up few mechanisms to evaluate the quality of VET programs.

The goal of this project is to help the Chinese government evaluate the effectiveness of the expansion of VET. It aims to provide empirical evidence on the returns to VET; the factors that might keep disadvantaged students from receiving quality schooling; and measure the quality and cost-effectiveness of VET programs.

This study will estimate the returns from VET versus general schooling using various “quasi-experimental” methods. It will follow a randomized control trial design and randomly assign junior high students to programmes that provide vouchers for VET schooling, vouchers for academic schooling, and academic counselling for students to become better informed about their schooling/employment options. The project will assess if students work harder, perform better and matriculate to academic high school and VET at higher rates when they have sufficient financial aid and counselling. Finally, it will also develop an Entrance/Exit Examination that can be used by principals of VET institutions and local officials in charge of VET to assess the quality of their programs. The findings of these quality studies of VET will be useful in influencing policy on one of China’s most debated education issues.

In early spring, historic health reform passes, extending insurance to millions of uninsured. Despite problems with workplace-based coverage, controversy over government subsidies for insurance premiums, and disparities across a large and diverse nation, dramatic shift to a single-payer system was seen as impractical.

Instead, reforms focus on expanding current social insurance programs as well as new initiatives to cover the uninsured, improve quality, and control spending. They provide a basic floor, subsidized for the poorest, but preserve consumer freedom to choose in health care. No government body dictates choice of doctor or hospital; investor-owned and private not-for-profits compete alongside government-run providers like community health centers and rural hospitals.

Left to be addressed in later phases are the difficult questions of how to slow the relentless pace of health care spending increases -- driven in part by technological change and population aging, but also perverse incentives embedded in fee-for-service payment and fragmented delivery. Pushed through despite multiple crises confronting the leadership, the final landmark health reform works in conjunction with measures enacted as part of the fiscal stimulus package to strengthen the healthcare system. Some provisions take effect immediately; others will take many years to unfold.

President Obama’s triumph on his top domestic priority? Actually, there were no votes along partisan lines, no controversy over abortion. I am describing health reform in China, which was announced almost exactly a year ago.

We do not hear much about the parallels in the US and Chinese social policy. But we cannot fully understand each other if we ignore these commonalities. We do not hear much about those who, in both societies, have been rendered destitute merely because they or a family member became sick or injured in a system with a social safety net full of gaping holes.

It will surprise many Americans to know that government financing as a share of total health spending was lower in socialist China over the last decade than in the United States. Now China has pledged about US$124 billion over 3 years to expand basic health insurance, strengthen public health and primary care, and reform public hospitals.

In China, the injustice of differential access to life-saving healthcare had sparked cases of social unrest. The April 2009 reform announcement was the culmination of years of post-SARS (2003) soul searching for a healthcare system befitting China’s dynamically transforming society. Special interests block change. (Sound familiar?) The CPC Central Committee and the State Council acknowledge that successful health reform will be “an arduous and long-term task”.  

If the US can pass sweeping health reform despite an unprecedented financial crisis, and China can envision universal health coverage for 1.3 billion while “getting old before getting rich,” then together we should be able to look past our many differences to focus on our common interests. Our two proud nations must work together to confront numerous challenges, such as upholding regional stability (e.g. on the Korean peninsula); redressing global economic imbalances (increasing health insurance can help spur China towards more domestic consumption); and investing in “green tech” for a warming planet and “grey tech” for an aging society.

 

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When searching for insights about how other countries deal with similar challenges, Americans often look to Europe and Canada. Rarer is the comparison to counterparts across the Pacific. Yet President Obama has clearly articulated the vision of the US as a Pacific Nation, and there are developments around the Pacific Rim that merit consideration in our debates.  

Australia pioneered cost-effectiveness in health care purchasing, while the US continues to debate whether cost should be part of comparative effectiveness research and policy decisions.

Both Japan and South Korea, like Germany, have enacted long term care insurance to smooth the transition to an aging society. Their experiences might be fruitful as we implement the first national government-run long-term care insurance program, a little-heralded component of the newly passed legislation (and a fitting legacy of Senator Edward Kennedy).

Japan and Singapore provide universal coverage to older populations than ours with health systems that, although surprisingly different from each other in terms of public financing and role of market forces, both ranked among the best in the world -- and far higher than the US -- in the World Health Organization’s ranking of health systems in the year 2000. Although one may quibble with the ranking, it is indisputable that Japan spends a much smaller share of GDP on healthcare than the US does, despite being one of the oldest and longest-lived societies in the history of the world and having (like the US) a fee-for-service payment system.

Japan and South Korea are also democracies, where health policies occasionally engender heated debates. In South Korea, physicians went on nationwide strike three times to oppose the separation of prescribing from dispensing. Although Japan’s incremental reforms rarely spur such drama, the passions aroused by end-of-life care – embodied in the bizarre “death panels” controversy in the US health reform debate of 2009 – has its counterpart in the bitter nickname for Japan’s separate insurance plan for the oldest old: “hurry-up-and-die” insurance.

Yet Japan, Singapore, and Hong Kong all offer health systems that provide reasonable risk protection and quality of care for populations older than ours, with a diverse range of government and market roles in financing and delivery, while spending far less per capita than the US.

No system has all the answers. But the US and our neighbors across the vast Pacific have a common interest in sharing what we’ve found that works for health reform. Despite divergence in our political and economic systems, we all value long, healthy lives for ourselves and our children -- and we’re united in health reforms that try to further that goal.