Most studies that look at whether democracy improves global health rely on measurements of life expectancy at birth and infant mortality rates. Yet those measures disproportionately reflect progress on infectious diseases — such as malaria, diarrheal illnesses and pneumonia — which relies heavily on foreign aid.

A new study led by Stanford Health Policy's Tara Templin and the Council on Foreign Relations suggests that a better way to measure the role of democracy in public health is to examine the causes of adult mortality, such as noncommunicable diseases, HIV, cardiovascular disease and transportation injuries. Little international assistance targets these noncommunicable diseases. 

When the researchers measured improvements in those particular areas of public health, the results proved dramatic.

“The results of this study suggest that elections and the health of the people are increasingly inseparable,” the authors wrote.

A paper describing the findings was published today in The Lancet. Templin, a graduate student in the Department of Health Research and Policy, shares lead authorship with Thomas Bollyky, JD, director of the Global Health Program at the Council on Foreign Relations.

“Democratic institutions and processes, and particularly free and fair elections, can be an important catalyst for improving population health, with the largest health gains possible for cardiovascular and other noncommunicable diseases,” the authors wrote.

Templin said the study brings new data to the question of how governance and health inform global health policy debates, particularly as global health funding stagnates.

“As more cases of cardiovascular diseases, diabetes and cancers occur in low- and middle-income countries, there will be a need for greater health-care infrastructure and resources to provide chronic care that weren’t as critical in providing childhood vaccines or acute care,” Templin said.

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Free and fair elections for better health

In 2016, the four mortality causes most ameliorated by democracy — cardiovascular disease, tuberculosis, transportation injuries and other noncommunicable diseases — were responsible for 25 percent of total death and disability in people younger than 70 in low- and middle-income countries. That same year, cardiovascular diseases accounted for 14 million deaths in those countries, 42 percent of which occurred in individuals younger than 70.

Over the past 20 years, the increase in democratic experience reduced mortality in these countries from cardiovascular disease, other noncommunicable diseases and tuberculosis between 8-10 percent, the authors wrote.

“Free and fair elections appear important for improving adult health and noncommunicable disease outcomes, most likely by increasing government accountability and responsiveness,” the study said.

The researchers used data from the Global Burden of Diseases, Injuries, and Risk Factors Study; V-Dem; and Financing Global Health databases. The data cover 170 countries from 1970 to 2015.

What Templin and her co-authors found was democracy was associated with better noncommunicable disease outcomes. They hypothesize that democracies may give higher priority to health-care investments.

HIV-free life expectancy at age 15, for example, improved significantly — on average by 3 percent every 10 years during the study period — after countries transitioned to democracy. Democratic experience also explains significant improvements in mortality from cardiovascular disease, tuberculosis, transportation injuries, cancers, cirrhosis and other noncommunicable diseases, the study said.

Watch: Some of the authors of the study discuss the significant their findings: 

What Templin and her co-authors found was democracy was associated with better noncommunicable disease outcomes. They hypothesize that democracies may give higher priority to health-care investments.

HIV-free life expectancy at age 15, for example, improved significantly — on average by 3 percent every 10 years during the study period — after countries transitioned to democracy. Democratic experience also explains significant improvements in mortality from cardiovascular disease, tuberculosis, transportation injuries, cancers, cirrhosis and other noncommunicable diseases, the study said.

Foreign aid often misdirected

And yet, this connection between fair elections and global health is little understood.

“Democratic government has not been a driving force in global health,” the researchers wrote.  “Many of the countries that have had the greatest improvements in life expectancy and child mortality over the past 15 years are electoral autocracies that achieved their health successes with the heavy contribution of foreign aid.”

They note that Ethiopia, Myanmar, Rwanda and Uganda all extended their life expectancy by 10 years or more between 1996 and 2016. The governments of these countries were elected, however, in multiparty elections designed so the opposition could only lose, making them among the least democratic nations in the world.

Yet these nations were among the top two-dozen recipients of foreign assistance for health.

Only 2 percent of the total development assistance for health in 2016 was devoted to noncommunicable diseases, which was the cause of 58 percent of the death and disability in low-income and middle-income countries that same year, the researchers found.

“Although many bilateral aid agencies emphasize the importance of democratic governance in their policy statements,” the authors wrote, “most studies of development assistance have found no correlation between foreign aid and democratic governance and, in some instance, a negative correlation.”

Autocracies such as Cuba and China, known for providing good health care at low cost, have not always been as successful when their populations’ health needs shifted to treating and preventing noncommunicable diseases. A 2017 assessment, for example, found that true life expectancy in China was lower than its expected life expectancy at birth from 1980 to 2000 and has only improved over the past decade with increased government health spending. In Cuba, the degree to which its observed life expectancy has exceeded expectations has decreased, from four-to-seven years higher than expected in 1970 to three-to-five years higher than expected in 2016.

“There is good reason to believe that the role that democracy plays in child health and infectious diseases may not be generalizable to the diseases that disproportionately affect adults,” Bollyky said. Cardiovascular diseases, cancers and other noncommunicable diseases, according to Bollyky, are largely chronic, costlier to treat than most infectious diseases, and require more health care infrastructure and skilled medical personnel.  

The researchers hypothesize that democracy improves population health because:

1. When enforced through regular, free and fair elections, democracies should have a greater incentive than autocracies to provide health-promoting resources and services to a larger proportion of the population;
2. Democracies are more open to feedback from a broader range of interest groups, more protective of media freedom and might be more willing to use that feedback to improve their public health programs;
3. Autocracies reduce political competition and access to information, which might deter constituent feedback and responsive governance.

Various studies have concluded that democratic rule is better for population health, but almost all of them have focused on infant and child mortality or life expectancy at birth.

Over the past 20 years, the average country’s increase in democracy reduced mortality from cardiovascular disease by roughly 10 percent, the authors wrote. They estimate that more than 16 million cardiovascular deaths may have been averted due to an increase in democracy globally from 1995 to 2015. They also found improvements in other health burdens in the countries where democracy has taken hold: an 8.9 percent reduction in deaths from tuberculosis, a 9.5 percent drop in deaths from transportation injuries and a 9.1 percent mortality reduction in other noncommunicable disease, such as congenital heart disease and congenital birth defects.

“This study suggests that democratic governance and its promotion, along with other government accountability measures, might further enhance efforts to improve population health,” the study said. “Pretending otherwise is akin to believing that the solution to a nation’s crumbling roads and infrastructure is just a technical schematic and cheaper materials.”

The other researchers who contributed to the study are Matthew Cohen, Diana Schoder, Joseph Dieleman and Simon Wigley, from CFR, the University of Washington-Seattle and Bilkent University in Turkey, respectively.

Funding for the research came from Bloomberg Philanthropies and the Bill & Melinda Gates Foundation. Stanford’s Department of Health Research and Policy also supported the work.

Something as simple as, "Are you taking your medications?" could conceivably prolong a life.

The study, detailed in a new working paper released this week by the National Bureau of Economic Research, was co-authored by Petra Persson, an assistant professor of economics; Maria Polyakova, an assistant professor of health economics at Stanford School of Medicine and core faculty at Stanford Health Policy; and Yiqun Chen, a doctoral student in health economics at Stanford School of Medicine. Persson and Polyakova are both faculty fellows at the Stanford Institute for Economic Policy Research (SIEPR).

Their study tackles the issue of health inequality and specifically examines the effects of having access to informal health expertise by having a doctor or nurse in the family. It finds that those with relatives in the health profession are 10 percent more likely to live beyond age 80. They are also significantly less likely to have chronic lifestyle-related conditions, such as heart attacks, heart failure and diabetes.

Younger relatives within the extended family also see gains: They are more likely to have been vaccinated, and they have fewer hospital admissions and a lower prevalence of drug or alcohol addiction.

In addition, the closer the relatives are to their familial medical source – either geographically or within the family tree – the more pronounced the impact of the health benefits, according to the findings.

The researchers used data from Sweden, where lotteries were used in the early 2000s to break ties among equally qualified applicants for admission into medical schools. The researchers then compared the health of the family members of lottery winners against lottery losers – a setup similar to a randomized control trial.

The strong findings of health benefits funneled from a familial sphere of medical knowledge suggest it would be worth ramping up access to health expertise in our health care system, the researchers say.

A doctor, for instance, could prescribe statins – a type of drug known to lower the risk of heart attacks – but whether the patient continues taking it from day to day is a decision made at home.

“Our work shows that there is a lot of value in trying to improve people’s decisions about their investment in their own health,” Persson says.

“If the government and health care system, including public and private insurers, could mimic what goes on inside families, then we could reduce health inequality by as much as 18 percent,” she says, referring to a main finding of the study.

Intra-family transmissions of health-related expertise might encompass frequent nagging to adhere to prescribed medications, get vaccinations or refrain from smoking during pregnancy, and “these behavioral changes are – from a society’s perspective – simple and cheap,” the study states.

Disparity despite access

The study also reveals limitations to the impact of equal access to medical care, underscoring the importance of other health efforts.

The researchers compared mortality data of Sweden – where there is universal access to health care – to the United States. They found the overall mortality was lower in Sweden but the level of health inequality largely mirrored that of the United States. In Sweden, despite its extensive social safety net, the rich also live longer and the poor die younger. Specifically, among people alive at age 55, more than 40 percent of individuals at the bottom of the income distribution in Sweden will have died by age 80 – as opposed to fewer than 25 percent for those at the top of the distribution.

“This health inequality appears to be extremely stubborn,” Persson says. “We can throw a universal health insurance system at it and yet substantial inequality persists. So, is there anything else that can help us close that health gap between rich and poor?”

According to their latest research, yes.

Health effects from having a medical professional in the family were substantial and occurred across the income spectrum, according to the study. And because the effects from the exposure to medical expertise was often even stronger for those at the lower half of the income distribution, the researchers estimated that information-driven behaviors could make a significant difference in getting rid of health disparities.

Closer ties, less churn

The study did not examine the complexity of family dynamics or specific actions that led to the positive health effects, but the researchers hypothesize that the mere presence of a medical professional in the family translates somehow to either a heightened health culture or, at least, having a coach of sorts to encourage healthy, good-patient behavior.

Although general public health campaigns (e.g., “Get Your Flu Shot Today!”) may not carry the same level of influence as intimate dinner-table discussions or persistent prodding among family members, there could be other ways society can improve its exposure to medical expertise to lead to healthier, longer lives, the researchers say.

Community health worker or nurse outreach programs can perhaps lead to more targeted, personalized communication efforts, they say. Digital nudges delivered through mobile phone apps could potentially make healthy dents.

Reminders of preventive care can also come by way of closer patient-doctor relationships and more consistent, longer-term ties to the same doctor.

“The idea of continuity of care and developing a true relationship with your doctor, who becomes someone who pays attention to you as an individual and sees you and your family over a long period of time, is well known,” Polyakova says. “Today, it’s what they might call old-fashioned primary care, where the whole family goes to the same doctor for many years. Many countries, the U.S. included, appear to be moving increasingly away from this model, and our results suggest that we might want to do the reverse.”

The finding of how a closer family connection or closer proximity leads to even stronger health outcomes helps substantiate the potential difference a closer bond between any doctor and patient could make – improvements that would be hard to glean from rushed and infrequent medical appointments, Persson and Polyakova say.

Communication-focused health initiatives don’t have to come with hefty price tags either, they say.

“We pour a lot of resources into getting even fancier machines inside hospitals, but the things that are making a difference here are not that expensive,” Persson says of their findings. “These are cheap, easily scalable preventative investments that are translating to gains in longevity, which is remarkable.”

Sweden’s medical school lotteries

Using large-scale data from Sweden, the researchers focused on quantifying the role of informal exposure to health expertise via a medical professional in the family while avoiding results that would be muddled with other differences between individuals with and without a doctor in the family.

The researchers used two different approaches. First, they took advantage of the fact that in some years, lotteries were used to break ties among equally qualified applicants to Sweden’s medical schools. This allowed the researchers to use medical school application records and track the health of family members of applicants who won and lost the lottery.

The researchers looked at more than 30 years of continuous health and tax records spanning four generations of family members, and examined health-related outcomes of the extended family members of newly trained doctors and nurses – including their siblings, parents, grandparents, children, aunts, uncles, cousins and in-laws.

Second, researchers sought to double-check whether higher income and higher social status associated with the medical profession had anything to do with the positive health benefits they found.

One of the ways they did this was to draw a comparison to lawyers, a similarly paid profession. The parents of doctors, they found, were 16 percent more likely to be alive than the parents of lawyers 20 years after their children matriculated. The parents of doctors also faced lower prospects of lifestyle-related chronic diseases.

In addition to the higher likelihood of their parents living past age 80 and the lower likelihood of heart diseases, the relatives of health professionals showed higher levels of preventive behaviors, including purchases of heart and blood-thinning medications, and vaccinations for HPV, or human papillomavirus. Younger family members also had fewer hospital admissions and addiction cases.

“People with health professionals in the family essentially make preventative investments that everyone should be doing,” Persson says.

Americans know that choosing a health insurance plan can tough. And once you’re retired and possibly on a limited or fixed income, it can become downright brutal.

Stanford Health Policy’s M. Kate Bundorf and Maria Polyakova and their colleagues set out to develop an online decision-support tool to test whether machine-based expert recommendations would influence choice among Medicare Part D enrollees — and make it easier.

“The use of technology seems like a natural way to address the challenges of choosing among plans,” they write in their study published in Health Affairs.

Medicare beneficiaries have been choosing among Medicare Advantage and Part D prescription drug plans for years, and more recently the Affordable Care Act established health insurance marketplaces for those who are younger than 65.

All that choice is supposed to create incentives for plans to offer a variety of low-cost, high-quality products that allow people to choose the plan that best meets their needs.

But sometimes too many good choices can lead to bad outcomes.

“Health insurance is a complex financial product with complicated cost-sharing rules, and the implications of different benefit designs for out-of-pocket spending and health care use vary across consumers depending on their needs,” wrote Bundorf, chief of the Department of Health Research and Policy and an associate professor of medicine at Stanford Medicine.

Another researcher in the study was Albert Chan, chief of digital patient experience and an investigator at Sutter Health, in Palo Alto, as well as an adjunct professor at the Stanford Center for Biomedical Informatics Research. Ming Tai-Seale, a professor of family medicine and public health at University of California San Diego, was also a principal investigator of the study.

Choosing Health Plan is Complicated

“Consistent with these challenges, researchers have documented that many consumers, both young and old, do not understand the characteristics of their plans,” they wrote in the March issue of Health Affairs, which is holding a public briefing on patients-as-consumers at the National Press Club on March 5th. Bundorf will present their research at the briefing in Washington, D.C., which will be streamed live and will be posted here once it has aired.

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“(Patients) often make decisions that may signal inaccurate evaluation of the costs and benefits of coverage — such as staying in their plan when better options are available, not enrolling in the plan that provides the best coverage for their drugs, or enrolling in plans that are objectively inferior to other available choices,” the authors wrote.

The Centers for Medicare and Medicaid Services (CMS) offers a tool to help beneficiaries choose among plans, but older adults — even those with high levels of formal education — find it difficult to use.

So, the research team developed a decision-support software tool called CHOICE to assist Medicare beneficiaries in choosing a Part D prescription plan. The software automatically imported the user’s list of current drugs from their electronic medical records (allowing users to adjust the list if desired); the algorithm would then crunch the numbers to come up with three recommended plans which were likely to be the least expensive for the user.

The team then conducted a randomized trial of this software tool among 1,185 patients of the Palo Alto Medical Foundation (PAMF), a large health-care provider in Northern California. Fifty-four percent of those patients were women, 65 percent were white, and 54 percent were married. Living in the Bay Area, their income and education levels were fairly high: They lived in areas in which the median income is $106,808 and 54 percent of the population has a college degree or more education.

While not representative of the general population of seniors in the United States, the researchers emphasized that it was important to conduct this study among these potential users, who are more likely to respond positively to an interaction with a computer. If these users didn’t find this software helpful or user friendly, it would not likely be a useful tool to roll out across the country as a whole.

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The study participants received access to one of two versions of the CHOICE tool: expert recommendations or individual analysis. Both versions automatically imported information on patients’ prescription drugs from their electronic health records and combined it with information on plan benefit design to provide individually customized information on users’ likely spending on both premiums and prescription drugs in each of the stand-alone Part D plans available in their area. The version of CHOICE that offered expert recommendations combined this information with an explicit recommendation on which plans were best for the user.

Willing and Able

The researchers found that providing an online tool not only increased older adults’ satisfaction with the process of choosing a prescription drug plan, but they also spent more time choosing that plan.

“The most significant finding of our trial is that individually customized information alone didn’t seem to be enough,” Bundorf, who is also a senior fellow at the Stanford Institute for Economic Policy Research (SIEPR), said in an interview. “The tool we developed was most effective when individually customized information paired with a clear-cut algorithmic expert recommendation that highlighted three plans that the computer thought were the best for the user based on total spending for prescription drugs.”

She said she was surprised to see that people spent more time choosing a plan and were more satisfied with the process when they had access to the CHOICE tool.

“Prior to our trial, I thought people might spend less time choosing a plan when they had access to expert recommendations because it would make the process easier,” Bundorf said. “But taken together, these results suggest that people are more engaged in decision-making when they have access to a patient-centered tool.”

Polyakova, who is also a faculty fellow at SIEPR, said a key takeaway from the trial is that people who are likely to use sophisticated tools are already more likely be more sophisticated shoppers of health care and prescription plans.

To prescribe or not prescribe? In the realm of the nation’s opioid epidemic, it’s an important question.

Research has shown that inappropriate use of prescription opioids is part of the reason behind a dramatic rise in opioid-related deaths since 2000. By 2015, the amount of opioids prescribed in the U.S. had tripled — enough for every American to be medicated around the clock for three weeks, at 5 milligrams of hydrocodone every four hours. 

Now, new research by a trio of Stanford scholars shows how different insurance strategies affect the volume of opioid use and could help stem inappropriate prescribing behaviors. 

The study, released in a working paper by the National Bureau of Economic Research, was co-authored by Stanford Health Policy’s Laurence C. Baker, M. Kate Bundorf, and Daniel P. Kessler. Baker and Bundorf are professors in the Department of Health Research and Policy at the Medical School; Kessler is a professor in the Law School and Graduate School of Business, and a senior fellow at the Hoover Institution.  All are also senior fellows at the Stanford Institute for Economic Policy Research (SIEPR).

Their study — the first to investigate the effect of the form of Medicare drug coverage on opioid use — found that enrollment in Medicare Advantage, a combined medical and drug insurance plan, significantly reduces the likelihood of beneficiaries filling an opioid prescription, as compared to enrollment in a stand-alone drug plan.

Compared to beneficiaries enrolled in stand-alone plans, those enrolled in the integrated Medicare Advantage plan were 37 percent less likely to get an opioid prescription, according to their analysis of drug claims from 2014.

The researchers also found that enrollment in integrated insurance coverage under Medicare Advantage had a disproportionate effect on the likelihood of filling an opioid prescription from the nation’s highest opioid-prescribing doctors — the top 1 percent of prescribers in Medicare Part D. The lower likelihood of prescriptions from these high prescribers to Medicare Advantage enrollees accounted for more than half of the reduction, according to their findings.

To understand the scope of this health plan-related effect and what’s at stake, consider the backdrop laid out in the study:

Since its implementation in 2006, Medicare Part D has become the nation’s largest purchaser of prescription opioids. More than 42 million Americans are enrolled in Medicare Part D — either under the stand-alone drug plan or the integrated Medicare Advantage plan.

What’s more, opioid prescriptions are concentrated among a relatively small group of “high prescribers.” 

According to research published in the 2016 edition of JAMA Internal Medicine, more than one-third of opioid prescriptions under Medicare Part D were made by about 8,000 doctors, making up the top 1 percent of prescribers. And according to the Office of the Inspector General of the Department of Health and Human Services, “extreme use” and “questionable prescribing” have put almost 90,000 beneficiaries at serious risk for opioid misuse or overdose.

Because the researchers did not examine patient health outcomes, they could not definitively determine that enrollment in Medicare Advantage reduced only inappropriate opioid use. However, because the reduction in opioid use came disproportionately from high prescribers, and previous work has found that Medicare Advantage enrollees had higher prescription drug use overall, the reduction in use that the researchers found was targeted rather than a result of a broader effort to restrict access to treatment.  

The researchers’ results support the conclusions of previous work that integration of prescription drug coverage with the other benefits provided by Medicare Advantage plans

improves the quality of care. Further study will be needed to drill deeper into the reasons behind the impact of Medicare Advantage plans, and whether a similar effect occurs in non-elderly populations, the researchers said.

The national opioid epidemic has grown at such breakneck speed that public health experts have been left scrambling to keep up. Though they understand the reasons behind the abuse — the solutions are complicated and costly.

Yet there appears to be some success at reducing at least one area of opioid abuse.

In new research by Health Research and Policy’s Eric Sun, the risk for chronic opioid use among patients with musculoskeletal pain actually decreased slightly between 2008 and 2014. 

The Stanford Medicine assistant professor of anesthesiology and pain medicine found that measures such as avoiding opioid use soon after diagnosis can further reduce the risk of addiction, especially among patients at highest risk for chronic opioid use.

"We found that early opioid use after diagnosis is predictive of opioid use longer term, suggesting that it may be prudent to minimize opioid use where possible for patients with musculoskeletal pain,” said Sun, whose research was published earlier this week in the Annals of Internal Medicine.

His co-authors are Jasmin Moshfegh, who is working on her PhD in health policy, and Steven Z. George, director of musculoskeletal research at Duke University School of Medicine.

Patients with lower back or chronic neck, shoulder and knee pain are at the highest risk for opioid abuse since pain meds are typically prescribed to help ease their spasms. 

Patients who suffer musculoskeletal pain may unwittingly transition to chronic opioid use, which means filling 10 or more prescriptions or having a supply for at least 120 days. The prescription drugs include hydrocodone, hydromorphone, methadone, morphine, oxymorphone, and/or oxycodone. Those don’t include heroin and synthetic opioids such as fentanyl.

Sun and his fellow researchers at the Stanford University School of Medicine used a large health-care database to assess the risk and risk factors for chronic opioid use among more than 400,000 “opioid-naïve” patients — those who have never been prescribed painkillers before — recently diagnosed with pain in the knee, neck, lower back or shoulder. 

The sample was restricted to privately insured patients, thereby excluding other policy-relevant populations, such as those who were prescribed pain medications under Medicare or Medicaid.

They found that risk for chronic opioid use ranged from 0.3 percent for knee pain to 1.5 percent for multiple-site pan and decreased for some anatomical regions during the timeframe studied. They discovered a relative decline of 25 to 50 percent across all pain types from 2008 to 2014.

Opioid Abuse

Opioid abuse has its roots in the late 1990s when pharmaceutical companies assured the medical community that patients would not become addicted to pain relievers. Clinicians began prescribing them at greater rates because they worked so well and seemed safe.

Today, more than 130 people die every day from opioid-related drug overdoses from prescription pain relievers, heroin and synthetic opioids such as fentanyl, according to the U.S. Department of Health and Human Services, From 2002 to 2017, there was more than a fourfold increase in opioid deaths, with some 49,000 people dying in 2017.

The Centers for Disease Control and Prevention estimates that the total economic burden of prescription opioid misuse alone in the United States is $78.5 billion a year, including the costs of health care, lost productivity, addiction treatment and criminal justice involvement.

“While our research found that only about 1 percent of patients with musculoskeletal pain progress to chronic opioid use, this is potentially concerning because it’s an extremely common diagnosis,” Sun said. “By pointing out the scope of the issue and identifying factors that place patients at risk, we hope this research will guide further efforts aimed at reducing opioid use among patients with musculoskeletal pain.” 

People who are acquainted with the work of Shorenstein APARC’s Asia Health Policy Program (AHPP) may be aware of the Innovation for Healthy Aging collaborative research project led by APARC Deputy Director and AHPP Director Karen Eggleston. This project, which identifies and analyzes productive public-private partnerships advancing healthy aging solutions in East Asia and other regions, encompasses an upcoming volume, co-authored by Eggleston with Harvard University professors Richard Zeckhauser and John Donohue, about public and private roles in governance of multiple sectors in China and the United States, including health care and elderly care. This volume, however, is not the first collaboration between Eggleston and Zeckhauser.

Zeckhauser, the Frank P. Ramsey Professor of Political Economy at Harvard University’s Kennedy School, is known for his many policy investigations that explore ways to promote the health of human beings, to help markets work more effectively, and to foster informed and appropriate choices by individuals and government agencies. In 2006, Eggleston and Zeckhauser co-wrote a paper about antibiotic resistance as a global threat, an issue that has since received much attention as it has become a critical public health and public policy challenge. Zeckhauser was a pioneer in framing antibiotic resistance as a global threat.

On October 20, 2018, Eggleston was among some 150 colleagues, students, and friends who participated in a special symposium at the Kennedy School to celebrate Zeckhauser’s 50th anniversary of teaching and research, and to anticipate what the next 50 years might bring in the multiple fields he has influenced throughout his long career.

Eggleston joined the first of two panels in that symposium, where she spoke about Zeckhauser’s impact on health policy and about what academics and policymakers should be tackling next on the path to addressing the global threat of antibiotic resistance.

The panel was moderated by Harvard Professor Edward Glaeser. In addition to Eggleston, it included Jeffrey Liebman, Daniel Schrag, and Cass Sunstein.

A video recording of the panel is made available by the Kennedy School. Listen to Eggleston’s remarks (beginning at the 8:42 and 36:20 time marks):

A cutting-edge treatment for blood cancer in children with promising short-term remission rates has nevertheless come under intense scrutiny due to its unprecedented cost.

Acute lymphoblastic leukemia (ALL) is the most commonly diagnosed pediatric cancer. Though treatment advances have driven five-year survival rates above 90 percent, relapse is common and ALL remains a leading cause of death from childhood cancer. Those surviving relapse typically require hematopoietic stem cell transplant (HSCT) to remain in remission.

The Food and Drug Administration last year approved tisagenlecleucel as the first anti-CD19 CAR T-cell therapy for relapsed or refractory pediatric ALL. While tisagenlecleucel-induced remission rates are encouraging compared with those of established therapies — more than 80 percent compared with less than 50 percent — a one-time infusion costs $475,000.

That makes it one of  the most expensive oncologic therapies out there, even though no studies exist to show how the therapy maintains remission in the long term.

So Stanford Health Policy’s John K. Lin, Jeremy Goldhaber-Fiebert and Douglas K. Owens, in collaboration with Kara Davis, an assistant professor of pediatrics at Stanford’s Lucile Packard Children’s Hospital, set out to determine whether the treatment is cost-effective. 

Their study was recently published in the Journal of Clinical Oncology.

“CAR-T cells are an exciting new therapy to help us cure more patients with ALL,” said Davis. “They use a patient’s own immune system to precisely target their leukemia and remission rates are impressive for patients with relapsed disease.”

The researchers note, however, it remains unknown whether tisagenlecleucel is sufficient to cure relapsed or refractory disease without a transplant.

Not only is it a very expensive treatment, it also has expensive and serious side effects, such as cytokine release syndrome, which can cause symptoms ranging from fevers and muscle aches to lethal drops in blood pressure and difficulty breathing, requiring ICU-level care.

“Given [its] high cost and broad applicability in other malignancies, a pressing question for policymakers, payers, and clinicians is whether the therapy’s cost represents reasonable value,” the authors wrote.

In order to evaluate the economic value of tisagenlecleucel, the authors created a computer simulation that modeled children with relapsed or refractory ALL. Since the durability of the therapy’s effects are unknown, they evaluated the therapy at different levels of long-term effectiveness.

Through their analyses, the authors found that at the simulation’s most optimistic projections, patients receiving tisagenlecleucel would, on average, live over a decade longer than those receiving alternative therapies. At these projections, the therapy would be cost-effective. However, at more modest long-term outcomes, its clinical and economic benefits declined.

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“The durability of CAR-T cell therapy is the main question. For many children with relapsed or refractory ALL, their disease is fatal — if the therapy results in sustained remissions, it would represent an important advance,” said lead author Lin, who is a VA Health Services Research and Development Fellow at Stanford Health Policy.

In the end, the researchers concluded that at tisagenlecleucel’s current price, its economic value is “uncertain,” as the true cost-effectiveness depends on its long-term performance, which has yet to be determined. They noted that substantial price reductions would improve its cost-effectiveness even if its long-term performance is relatively modest.

“A commonly asked question for many expensive, novel therapies is why can’t prices be lowered at least until we know how well they work,” said Goldhaber-Fiebert. 

The “Catch-22” here is that long-term effectiveness data are needed to justify a drug’s price, but current uncertainty about its effectiveness, along with its high price, means developing the data to justify its price occurs much more slowly.

“CAR-T is an individually tailored treatment that has thus far been produced for a relatively small number of patients,” Goldhaber-Fiebert said. “Its current production costs may well be very high, and certainly the companies that have spent heavily on its research and development are interested in achieving returns on their investments.”

When the effectiveness of a therapy is uncertain, some pharmaceutical companies and health policy experts have proposed something called outcomes-based payment, which is essentially a “money-back guarantee” if the therapy doesn’t work as intended.

Novartis, which developed tisagenlecleucel, has a money-back guarantee; if the patient does not achieve initial remission within the first month, they are not responsible for the payment of the therapy.

“However, we find that because most children have an initial remission, this does not materially improve cost-effectiveness,” Lin said.

He suggested that if the money-back guarantee were extended to see whether the patient relapses within a year, such a guarantee would improve the treatment’s cost-effectiveness.

The other co-authors of the study are James I. Barnes, Alex Q.L. Robinson, Benjamin J. Lerman, Brian C. Boursiquot and Yuan Jin Tan.