Archive for the ‘epidemiology’Category

Testing treatments in policy

The students at the Woodrow Wilson School have a group blog on public policy called 14 Points. I’ve been helping promote the blog for a while but just got around to writing my first submission this week. It’s titled “Testing Treatments: Building a culture of evidence in public policy”. Here’s an excerpt:

Similar lessons can be gleaned from the history of surgical response to breast cancer. In The Emperor of All Maladies (2010), a new history of cancer, oncologist Siddhartha Mukherjee chronicles the history of such failed interventions as the radical mastectomy. Over a period of decades this brutal procedure – removing the breasts, lymph nodes, and much of the chest muscles – became the tool of choice for surgeons treating breast cancer. In the 1970s rigorous trials comparing radical mastectomy to more limited procedures showed that this terribly disfiguring procedure did not in fact help patients live longer at all. Some surgeons refused to believe the evidence – to believe it would have required them to acknowledge the harm they had done. But eventually the radical mastectomy fell from favor; today it is quite rare. Many similar stories are included in a free e-book titled Testing Treatments (2011).

As a society we’ve come to accept that medical devices should be tested by the most rigorous and neutral means possible, because the stakes are life and death for all of us. Thousands of people faced with deadly illnesses volunteer for clinical trials every year. Some of them survive while others do not, but as a society we are better off when we know what actually works. For every downside, like the delay of a promising treatment until evidence is gathered properly, there is an upside – something we otherwise would have thought is a good idea is revealed not to be helpful at all.

Under normal circumstances most new drugs are weeded out as they face a gauntlet of tests for safety and efficacy required before FDA licensure. The stories of the humanitarian-exemption stent and the radical mastectomy are different because these procedures became more widely used before there was rigorous evidence that they helped, though in both cases there were plenty of anecdotes, case studies, and small or non-controlled studies that made it look like they did. This haphazard, post-hoc testing is analogous to how policy in many other fields, from welfare to education, is developed. Many public policy decisions have considerable impacts on our livelihoods, education, and health. Why are we not similarly outraged by poor standards of evidence that leads to poor outcomes in other fields?

Read the rest at 14 Points, and check out the posts by my classmates.


12 2011


I highly recommend Patient Zero, the  latest episode of the podcast RadioLab. It covers Typhoid Mary, the origin of HIV, and the diffusion of ideas. Evocative as always, but what I like the most is how they add new information to stories you think you know. For one, you really feel sorry for Mary. And I’ve read quite a bit on the origin of HIV (a great way to learn more about phylogenetics!) but RadioLab takes it back even further and highlights some research I hadn’t seen.

Related: I haven’t read it yet, but Tyler Cowen really likes Jacques Pepin’s new book, The Origin of AIDS more happy reading for Christmas break.


11 2011

Discarding efficacy?

Andrew Grove, former CEO of Intel, writes an editorial in Science:

We might conceptualize an “e-trial” system along similar lines. Drug safety would continue to be ensured by the U.S. Food and Drug Administration. While safety-focused Phase I trials would continue under their jurisdiction, establishing efficacy would no longer be under their purview. Once safety is proven, patients could access the medicine in question through qualified physicians. Patients’ responses to a drug would be stored in a database, along with their medical histories. Patient identity would be protected by biometric identifiers, and the database would be open to qualified medical researchers as a “commons.” The response of any patient or group of patients to a drug or treatment would be tracked and compared to those of others in the database who were treated in a different manner or not at all.

Alex Tabarrok of Marginal Revolution (who is a big advocate for FDA reform, running this site) really likes the idea. I hate it. While the current system has some problems, Grove’s system would be much, much worse than the current system. The biggest problem is that we would have no good data about whether a drug is truly efficacious, because all of the results in the database would be confounded by selection bias. Getting a large sample size and having subgroups tells you nothing about why someone got the treatment in the first place.

Would physicians pay attention to peer-reviewed articles and reviews identifying the best treatments for specific groups? Or would they just run their own analyses? I think there would be a lot of the latter, which is scary since many clinicians can’t even define selection bias or properly interpret statistical tests. The current system has limitations, but Grove’s idea would move us even further from any sort of evidence-based medicine.

Other commenters at Marginal Revolution rightly note that it’s difficult to separate safety from efficacy, because recommending a drug is always based on a balance of risks and benefits. Debilitating nausea or strong likelihood of heart attack would never be OK in a drug for mild headaches, but if it cures cancer the standards are (and should be) different.

Derek Lowe, a fellow Arkansan who writes the excellent chemistry blog In The Pipeline, has more extensive (and informed) thoughts here.

Update (1/5/2012): More criticism, summarized by Derek Lowe.

Happy Hep Day

Today is the first ever WHO-sponsored World Hepatitis Day:

These successes and challenges are amplified because viral hepatitis is not a single disease. Hepatitis is caused by at least five viruses—including two spread by water or food contaminated with feces(hepatitis A and E) and three transmitted by blood and body fluids (hepatitis B, D, and C) during childbirth (from infected mother to child); through injecting drug use, needle sticks, or transfusions; or through sexual contact. Hepatitis B and C infections can cause cirrhosis of the liver and lead to liver cancer.

Today, more than 500 million persons worldwide are living with viral hepatitis and do not have adequate access to care—increasing their risk for premature death from liver cirrhosis and liver cancer. Each year, more than 1 million people die from viral hepatitis and millions of new infections add to this global burden of disease and death.

It is not, however, the first ever World Hepatitis Day – it’s just the first one recognized by WHO. Many of these international attention-raising events grow out of smaller things which pick up steam and eventually get official recognition from international organizations. It turns out that World Hepatitis Day has been going on for several years.

On a related note, did you know that Hep B is a cause of discrimination in China, and that there is a burgeoning carriers’ rights movement? I didn’t either until I started browsing the impressively worked out Wikipedia Hepatitis B page (some epidemiologist had a field day) and found that there’s an entire page for Hep B in China. An excerpt:


Hepatitis B sufferers in China frequently face discrimination in all aspects of life and work. For example, many Chinese employers and universities refuse to accept anyone who tests positive. Some kindergartens refuse admission to children who are carriers of the virus. The hepatitis problem is a reflection of the vast developmental gap between China’s rural and urban areas. The largest problem facing Chinese people infected with HBV is that illegal blood testing is required by most employers in China.[17] Following an incident involving a Hepatitis B carrier’s killing of an employer and other calls against discriminatory employment practices, China’s ministries of health and personnel announced that Hepatitis B carriers must not be discriminated against when seeking employment and education.[18] While the laws exist to protect the privacy of employees and job seekers, many believe that they are not enforced.

“In the Hepatitis B Camp”

“In the Hepatitis B Camp” is a popular website for hepatitis B carriers’ human rights in China. Its online forum is the world’s biggest such forum with over 300,000 members. The website was first shut down by the Chinese government in November 2007. Lu Jun, the head of the rights group, managed to reopen the website by moving it to an overseas server, but the authorities in May 2008 began blocking access to the website within China, only 10 days after government officials participated in an event for World Hepatitis Day at the Great Wall of China. An official had told the head of the rights group, Lu Jun, at the time that the closure was due to the Beijing Olympic Games.[19]

(h/t to Tom)


07 2011

Football epidemiology

In an attempt to prove Cowen’s First Law — “there is literature on everything” — I enjoy highlighting unusual epidemiological studies (see tornado epidemiology, for one.) These studies may seem a bit odd until you start thinking like an epidemiologist: measurement is the first step to control.

The latest issue of Pediatrics has a new study by Thomas et al. on the “Epidemiology of Sudden Death in Young, Competitive Athletes Due to Blunt Trauma.” Some of the methods seem a bit sketchy, but that’s kind of the authors’ point as they note,

“without a systematic and mandatory reporting system for sudden cardiac deaths in young competitive athletes, the true absolute number of these events that occur in the United States cannot be known.”

While this study is mostly concerned with the sudden deaths not caused by cardiac events, the same principle holds true: if anything, the problem is under-reported.

Thomas et al. use 30 years of data from the “US National Registry of Sudden Death in Young Athletes,” looking at 1980–2009. Deaths in the database came from a variety of sources including LexisNexis searches, news media accounts assembled by other commercial search services, web searches, reports from the US Consumer Product Safety Commission and the National Center for Catastrophic Sports Injury Research, and direct reports from schools and parents.

Of the total deaths included in the study, about 261 were caused by trauma, or around 9 deaths per year. 57% of the 261 deaths were in a single sport, football. Notably, there were about four times as many deaths due to cardiac causes as to trauma.

In football they find defensive positions have more deaths than offensive positions, “presumably because such players commonly initiate and deliver high-velocity blows while moving toward the point of contact.” While the majority of deaths were in defensive players, the single most represented position was running backs.

Why the focus on deaths in young athletes? The authors note by comparison that lightning causes about 50 deaths per year, and motor vehicle injuries case 12,000 deaths per year. (Aside: You can tell the authors don’t work in injury prevention since they say “motor vehicle accident” rather than “injury” — injury prevention researchers prefer the latter terminology because they believe “accidental” deaths sound unavoidable.) The authors explain their own focus by noting that these sudden deaths attract “considerable media attention, with great importance to the physician and lay communities, particularly given the youthful age and apparent good health of the victims.”

In related news: “The Ivy League [announced that…] in an effort to minimize head injuries among its football players, it will sharply reduce the number of allowable full-contact practices teams can hold.”


07 2011

Measles is big this year

The CDC just put out a Health Advisory describing measles’ big comeback. Though endemic transmission is the US has been interrupted, but importations keep happening when the unvaccinated population travels or come into contact with travelers:

The United States is experiencing a high number of reported measles cases in 2011, many of which were acquired during international travel. From January 1 through June 17 this year, 156 confirmed cases of measles were reported to CDC. This is the highest reported number since 1996. Most cases (136) were associated with importations from measles-endemic countries or countries where large outbreaks are occurring. The imported cases involved unvaccinated U.S. residents who recently traveled abroad, unvaccinated visitors to the United States, and people linked to these imported cases. To date, 12 outbreaks (3 or more linked cases) have occurred, accounting for 47% of the 156 cases. Of the total case-patients, 133 (85%) were unvaccinated or had undocumented vaccination status. Of the 139 case-patients who were U.S. residents, 86 (62%) were unvaccinated, 30 (22%) had undocumented vaccination status, 11 (8%) had received 1 dose of measles-mumps-rubella (MMR) vaccine, 11 (8%) had received 2 doses, and 1 (1%) had received 3 (documented) doses.

Measles was declared eliminated in the United States in 2000 due to our high 2-dose measles vaccine coverage, but it is still endemic or large outbreaks are occurring in countries in Europe (including France, the United Kingdom, Spain, and Switzerland), Africa, and Asia (including India). The increase in measles cases and outbreaks in the United States this year underscores the ongoing risk of importations, the need for high measles vaccine coverage, and the importance of prompt and appropriate public health response to measles cases and outbreaks.

Measles is a highly contagious, acute viral illness that is transmitted by contact with an infected person through coughing and sneezing. After an infected person leaves a location, the virus remains contagious for up to 2 hours on surfaces and in the air. Measles can cause severe health complications, including pneumonia, encephalitis, and death.

The message is simple: parents should vaccinate their children because not doing so has serious health effects not only on those children, but also on those who are unable to be vaccinated because they are either too young or have medical contraindications. If everyone who believed (wrongly) that vaccines are unsafe would move to one country (let’s call it Unvaccinstan) then the choice would have fewer ethical pitfalls: you make a bad choice, and your kids might get sick. But as it is there are many people who simply can’t get vaccinated — kids with cancer for example, or kids in the window between when your maternal antibodies aren’t that effective against measles but still interfere with the vaccine — so the choice has much broader societal impact. I imagine that many of the parents who choose not to vaccinate — who are often of higher educational status and more liberal politics — view themselves  as virtuous; the reality is sadly the opposite.


06 2011

Lead poisoning in China

It’s a huge problem — the Times calls it a Hidden Scourge:

Here, Chinese leaders have acknowledged that lead contamination is a grave issue and have raised the priority of reducing heavy-metal pollution in the government’s latest five-year plan, presented in March. But despite efforts to step up enforcement, including suspending production last month at a number of battery factories, the government’s response remains faltering.

At a meeting last month of China’s State Council, after yet another disclosure of mass poisoning, Prime Minister Wen Jiabao scolded Environmental Minister Zhou Shengxian for the lack of progress, according to an individual with high-level government ties who spoke on the condition of anonymity.

The government has not ordered a nationwide survey of children’s blood lead levels, so the number of children who are at risk is purely a matter of guesswork. Mass poisonings like that at the Haijiu factory typically come to light only after suspicious parents seek hospital tests, then alert neighbors or co-workers to the alarming results.

And relevant to my current work, which I hope to write about more soon.


06 2011

Tornado epidemiology

The news out of Joplin, Missouri is heartbreaking, and it comes so quickly on the heels of the tornadoes that hit Tuscaloosa, Alabama. Central Arkansas, where I grew up, gets hit by tornadoes every spring, so I have plenty of memories of taking shelter in response to warnings. College nights with social plans ruined when we had to hunker down in an interior hallways. Dark, roiling clouds circling and the spooky calm when the rain and hail stop but the winds stay strong. Racing home from work to get to my house and its basement — a rarity in the South — before a particularly ominous storm hit. Neighboring communities were sometimes hit more directly by storms, and Harding students often participated in clean-up an recovering efforts, but my town was spared direct hits by the heaviest tornadoes.

So what does epidemiology have to say about tornadoes? Their paths aren’t exactly random, in the sense that some areas are more prone to storms that produce tornadoes. Growing up I knew where to take shelter: interior hallways away from windows if your house didn’t have a basement or a dedicated storm shelter. I also knew that mobile homes were a particularly bad place to be, and that the carnage was always worst when a tornado happened to hit a mobile home lot.

But there is some interesting research out there that tells us more than you might think. Obviously and thankfully you can’t do a randomized trial assigning some communities to get storms and others not, so the evidence of how to prevent tornado-related injury and death is mostly observational. What do we know? I’m not an expert on this but I did a quick, non-systematic scan and here’s what I found:

First, the annual tornado mortality rate has actually gone down quite a lot over the last few decades. That says nothing about the frequency and intensity of tornadoes themselves, which is a matter for meteorologists to research. The actual number deaths resulting from tornadoes would probably be a function of the number of people in the US, where they live and whether those areas are prone to tornadoes, the frequency and intensity of the tornadoes, and risk factors for people in the affected area once the tornado hits.

This NOAA site has the following graph of tornado mortality where the vertical axis is tornado deaths per million people in the US (on a log scale) and the horizontal axis covers 1875 – 2008.

Second, many of the risk factors for tornado injury and death are intuitive and suggest possible interventions to minimize risk in tornado-prone areas. Following tornadoes in North and South Carolina in 1984, Eidson et al. surveyed people hospitalized and family members of people who were killed, along with uninjured persons who were present when the surveyed individuals were hurt. The main types of injury were deep cuts, concussions, unconsciousness and broken bones. Risk factors included living in mobile homes, “advanced age (60+ years), no physical protection (not having been covered with a blanket or other object), having been struck by broken window glass or other falling objects, home lifted off its foundation, collapsed ceiling or floor, or walls blown away.” Some of those patterns might indicate potential tornado education interventions — better shelters for mobile home residents, targeting alerts to older residents, covering with a blanket, and staying in interior hallways, to say nothing of building codes to make more survivable structures.

Third, some things are less clear, like whether it’s safe to be in a car during a tornado. Daley et al. did a case-control study of tornado injuries and deaths in the aftermath of tornadoes in Oklahoma in 1999. They found higher risk of tornado death for those in mobile homes (odds ratio of 35.3, 95% CI 7.8 – 175.6) or outdoors (odds ratio of 141.2, 95% CI 15.9 – a whopping 6,379.8) compared to other houses. They found no difference in risk of death, severe injury, or minor injury among people in cars vs. those in houses. And they found that risk of death, severe injury, or minor injury was actually lower among those “fleeing their homes in motor vehicles than among those remaining.” That’s surprising to me, and contrary to much of the tornado-related safety warnings I heard from meteorologists and family growing up. I wonder if this particular study goes against the majority of findings, or whether there is a consensus based in data at all.

Fourth, our knowledge of tornadoes can be messy. One demographic approach to tornado risk factors (Donner 2007) is to look for correlations between tornado fatalities and injuries with rural population, population density, household size, racial minorities, deprivation/poverty, tornado watches and warnings, and mobile homes. Donner noted that “Findings suggest a strong relationship between the size of a tornado path and both fatalities and injuries, whereas other measures related to technology, population, and organization produce significant yet mixed results.”

That’s just a sampling of the literature on tornado epidemiology. The studies are interesting but relatively rare, at least from initial perusal. That’s probably because tornado deaths and injuries are relatively rare in the US. Still, the storms themselves are terrifying and they often wreak havoc on a single community and thus generate more sympathy and news coverage than a more frequent — and thus less extraordinary — problem like car crashes.

Update: NYT has an interesting article about tornado preparedness, including some speculation on why the Joplin tornado was so bad.


05 2011

Sentinel chickens

“In May 2000 Canadian Health authorities stationed cages of sentinel chickens along 2500 km (1550 miles) of the border with the United States in an effort to identify the presence of West Nile virus in susceptible animals before the disease was detected in humans in Canada. Ultimately, the sentinel chickens were key in detecting a new viral epidemic.”

Source here. And then there are “Super Sentinel” Chickens


03 2011


From a lab assignment for my Professional Epidemiology Methods course:

…but part of this exercise is to remember that public health practice does not happen in a vacuum.  And if you do your job well, nothing happens and you may be blamed for interrupting daily life activities.  If you do not do your job well, people get sick or die–and you still get blamed.


02 2011