The essence of epidemiologic field trials is the RCT (randomized control trial). A random set of people get some sort of treatment (like a new drug), another random set of people don’t and we compare the results. It’s pretty simple stuff.
The trouble with RCTs is that they don’t necessarily work well when people from the two groups are able to influence each other’s outcomes. As a simple example, a trial of a vaccine which prevents people from getting infected with some pathogen might have impacts on people who don’t get the vaccine, since the number of opportunities for transmission are reduced. This is a welcome outcome (and may even be the point of the study), but it doesn’t help us to understand exactly how effective the vaccine is in the individuals who actually receive the vaccine.
Many RCTs make the (flawed) assumption that individuals are independent entities, following a long tradition of statistical analysis. This is a reasonable assumption to make in some cases, but entirely wrong in others (i.e. most public health outcomes).
Development economists have recently adopted the RCT as a means of evaluating the effectiveness of programs intended to relieve poverty or improve human well-being. On the surface, there’s nothing wrong with adopted public health methods to deal with economic problems, as most public health problems have their roots in economics. Jeff Sachs, or course, would argue that many economic problems have their roots in public health problems.
The major problem with RCTs is that while we do our best to control for all of the possible other factors that might impact outcomes given a particular treatment, without a trove of detailed data and prior knowledge of context and contingencies, we really have no idea at all whether and how some public health intervention works. Epidemiology tends to fall back on the “reasonable suspicion” argument, backing up claims of effectiveness with potentially reasonable assumptions of causal pathways. This is clearly quite easy when doing drug trials, where animals models and a century-plus of medical research has given us a reasonably clear pictures of the pathophysiological pathways that might lie between drug and outcome.
But with issues of human behavior and economics (which is essentially a science which seeks to uncover mysteries of human behavior), the causal pathways are much more difficult to assess and the factors which lie between intervention and outcome are for more difficult to measure. For example, assessing the outcome of an education program on reproductive behavior is really, really difficult without monitoring all of the possible things that happened between the time that a woman attended an NGO sponsored event at a clinic and the time when she chose to use or not use a condom. In fact, we can’t even really verify that she used the condom, since we weren’t around to observe it.
But we assume, and assume to the point of falling back to faith that our efforts did what we intended them to do.
Lant Pritchett, a Harvard economist that I’m a great fan of for his work on economic measurement in developing countries, penned an interesting article on the website of the Center for Global Development seemingly questioning the merit of the RCT as an rigorous and necessary evaluation tool for poverty alleviation development programs.
First of all, the argument that RCTs had, until recently, been used sparingly, if at all, and yet are important in achieving good outcomes sits in kind of embarrassing counterpoint with the obvious fact that lots of countries have really good outcomes. That is whether one uses the Human Development Index or the OECD Better Life Index or any social indicator—from poverty to education to health to life satisfaction—there is a similar set of countries near the top. (In the HDI the top five are Norway, Australia, USA, Netherlands, and Germany. In the OECD Better Life Index they are Australia, Sweden, Canada, Norway, and Switzerland.) No one has ever made the arguments that these countries are developed and prosperous because they used rigorous evidence—much less RCTs—in formulating policy and programs. While one might have faith that RCTs can help along the path to development, RCTs didn’t help for those that are there now.
It is very true that development in the United States occurred without the help of RCTs. In fact, malaria elimination in the United States occurred without any of the complex set of interventions that we’re so desperately selling to malaria-endemic countries. It’s even true that, despite more than a decade of research on ITNs, that we aren’t really sure whether the declines in malaria that we’ve seen all over Sub-Saharan Africa are due to ITNs or just simply due to processes associated with urbanization and development (as in the US). Actually, a lot of research is telling us that the declines in malaria might be false and that we are simply suffering from a paucity of accurate measurement in malaria endemic countries.
And this is where Pritchett comes in. He’s right. Research in developing countries is inherently challenging to the point where the conclusions we draw from research are somewhat contentious at best, and the result of blind faith at worst.
But coarse and incomplete data and loose assumptions shouldn’t discourage public health (or even economic) professionals from doing research in developing countries. While I have issues with the condescending, neo-classical nature of RCTs in economics (another discussion, but can a peasant lady’s behavior in Western Kenya be reduced to that of Homo economicus? ), the truth is that policy makers don’t care about data. They care that people are making the case for action in an impassioned and convincing way. While academics should strive to be as rigorous as possible, the sell won’t happen based on our complex data collection strategies and statistical methodologies. They (and the public) are convinced through impassioned calls for action.
We went and visited Kwale, a relatively small community of Duruma and Digo in Eastern Kenya. I’ve been to so many of these African towns that I’m honestly somewhat bored. Five years ago, I might have been more excited. Perhaps I’m just tired.
People speak Swahili here. For real. In the rest of Kenya, Swahili is a language to connect disparate tribes, Kenyans happily mangle and make a mess of Swahili, but it does its job well enough. Here, I’m struck that even the kids speak Swahili, something you never see in other parts of Kenya.
I keep running into people who don’t speak anything but Swahili forcing me to communicate as best I can with my limited vocabulary. Fortunately, it’s all easy to understand out here.
But, to be honest, it’s quite boring out here. Life is fairly content, it lacks all of the huge and obvious problems of economics and health that persist in the rest of Kenya, and the ubiquity of Islam makes is a safe and tranquil place, if one is willing to ignore the oppressive patriarchy.
We spend the day at the hospital, meeting person after person. I’m growing agitated. Lunch is being pushed back later and later. I’m so bad at this, but its necessary and everyone is well meaning and kind.
Why are we doing this? All of Kenya’s problems are a failure of government. It’s not fashionable to say, but you can’t help but be annoyed when people spin the tired old narratives of colonialism and corruption. You guys voted these assholes in.
We finally get to lunch. I order pilau (mixed rice and beef) and some fried goat, knowing that it will be quick and we can be back on the road. Since he’s not paying, our Kenyan host orders to most expensive thing on the menu, the thing they never have prepared, the thing you have to wait an hour for. It’s hard not to be annoyed, but you just let it slide.
People are telling me what a great President Moi was, claiming that everything was ok during his reign. It was at the beginning, thanks to his predecessors, but his awful policies pushed Kenya to a horribly repressive one party state and spurred a complete collapse of the Kenyan economy, leaving the mess for his successors to clean up. In politics, timing is everything.
Now the entire health system has been devolved to the provincial governments. I’m thinking this is going to become a disaster of epic proportions. While the devolution of powers to local governments makes some sense in diverse and fractured Kenya, health problems usually don’t recognize political boundaries. A failure of health policy in HIV and malaria infested Nyanza could have devastating effects for Nairobi.
We’ve stopped in a tiny market center in the middle of nowhere. I say “shikamoo” to an old man, a respectful greeting reserved for elderly people. He asks me for 20 schillings. I’m having fun saying “shikamoo” to people younger than I am. It confuses the hell out of them.
The area is partially semi-arid and partially forested. Elephants come out of the national park and wander through the streets, I’m told. Baboons rifle through the trash. The areas close to the forest are doing better than the other areas, but there’s no real economy out here and the wildlife and igneous terrain prevent people from doing any substantial agriculture out here. The houses are in great shape, some even have power, but there’s malnutrition everywhere. The markets are mostly devoid of decent food outside of bags of rice trucked in from other areas. There are signs of American food aid and a World Food Program truck passes us.
A Japanese group is doing a survey on diet and malnutrition. It’s explained to me, but I think it’s pretty stupid. We already know that a lack of food causes malnutrition. They say they want to help. While I’m listening, though, I’m thinking that it’s a colossal waste of time and money. Perhaps it might be more helpful to come up with a better plan.
I realizing that this post is full of complaints, but here not every day is full of wonder and excitement.
We get dinner. It’s nyama choma (BBQ) again. I’m not disappointed but the conversation turns to Japanese academics. I can’t help but remark that I find a lot of it horribly uninteresting. I’m not sure why many of these groups do projects here, and even less sure what the tangible results will be, outside of raising the domestic status of ineffective Japanese researchers. Public health research really has to do one of two things. Either it should push science forward, or provide meaningful public health services to developing countries. The projects that are being described to me fail on both points. My anxiety level is high.
It’s time for me to stop complaining, though complaining is healthy and sometimes leads to substantive change. I’m getting ready to go to get some Ethiopian food at one of my favorite spots in Nairobi, Queen Sheba, which is run by Ethiopian refugees who fled the war there some years ago. Fortunately, it’s not expensive, unlike other places in Nairobi. See, the complaints never stop.
Does malaria facilitate the development of exploitative agricultural estates? Interview with Dr. Luis Chavez
My friend Luis just published a paper in PlosOne on land consolidation or the formation of “latifundia” in Spain. Latifundia were large agricultural estates owned by the Romans, often dependent on slave labor, the growth of which has been implicated in Rome’s fall.
Luis creates a mathematical model to describe the formation of these large estates. He then tests the hypothesis that malaria transmission exacerbated the situation, by forcing land owners to sell cheaply to opportunistic land owners in less malarious areas.
Luis, an ecologist who works on issues of disease transmission (and all around great guy), is somewhat unique in the world of quantitative sciences. He took a few minutes to talk to me so that you can see why.
Who are you and what’s your background?
If you ask the japanese they might say: O gata no hen na gaijinsan. As to my academic background, I studied biology/parasitology as an undergraduate, then mathematical ecology for a M.Sc. and then was granted a Ph.D. in ecology and evolutionary biology (note: at the University of Michigan).
Nevertheless, I have always been interested in the humanities, especially history since it gives the best vantage point to understand the present. I grew up in a household where mixing things/topics was usual. Both my father and grandfather went to grad school, something unusual in Latin America, and since i was child lunch time talk was heavy on the side of human rights and solidarity, science and the need for change. When Nelson Mandela died i remembered that a lovely family activity during my childhood was going to a cultural/educational event in solidarity with Nelson Mandela and the South African people to end the apartheid.
For lay people, what’s the paper about and what motivated you to explore it?
The paper presents a mathematical model that can explain the formation of latifundia (large estates) when the profitability of land varies across landowners in a landscape. The model is also used to show that when such differences are not present latifundia still can emerge if there are differences in the risk of acquiring an infectious diseases. I built the model based on historical records to show that both patterns have been observed in societies as different as “latin” Europe (Italy and Spain) and China.
What’s a “latifundium” in Spain? I dug around a bit and could find some things about Rome and Latin America, but not so much about Spain. Why choose Spain?
A latifundium is a large estate, which requires the labor of people that do not own the land. I chose Spain because a essay by Chantal Beauchamp presented a couple of striking maps showing that places where malaria was common were those where Latifundia were common during the 1930s (Fig. 2): http://www.persee.fr/web/revues/home/prescript/article/ahess_0395-2649_1988_num_43_1_283483
The pattern of association between malaria and latifundia was not new, but only Beauchamp had data amenable for a quantitative analysis.
Are you trying to say that malaria helped enable capitalist land appropriation?
It might be the case. The hypothesis that malaria helped to enable land appropriation was put forward by the great italian malariologist, Angelo Celli. He has a book on the topic [reference 8 in the paper, available at the UMICH SPH library]. Celli was probably the most advanced malaria epidemiologist at the turn of the 20th century.
Unfortunately, he and other italians [most notably Grassi] were blackbolded in the Anglo-Saxon world because they threatened the ego of Ronald Ross by saying malaria was not just due to a parasite transmitted by the bite of a mosquito [a biological fact that, nevertheless, they independently showed and published in Italian]. If you are interested just check the oldest records for malaria in the Nature archives.
Though issues of land tenure are very different in the US (given that we killed all the natives and stole it all), we did have some big and awful land plantations in the South along with a serious malaria problem. Might we also try to apply this to the United States, and, if so, how?
I think it might have helped to the consolidation of large estates in the south. Interestingly in the Midwest you never had the latifundia observed in the south, but you had malaria in Michigan (the midwest) at some point (See Humphreys M. 2001. Malaria: Poverty, Race, and Public Health in the United States. Baltimore (MD): Johns Hopkins University Press.).
Nevertheless, in the south due, for example, to Jim Crow laws there might have been a differential risk of malaria infection not observed in the Midwest. However, i found no data to go beyond speculation, well other that in the Canal Zone the Jim Crow housing organization showed the differential malaria risk: http://www.jstor.org/stable/10.1086/529265
I find these quantitative approaches to historical problems fascinating (I also started work on a paper on malaria in post-conflict Angola, maybe I should publish it). Do you think applying these methods to history as informative to present day problems? If so, how?
I think so, history probably gives the best vantage point to understand the present (Rendering history a tinker damn’s is a good strategy to sell things no matter if they are useful or even safe, Henry Ford was clear about this). In theory failures can be highly educational, something the model suggests is that equity in land tenure is an unstable equilibrium that could only be maintained by an external policy as the Chinese did before the An Lushan rebellion, and that any kind of unfair land redistribution could only be expected to not work (latifundia will be eventually formed), as observed over and over in most Latin American nations.
The mix of methods is rather novel. However, in the discipline focused and partitioned environment of academia, do you find that its hard to get an audience for this kind of work? Is there a future in it?
I can tell you this stuff is only suitable for publication on the Arxiv.org or PLoS One/ Springer Plus, if you want it to be peer reviewed and you don’t sign your paper with an address in Princeton or Oxford. I think the audience does not belong in any department, though scholars working on the diverse fields of ecology, health, sociology, maths, economics and even history might find it interesting. I think there is some future, there is the emerging field of cliodynamics that looks at historical dynamics and there is even a journal for cliodynamics where they, every once on a while, publish good food for thought like this paper: http://escholarship.org/uc/item/1ks0g7dr#page-1
I thought my data was not dynamical enough, so I didn’t try there.
This work is heavily political. Do you think there is a place for politics in science?
I think everything gets embedded in politics. Otherwise there would have been no shutdown in the CDC and other US government agencies few months ago, etc. I don’t think my work is more or less political than a risk factor analysis for lung cancer and smoking. I think i might be blackbolded by some of the references I cited, but to understand Capitalism even the Catholic Church is studying Marx [Funny the leading scholar is the Munich Bishop, whose last name is Marx]:
For those keeping up, you may remember that I spent the summer in Kenya, working with a team extracting blood samples from camels, cows, goats and sheep. We were in contact with all of these animals on almost a daily basis. We weren’t wearing any protection at all, but it’s inconceivable to wear a full hazmat suit while taking blood from goats in a Maasai community. You’d get laughed out of town.
My days right now are running in a fairly predictable pattern. I wake up, feel pretty good, eat breakfast and drink some coffee. At about 10-11 a.m. I begin to feel dizzy, sweat somewhat, a low grade fever kicks in and a horrible taste develops in my mouth. My peripheral vision is limited and I have trouble focusing on distant objects. It gets progressively worse throughout the day, but improves before dinner. After dinner, I feel worse than before. I’m positive that the brunt of the physical symptoms are associated with anemia. It’s like a low grade malaria.
The psychological effects are fascinating. Again, in the morning, I feel fine. As the day progresses, I am less and less able to string coherent sentences together (not that I’m good at it in the best of times), lose thoughts in mid sentence and can’t remember important vocabulary words. I’m stuck in an existential funk where the thought of tomorrow is dark, I’ve forgotten the past and the present isn’t all that meaningful. I often find myself staring into space and time passes quickly.
Though I have no other negative physical effects and am able to leave the house and move around, I’m finding this incredibly debilitating. Even writing this blog post is a challenge.
From the pathogen’s standpoint, this situation is ideal. It doesn’t immediately kill the host, and the bacteria tends to incubate in cells so that it can avoid the body’s immune response. If I were a herd animal, eating and defecating in the same space, I would be able to transmit for, conceivably, the rest of my life. The low grade anemia keeps the animal mobile, yet impedes its ability to evade predators, allowing transmission to occur from herbivorous ungulates to carnivorous animals.
Again, because the bacteria hides out in cells, it’s a bear to kill. I have two months of two types of antibiotics to look forward to, both with different schedules and dietary requirements. One causes awful nightmares (doxycycline).
If left untreated brucellosis can include abscesses in the joints, spinal problems, blindness and inflammation of the testicles. It is anecdotally associated with elevated rates of suicide in veterinarians. I’m wondering how much chronic brucellosis there is in pastoralist communities in Sub-Saharan Africa. The burden must be quite severe.
This is going to be rough, but it’s better than a lifetime of these symptoms. I’m certainly finding this scientifically interesting, though I will be happy to have it gone for good.
My friend, Gabriel, though, knowing I’m into weirdness, took me to one tonight. By sheer coincidence, we happened to run into him on the way walking with a young gentleman. After a brief exchange, he was kind enough to agree to see us and led us back to his house.
Through Gabriel (my Luo is beyond poor), I asked him what the young man was doing there. The healer told me that someone had stolen some items from the guy. He had come to the healer to ask him to use his magic to reveal the identity of the thief and purchase some medicine with with to curse the man who had stolen his property. I asked him if people came to him often with such troubles. He replied that yes, indeed, many people do.
I tried to be snide and ask him what he would do if the thief came to him to try and get the curse removed and put on the guy that cursed him (fueling a never ending cyclic hell of cursing), but he didn’t really get what I was after.The healer then turned to me and asked me what my troubles were. I tried to tell him my knee hurts (which it does), but he kept insisting that my stomach hurt (it does not). Finally, I had to cave and just tell him that I was suffering from stomach pain. When he was describing the pain, he kindly tried to include the knees.
The healer learned his trade from his parents. He claims that his particular magic is strong because he learned it from his mother (rather than his father). I was told that that was a secret but I guess I’ve let it out. I’m sure it’s still a secret here. (My readership numbers show that it’s a secret anyway.)
He took us back to his house, a shack in a fishing compound on the edge of town, which usually smells of weed. He took us inside and had us sit down on his couch while he started pulling out various bottles and bags of powders. I was sitting next to him. Suddenly he jumped up and insisted that the medicines wanted me to move to the far side of the couch. I asked him if the medicines talked to him to which he replied yes, indeed, they do. I figured out pretty quickly that he’s half deaf and wanted Gabriel closer to him so he could hear.He went about mixing up some medications. The first was a small amount of powder that I thought was going to cure my alleged stomach problems, but instead was intended to get me a job. In fact, this medicine is so powerful, that I will never get fired from the job once I get it. I guess this means I’ll get a tenured faculty position any day now.
Next, he produced a number of bags of what looked like Indian spices and proceed to mix a heaping amount of what could be easily mistaken for garam masala. This medicine is what’s supposed to cure my diarrheal ills (which he also insisted I had). He poured some in my hand and told me to taste some. I hesitated but did it anyway. Definitely chili peppers in there. My mouth immediately went numb and my head started to spin a bit. Could be something like kava, definitely not weed. I have no clue what’s in this stuff, but there’s most certainly some active ingredient in it. I suspect that he produces it to emphasize his powers.He gave me very specific instructions on how to mix it, and when to use it. I am only supposed to use it between the hours of 8 and 9 p.m. All of my diarrhea and abdominal pains will immediately disappear. I am to go back to see him after two days (presumably to buy more).
Finally, he recognized that my knee hurts. He asked me if I had time to wait. I said yes, and he left the house to go and get some herbs. We could hear him pounding it into a powder outside. He returned, and said that I should mix the power with Vaseline and cover my entire body with it. I would need a partner to do it. After covering my entire body with the vaseline/powdered grass mixture, I should shake my limbs a bit. After two days, all of my pain would cease. I was to see him again (and again buy more, presumably).
We asked him how much it would be. “This is very expensive. 2,000 Schillings ($24.00).” to which we both balked. Eventually, we talked him down to 500 (about $6.00). Gabriel wanted to talk him down to 100, I just let it go figuring it was a small price to pay for such a weird experience.
Eventually, we had to go. Patients were lined up outside waiting.
as one would expect. The Institute of Medicine within the National Academies of Sciences recently produced a 230 page report addressing the concerns of parents that the current recommended vaccine schedule is too “crowded” and thus puts children at excessive risk.
Upon reviewing stakeholder concerns and scientific literature regarding the entire childhood immunization schedule, the IOM committee finds no evidence that the schedule is unsafe. The committee’s review did not reveal an evidence base suggesting that the U.S. childhood immunization schedule is linked to autoimmune diseases, asthma, hypersensitivity, seizures, child developmental disorders, learning or developmental disorders, or attention deficit or disruptive disorders.
Existing mechanisms to detect safety signals — including three major surveillance systems of FDA-approved products maintained by the CDC and a supplemental vaccine safety monitoring initiative by the FDA—provide further confidence that the current childhood immunization schedule is safe.
It’s quite a tempting narrative. Small defenseless children are jabbed multiple times, allowing harmful foreign substances to enter the body, all with the nefarious intent of making profits for large pharma giants. However, children are assaulted by pathogens from the second they exit the birth canal, and continue to be throughout the course of their lives.
The inactivated versions of the pathogens they might otherwise come into contact with should present no extra burden to an immune system that already anticipates invasion. Of course, coming into contact with a dead version of a pathogen is far preferable to coming into contact with the live version. The assertion that the schedule is “crowded”, given daily attacks on the immune system, is completely absurd.
Moreover, the report found that States with loose vaccine policy, have higher incidence of disease, in this case Pertussis:
While parents generally worry about children’s health and well-being, and their concerns about immunization safety can be viewed in that context, delaying or declining vaccination has led to outbreaks of such vaccine-preventable diseases as measles and whooping cough that may jeopardize public health, particularly for people who are under-immunized or who were never immunized. States with policies that make it easy to exempt children from immunizations were associated with a 90 percent higher incidence of whooping cough in 2011.
Of course, we are experiencing record numbers of Pertussis cases. It must be noted, that like influenza, most cases of Pertussis are asymptomatic. In fact, it is estimated that 5 out of 6 cases of Pertussis come without symptoms, yet transmission occurs. (2 out of every 3 influenza cases are asymptomatic. Next time someone tells you they never get the flu, don’t believe them.) Unvaccinated people may still contract the disease, not experience symptoms, and still pass it one to an unvaccinated person, who, of course, could very well die.
Many of the diseases on the vaccine schedule are very much still in circulation. One excellent example is tetanus, a bacteria which lives happily in soil (not rust, as commonly believed). Tetanus passes through our digestive tract regularly through food, but when the bacteria enter the other parts of the body, particularly the low-oxygen environment of the muscles, the usual outcome is to suffer for months and often die a truly horrible death. Nearly all cases of tetanus in the US occur in unvaccinated individuals.
Given tetanus’ ubiquity in the environment, I often scratch my head when parents tell me they don’t vaccinate their children as the risks of the disease far outweigh the risks of the vaccine. Here, of course, it isn’t the vaccine that’s killing kids, but politics and self-serving conspiracy hacks.