Tallow and unsaturated fats: What is "natural" and what is good -- not the same!

The NY Times “Eat” section recently had an article titled ‘How Beef Tallow Made a Comeback’, asking in the subhead ‘When McDonald’s stopped frying with beef tallow in the 1990s, most people saw it as a win for America’s health. What changed?’. The short answer, in terms of the science of the relative benefits of saturated animal fats like tallow and lard versus the unsaturated (olive oil) and poly-unsaturated (several types of vegetable oil) fats, nothing. What has changed, at least to some degree including among the restauranteurs cited, is people’s opinions and beliefs. One of them ‘said he felt a “moral and ethical obligation” to change his menu earlier this year…after reading that seed oils, like the canola oil he used to cook his fries and tortilla chips, carried potential harms. Tallow, he said, made for a healthier, more “natural” frying oil.’

There is a lot to unpack here. First is whether “seed oils” carry potential harms. Where did he read it? A reliable source? A wackjob? An earlier “Eat” piece, in January (link in the previous paragraph) was called ‘Are Seed Oils Actually Bad for You?’. It concluded that, new (not yet confirmed when the article appeared) Secretary of Health and Human Services ‘Robert F. Kennedy Jr., and others, claim they’re harming our health but the evidence suggests otherwise.’ In both articles, accomplished and respected nutrition scientists dispute this claim, and emphasize the increased risk of heart disease (and cancer) from animal fats like tallow and lard. There are physicians in the US, certainly here in Tucson, who dispute the idea that saturated fats are bad for you in terms of causing a higher risk of heart disease, but they are a distinct minority. There are at least a couple of research studies indicating they are not, but hundreds indicating that they are.

‘In 2002, a review study raised the question of whether consuming foods with high levels of omega-6 fatty acids relative to omega-3 fatty acids (a ratio typical of many seed oils) might increase inflammation in the body. “But I’ve gone through these papers and there’s not a single shred of evidence that this is actually true,” Dr. [Walter] Willett [Harvard School of Public Health] said. “This is all theoretical.”’

It should go without saying (but apparently doesn’t) that it is illegitimate to pick and choose the research you cite based not on its quality or methods but on whether it gets the results you already agree with. The American Heart Association (AHA) recommends diets with lower levels of saturated and higher levels of unsaturated fats, but critics say that this recommendation is tainted because AHA got money from Procter and Gamble, which manufactures Crisco, which contains both saturated and unsaturated fats and is not actually a particular favorite choice in the polyunsaturated sphere. While the appearance of bias/corruption always can exist when money is involved (see my piece from August 20, 2010 The AAFP, Coca-Cola, and Ethics: Serving the public interest?), it does not necessarily, or usually, mean the research supporting recommendations is flawed. P&G denies any association, but much more important is the breadth and consistency of the research supporting the use of unsaturated fats.

The other big issue is ”natural”. This one is huge. People of all political stripes love “natural”. It sounds so – well, natural! If it’s natural, it must be good – or at least better – right? Well, first of all, for this discussion, seed oils are also natural. They are, indeed, usually processed, but there is nothing in that processing that would make them less healthful, or natural. Tallow and lard when sold commercially are purified as well. A lot of stuff that is natural can be good for you, but a lot of stuff can also be bad for you. Many people advocate for the use of herbal remedies (natural, right?) and in fact many plants do have physiologic effects that can treat symptoms and diseases. Some have been the basis of commercially-produced medicines, e.g., aspirin from willow bark, digitalis from foxglove, colchicine from autumn crocus (Drug prices and corporate greed: there may be limits to our gullibility, December 27, 2015). Even in these cases the standardization of dose is much better in commercially produced drugs (and I am no fan of pharmaceutical companies or their practices, especially advertising and pricing). How many leaves of foxglove is good for your heart and how much is going to kill you (digitalis has a very narrow therapeutic:toxic ratio)? And there are many other natural things that are not good for you…I do not recommend rubbing poison ivy on your skin! Tobacco is a natural product, and Native people used it to treat wounds, as well as smoked it. Respecting those traditions and putting it on wounds, or especially smoking it, may not be the best thing for your health.

One thing that is sometimes cited as an indication of what natural things are good is the behavior of other animals. This is worth observing, but it is also worth noting that people are not the same as other animals, and the fact that they like something doesn’t mean it is god for people (or even for them!):

‘Mathaus Myga, 37, who owns a German takeout restaurant in Wisconsin, started frying his pork and chicken schnitzel in locally sourced beef tallow a year and a half ago….When Mr. Myga returns home after a day of frying with tallow, his two dogs lick his fingers. “They would never do that with rapeseed oil,” Mr. Myga said, referring to a common vegetable oil. “These are animals that have natural instincts.”’

I don’t know about Mr. Myga’s dogs, but the things my dogs’ natural instincts lead them to eat are not always things I’d recommend to people. Horse droppings are one of their favorites!

You can believe whatever you want. You can act on those beliefs in living your life (as long as they don’t hurt others). You can prepare your food based on those beliefs. But this does not necessarily make what you believe true. Finding “an article” by a reputable researcher that supports your belief is not a legitimate scientific approach, it is cherry-picking. To know what the science actually says, you have to form your belief based upon the overwhelming consensus of the research.

Of course, that is not a problem if you don’t believe in science.

Baselga, graft and corruption in medical research: why should we tolerate it?

On September 8, 2018, the NY Times reported that José Baselga, MD, Chief Medical Officer at the prestigious Memorial Sloan-Kettering Cancer Center in New York, and a world-renowned cancer researcher, had received at least hundreds of thousands of dollars in payments from drug companies and manufacturers of radiation equipment bought by his hospital. The number of companies from which Dr. Baselga was receiving payments turned out to be in the dozens. The emphasis in this article was not so much that he had received the money, for him personally, but that he had not reported this conflict of interest (COI) to the many journals that had published articles he had written. These articles were often studies of drugs produced by the companies that had paid him money.

 ‘Dr. Baselga did not dispute his relationships with at least a dozen companies. In an interview, he said the disclosure lapses were unintentional. He stressed that much of his industry work was publicly known although he declined to provide payment figures from his involvement with some biotech startups. “I acknowledge that there have been inconsistencies, but that’s what it is,” he said. “It’s not that I do not appreciate the importance.”’

He in fact DID let it affect his science, as the article reports:

‘At a conference this year and before analysts in 2017, he put a positive spin on the results of two Roche-sponsored clinical trials that many others considered disappointments, without disclosing his relationship to the company. Since 2014, he has received more than $3 million from Roche in consulting fees and for his stake in a company it acquired.’

This is important stuff. He took bribes from drug companies and spun the data to make their drugs look good. This is corruption. It is important to separate this from conflict of interest. COI, as I discussed on August 20, 2010 (“The AAFP, Coca Cola, and Ethics: Serving the public interest?”), exists when you have – surprise – conflicting interests! As when you receive money from your employer, and also money from some other company, thus creating a conflict. As medical ethicist Howard Brody, MD, pointed out in his article on the AAFP:

‘imagine that a judge who is sitting on a case involving a contract dispute between two companies is discovered to own $100,000 worth of stock in one of the companies. The judge cannot divert criticism of this conflict of interest by saying, ‘But you haven’t waited until I delivered my verdict—how do you know that I won’t rule against the company in which I own stock?“

He has a conflict of interest. You don’t have to actually do anything to the detriment of one of your funders to be in COI; most journal policies require reporting it so that readers can be aware of the COI, but it does not necessarily mean that if impacts your work. In Baselga’s case, however, it obviously did.

I guess he realized it. On September 13, 2018, the Times reported Baselga’s resignation from Memorial Sloan-Kettering. You can just imagine the Sloan-Kettering board of directors holding their breath to see if this would just blow over, and I am sure mostly that it would not affect donations from rich people. On that same day, the Times also published several letters from readers about the topic, all of them critical of Baselga, but emphasizing different issues. Charles Fried, a law professor from Harvard, notes that Baselga received $1.5 million in income from his employer, Sloan-Kettering, and wondered “Why isn’t $1.5 million enough?” Of course, for some people, nothing is ever enough. But the important point here is that Baselga was scarcely a penniless medical researcher barely scraping by and thus in need of this graft to pay a mortgage on a modest home, or buy a second bass boat. He was just really greedy.

Other letters emphasize other aspects of this practice, noting that Baselga may be a famous and particularly corrupt example, but that he is far from the only one receiving payoffs. Daniel J. Brauner, MD, a geriatrician and ethicist from the University of Chicago, notes that revealing COI is insufficient, observing that ‘The sad fact is that the current system of medical research and care conducted by physician-scientists like Dr. Baselga is fundamentally flawed and does an extreme disservice to patients, who deserve an unbiased accounting about the true worth of potential treatments.’  Frances M. Visco, president of the National Breast Cancer Coalition, bemoans the fact that ‘Breast cancer patients are tired of “breakthrough” therapies that do not extend life for even a day but do bring millions of dollars to industry, medical institutions and the doctors who care for us,’ and demands that researchers and journals ‘Just stop circling the wagons, focusing on financial gain and fame.’

On September 16, 2018, the Times published a full-column editorial on the issue in its widely-read Sunday Review. It notes how common the practice of paying corporate money to doctors and researchers is, observing that ‘A 2015 study in The BMJ found that a “substantial number” of academic leaders hold directorships that pay as much as or more than their clinical salaries.’ In addition, it report that ‘nearly 70 percent of oncologists who speak at national meetings, nearly 70 percent of psychiatrists on the task force that ultimately decides what treatments should be recommended for what mental illnesses, and a significant number of doctors on Food and Drug Administration advisory committees have financial ties to the drug and medical device industries.’ In its analysis of the problem, the editorial leaves out one major issue: much, or most, of the basic research that is done and leads to the production of these hugely-profitable drugs is funded by the federal government through the National Institutes of Health (NIH); that is to say, you and me. The drug companies pick up the work later when they think that the drug may represent a big financial boon for them.

The Times calls for greater safeguards to protect the public, with several suggestions including: 1. Ban paid appointments to outside boards, 2. Create uniform reporting standards, 3. Establish real consequences for violations, and 4. Build a culture of transparency. These are good suggestions, and should be implemented, although how one does #4 is not entirely clear, and the likelihood of #1 happening is low. But the real issue is the degree to which we, the American people, are willing to tolerate graft and corruption. We may – or may not -- dislike it when it occurs in the private sector (certainly President Trump was a major practitioner in his pre-Presidential years). We condemn it when it involves politicians, though it is rampant in federal, state, and local government (although what is illegal graft for state legislators is legal, if sometimes embarrassing, for Congressmen), but we expect it when it comes in the form of “campaign contributions”. And we should not be surprised when it infects medical researchers and physicians, who we hope have our health interests, not their own financial interests, at heart in what they do.

Corruption and graft is corruption and graft. It happens, and shouldn’t, and won’t stop until we demand it. And it won’t stop in health care until we get the profit incentive out of it.

Battling for Biomedical Supremacy? How about improving the people's health?

In an editorial on August 30, 2015, the New York Times discusses the “Battle for Biomedical Supremacy”, looking at the practice of what they call “poaching” of biomedical researchers by one state or university from another. Their main focus on the receiving end is Texas, because it has the highest profile of spending really big money to recruit researchers from universities in other states, and its main concern is (unsurprisingly) New York, which has more medical schools than any other state, and especially private medical schools with big endowments and big research programs to be “poached”. They raise the issue, but I am not (after reading it a few times) quite sure what their position is and I am afraid that they may not be either, since usually the position of the Times editorialist is clear. It seems to be saying “Well, New York needs to join this, but not spend too much public money on it.” But the editorial certainly does not condemn the practice.

I am not sure that I am wholly against it, either. Biomedical research is important. Researchers who can get better jobs (higher paying, more money to support their work) should not generally be criticized for accepting them. People have that right. On the other hand, from the point of view of the institutions that are being poached from, there can be not only feelings of sadness, betrayal, and anger, but in many cases financial losses that result from money they spent to recruit these “top researchers”, and now is down the drain, or so it seems. Sometimes these researchers are signed to contracts, just as physicians who bring in lots of money for a hospital are. These contracts for physicians may contain “non-compete” agreements, which (try to) restrict the area in which a physician leaving their employment can practice. They are more enforceable when they are more local, preventing them from going over to direct competitors, but not when someone is moving from NY to Texas. And the competition in biomedical research is much more national than the competition for direct medical care. On the other hand, if you hire mercenaries, you run the risk that someone will offer them more.

So it can increase the income and resources for the individual investigator (and his/her “team”) and can increase the status of the successful university, and might (in some cases) impact directly or indirectly on the economies of the local area, and thus state. Whether it is “worth it” from a direct financial return-on-investment (ROI) point of view probably depends upon the individual situation. It is almost never financially “worth it” directly; universities (medical especially) almost always lose money on their research endeavors even when you don’t factor in multi-million dollar recruitment packages; most “wet-lab” (biomedical) research (as opposed to say, community based or epidemiologic research) costs a lot more than even the sum of the “direct” dollars from the National Institutes of Health (NIH) and the indirect dollars (often 50% or more of the “direct”) that is supposed to help support the infrastructure. Add in another $5, $10, $20, $40 million more and you have a really hard time coming out anywhere close to break even.

But so what? The money for biomedical research has to come from somewhere; the usual source is NIH, but if states want to sweeten that, why not? After all, there are privately funded research institutes (the Stowers Institute in Kansas City is a local example); why not state, as well as federal. There are some concerns in that the federal (NIH) funds are the result of a competitive peer-review process, while these state funds are often just awarded to researchers based upon cachet. Still, if the state believes it has a chance for direct or indirect economic benefit, maybe it should “go for it”.

The bigger issue is not whether biomedical research should occur or who should support it, but why there should be competition for which university or state gets the big researchers. Does this facilitate biomedical researchers finding out more about how to treat or cure disease? I guess if more money is available, more progress could be made. But the bidding wars between universities and states seem to me to be more about local glory and (if lucky) economic development than real advances in biomedical research. It is similar to states and localities trying to lure employers by tax breaks, which may sometimes cost more than the economic benefit. Or, in the case of the Kansas City metropolitan area which straddles two states, luring companies back and forth across the state line (so that employees don’t even have to move) in what seems not-even-break-even mode (considering the cost of tax breaks). There may sometimes be benefit to science or the public good from relocating researchers and their laboratories but certainly not at the level and frequency it is occurring, and not enough to justify the huge expenditures. Often there is little or no new value being generated, but rather a shifting of resources from one place to another, maybe with a little loss in the process. However, this is how much of our economy works; the stock market and most of the financial industry – moving money around, skimming off profit (HUGE profit – the profiteers here are most of the richest of the billionaires) without creating any real value for the society.

Even more important is the implication that this is benefiting people’s health. If we wanted, as a society, to actually benefit people’s health, there are a lot more direct, effective, cost-effective and rational ways to do so. This, of course, could partly be providing financial access to health care for everyone regardless of their socioeconomic or other status, including those who have been left out of the ACA expansion because they life in states that have not expanded Medicaid, because they are undocumented, or because the level of health insurance that they can afford on the exchanges doesn’t meet all their health needs. A single-payer health system, Medicare for all. It also could mean enhancing geographic access, for those who are in rural areas or underserved urban areas, by using whatever is necessary (like financial incentives) to get doctors and hospitals to service these communities. It could also mean increasing the number and percentages of health care providers entering our most needed specialties, such as primary care, either by direct subsidy or by stopping the skewed and counterproductive reimbursement of subspecialists at much higher levels. (In Denmark, I discovered, general practitioners usually earn more than subspecialists! It is all about policy, not about the market.)

But, even more narrowly, talking about research, there is the question of getting out the therapies that research has already shown work, and are effective, and often cost-effective, to the people who need them. Continuing to do more research and find out more things is great, but actually having a national (or even state) system to ensure that the important discoveries are disseminated and implemented, is a greater priority. There are many common conditions, such as diabetes, for which we have treatments that are simply not available to many people, for many of the reasons above. Some of the unavailability of effective treatments are cost (the rapacious prices and profits charged by drug companies), but there are also treatments that are unavailable because – well, we don’t know why. While we continue to do more research on discovery, we need to do even more on efficacy, and fidelity, and finding out how to get our people to actually have improved health. Competition for researchers without increasing value is as wrong as it is in any arena.

The most effective treatments need to be available to all, the ineffective to none. We don’t need biomedical supremacy of Texas over New York, or California universities over those in Massachusetts, or even in the US over the rest of the world. We don’t need one university to “win” over another. We need better health for all our people.

Medical schools are no place to train physicians

Doctors have to go to medical school. That makes sense. They have to learn their craft, master skills, and gain an enormous amount of knowledge. They also, and this is at least as important, need to learn how to think and how to solve problems. And they need to learn how to be life-long learners because new knowledge is constantly being discovered, and old truths are being debunked. Therefore, they must learn to un-learn, and not to stay attached to what they once knew to be true but no longer is. They also need, in the face of drinking from this fire-hose of new information and new skills, to retain their core humanity and their caring, the reasons that (hopefully) most of them went into medicine.

Medical students struggle to acculturate to the profession, to learn the new language replete with eponyms, abbreviations, and long abstruse names for diseases (many are from Latin, and while they are impressive and complicated, they are also sometimes trite in translation, e.g., “itchy red rash”). They have to learn to speak “medical” as a way to be accepted into the guild by their seniors, but must be careful that it does not block their ability to communicate with their patients; they also need to continue to speak English (or whatever the language is that their patients speak). “Medical” may also offer a convenient way of obscuring and temporizing and avoiding difficult conversations (“the biopsy indicates a malignant neoplasm” instead of “you have cancer”).  But there needs to be a place for them to learn.

So what is wrong with the places that we are teaching them now? Most often, allopathic (i.e., “MD”) medical schools are part of an “academic health center” (AHC), combined with a teaching hospital. They have large biomedical research enterprises, with many PhD faculty who are, if they are good and lucky, are externally funded by the National Institutes of Health (NIH). Some or many of them spend some of their time teaching the “basic science” material (biochemistry, anatomy, physiology, microbiology, pharmacology, pathology) that medical students need to learn. By “need to learn” we usually mean “what we have always taught them” or “what they need to pass the national examination (USMLE Step 1) that covers that material”. This history goes back 100 years, to the Flexner Report of 1910. Contracted by the AMA, educator Abraham Flexner evaluated the multitude of medical schools, recommended closing many which were little more than apprenticeship programs without a scientific basis, and recommended that medical schools be based upon the model of Johns Hopkins: part of a university (from the German tradition), grounded in science, and based in a core curriculum of the sciences. This has been the model ever since.

However, 100 years later, these medical schools and the AHCs of which they are a part have grown to enormous size, concentrating huge basic research facilities (Johns Hopkins alone receives over $300 million a year in NIH grants) and tertiary and quarternary medical services – high tech, high complexity  treatment for rare diseases or complex manifestations of more common ones. They have often lost their focus on the health of the actual community of which they are a part. This was a reason for two rounds of creating “community-based” medical schools, which use non-university, or “community”, hospitals: the first in the 1970s and the second in the 2000s. Some of these schools have maintained a focus on community health, to a greater or lesser degree, but many have largely abandoned those missions as they have sought to replicate the Hopkins model and become major research centers. The move of many schools away from community was the impetus for the “Beyond Flexner” conference held in Tulsa in 2012 (see Beyond Flexner: Taking the Social Mission of Medical Schools to the next level, June 16, 2012) and for a number of research studies focused on the “social mission” of medical schools.

The fact is that most doctors who graduate from medical school will not practice in a tertiary AHC, but rather in the community, although the other fact is that a disproportionate number of them will choose specialties that are of little or no use in many communities that need doctors. They will, if they can (i.e., if their grades are high enough) often choose subspecialties that can only be practiced in the high-tech setting of the AHC or the other relatively small number of very large metropolitan hospitals, often with large residency training programs. As they look around at the institution in which they are being educated, they see an enormously skewed mix of specialties. For example, 10% of doctors may be anesthesiologists and there well may be more cardiologists than primary care physicians. While this is not the mix in world of practice, and still less the mix that we need to have for an effectively functioning health system, it is the world in which they are being trained.

The extremely atypical mix of medical specialties in the AHC is not “wrong”; it reflects the atypical mix of patients who are hospitalized there. It is time for another look at the studies that have been done on the “ecology of medical care”, first by Kerr White in 1961 and replicated by the Robert Graham Center of the American Academy of Family Physicians in 2003 (see The role of Primary Care in improving health: In the US and around the world, October 13, 2013), and represented by the graphic reproduced here. The biggest box (1000) is a community of adults at risk, the second biggest (800) is those who have symptoms in a given month, and the tiny one, representing less than 0.1%,  is those hospitalized at an academic teaching hospital.  Thus, the population that students mostly learn on is atypical, heaving skewed to the uncommon; it is not representative of even all hospitalized people, not to mention the non-hospitalized ill (and still less the healthy-but-needing-preventive care) in the community.

Another aspect of educating students in the AHC is that much of the medical curriculum is determined by those non-physician scientists who are primarily researchers. They not only teach medical students, they (or their colleagues at other institutions) write the questions for USMLE Step 1. They are often working at the cutting edge of scientific discovery, but the knowledge that medical students need in their education is much more basic, much more about understanding the scientific method, and what constitutes valid evidence. There is relatively little need, at this stage, for students to learn about the current research that these scientists are doing. Even the traditional memorization of lots of details about basic cell structure and function is probably unnecessary; after 5 years of non-use students likely retain only 10% of what they learn; even if they need 10% -- or more – in their future careers, there is no likelihood that it will be the same 10%. We have to do a better job has of determining what portion of the information currently taught in the “basic sciences” is crucial for all future doctors to know and memorize, and we also need to broaden the definition of “basic science” to include the key social sciences of anthropology, sociology, psychology, communication, and even many areas of the humanities such as ethics. This is not likely to happen in a curriculum controlled by molecular biologists.

Medical students need a clinical education in which the most common clinical conditions are the most common ones they see, the most common presentations of those conditions are the most common ones they see, and the most common treatments are the ones they see implemented. They need to work with doctors who are representative, in skills and focus, of the doctors they will be (and need to be) in practice. Clinical medical education seems to work on the implicit belief that ability to take care of patients in an intensive care unit necessarily means one is competent to take care of those in the hospital, or that the ability to care for people in the hospital means one can care for ambulatory patients, when in fact these are dramatically different skills sets.

This is not to say that we do not need hospitals and health centers that can care for people with rare, complicated, end stage, tertiary and quarternary disease. We do, and they should have the mix of specialists appropriate to them, more or less the mix we currently have in AHCs. And it is certainly not to say that we do not need basic research that may someday come up with better treatments for disease. We do, and those research centers should be generously supported. But their existence need not be tied to the teaching of medical students. The basic science, and social science, and humanities that every future doctor needs to learn can be taught by a small number of faculty members focused on teaching, and does not need to be tied to a major biomedical research enterprise. Our current system is not working; we produce too many doctors who do narrow rescue care, and not enough who provide general care. We spend too much money on high-tech care and not enough on addressing the core causes of disease.

If we trained doctors in the right way in the right place we might have a better shot at getting the health system, and even the health, our country needs.

Research on disparities/inequities, in practices and communities needs much greater funding

This is my first attempt at a blog in several weeks; indeed only one in the last month. I took (and time will tell if I passed) the Family Medicine recertification exam, so I am now able to raise my head above water.

Research is the way we gain new knowledge. It is how we discover if the things that we are doing are the right things to do, or if they are of little or no value, or perhaps even of harm. In the decades after World War II, when the country was optimistic and growing and seeking new frontiers, science was a major area for investment by our government. Things were getting better, returned GIs found a plethora of well-paying jobs, were able to buy houses and cars and plan to send their children to college. American industry did extremely well, if not solely because of great planning and management here, because there was no competition from the rest of the world which had been devastated by the war.

Things were not all good, especially on the political front; there was the cold war, and the associated fanatic fear of Communists epitomized by Senator McCarthy, and there was a legitimate fear of nuclear. But, on the economic front, things were going well for the US. The growth benefited many more people, and the gap between the income of the average worker was large but not unconscionable. Not like today, where as demonstrated by much research, and the title of this HuffPost article, “CEO Pay Grew 127 Times Faster Than Worker Pay Over Last 30 Years”, (“It’s good to be a CEO!”), or in this graphic from Prof. GW Domhoff of UC-SC.

The most dramatic expenditures on science were on space travel; after the Soviet Union launched Sputnik, the first artificial satellite, in 1957 and the space race was on. With the election of John Kennedy in 1960, space exploration moved front and center. All of us who were schoolchildren, in addition to hiding under our desks to protect us from nuclear weapons, were much more productively engaging in a new-found, broad-based physical fitness program encouraged by the President. While Harry Truman was unsuccessful in passing a national health insurance plan, thanks to both the reactionary opposition of the AMA, and the fact that labor unions chose to demonstrate their effectiveness by negotiating health coverage rather than seeking political change as the Labour Party successfully did in Britain, in other areas of science, health moved to the forefront.

The National Institute of Health (NIH) became the major government institution funding medical research and saw enormous growth in the ensuing decades, including a doubling of the budget from about $15B to about $30B in the decade surrounding the last millennium. This fueled the development of an enormous expansion of medical research in laboratories, primarily in universities and medical schools. In addition, corporate support, mainly from pharmaceutical research companies, further enhanced the growth of these laboratories. There were many successes, of which the most famous is the sequencing of the human genome, but our understanding of human biology and how it might contribute to human health and diseases has been remarkably enhanced. Some of this research has led to true medical breakthroughs, with the creation of new drugs and treatment modalities that have sometimes been of great help to large numbers of people with common diseases, and sometimes of enormous help to a few with uncommon ones.

However (and you knew that there was going to be a “however”), the focus on laboratory research and new discoveries at the molecular, protein and genetic levels left unfunded areas of research at least as critical, but not seen as “hard science”, and thus not generally funded by NIH and drug companies. This is a problem. Yes, there are “clinical” research studies, but these are mostly trials of drugs and interventions in populations. The number of studies based in communities, looking at health disparities, and trying to discover how most effectively to have a positive influence on the health of people, populations, rather than occasional individuals, remains small.

 

Certainly, it has grown. As demonstrated in the graph, after the NIH budget doubled, it leveled off, “stagnated” given inflation, until the one-time infusions of American Recovery and Reinvestment Act (ARRA) funds in 2009. Funding for health disparities research has increased, both from NIH and from other federal agencies such as the Centers for Disease Control (CDC) and the Agency for Healthcare Quality and Research (AHRQ), which has but a tiny fraction of the funding that NIH does. NIH created Clinical Translational Science Awards (CTSAs) which funded centers at many medical schools to look at moving research into the community, but much more from the basic science laboratory to first-in-humans trials (or even from one basic science laboratory to another). A major new initiative of the Affordable Care Act (ACA) is the creation of the Patient-Centered Outcomes Research Institute (PCORI), designed to evaluate not just new treatments but how they affect people. However, even the community-based research has focused largely on the recruitment of research subjects to studies designed by academic researchers, rather than on directly studying issues that would improve the health of the people in those communities.

Part of the problem is that it is difficult to get community members to think about what would be in the best interests of their health and that of their communities. They are, after all, not trained in such assessment. In addition, particularly in the communities that are the most vulnerable, that have to greatest health inequities, people are just focused on getting by, paying the rent, buying food, working multiple low-wage jobs. However, another part of the problem is that research at this level is seen as less important and significant, particularly by those who have always focused on new discoveries in the lab and who control most of the agencies such as NIH.

But it is not true. No matter how wonderful the discoveries in the lab, no matter how much they might lead to new understanding, new drugs, new treatments, these are only of value if people benefit from them. So this requires clinical research in the real world, with actual people. But beyond this, if they are to benefit not just a chosen few, the interventions have to be studied among diverse populations, including people facing economic, social, psychological and environmental challenges. In addition, the delivery of these treatments is sporadic. It is clearly demonstrated that administration of aspirin is of benefit to people who have had heart attacks. So it should be used. Why, then, are half the Americans who should be on aspirin not? I don’t know. It probably isn’t cost. It requires research to find out why and to change it. Saying (as is often done) that “new medical knowledge takes 10-20 years to penetrate into practice” is not adequate. Finding out how to get this effective treatment to the people who need it is as important as discovering the treatment. This is known as “fidelity” research.

Finally, effective research on improving people’s health needs to involve medical practices, where the people are being seen. There are many Practice-Based research networks (PBRNs) around the nation, but they are all challenged by how busy the providers are seeing patients; this is at least as true in practices such as Federally-Qualified Health Centers (FQHCs) that care for poorer populations. And yet, without involving them in research, how can we know what is effective in delivering the “best quality” care, and how can practices at the point of care be changed?

This is not to say that we should not fund basic biomedical research or early clinical trials. Nor is it to say that the current programs from NIH and PCORI and others to fund work in health disparities and inequities, and in population and community health are not good. But they are too little. People working in basic laboratory research, early clinical research, practice-based research, and community health should not be competing with each other. There should be more money for all of it, but especially a lot more for fidelity research, community-based participatory research, and practice based research.

Where will the money come from? From policies that are used in every other successful country, and every time the US has been successful, progressive tax policies that take some of our wealth out of the control of private corporations, who use it only to sock away more money, and into the public sector where it can be used to benefit us all.

Research basic and applied: we need them both

 “Not every mystery has to be solved, and not every problem has to be addressed. That’s hard to get your brain around.”

This statement was the coda of a very good article, “Overtreatment is taking a harmful toll”, by Tara Parker-Pope, in the NY Times, August 28, 2012. The topic of the article, and the implication by the speaker, who was talking about her own family’s health care and unnecessary testing, is one that I have written about several times recently, in terms of both screening tests (“The "Annual Physical": Screening, equity, and evidence”, July 4, 2012) and investigation and treatment of disease (“Rationing, Waste, and Useless Interventions”, June 21, 2012). Thus, I certainly agree that there is too much testing and too much intervention, and that it has a high cost in both dollars and in potential risk to people (the English word for what the health system calls “patients”). So why do I feel a little uncomfortable with the quotation above?

I think it is because I very strongly believe that the decision on what tests to do and what interventions to take should be informed, as much as possible by the evidence. That evidence, I have also argued, should come from research, from well-designed studies, from science. This is also costly, but it is necessary. Your treatment should be based on evidence and probability gathered from studies of large populations. Without it, doctors and other health professionals are flying blind, with treatments based on their own experience, or worse yet “what makes sense”. Sometimes the doctor’s own experience is a good guide, if they see a lot of patients with the same problem, and have reason to know what works. It is even better when they can bring in knowledge of the local community (e.g., what antibiotics are common bugs resistant to here? What are the common belief systems of the people that I care for?) and better yet if they actually know you, and what you value, and what your medical history is, and what your belief system is, and what is most likely to engage your effort in the interest of your health.

But it is better if the set of options from which they choose are all based in evidence. That something makes sense, I have often pointed out to medical students and residents, makes it a research question, not an answer. If something makes sense, based on what we already know, it is likely to be a more valuable thing to study than something that does not make sense. However, until the study, or more likely several studies, are done we won’t know if it is, in fact, true. Human beings, both in terms of their biology and behavior, are too complex, and have too many different systems interacting with each other, to predict accurately how something that “makes sense” based on one of those dimensions is likely to turn out.

The thing is that not all research is immediately clinically relevant. Sometimes it is; the “Ottawa rules”, developed by research done in Canada, provide physicians with evidence based guidelines about when it is appropriate to do x-rays for injured ankles, knees, and feet – common problems. Other studies investigate whether particular drugs may provide real benefit to people with more uncommon problems. This is particularly satisfying when the drug is not some new, expensive blockbuster but something cheap and common like aspirin or folic acid. Or when an old drug, all but abandoned for its original purpose, turns out to be very effective for another condition entirely. (One of my colleagues just demonstrated this for an old heart drug that works for a rare neuromuscular condition – coming soon to your local JAMA!) But much research is at a very basic level. Before those drugs can be tested on particular conditions, they have to be developed. Before they can be developed, the biological and biochemical mechanisms upon which they have an effect have to be identified. Just as, before we can send rockets to the moon, we need to understand physics. Science, what in medicine we call “basic science”, has to continually move forward, and this requires not solely focusing on what might be of practical use tomorrow, but what is still a mystery that has to be solved.

I find it almost ironic that I am writing this defense of basic science research. Just recently, I was in NYC and went to brunch at the riverpark restaurant. On the block leading to it is a big vegetable gardens where they grow many of their own ingredients, much of it surrounded by a big wooden fence. And, since it is right there at Bellevue Hospital and NYU Medical Center and Rockefeller University, that fence is decorated with pictures and biographies of Nobel Prize winners in Medicine who had ties to NYC. My reaction was that all of these people (even if they had MD degrees) were doing laboratory, basic science research, not clinical research, even though the prize is for “Medicine”. Of course, having won Nobel Prizes, their research led to important practical breakthroughs, but for every Nobel Prize winner who discovers something that will make a major difference in health, there are thousands and thousands of others, working in laboratories everywhere, and this work is necessary.

Personally, I don’t think it is necessarily necessary that it  be done in medical schools, whether NYU or the University of Kansas, rather than in research institutes like Rockefeller or Kansas City’s Stowers Institute (or Karolinska in Sweden or the Pasteur Institute in France). I find, as a family doctor, that the fact that much basic research in human biology is done at medical schools leads to what I think are negative “side effects”. I believe that there is an over-emphasis on teaching medical students biological sciences in great detail (often at the level of minutia) and an under-emphasis on the social sciences. I think that these areas are just as important – maybe more important for the practicing physician -- but are usually not considered as “core” to medical student teaching.

In part this is because those working in the social sciences are most often “there”, at the main campus, not “here”, at the medical school. I am proud that the research conducted by faculty in my department is mostly community-based, looking at determinants of health and health disparities. But, whether biomedical research should be as important a part of medical schools as it usually is, or not, it is absolutely clear that it needs to occur, and that scientists need to solve mysteries.

Every mystery? Well, of course, that will never happen. And even for the ones they solve, the results are not always beneficial for folks. We can map the human genome! We can tell you if you and your family members are at increased risk for a terrible disease! Of course, often we cannot do anything about it, but it can make you depressed and pessimistic, and maybe you’ll lose your health insurance. So maybe we don’t need to tell your insurer, or even tell you, but getting to be able to do something about it first requires doing the science.

And of course there is a big difference between uncovering the mysteries of the universe, and even of finding evidence for what is appropriate diagnosis and treatment in populations, and in having to investigate everything in you. The father of another person quoted in the article developed delirium from overtreatment with drugs that was mistaken for dementia. “I don’t know if we have too many specialists and every one is trying to practice their specialty, but it should not have happened.” I agree; too many mistakes, too many errors (see Medical errors: to err may be human, but we need systems to decrease them, August 10, 2012) can come from there being too many specialists combined with too little communication.

The quote at the top of this piece notes that not everything has to be addressed and that this is hard to wrap your brain around, but it shouldn’t be.  All that research in the basic and clinical sciences should help us to understand when we need to investigate (do a CT scan for a black eye, in another example from the article, say) and when we don’t.

Often we should leave well enough alone. 

Breast cancer screening: conflicting evidence? what are the important questions for health?

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Several new, and sometimes contradictory, studies about breast cancer and screening mammography have recently appeared in the medical literature. In a recent study from Norway, published in the New England Journal of Medicine, Kalager et. al[1] looked at the impact of mammography screening of women 50-69 years old in that country by comparing groups of women who were screened and those who were not screened between 1996 and 2005 and comparing them both with comparable groups for the 1986-1995 period. They discovered a significant decrease in the rate of breast cancer detected in women who were screened – but also in women who were not screened. The decrease was greater in the women who were screened, but this only accounted for 1/3 of the reduction in breast cancer mortality in that group; while the reductions in each group were statistically significant, the difference between them was not (quite). Overall the reduction in the death rate in screened women was 7.2 per 100,000 woman-years, and in the non-screened group 4.8 per 100,000 woman-years.

Meanwhile, Cancer published an article from Sweden looking at mammography screening for women who were 40-49 years of age. Because not all Swedish counties screened women that age, they were able to do a retrospective comparison between those counties who began screening at 40 compared to those counties who began at 50. Hellquist, et. al.,[2] found a significant risk reduction (a relative risk of 0.74 for women invited to screening and of 0.71 for those actually screened). Over 16 years of the study “…there were 803 breast cancer deaths in the study group (7.3 million person-years) and 1238 breast cancer deaths in the control group (8.8 million person-years)”, or converting to the same units as the other study, a reduction of 3 deaths per 100,000 woman years, from 14 to 11. The authors note that 1252 women this age would need to be screened to prevent one death.

The Swedish study provides data to support screening women at 40 (although the reduction was greatest in the 45-49 group, which is not surprising as the incidence of breast cancer increases with age). The Norwegian study shows that the rate of breast cancer has decreased anyway. The Swedish study is not a randomized controlled trial, but rather solely a historical comparison, and thus did not control for differences between the women who got screening and those who did not that might have affected breast cancer risk.

So which are we to believe? Both, to the extent that we can understand the methods used. The question is what are we to do? “We”, here, being both women who might choose to undergo mammography screening, and doctors who have to decide whether to recommend it, especially to those under the age of 50. For me, it will involve discussions with each woman, dependent on her individual risks and preferences. The population health benefit is small but significant; while for any woman the risk reduction might be of value regardless of the cost, that woman (and everyone else) has to also bear the cost of screening all those women – 1252 to save the life of one woman 40-49 in the Swedish study. Clearly, women who have a higher risk (family history) will benefit more, since they are more likely to have breast cancer than those without such a family history.

The cost is not only all those mammograms, but the cost of further tests (additional views or ultrasound) in women with questionable results (more common in younger women who on average have denser breasts), in biopsies – not without risk, though low – and pathology reports, discomfort etc. Not to mention what that money might otherwise be spent on. Feeding the homeless? Providing prenatal care? Fighting HIV/AIDS? Building more bombs? Bailing out big financiers? I would certainly agree that there are social programs that could more effectively use the money currently being spent to screen low-risk younger women for breast cancer with far more social benefit; I would also acknowledge the very low likelihood of any saving in mammography screening being used for such purposes rather than other high-tech medical care or further health system profit.

A more important question, perhaps, is why, at any age level, are certain parts of the population – poorer and minority women – less likely to be screened? To the extent that screening does detect cancer in earlier stages, when intervention can be done, and thus make a difference in mortality, why is it not being done as effectively with minority women? For example, African American women are less likely to get breast cancer, but more likely to die from it.

But people do want “answers”, definitives. Newspapers like to publish “breakthrough” research that seems to provide them. When the “answers” seem contradictory, it leads to frustration for many, and a decision to do what they had planned to do anyway, to do what seems to make “sense” (and what they can afford). After all, if sometimes we hear that Vitamin C or E or beta-carotene is a wonder drug to prevent cancer, or Alzheimer’s, and later studies show that it isn’t, and sometimes may even create greater risk, what are we to do?

One thing we could choose to do is to listen to those who are sure that they have the answers, even when these are based upon no data or carefully-selected data. If someone advises people based upon a single study, regardless of the scientific quality of that study and how often its results might have been refuted by later studies, they can be more confident and sure of themselves. This can inspire confidence on those they advise. (I am reminded of the story told by a colleague, fresh out of residency, who was practicing with farmworkers in the Imperial Valley of California. These folks, he said, are used to going to a doctor who listens to their problem, nods, tells them what they have, and gives them a shot to fix it. “I,” he noted, “listen, then tell them to take off all their clothes, examine them for a long time, and then finally tell them I’m not sure what it is, but it probably doesn’t need a shot – and that the shot might even be bad for them – and likely it will go away with time. Who are they going to trust?”). Showing confidence in your opinion is very persuasive. Thus the term “confidence men” (now shorted to “con”).

By the way, I don’t think this is such a good choice. That studies may seem contradictory is part of the nature of science, of how the studies were conducted, on whom, with what controls, using what methods. A future blog will discuss the work of Dr. John Ioannidis, whose work has raised questions about how much of the work published as research is true, made recently au courant by David H. Freedman’s article in the November Atlantic “Lies, damned lies, and medical science,” and some of the important lessons to be learned – and not learned – from his work. Nonetheless, this confusion does not justify complete nihilism – do whatever you want and it’s all the same – or much less undertaking treatments that have never really been studied. (See Drugs, Tobacco, Doctors and the Health of the Public, September 10, 2010.)

In the meantime, remember that there are probably not too many magic shortcuts to better health. A healthful diet and more exercise will make you fitter and stronger and able to do more things; reading and thinking and doing puzzles are interesting, stimulating and fun, whether they prevent Alzheimer’s disease or not.

[1] Mette Kalager, M.D., Marvin Zelen, Ph.D., Frøydis Langmark, M.D., and Hans-Olov Adami, M.D., Ph.D, Effect of Screening Mammography on Breast-Cancer Mortality in Norway, N Engl J Med 2010; 363:1203-1210.

[2] Hellquist BN, et. al., Effectiveness of population-based service screening with mammography for women ages 40 to 49 years, Cancer published online Sept 29 ,2010
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