Search This Blog


Follow by Email

Monday, October 26, 2015

How can we start coming up with new therapies that actually save money?

In the United States, biomedical research, including basic science and clinical studies, is paid for mainly by companies that expect to make money off of new discoveries. The government, through the National Institute of Health (NIH) funds a little over a quarter of it, but most of the money comes from drug and device manufacturers.

This means that interesting research that might result in breakthroughs that save patients money is unlikely to find funding. This is terrible. If gummy bears cured cancer, we might never find out about it. If anything that is easy to come by, from various sources, were to show promise therapeutically, we as US citizens would not be likely to find out about it through our own research.

Some examples:

1. Red yeast rice, a dietary supplement made of rice fermented with the fungus Monascus purpureus in a centuries old process, contains a widely marketed cholesterol medication (lovastatin) that is naturally produced by Monascus. The doses are high enough to reduce cholesterol significantly. The best study of this product was done in China, with an extract of the yeast rice, and showed that it reduced bad heart outcomes more than did lovastatin in clinical trials here. The FDA has banned red yeast rice periodically (though it is now easy to find online) saying that it could be dangerous. For awhile, the only red yeast rice products that could be sold in the US were ones which either didn't mention how much active ingredient they contained, or contained little to none of it. Now that we can buy it again, it is unclear which brands actually work to reduce cholesterol.

2. Aspirin, which was first widely adopted for treatment of pain and fever in the late 1800s, was found in the 1970's to be very effective for treating and preventing disorders due to blood clots, particularly heart attack and stroke. I wondered how, since this drug was widely available at a very low price, research had been done in the US to show how effective it was. It turns out that the groundbreaking work was done in Britain, where most research is funded by the government (which would stand to gain, along with patients, from discovering an inexpensive approach to a common problem.) To be fair, in the 1970's research in the US was much more often paid for by the government, so the aspirin research probably could have been done here.

3. Corticosteroids (prednisone and others) are widely available and inexpensive medications which reduce inflammation. They have various side effects and so are used sparingly in most situations. It turns out that, when used along with antibiotics in severe community acquired pneumonia, they make people improve faster and die less frequently. A review of 13 randomized controlled trials came out in the Annals of Internal Medicine earlier this month. Dr. Reed Siemieniuk was the first author. He and his coauthors are from Canada and Europe and the vast majority of the articles reviewed were done in Europe. Studies like this don't happen in the US because drug companies have no incentive to fund them. Full color, full page ads or TV infomercials will not tout the importance of this discovery, so it will be a little more difficult than it might be to change the habits of US physicians to incorporate this life and money saving approach.

4. Nicotinamide, also known as vitamin B3, a derivative of niacin, was just reported to reduce pre-cancerous skin spots, known as actinic keratoses. These are the little scaly spots that happen on the arms, heads and faces of aging people who have spent time in the sun. It also appears that topical nicotinamide may do the same thing, as well as reducing wrinkles and other signs of aging. This vitamin is available widely and costs pennies a pill. How could such research have been done, since this discovery will likely decrease the amount of money spent on other expensive treatments and prescription potions for this problem? It was done in Australia, funded by the National Health and Medical Research Council. Nicotinamide, though it is related to Niacin, does not cause flushing and does not reduce cholesterol levels, though it has reversed symptoms of Alzheimer's disease in an experimental mouse model.

What can we do in the US to re-purpose our considerable intellectual resources and vast research machinery away from increasingly complex and costly new technology and toward elegant and ingenious cost-saving approaches? In the big picture, we could figure out a way to move money that will likely be spent on useless or overly expensive healthcare toward research that leads to lower consumption of resources. The NIH in the US is the organization that can fund non-biased research, and is perfectly suited to doing so. Money spent on cost-saving technology will pay for itself many times over.

Drs. Arthur Kellermann and Nihar Desai, from Bethesda and Yale respectively, discuss in a recent JAMA article several specific recommendations from RAND health, a think-tank charged with improving global health and reducing costs. These include creating a public-interest investment group to fund good projects, giving cash prizes to inventors, buying out patents to allow reasonable pricing and reducing unnecessary regulatory hurdles. They conclude:
"Realigning incentives to encourage inventors and their investors to develop cost-lowering products could transform technology, which is currently one of the most potent drivers of health care spending in the United States, into a powerful creator of value. Once that is done, ingenuity will take care of the rest."

Sunday, October 18, 2015

Repatha and Praluent: VERY expensive drugs to lower cholesterol which may not actually work to prevent heart attacks (then again, perhaps they will.)

In July of 2015 the US Food and Drug Administration (FDA) approved an injectable monoclonal antibody alirocumab (Praluent) which lowers the LDL or "bad cholesterol". The drug is produced by Regeneron, given by injection once every 2 weeks, and will cost $14,600 wholesale per year. In August, evolocumab (Repatha) was FDA approved. It, too, is a monoclonal antibody and will cost $14,100 wholesale when it is finally released. It was developed and will be marketed by Amgen.

These drugs are antibodies, produced in hamster ovary cells in vats, which, when injected, bind to proprotein convertase subtilisin/kexin type 9 (PCSK9), making it less active. PCSK9 normally reduces the liver's ability to remove low density lipoprotein (LDL) from the blood. The main drug class that we have now which reduces LDL is the statins, also known as HMG CoA reductase inhibitors, which reduce the production of cholesterol. A couple of common statins are atorvastatin (Lipitor) and simvastatin (zocor.) I have ranted about them copiously in the past.

The reason we worry about LDL is that high levels of it seem to be associated with heart attacks and strokes, and people with a genetic defect that raises their LDL to very high levels often die young of heart attacks. There are many drugs which can lower the LDL levels, but the statins work best and also have been shown to reduce the risk of heart attacks and strokes in high risk patients. The studies are less clear about their benefits for lower risk people. Many drugs which lower the LDL do not reduce the risk of strokes or heart attacks, and it may be that statins have positive effects due to their reduction of inflammation or some other positive effect on blood vessels.

In 2013, recommendations from the American Heart Association and the American College of Cardiology changed from recommending using medications to lower cholesterol below certain levels, depending on level of risk, using diet and medications, to simply using statins for everyone at elevated risk of vascular disease, such as heart attack or stroke. Statins don't appeal to everyone, primarily due to side effects of muscle pain and weakness, also sometimes problems with thinking and memory, so this approach is not universally applicable. But with statins now mostly generic, this approach costs only about $150 per year and is pretty effective.

There is another problem with this approach (besides the fact that it puts huge numbers of people who might never have trouble with vascular disease on a statin drug with unclear long term side effects). There is no room in these statin-based recommendations for non-statin drugs, especially absurdly expensive ones that were finally released after more than 10 years of research by powerful drug companies.

The PCSK9 drugs have been approved for use in patients with familial high cholesterol syndromes and those with known disease of the coronary arteries whose cholesterol remains high despite statins. Insurance companies and anyone else with concerns about rising medical costs are concerned that doctors will start prescribing these drugs with gay abandon to everyone whose cholesterol worries them, with a multi-billion dollar impact on health care costs. The drug companies promise to provide the drugs for less money to patients who can't afford them and to cut deals with insurance companies, but the costs may still be staggering.

In the last two days I saw two articles suggesting that we start to obsess about cholesterol levels again, shifting away from the recently accepted approach of simply treating everyone at high risk of heart disease with statins. The first, in JAMA, was authored by 3 physicians employed by the healthcare company CVS, saying that if we don't start checking LDL levels and targeting higher ones for treatment, anyone with very high risk will be put on PCSK9 injections. CVS, as a pharmacy benefit management company, stands to lose money if patients' drug bills go up astronomically. Then again, they might pass the costs on to consumers and manage to make money. Plus CVS sells point of care cholesterol blood tests, so I'm not sure where their interests lie.

The second was an "educational activity" presented by Medscape, featuring a discussion by 3 physicians with academic affiliations (two from Harvard Medical School) who would all like to go back to checking LDL levels and using medications to get the LDL as low as possible so as to reduce the risk of heart attacks. The activity was financed by Regeneron and Sanofi, who make the new injectable super expensive cholesterol drug, and all of the experts have been on the payrolls of one or both of the companies that produce these drugs. They are very excited about how well these new drugs lower the LDL, and they expect that when studies come out looking at reducing risk of heart attacks they will actually have some clinical benefit. They talk about how many patients might be "candidates" for this therapy, as if it's some kind of a sought after political office. That part is just plain creepy.

There are so many problems with all of this. First and most importantly, we don't know if these super expensive drugs actually reduce the risk of heart attacks. We won't know until 2017, when the first of the many studies which are ongoing will be available. It doesn't matter at all if they lower LDL levels, since high LDL levels aren't actually a sickness. The excitement about this new drug will again focus us away from the fact that lifestyle changes such as quitting smoking and becoming at least moderately active are even more effective in reducing risk for all kinds of vascular disease and other miseries than any medication we have produced. It's very likely that patients who continue to smoke and abuse their bodies in other ways will be put on these drugs, because those are the patients who are at highest risk of heart disease. Do we really want to be directing resources in this direction?

And what about the cost? Why $14,600 per year? What a crazy number. Probably we should just shelve it until we know if it works, then, if it does, figure out who actually needs it.

Friday, October 2, 2015

Medical bills: why are these completely inscrutable and full of mistakes?

Within the last two days I received a bill for my glasses and read a post by a friend ranting about medical billing mistakes. This is a huge problem that is so common that it could be considered the norm. It is ridiculously expensive and could probably be fixed.

My exposure to medical bills has been through patients who show them to me, hoping I can make sense of them, my occasional foray into the world of being a healthcare consumer and the woes of friends and family. I can say, with confidence, that I have never read a medical bill that I understood. When I do choose to dig a bit deeper, overcharging and errors are more common than not.

It is very hard to get good statistics on this, but the lower end of what I'm seeing suggests that one in 10 bills contain errors. It's probably higher than that.

Common billing errors include being billed for procedures that were cancelled, being billed twice for the same thing, under different names, being billed for a more complex version of what was actually done and being billed for more time than was actually spent. How do these happen? In general the errors aren't deliberate fraud. Frequently staff in the billing office do not talk to doctors but produce bills based on what the doctors write. Doctors don't document what happened right away if they are busy and so by the time they do make a note, details are often fuzzy. In the case of billing for canceled procedures, the only paper trail available to billers may be the order for the test, and the cancellation may have been communicated by voice, on the fly. When doctors do bill for themselves, it may be difficult to find the correct code, so, in a hurry, we just settle on the first one that resembles what we did. Most of us are not interested in getting better at billing because we hate it. We weren't trained to do it and it takes us away from patient care.

Patients often (but certainly not always) know what did happen. Their bills, though, are written in some long forgotten Martian dialect which makes it really difficult to correct the errors.

My bill for glasses, which turns out to have been correct (after two phone calls) is a good example of what is wrong with medical bills. I apparently owed $137 for "lens sphcyl bifocal 4.00d/0.1, and $155 for "progressive lens per lens" and also more money for "lens polycar or equal" (which I would have assumed was my lens sphcyl, but I guess not), also the anti reflective coating and a miscellaneous vision service and a miscellaneous product which apparently meant that they charged to drill a hole in the lens and polish it. Sales tax I could figure out on my own. Also the bill didn't say anything about insurance, which does pay some portion, and the biller was not planning to submit it. A separate bill has arrived detailing the cost for my exam, also written in some language that I don't speak. The bills are dated a week apart, for unclear reasons. Theoretically I should be pretty well positioned to understand this sort of thing, after 3 decades in the medical field. I'm guessing others, who might be less educated, sicker, more fatigued or less assertive would simply give up and not check the bill at all.

My friend's issue was being billed for copays that he actually paid at the time of service, then getting notices that he was delinquent for not paying them, having to call the billing office multiple times and eventually having to appear in person in order to get it fixed.

Because billing in excess of services usually leads to making more money, there is no real economic incentive to do this right. A responsive and intelligent problem solver in the billing office may actually lose the practice money, if he or she uses the relevant skills to solve customer complaints. The only economic reason to reduce inadvertent overbilling is to avoid being caught and penalized by insurance companies. There are definitely medical billing specialists who delight in doing their jobs accurately, but there is no cash reward for this sort of behavior.

The most effective first step toward taking care of the problem would be a requirement (it could even be a law) that medical bills be descriptive enough that regular people can actually understand them. The affordable care act made health insurance companies describe their services in ways that average people could know what they were buying. If people could actually read and understand their bills, they could see if they were correct. We could even tack on to the law a time limit for resolution of a query. Wouldn't it be sweet if a billing question would be fielded in 24 hours and resolved in a week? That doesn't sound too difficult.

The whole issue of medical billing is, of course, wrong in a very big way, since its existence is based on fee for service. As long as providers can make more money for doing more things and more complex and difficult things, their will be economic pressure to do more intense medicine on more people, thus creating more people who have been medicalized into being sick. We do, though, have fee for service medicine at present, so it's time to support the (not yet written) "Medical Bill
Clarity Act of 2015."

Sunday, September 13, 2015

Marketing medicine and the treatment of high blood pressure

I just read a disturbing article about a recently completed study on treating high blood pressure. The SPRINT (systolic blood pressure intervention) trial was conducted at around 100 locations in the US and Puerto Rico, comparing treating blood pressure intensively to usual care. According to recently adopted guidelines, we now treat blood pressure with the goal of reducing the top number, the systolic blood pressure, to below 140 for adults younger than 60 and below 150 for those 60 an over. The goal for the bottom number, the diastolic blood pressure, is below 90. We recommend lifestyle changes, encouraging exercise, weight loss and reduction in salt intake, and use medications when the blood pressure stays too high. In the SPRINT trial, a comparison group was treated with blood pressure medications, sometimes 3 or more different types, to lower the systolic blood pressure below 120. The patients in the comparison group (more intensive treatment) apparently did better, with a 30% reduction in heart attacks, heart failure and stroke, and 25% reduction in risk of death.

The SPRINT study only looked at patients 50 years of age or older with other risk factors for cardiovascular disease, including heart disease, kidney disease and a calculated risk of cardiovascular events of greater than 15% in the next 10 years. The data still hasn't been released in a way that we can really understand it, and there may be important caveats, such as subgroups who have particularly better or worse outcomes with intensive management, and other beneficial or terrible effects of the interventions. The news so far is just in the form of a press release, with an actual scientific article eventually to be published.

What bothers me is that now a whole group of people who think they are actually well will be encouraged to take medicine, with associated significant side effects, and will identify themselves as vaguely sick and needing medical attention. Also those patients who already are treated for hypertension and have "good control" will be started on yet more medications with drug interactions, high costs and potentially dangerous side effects. It will be difficult to lower the blood pressure below a systolic of 120 without causing symptoms of dizziness and fainting in some patients, and there will be an increase in the number of doctors "failing" to treat high blood pressure adequately and patients "failing" medications.

Already, at our present definition of high blood pressure (hypertension) one in three adults has it. Three out of 4 patients 75 years of age or older has hypertension. The CDC (Centers for Disease Conrol) estimates that treating hypertension costs over $46 billion per year. According to data from various randomized trials, at least 100 people must take blood pressure medications for 5 years to avoid 1 heart attack. This number varies significantly depending on a person's age and overall risk for heart disease, so more than 500 fifty year old women must be treated for 5 years with anti-hypertensive medications to avoid a heart attack, whereas 65 year old men can expect more of a benefit, with a "number needed to treat" of 101. If we lower the target blood pressure to 120, essentially every adult, with a few exceptions, will be on pills for their blood pressure, and the vast majority of them will see no benefit.

The side effects of treating high blood pressure, besides the cost of medications and doctor visits, which aren't trivial, include life threatening electrolyte imbalances, kidney failure and facial swelling as well as annoying dizziness, swelling of the feet and a cough. A sizable portion of the people who are treated with blood pressure medications, or would be, will experience side effects and no actual benefits.

Treating everyone with an elevated blood pressure with medications and defining them as having a medical condition was a huge expansion of the scope of medical care. The first effective anti-hypertensive medications were released in about 1958 and now there are hundreds of them, varying in mechanism, price and effectiveness. Hypertension was really the first symptom-free condition to be widely treated and marked a transition in doctors' roles to include more care that was focused on preventing actual disease than treating it. Most of us like the sound of that, but it means that one in three adults "needs" a doctor for their hypertension, and if hypertension is redefined at a lower number, virtually everyone will be under medical care.

There is a complex interplay of values going on here, and it is strongly influenced by the fact that medicine, as an economic entity, successfully markets itself and expands its markets by identifying conditions that increase risk for actual misery. These conditions then become targets for treatment, which increases doctor visits and medications prescribed. Treating high blood pressure has been perfect in this regard because the need is real in many cases and the outcomes have often been gratifying. People with significantly elevated blood pressure, especially those in whom it is persistent, do develop devastating strokes, heart attacks and kidney failure and treatment to lower the blood pressure, if taken regularly and over long periods of time, really does reduce their risk. Still, vast numbers of people are treated for high blood pressure who experience high costs, significant side effects and medicalization with no benefits, at huge costs to society in general.

Research shows that the vast majority of blood pressure measurements are taken in such a way that blood pressures may be artificially elevated. One way to narrow the scope of treatment would be to measure blood pressure more accurately--either by actually having patients rest for 5 minutes before taking blood pressures or by using ambulatory monitors which take blood pressure throughout the day during a person's regular activities. Both of these methods would serve to focus our efforts on people who might actually benefit from them.

What would be a good direction to move with treatment of hypertension that would help reduce overtreatment and increase benefits of treatment? Research focused on truly identifying who needs antihypertensive medication would be great. If 500 people like me need to be treated for 5 years to avoid one heart attack, that means that too many people are being treated. Research could help determine which of those 500 people actually need treatment, if it was designed to answer that question. The SPRINT trial was designed in such a way that it will likely increase both the number of patients in treatment and the number of drugs prescribed. That is not what most of us want. It is, however, the kind of research that grows medicine's market share.

If the treatment of hypertension was focused on patients who would truly benefit, and the intensity of treatment was proportionally higher for those with the greatest need, quite a bit of the tens of billions of dollars spent on hypertension might be liberated. The money not spent on medications and doctor visits could go to other interventions that would reduce cardiovascular disease. The amount of money that goes into overtreatment of hypertension could buy cooking classes and exercise rooms, swimming pools and dance classes. Unlike doctor visits and medications, this type of preventive medicine also makes us happier and helps make our lives richer.

Monday, August 17, 2015

Medicare Part D--the insurance plan to cover medication for seniors: has it helped?

In 2003 the Medicare Modernization Act added a prescription drug plan to the benefits available to seniors and disabled adults. The act did a few other things, including introducing health savings accounts and defining Medicare Advantage Plans. The prescription drug plan rolled out in 2006, after which time seniors who bought the extra coverage had some help paying for their ever more expensive drugs. Today the government pays about $70 billion per year to provide this service, 11% of the total cost of Medicare.

The purpose of Medicare Part D was to allow seniors, often the most financially vulnerable of our patients, to be able to afford to pay for medications without impoverishing themselves. Since medications are such an important part of treating the diseases of aging, the government hoped that seniors who were able to pay for necessary medications would be healthier, requiring fewer hospitalizations and emergency room visits. This improvement seemed likely to, at least partially, offset the costs of the program.

Medicare Part D is a private insurance plan which costs the insured, on average, $30 a month and pays some or all of the costs of prescription drugs, depending on how expensive they are. Different plans are different, but most stop paying after having paid out $2970, but will pay all but a small amount once the patient's out of pocket costs exceed $4750. The period of time during which the patient must pay all of their drug costs is called, euphemistically,  the "donut hole." Since the total cost of medications is not covered by the premiums people pay, Medicare subsidizes the difference.

In June, the Annals of Internal Medicine published an article which looked at the health benefits experienced by patients on Medicare due to Part D. They were unable to detect any improvement in health or utilization of hospital or emergency room services in Medicare recipients after the initiation of part D in 2006. They did find, however, a 14% increase in the use of prescription drugs. The study certainly would not be able to detect the fact that some seniors certainly did benefit by being able to afford life-saving medications, but on the level of the total population of patients on Medicare, there was no evidence that Part D improved health.

In some ways, Part D coverage is wonderful, despite this study's results. It is definitely less common, since its inception in 2006, to see older people stopping their medications because they can't pay for them. It is also less common for patients to have to choose between having money for food or doctors' appointments and paying for prescriptions. Sometimes I find that, because of the occasionally wonderful oddities of insurance, Medicare insured patients can actually afford the newest and best drug that truly has a positive impact on their lives.The ability to take a drug with a more convenient dosing schedule or with fewer side effects may not keep a patient out of the hospital but it can surely improve their quality of life. Having to stop a medication because of the "donut hole" coverage gap can lead to emergency room visits or hospitalizations, however. A much more expensive Part D without a "donut hole" might have a more impressive outcome.

On the other hand, however, prescription drug coverage that leads to a 14% higher utilization of medications might very well lead to worse health outcomes, which could help explain the findings of this study. In the years since Part D was rolled out, there has been a huge increase in the amounts of opiate pain medications prescribed, and many of the patients who use these are seniors. The epidemic of chronic prescription opiate use and abuse often reduces older peoples' ability to get around and increases falls. Other prescription drugs, even those felt to be pretty much harmless, often have interactions that are much more prominent in bodies that are aging. Side effects are also more common as we age, and can be devastating. Being able to afford more drugs undoubtedly can increase the risk of hospitalization, emergency room visits and disability in a significant subset of patients on Medicare.

When Medicare Part D was adopted it was clear that it benefited the pharmaceutical industry. It was expected, however, to be a win/win situation, with newly insured patients healthier as a result of their improved access to medications. The bill included the requirement that the government not be able to negotiate drug prices with drug companies, which the Veteran's Administration is allowed to do. This results in considerably higher costs for drugs for Medicare recipients than for VA insured patients. So Part D is expensive, and is probably considerably more expensive than it needs to be. People do like being able to get any medication prescribed or recommended by their physician, which is a limitation in a system like the VA's where there is a pretty set and pretty narrow formulary of drugs available. But formularies don't define which medication a patient can take, only which one will be provided at low cost by the dispenser. Negotiating prices within Medicare Part D, with an associated formulary could still allow choice and probably save lots of money.

Does Medicare Part D prescription drug coverage help? It depends on the patient. It clearly does help the person on a fixed budget who finds him or herself in need of  several medications which might add up to a few hundred dollars a month or more. A healthy but not wealthy 70 year old might have a sudden heart attack and find that he has diabetes which he had known nothing about having not visited a doctor for years. That patient might well be discharged from the hospital on 6 new medications which would throw his budget into an uproar, but might well keep him in good health for years. For patients with fewer needs or more abundant income, prescription drug coverage may do no good at all. For some patients whose ability to afford medications means that they will take ones which adversely affect their health, Part D is a hazard. Certainly 70 billion dollars a year and 11% of the healthcare budget is pretty pricey. The Medicare drug benefit probably needs a major overhaul in light of the data that it does not appear to have a significant or cost saving health impact on the population.

Saturday, August 15, 2015

Another rant about how drug companies are not acting for the common good

A few weeks ago I was feeling angry and disappointed when I noticed that many of the articles I was reading in my favorite medical journal were funded by companies who made the products those articles evaluated (that blog here). This is nothing new, but it looks to me like there are increasingly more of these articles which celebrate products and fewer interesting articles about the science of medicine. The other thing that is particularly irritating about this trend, if it is a trend, is that the drugs and devices that are being sold are increasingly more expensive and benefit fewer and fewer people. The reason they benefit fewer people is that they are designed for very specific, and often pretty rare, diseases. Also, since they are so expensive, only a subset of these few people can afford them. They must be very expensive because they benefit fewer and fewer people, so in order to make the money to pay for the research to come up with these drugs and devices, the companies charge small fortunes, which are paid, usually by insurance companies for those who have insurance, and those costs are handed on to everyone who buys insurance or pays taxes.

So drugs and devices are getting more expensive and less useful. But why is this true? Apparently the low hanging fruit of drugs has been picked. We have more drugs for high blood pressure, high cholesterol, infections, diabetes, seizure disorders, depression and lung disease than you can shake a stick at. What's left is rare conditions or subsets of what people commonly get, like like cancers with specific genetic profiles. Also treating diseases that have millions of sufferers is fraught with trouble. If a company produces a drug or device that helps many people who are likely to live a long time in basically good health, any side effect, even a rare one, will eventually become evident, with terrible consequences including lawsuits and even withdrawal of a blockbuster from the market. If a company produces a drug that gives a few people with terrible diseases a few more months or even years of life, not only are those patients often willing to spend a fortune on the drug, but they are very unlikely to notice a rare side effect or be able to connect it with the drug.

So what we are getting now from the pharmaceutical industry (with occasional exceptions) is wickedly expensive drugs of limited scope, whose safety and effectiveness is never studied adequately. These cost so much that they will likely increase the already unsustainable price of medical care. We all share the burden of those costs. The only non-regulated way to fix this problem is to quit agreeing to pay these high costs for miracle (or not so miracle) drugs. I'm not sure that, in our culture, we are willing to make that choice.

Saturday, July 18, 2015

Drug company funded research in the New England Journal of Medicine: this feels like a conflict of interest

Today I thought I'd read the New England Journal of Medicine (NEJM) and learn something deeply meaningful. I usually love the New England Journal (Wikipedia says it is "among the most prestigious peer-reviewed medical journals and the oldest continuously published one") because I feel like it has such a strong history of academic excellence that whatever they print will have value. This is probably not true.

The New England Journal
In 2009, Marcia Angell MD, a senior lecturer at Harvard University and the former Editor in Chief of the NEJM wrote an article entitled "Drug Companies and Doctors, a Tale of Corruption" in the New York Review about the way drug companies skew research to encourage increasing and inappropriate use of medications. It was based on what she had seen published in the New England Journal and others. This might have been a hint that there was something amiss in the contents of my favorite professional publication.

In 2012, the Washington Post published an article about a diabetes drug, Avandia (rosiglitazone), which has proved to increase the risk of heart attacks and heart failure. The New England Journal decided to publish articles which reported results of studies funded by GlaxoSmithKline, the company which produced the drug. These articles concealed information that showed that the drug was harmful. Editorial decisions were made which, at least in hindsight, were bad. The Washington Post article discussed the many ways in which a drug company which funds research for a medication can manipulate the presentation of the data and get that version published in a prestigious journal which doctors like me tend to believe.

The New England Journal has several sections, but the Original Articles is the one I like best. This is the section where new research is reported. There is also the Perspective section, which has gotten more prominent in recent years, and consists of articles by people who are in the thick of something, maybe mass casualty situations, maybe health policy, big picture articles. There are also editorials, usually about the original articles, and there are letters and image challenges and case presentations and educational updates about specific topics.

Articles this week: not great
This week's Original Articles were primarily about new drugs, and were mostly funded by the drug companies that will or do make money off of those drugs. Oh yeah, and one about a new diagnostic test, funded by the company that will make money off of that diagnostic test. There was one article not funded by industry which looked at the causes of pneumonia in patients who were admitted to the hospital with it, reporting that the majority were caused by viruses.

The first article was funded by Pfizer and reported a new chemotherapy drug for breast cancer that, combined with another chemotherapy drug which costs over $10,000 per month results in longer survival. The new drug's is not yet marketed and so a price has not yet been decided.

The second was funded by a Boston company, Vertex, for their new product that can reduce the lung problems that go along with cystic fibrosis, a genetic disease that causes pneumonia and problems with breathing. If the cost of other drugs for cystic fibrosis is a guide, its cost will be sky high.

The third article is funded by Merck Sharp and Dohme, and studies their drug sitagliptan (Januvia), one of the many drugs that reduce blood sugar in patients with type 2 (generally adult onset) diabetes. The study was primarily to see if their drug caused heart problems, because people thought that it might. They studied more than 14,000 patients for about 2 years and found that their drug did not cause heart problems at least over the course of those two years. It also didn't work very well to reduce blood sugar, but not much was made of this in the conclusions. The drug, which helps reduce blood sugars by just a smidgen, costs $3000 a year or thereabouts, far more than generic medications which work better.

The fourth article evaluated a test that could be done to more accurately determine if a person has lung cancer at the time of a bronchoscopy. Since the test can simply be ordered at the time of the bronchoscopy it will probably be ordered nearly all of the time this test is done, and, I'm just guessing, may just about double the cost of the procedure. The first noted funding source for this study was Allegro Diagnostics, which will be marketing the product.

Then came the pneumonia article (yay, information I can sink my teeth into.) If viruses cause most cases of severe pneumonia, there may actually be some argument for not putting everyone we see with pneumonia on antibiotics.

The final article which was funded by GlaxoSmithKline looked at the ability of an antibody to clear amyloid from the liver in a very rare condition called systemic amyloidosis, which mainly causes death and disability through deposits of a protein in various tissues, of which the liver is one. If this is released it will be very very very expensive and will probably serve only to palliate a very rare disease.

Not to put down miracle drugs, because they are pretty cool, but perhaps the Original Articles section should be renamed Articles Funded by Drug Companies Supporting the use of Very Expensive Medications.

Drugs and Doctors
Doctors are increasingly prescribing more and more expensive drugs for just about any complaint. Even the Onion has noticed (read this brief article and chuckle.) This is in no small part because we believe that drugs are the answer, because the research tells us so. The research that tells us so is funded by the companies that make the medications, because they have the money to fund expensive studies. There is much less money in research on cool stuff like what causes severe pneumonia. According to the Washington Post article, the NEJM had published 60 articles about new drugs that were funded by drug companies in the year prior to the report in 2012. Since it publishes 54 times a year, that's just a touch over 1 article per issue. This week's issue had 4 such articles plus the one about the lung cancer test. It seems like they may be escalating.

But why does the New England Journal publish this stuff?  I think this may be a big part of it: we all love magic potions--it's in our basic makeup as people. Even societies nearly untouched by pharmaceutical companies delight in miracle cures. Doctors and chemists love to dabble in potion making and testing, hoping for that amazing discovery that abolishes misery and old age. They have even been successful--look at penicillin and many others. But when big money backs these endeavors to the exclusion of other good science, we tend to focus on them, and our professional publications will reflect that in what they publish. Unfortunately the economic forces at work favor creating potions that sell, and not necessarily ones which work. Even though I think I understand the rationale, it's pretty disappointing that one of the "oldest and most prestigious peer reviewed journals" is filling its pages with research that is funded by the companies that financially benefit from positive results and therefore is likely to be skewed and misleading.