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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.

Tuesday, July 7, 2015

Ultrasound in Tanzania--the gift that keeps giving

Another great trip! I have gotten to go with University of California at Irvine medical students to Tanzania for three years as their supervising MD. They do all of the work, pretty much, preparing lesson plans to teach clinical officer students basic ultrasound as well as designing study protocols, getting institutional review board approvals, and carrying ultrasound machines on fatigued shoulders through multiple airports. I get to teach them a bit about clinical medicine, field questions that they couldn't possibly answer and flaunt the MD on my nametag.

Ten students, just done with a pretty grueling first year, came to Mwanza, Tanzania this year and worked like dogs for a month teaching and doing research. Each year the project is a little bit different, with different research protocols along with improved and adjusted curricula. Their primary project is to teach a large group of students (this year about 100) who are in school to become clinical officers, roughly the equivalent of nurse practitioners. These students will go on to practice medicine in a country which has only 1 doctor per 125,000 people, the worst ratio in the world (Germany has one doctor for every 263 people, per the Economist 2015 World in Figures.) UC Irvine teaches their medical students, starting in the beginning of the first year, how to do ultrasound at the bedside, which cements their knowledge of living anatomy and gradually expands during their 4 years to competence in recognizing all kinds of diseases which have ultrasound findings. This group of students is comfortable teaching basic ultrasound to their African counterparts, who are amazingly knowledgeable in anatomy and physiology. The African students get 3 weeks of lectures and daily hands-on sessions, learning how to get good ultrasound views of the heart, lungs, abdomen and even the womb in pregnancy. Having a cadaver to dissect is apparently a luxury not available to these students, so ultrasound is their first opportunity to actually see inside a human body. Unfortunately 3 weeks is not nearly enough training to become competent in performing and interpreting ultrasounds, but these students will never be afraid to take the steps necessary to learn more, and they will never forget how the heart looks when it beats and how the liver, spleen and kidneys nestle close to each other at the peritoneal reflections.

There are ultrasound machines in Tanzania, and few people who know how to use them. There are not enough ultrasound machines in Tanzania, at least not ones that work, but as the technology gets cheaper, the older machines will be even cheaper, and if there are people who understand how powerful the technology is, they will buy them. The teaching project will not create radiologists, but it will make general practitioners push medical practice in the direction of including more bedside ultrasound. In my experience, this will save lives and reduce suffering.

Beside improving their understanding of anatomy, after 3 weeks most of the clinical officer students who were in the ultrasound class had skills which could have profound clinical impact. If provided with a functional ultrasound machine, they could determine the age of a fetus, the position of the placenta and the head, and determine the fetal heartbeat, an important indicator of fetal health. This information could result in appropriate referral for caesarian section, potentially saving the lives of both the infant and the mother. They could identify a pneumothorax (collapsed lung) in a patient with a traumatic chest injury, which would be easily treatable if found in time and maybe fatal if missed. They could identify bleeding into the abdomen or chest in patients who presented after motor vehicle crashes, which are terrifyingly common. They will be able to look at an ultrasound picture and see more than a bunch of blurry gray, black and white shapes.

This project is cool in so many ways. I love that students teach students. The process is very gratifying and makes the material even more exciting. The UC Irvine med students are now completely awesome at basic ultrasound, and they were only just good when we started. The teaching goes both ways--the African students have an accelerated curriculum so they teach the UC Irvine students things they don't know, as well as asking questions that make all of us think harder. I have done overseas projects which directly help people in need, which is wonderful in its way, but this project potentially has legs. Teaching medical practitioners to be better at their jobs is really powerful and has the ability to affect the lives of many patients. In teaching what they have just learned themselves, while they are still excited about it, the US medical students show the Tanzanian ones how to be teachers of each other and to love learning, which could end up being as important as what they actually teach. In Tanzania, medical students work incredibly hard for the opportunity to continue to work incredibly hard in overcrowded hospitals and clinics with inadequate resources. It feels like this project may make them just a little more effective and a little bit happier in the process.

Thursday, May 28, 2015

Actinic Keratoses and Carac (fluorouracil) cream: why is this so expensive?

First, a disclaimer: I don't know why Carac (0.5% flourouracil cream) is so expensive. I will speculate, though, at the very end of this blog.

Sun and the skin: what happens
If a person reaches a certain age, has very little pigment in her skin, and has spent lots of time in the sun, bad stuff happens. The ultraviolet radiation of the sun does all kinds of great things: it makes us happy, causes us to synthesize vitamin D which strengthens our bones and it gives us this healthy glow until we get old and wrinkled and leathery. And even that can be charming. The skin cells put up with this remarkably well for a long time, partly aided by melanin pigment which absorbs the radiation, which is why we tan and freckle, if we are fair skinned. Eventually, though, we absorb enough radiation that it injures the skin and produces cells which multiply oddly. It also damages the skin's elasticity which creates wrinkles.

The cells which reproduce in odd ways peel, creating dry skin or dry spots, or warty growths or even small hard horns. The scaly spots are called "actinic keratoses" which just means sun induced scaly spots. Sometimes the skin cells become cancerous and lump up and create non-healing sores. This is when we regret going out without a hat or sunscreen, but, of course, it is too late.

Topical chemotherapy: good idea or great idea?
In 1957 scientists published a paper showing that flourouracil, a flourine attached to a nucleotide (RNA building block), inhibited liver cancer cells. This became one of our early chemotherapy drugs, and is still an important drug in treating colon cancer. When mixed up in a skin cream, it can kill the abnormal skin cells which grow on our sun exposed skin, allowing the normal ones to take their place.

The way fluorouracil cream was initially used was awesome and terrible. It was applied daily for 4-6 weeks to the affected area and the skin became a war zone. The abnormal cells died, leaving red swollen places where sun damage was most severe. Generally people using it looked pretty bad for weeks or longer. Eventually they healed and got rid of their scaly spots. Many people still use it this way, to good effect. We also found that we could treat just small areas at a time, and even just the scaly spots themselves, and that we could use the cream for shorter courses and avoid the intense inflammation. This was a major advance in therapy since our other main option was to freeze the spots with liquid nitrogen, which was a painful, expensive and seemingly never ending process, and which left little white scars.

A slight catch was that the fluorouracil cream was expensive. It was over $100 for a 30 gram tube. Maybe insurance would pay, but it was top tier, and at least some of the cost made its way to the consumer.

Several years ago my husband was prescribed Carac, one of the first fluorouracil creams. It was expensive, so we have made it last, far longer than the expiration date. It is a prized possession, that tube. We have both spent far too much time in the sun without protection, loving every minute of it, and regretting it now in hindsight. When the scaly spots become too annoying, we use the cream until they go away. But the tube is almost empty. Time to buy some more.

Pretty pricey
I looked online to find out how much it would cost if I bought it internationally. I found a product from India that was not too expensive. It was 5% flourouracil rather than the 0.5%, but that is the percentage in the brand name Efudex which is one of the alternatives in the US, so it seemed reasonable. I got the cream in the mail and tried it and it was slightly granular and didn't work. The effect of the Carac was dramatic. The effect of the Indian cream was essentially nothing. "You get what you pay for," I thought. I asked a compounding pharmacist acquaintance to make me some. I respect this pharmacist. He mixed up flourouracil in a skin cream base at a concentration of 5%. The cream was also grainy and didn't work. It seemed to do a little better than the Indian cream, but nothing like the Carac. Finally I decided to just get the Carac. I asked my friendly neighborhood pharmacist what it would cost. She told me that a tube of Carac, 30 grams, costs around $2000. NO! I will not do that! The amount of active chemical in that little tube, the fluorouracil that is used as intravenous chemotherapy, would cost about $40 retail. It is possible to get generic or brand name 5% fluororuacil creams for prices ranging from $170-$500 for a tube, but that is still horribly expensive, and if they didn't work, that would be an annoying next chapter in this tale of woe. Looking a bit harder I found that there is now a 2% solution which is a little less pricey, though there is nothing that I've read that tells me how or if this works. Maybe I should just make some, but playing around with chemotherapy drugs sounds like a bad idea.

Other options
What, then, should someone do with their actinic keratoses? It is just not reasonable to pay $2000 for a tube of cream. Uptodate, which is an online resource used by many physicians to keep abreast of expert management of diseases, says that the treatment of actinic keratoses, besides 0.5% fluorouracil cream, includes use of sunscreen to prevent further appearances of the little spots, dermabrasion to remove the affected skin (ouch)and that the use of topical retinoids (vitamin A derivatives) can help. They also mention that ingenol mebutate and imiquimod creams (both horribly expensive) are better than placebo as is chemical sensitization plus light therapy (I can only imagine what that costs.)

I have decided to use a retinol preparation which is pretty darn cheap and calls itself "wrinkle cream." It is in the cosmetic section of my local drugstore. Retinol is one of several retinoids that are approved for use on the skin, and also treat acne. I will also wear sunscreen and a hat. So far the retinol, when applied to the whole sun-damaged area (for me, the forehead) is helping reduce my sun induced roughness and scaling. Retinoids appear also to reduce the risk of developing squamous cell cancer, a common malignancy in sun exposed skin. For now, at least, my path is clear.

Mysteries persist
But there remain mysteries which I have been unable to solve using books and the interwebs. Why is 0.5% flurouracil 10 times more expensive than 5% fluorouracil, even though the latter is theoretically 10 times stronger? Why do they even make 5% flourouracil cream if the 0.5% stuff works just as well? Is it in some way very difficult to mix flourouracil into a cream? Why does Uptodate recommend 0.5% flourouracil and not 5%? I have no idea. I can speculate a bit about the costs, though.  It's possible that the cost of the 0.5% flourouracil is made to be as high as the newer creams, like imiquimod, which were priced that high because they were relatively new, and are still not generic. All of these creams are still financially viable because they were cheaper and more acceptable than going in to the doctor every few weeks to have him or her freeze a bunch of spots, resulting in what looked like a mild case of chicken pox which healed to make white scars. It's still really hard to believe that anyone would pay $2000 for a little tube of skin cream and that we, as physicians would regularly recommend that they do so.