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.

Cancer, cost, hope, and the responsibility of physicians

The headline on a recent article by Marilynn Marchione of the Associated Press, as featured in the Arizona Daily Star, is “Few doctors discuss cancer costs with patients, study finds”, and that about covers it. The actual study previewed in the article, which will be presented at the American Society for Clinical Oncology (ASCO) conference in Chicago in June, was led by Dr. Rahma Warsame of Mayo Clinic. It recorded clinical encounters at three cancer sites (Mayo, USC, and LA County) and discovered that the often extraordinarily high cost of cancer care was not usually discussed; discussion happened in just 151 of 529 visits, and in only 45 of those cases, less than 1/3, was the issue brought up by the doctor rather than the patient.

The article suggested several reasons for this. One was that the visits were short, 15 minutes at USC and LA County (about typical, though, across the country), and 30 minutes at Mayo. Another was that doctors are trained to diagnose and recommend treatment rather than to focus on the cost. A third is that the doctors themselves might not know the costs of the treatment. And, for a combination of both of those reasons, they might be uncomfortable talking about the cost. Given that these treatments can easily cost $100,000 a year or more, this is not fair to patients. While good insurance might cover the cost, not everyone has good insurance. In addition to the uninsured, many more people have crappy insurance plans with poor benefits and lifetime caps that are easily exceeded with the cost of cancer care. For most of these folks, the answer is go broke and bankrupt, or die without treatment. From a health point of view, this is not a desirable state of affairs. From a medical point of view of trying to do the best for a patient, it is an abrogation of the obligation to provide the best care. From a moral point of view, it is reprehensible. From some points of view, however, it must be ok, because this is the situation we are in, and it is not by accident. And that is tremendously distressing.

But who would have such a despicable point of view? We can start with the organizations that make money from such care. Of course, this includes the very clinical oncologists who are the members of the ASCO, but they are the least of the beneficiaries. Indeed, I feel comfortable saying that most oncologists would enthusiastically welcome lower costs for chemotherapy. The biggest winners are the drug manufacturers, who charge fantastic amounts for these drugs, and the hospitals and “cancer centers” that provide them. A large part of this profit comes from the reimbursement from insurance companies, which, in addition to paying the cost of the drug, also pay an fee to the hospital for administering the drug that is, frankly, exorbitant and far more than is paid for comparable work in provision of most other care. Indeed, this is why there is such an apparent explosion of cancer centers. It is not because of the explosion of cancer; it is because they are big profit centers and every hospital wants their own to try to lure cancer patients (those who are well-insured, it goes without saying) away from their competitors. And, in a step back from my confidence in the patient-centeredness of oncologists, those groups of oncologists who own independent cancer centers outside of hospitals, and make lots of money on it.

Why would insurers pay such high prices? Medicare pays a pretty high “administration fee”, and most private insurers reimburse at multiples of Medicare. Also, insurers can just raise their rates to cover these costs, especially if they value (as in “appreciate the clout because of the number of patients they control”) the relationship with a particular hospital, cancer center, or health system as described in Elisabeth Rosenthal’s “An American Sickness” and discussed in my blog post “United Airlines, health care, and a system designed to privilege the powerful” (April 15, 2017).

Students learn very little about the cost of care in medical school. There are beginning to be some courses that introduce cost-consciousness, but they are uncommon and limited, although even residents and students have access to smartphone information, through apps such as ePocrates®, that provides information about drugs, and often cost.  But is true that these doctors do not know the cost of the care that they are providing? Certainly while the clinical oncologist may not know the exact dollar amount, they know that it is a lot. And it is irresponsible to not discuss this with patients, to help them understand what they are getting into when they start treatment.

Drugs are only one component of the cost of care; a huge one in cancer, but radiation therapy can be even more. As I have discussed before, the real problem is that no one knows what anything actually costs. Yes, hospitals have “charge masters”, but they are not only dense and hard to find (especially for patients) but not that relevant; these charges are adjusted dramatically depending upon insurance. Medicare is unique in that it sets the amounts that it will pay (a lot for chemotherapy), but other insurers pay varying amounts depending upon the contracts that they have arranged with the hospital. Thus we have the irony (which I discussed in “Integrated Health Systems and Cost: The Price is the thing!”,December 20, 2015) that smaller cities with large integrated health systems have some of the lowest costs for Medicare (because they can create efficiencies) but some of the highest costs for private insurers (because they “own” the market and can charge more).

The real issue is that people should be able to get the care that they need and is medically indicated and has evidence to back its effectiveness without going broke. Physicians can no longer hide behind the first half of that sentence, saying “I recommended the care that they need and is evidence-based” (although certainly their recommendations should always be evidence-based!) without considering the cost. On the other hand, the health system of the US should ensure that everyone is covered for necessary care. One way of having enough money to do this is not providing unnecessary, evidence-free care to some people just because they or their insurance will pay for it.

This also means that people should not expect it. As horrific as it is for you or a loved one to be dying of cancer, it is unreasonable to expect that experimental, hopeful, or completely wishful-thinking treatments would or should be paid for by someone else, and it is generally a bad idea to try to pay for them yourself since they won’t work. Some years back, my friend was dying of an aggressive cancer. A bone marrow transplant failed. The genetics of his cancer were such that it was destined to fail. The cancer center (arguably the “best” place in the US for his type of cancer) offered him the opportunity for a second transplant, but the insurance company rightly refused to pay. His family cashed in his entire retirement to pay. Predictably, the transplant failed, and his family was left without any savings. The doctors knew that it would almost certainly fail, and should have known what it would cost, and thus not recommended it. An agnostic stance on cost is unacceptable.

The media coverage of the ACA and the Republican repeal plan makes clear that there are many people who do not want to pay for insurance coverage when they are healthy, but want everything taken care of when they or their family are sick. Then they get desperate and might spend the last of their savings on treatments that will not work, whether quack drugs like laetrile or futile attempts offered by the medical community, such as happened to my friend. It is the responsibility of doctors to know the cost of treatments they recommend and discuss this with their patients, and to not offer ineffective treatments. It is wise for patients also to ask for this, although many are unempowered and intimidated by the medical system.

But if we all pay in when we can and benefit when we need it, the system would work. It’s called single payer, or Medicare for all. Unfortunately, our system, with or without ACA, is nowhere close.

"Hidden Figures": Racism, sexism, anti-science, public health and cancer

I recently saw the wonderful film “Hidden Figures”, which tells the story of the African-American women who worked as “computers” (when the word meant “people who do computations”) on the NASA program that sent men (and later some women) into space. The focus was on three of the most significant of these women, Katherine Goble Johnson, Dorothy Vaughan, and Mary Jackson. Ms. Johnson (played by Taraji P. Henson) is a gifted mathematician who calculated the trajectories of many of the early space flights (including, as portrayed in the movie, John Glenn’s orbital flight in February, 1962) and the later Apollo 11 moon landing in July, 1969. Ms. Vaughan (played by Octavia Spencer) became an early and leading computer programmer, a supervisor at NASA. Ms. Jackson (played by Janelle Monáe) was the first African-American female engineer at NASA. All of these women, and no doubt many others, were critical to the NASA space program.

             

All of them, as the film documents, were “firsts”. Among many such firsts, Katherine Johnson (then Coleman) was one of the first African-Americans and first African-American woman to desegregate the graduate school of West Virginia University. Dorothy Vaughan was one of the first programmers and first African-American woman supervisor at NASA. Mary Jackson became NASA’s first African-American woman engineer, after winning a court case that allowed her to desegregate Hampton High School to attend night classes. When asked in the film by a white supervisor if she would still want to be an engineer if she were a white man, she says that if she were “I would already be an engineer!” She also gives a terrific speech to the judge in her desegregation case about the significance and importance being a “first”.

“Hidden Figures” portrays and does not downplay the blatant and overt racism and sexism that existed in that period, legally in the Jim Crow South where the film takes place at the NASA Langley facility in Hampton, VA, in 1961, after Brown vs. Board of Education but before the Civil Rights Act of 1964. There are separate drinking fountains, and a separate coffee pot for Ms. Johnson, and as graphically depicted in the film, a half-mile run for her to go to the only “colored women’s” rest room to relieve herself! The laws in the South came down, but racism – and sexism – there and in the rest of the country are hardly things of the past.

But this is not a movie-review blog; it is about medicine and public health and social justice. The social justice aspect should be obvious, but let me start the discussion of health and medicine with science. Clearly, science was at the forefront of NASA’s mission, and the film depicts how the need for “best and the brightest” overcame even the structural racism of the American South for these women. On a larger scale, though, the idea that science was the future, that knowledge and education and learning and discovery were critical to America and the world, are also implicit, scarcely discussed in the film (save for a few inspirational speeches, such as President John Kennedy’s). In 1957 Sputnik, the first satellite, was launched by the Soviet Union, in April 1961 cosmonaut Yuri Gagarin orbited the earth and a month later Alan Shepard was the first American to do suborbital flight. Glenn’s 1962 orbital flight was only 7 years before the Apollo 11 landed on the moon!

I was alive then, a fairly young child for Sputnik, older for Gagarin and Shepard and Glenn, and just graduated from college for Neil Armstrong’s “a small step for a man, a giant leap for mankind” speech. I was a part of (maybe at the time I thought “victim of”) President Kennedy’s physical fitness program, doing push-ups and sit-ups and chin-ups so we could “beat the Russians”. I was also a student, learning and excited by science. I was impressed by the space program, but not as dedicated a devotee as many others. Perhaps this was because I was not enough of a science geek, but perhaps it was also in part because it seemed natural, the advancement of knowledge and science was natural, progress was natural. Maybe I was less awestruck than older people in the same way that more recent generations have been less impressed by the technology of computers and cell phones. But we all (I thought) believed that science, and learning, and advancement were what the future was about. We had come through “the war” (WWII), and Americans had jobs, and their children were going to school, and while there were still fights to be waged for racial and gender and economic justice, the outcome was, we knew, unquestionable progress.

But maybe not any more. While we built the Interstate Highway system in the 1950s, while we were able to go from suborbital flight to a man on the moon in 8 years in the ‘60s, now we are in an era where many Americans – including many of our leaders – deny the incontrovertible facts of man-made global warming and climate change. An era in which science and scientists and not to be trusted, where, when facts challenge our beliefs, we make up “alternate facts”, where education and knowledge, rather than things to be sought after and admired are seen as “elitist”, where the only persistent “good” is the enrichment of the already richest, whatever the cost to the rest of us and to the planet. On April 23, 2011 (“Cabaret" and "Inherit the Wind": Will we again reap what is being sowed?) I wrote of how the play “Inherit the Wind”, written in the late 1950s, was meant as an allegory for McCarthyism, since the “ignorance” that denied evolution in 1920 Tennessee was no longer an issue; evolution was fact. And yet 60 years later it was still being questioned. We see the same, today, for all aspects of science and knowledge; this is a real test given by a “Christian” school!

But what about medicine and health? Is that not still the New Frontier? We may have abandoned even the shuttle program with manned spaceflight, and the launches from Cape Canaveral may be all private satellites out to make a profit (or spy on us), but isn’t NIH our new NASA? Didn’t President Obama promise a campaign to defeat cancer in the same way President Kennedy declared our intention to get to the moon? Well, maybe. NIH’s budget is not only stagnant, but its funding overwhelmingly goes to very basic research and to find “bullets” to kill cancer, as if it were a disease rather than scores of diseases, almost all different. But there is far, far less funding to prevent cancer, not only to find the causes of these diseases, but to even eliminate the causes when we know them. Where is the funding for public health? Sure, there are some victories. Smoking, the major cause of death for decades (and, although it is a cause of many cancers, more of the deaths it causes is from increased heart disease and chronic lung disease than cancer), is down, but the fight against it has been a long and hard one and is not over. Other environmental causes of cancer such as air, water, and soil pollution are minimally addressed, because, like smoking bans, they might decrease the profits for some businesses and the wealth of the wealthiest.

“Hidden Figures” has some brave acts by its white characters. John Glenn (Glen Powell) refuses to fly unless Katherine Johnson rechecks the calculations (and thus she gets her job back). Al Harrison (Kevin Costner), the NASA chief, takes a crowbar to the “Colored Women’s Restroom” sign when he discovers that it is traveling to far-off segregated restrooms that is taking Ms. Johnson away from her job. Yes, these can be seen as self-serving (helping them to get their jobs done) but they are also, in the context, heroic. I was recently sent copies of archives of mimeographed newsletters from civil rights groups based in southern Brooklyn, where I grew up; one of them contains an article from 1965 about young African-American women being denied membership in a “cabana club” (in the NORTH! In Brooklyn, NY! In 1965!), until the singer Julius LaRosa shows up asks the folks picketing outside why they are there, says “I don’t perform in segregated places”, and intervenes.

John Kennedy said we should go into space not because it was easy but because it was hard. Maybe we shouldn’t do things just because they are hard, but we need to not deny what we don’t completely understand just because it is easy. We need science and we need progress and we need public health. People may not know everything themselves that environmental scientists and scholars and mathematicians and physicists and doctors and public health workers know, but they should be proud of those who do, and encourage and support them. We need more girls and minorities to enter the STEM fields, as in programs such as that in NYC documented in the February 17 New York Times.  We need more Katherine Johnsons, and Dorothy Vaughans, and Mary Jacksons, and the love and respect for learning and truth that they stood for.

We even need more Julius LaRosas.

More on mammography: just because you don't like the results doesn't make research junk science

A recent study published in the New England Journal of Medicine, “Effect of three decades of screening mammography on breast-cancer incidence”, by Archie Bleyer and H. Gilbert Welch[1], has generated enormous controversy. This has been caused by a combination of the study’s findings, the interpretation of them by the popular press, and the reactions of those who have a vested interest in the status quo – a combination that regularly occurs any time anyone publishes any research questioning the current conduct of screening or treatment for breast cancer (see, for example, my blog post Breast cancer screening: conflicting evidence? what are the important questions for health?, October 30, 2010). It happens in other areas, also, but breast cancer is the most common and in some sense most personal of cancers for women, and has a huge advocacy community, as well as powerful groups who profit from both treating it and screening for it.

What did the study show, what does it mean to people, what is the implication for cancer screening and most important, for the health of people (overwhelmingly women) who might get breast cancer? Before addressing these questions, I think it might be helpful to review a little about screening tests, cancer, and people’s hopes and beliefs. People want to not get sick, and especially don’t want to get cancer. If they do get it, they want to be treated and get all better. Of course, despite the use of “cancer” as if it were a single disease, and the existence of organizations such as the American Cancer Society, the federal National Cancer Institute, and the many Cancer Institutes, hospitals, and specialists, it is in fact a variety of diseases that all share certain characteristics but differ in many others. These include commonness, severity, cause, and likelihood of progression or death with or without treatment. Known causes for some cancers include smoking, radiation and viruses, and for many (including most breast cancer) the cause is unknown. It is even more complicated, because just naming the organ affected (breast, lung colon) is not all there is to it, as there are different kinds of cancer that affect the same organ. Whew. This is why the idea of “a cure for cancer” is unlikely; there are cures for some, and may be cures for others in the future, but there is unlikely to be “a” cure.

Some cancers, like breast cancer, are common enough, and well-publicized enough, that women realize that there is a real risk. In that case, the hope is that there exists a screening test that can identify it early enough to intervene and make a positive difference in the outcome. The first thing is that screening tests, by definition, are only for people who have no symptoms of a disease; once they do, a test, even if it is the same test, is no longer “screening” because the probability of the disease is greater in people with a symptom. For example, if one has a lump in the breast, a mammogram may be a good diagnostic test, but it is no longer a screening test. In looking at the criteria for a good screening test, there must be:

1)      A disease a test can screen for (while this seems obvious, doctors still do tests in asymptomatic people that do not effectively screen for any disease),
2)      A reasonable sensitivity and specificity to the test (meaning people with disease are more likely to have a positive test and those without the disease to have a negative test),
3)      A test that is reasonably cheap and acceptable to patients (tests like mammography and colonoscopy, for example, are both more expensive and more uncomfortable than, say, a blood test),
4)      A more definitive test available to say more definitely whether people who screen positive actually have the disease (for most screening, although those who screen positive are more likely to have the disease than those who do not, the majority of those who screen positive still may not have the disease),
5)      An intervention that can be done in the asymptomatic stage that will prevent the disease from progressing (or else, why not wait until it is symptomatic?)

So how does mammography stack up? This is a big part of what is addressed by the Bleyer and Welch study. They have looked at 30 years of screening in the US and found that screening mammograms have uncovered a large number of early-stage breast cancers; in fact, over that time, the number of early-stage breast cancers identified has doubled (from 112 to 234 cases per 100,000 women per year). This is a good – particularly if criterion #5, above, is met – and they can be treated and prevent women from dying or suffering serious morbidity. If this is happening, then (assuming the actual rate of cancer stays the same) the number of cancers diagnosed in later stages, where intervention is less successful, should go down. That is, those cancers detected early and treated would not progress and should mean that many fewer women present with later stage cancer.  Unfortunately, this study demonstrates, that has not occurred. The decrease in late-stage cancer diagnosis has been about 8%, or 8 per 100,000 women per year. So, for every 100,000 women, we are diagnosing an additional 122 early stage cancers, but only decreasing the number of late stage cancers by 8. This means that most of the additional women found by mammography to have early stage breast cancer would not have progressed to late-stage cancer. This, then, leads to their assertion that cancer was over-diagnosed – in 70,000 women in 2008 alone. Any estimate of the number of lives saved by screening and early intervention is inflated if it includes large numbers of women whose cancers would not have progressed. In other words, many of these women diagnosed with cancer, many of whom had non-trivial interventions (surgery, radiation chemotherapy) had cancers that would, basically, have not required any treatment.

Some radiologists who do mammograms have said that this is “junk science” (“Study links mammograms to overtreatment”, Boston Globe, November 21, 2012), but it is clearly not; the findings are the findings. The implications, however, are harder to assess. Does this mean women should not get mammograms? No, certainly that would be a premature conclusion. Some of the women diagnosed with early stage breast cancer would have gone on to develop late stage cancer; if you are one of the 8, you are lucky to have been found; if one of the 114, maybe not, especially if you had to endure the potential harms of chemotherapy or radiation or both, not to mention mastectomy. It may suggest that aggressive interpretation of mammography findings are not warranted. What would be useful would be to identify mammographic findings and subsequent pathology findings on biopsy that required aggressive intervention and those that could be safely followed. One type of breast cancer that is likely to be the subject of future studies is that called ductal carcinoma in situ, or DCIS, which may be more likely than some other types to resolve.

It may well be too soon to know the answer on mammographic screening, but it is clear that it is far from the perfect screening test that everyone would like it to be. We need more studies, and more information, and mostly we need a willingness to accept the accumulated findings of research. Certainly, what we do not need is for those who have a financial stake in screening and treatment to call good research “junk science” because it comes to conclusions that they do not like.

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[1] Bleyer A, Welch HG, “Effect of three decades of screening mammography on breast-cancer incidence”, NEJM 22Nov2012;367(21):1998-2005.

"Eggs Benedict" and "Choosing Wisely": often the best thing to do is nothing

Years ago (OK, decades ago), when Woody Allen was a standup comic, he did a short, famous bit called “Eggs Benedict”. The narrator (let’s say “Woody”) is having pain in the chestal area (a great formulation which has long been popular in my house). He is pretty sure it is heartburn, but is worried and doesn’t want to pay the $25 to see a doctor (I told you it was a long time ago). Luckily his friend, Eggs Benedict, is having the same kind of pain. He figures if he can get Eggs to go to the doctor, he can find out what it is and save money. It works, and Eggs finds out it is heartburn. Two days later, he discovers Eggs is dead. He immediately checks into the hospital, has all kinds of tests, and discovered he has – heartburn. The bill is $110 (it was a really long time ago!) He goes to see Eggs’ mother and asks if his friend suffered much. “No,” she says, “the car hit him and that was it!”

I was thinking about this story when I was asked to call into a local radio talk show to comment on “Choosing Wisely”, an initiative of the American Board of Internal Medicine (ABIM), which calls on medical specialty societies to list 5 tests or treatments frequently performed in their specialty that they recommend not be done, or not be done on most patients. In the recently released report, 9 medical specialty societies are represented, for a total of 45 recommendations, which can be found here. The 5 for my own specialty, Family Medicine, listed by the American Academy of Family Physicians’ (AAFP), were:

1.  Don’t do imaging for low back pain within the first six weeks, unless red flags are present.

2. Don’t routinely prescribe antibiotics for acute mild-to-moderate sinusitis unless symptoms last for seven or more days, or symptoms worsen after initial clinical improvement.

3.  Don’t use dual-energy x-ray absorptiometry (DEXA) screening for osteoporosis in women younger than 65 or men younger than 70 with no risk factors.

4.  Don’t order annual electrocardiograms (EKGs) or any other cardiac screening for low-risk patients without symptoms.

5. Don’t perform Pap smears on women younger than 21 or who have had a hysterectomy for non-cancer disease.

Each is backed by the evidence, and is accompanied by a summary of the reasons. For example, for #2: “Most sinusitis in the ambulatory setting is due to a viral infection that will resolve on its own. Despite consistent recommendations to the contrary, antibiotics are prescribed in more than 80 % of outpatient visits for acute sinusitis. Sinusitis accounts for 16 million office visits and $5.8 billion in annual health care costs.” Big money for a treatment that doesn’t work, and can cause bad side effects (allergies to the antibiotics and increased resistance of bacteria to antibiotics, for two).

The talk radio hosts had questions, especially about treatment of cancer. One of the American Society of Clinical Oncologists’ (ASCO) recommendations is “Don’t use cancer-directed therapy for solid tumor patients with the following characteristics: low performance status (3 or 4), no benefit from prior evidence-based interventions, not eligible for a clinical trial, and no strong evidence supporting the clinical value of further anticancer treatment.”  That seems like a no-brainer to me, but they wanted to know “What if a patient wants treatment for cancer anyway?” I said I thought it was the responsibility of the doctor to point out that the treatment would not help, and would not only cost money but would have a lot of toxic side effects; I said that I thought most people, if they knew they were going to die from their cancer and the treatment would not help, would not wish to spend their last days and weeks nauseated, losing their hair, and being unable to interact comfortably with their loved ones.

The radio hosts also said “We are always told patients should be self-advocates. What if advocating for ourselves we say we want antibiotics for our sinusitis?” I said that self-advocacy was really important, because no one but the patient and their family could really identify what their health goals were. But this was different from deciding what treatment you wanted; going to the doctor is not going to the grocery store with your shopping list that may include both healthful and bad-for-you foods. It is critical that you identify where you want to go and work with the doctor, or other provider, to come up with a plan that is mostly likely to get you there safely and effectively.

Coincidentally, the same week I facilitated the discussion about futile treatment at the end of life for a group of third-year medical students in their medical ethics course. They had just received a lecture from a distinguished medical oncologist, who presented the four core principles of medical ethics: Autonomy, Beneficence (do good), Non-maleficence (do no harm), and Justice. They also read several articles documenting cases in which end of life decision-making did not go smoothly or well, and the article “How Doctors Die” by Ken Murray, that I have previously discussed (How people die, and how should we?, April 7, 2012). One of the cases involved a patient with terminal cancer who had already failed treatment, and for whom further treatment would be futile (although not without adverse effects). He had agreed to hospice, and to comfort care, until a relative (a physician!) came to town and demanded additional treatment for him, and convinced him to as well.

The medical students, who had  all been through clinical experiences and most of whom had been part of teams that confronted dealing effectively with dying patients, were in agreement with the physician in the article, and with each other, that the treatment was futile and would be a bad idea. However, several felt that, if the patient demanded it, the principle of Autonomy required that it be given. Others noted that this might violate the principle of Non-maleficence. I pointed out that that there were many areas in which we do not allow the patient to pick his/her treatment of choice. For example, we do not allow people to walk into a pharmacy and buy narcotic pain relievers without a prescription, no matter how much they might want them. Certainly the effects of chemotherapy poisons were at least as great.

These are not always easy decisions, but it is one of the reasons being a doctor is hard, respected, and well-paid. If everything were a simple algorithm and one could just memorize the right answer as these medical students were expected to do so often on their multiple-choice tests, it could be done by someone with much less training. Sure, it is possible that someone getting antibiotics for viral sinusitis to get better – indeed they usually do, with our without the antibiotics. Temporal association is not cause. Thus, even when you do the right thing, based on the evidence, and do not get a test or treatment, it is still possible that you will end up worse.

As Eggs and Woody discovered.

The high cost of drugs: treating cancer and cholesterol while building profit

The cost of drugs can be enormous, as anyone who is on many of them, or even one expensive one, can tell you. For most people with good health insurance, the amount that they pay is only a portion of the cost (as with much of health care); still, the co-payments for some drugs, particularly non-generics, can be high enough to be significant for even upper-middle-class people. Lower income people may have to choose between medication and other frivolities – like food. For very high cost drugs, like many of those made artificially by “recombinant DNA” that are used for conditions including cancers, autoimmune diseases like rheumatoid arthritis, neurologic conditions like multiple sclerosis, and inflammatory bowel disease like Crohn’s, the cost is enormous.

The high cost of cancer drugs, in particular, is the foundation of several industries. The most obvious, of course, are the drug companies who manufacture them, and make great profits. The markup price that health insurers (including Medicare) pay for the administration of these drugs, however, is a major source of revenue for hospitals and the doctors who supervise their administration. The staggering growth of “cancer centers” in almost every hospital that can put one together is testimony to this. Most hospitals pursue certain “product lines” (sorry if it offends you to be a widget in a product line) that they see as the most profitable. Yes, medical need is one component; there has to be demand. Clearly cancer, and heart disease are very common and very serious for the people who have them, as well as being high-profit product lines. If less common, diseases that can be treated by neurosurgery are also serious. Indeed, even some neurological conditions that have not been historically treated by surgery, such as stroke, are becoming profit centers when procedural intervention (by, “interventional radiologists”) can be used to treat them. But there are lots of conditions which are also common and serious and are not among the “product lines” hospitals often develop because they are not “profit lines”; obstetrics and psychiatry and pediatrics come to mind (although neonatal intensive care and pediatric cancer treatment, as well as certain types of high-intervention obstetrics, are exceptions).

It is that cancer-drug markup that makes treating cancer profitable. Anecdote: a relatively high-income colleague received the bill for her first set of breast cancer chemotherapy. $30,000. Her husband hid it for several months. (“That’s not so bad,” she was told by a staff member, “we recently had an uninsured woman get a bill for $45,000.” Didn’t make her feel a lot better.) After that initial event, her copayments for treatment were on the order of $600 a month. Because she had good insurance. And she could afford it. Not without some pain, you understand, but much more than someone in one of the lower income groups. Or who is uninsured. Sure, she is happy her cancer could be treated. The point is that hospitals invest in – and advertise their expertise in -- treatment for this kind of disease, and not that kind of disease based on the profitability of it, not the seriousness of the disease.

In addition to the hospitals and the pharmaceutical manufacturers, scientists and the universities that they often work for depend on deals with drug manufacturers to bring their discoveries to market. This can be very lucrative for the universities who employ these scientists, as well as (often) the scientists themselves. It is big business. Bad? Not necessarily. Only a small percentage of the compounds being researched lead to profitable drugs, which is one of the main arguments that pharmaceutical companies use for their high prices and profits (they are consistently, and by far, the most profitable industries in the world if we include only those industries that produce something; the financial industry is something else). Of course, by the way, most of the initial research that produces these new drugs is supported by the National Institutes of Health (NIH) -- which would be you, the taxpayer. So most of those compounds are developed and studied at public expense; then only the most promising are bought by drug companies. Yes, many of these don’t become marketable, not to mention blockbuster profit centers, but the yield is much greater than it was before all the publicly-funded research culled them out. Oh, by the way, even though you funded that research, you don’t get a discount on the drugs that finally come to market. Sorry.

Sometimes, of course, there are drugs that are “blockbusters”, and they are not always the most expensive cancer drugs. They are big because they treat (or sometimes are thought to treat) conditions that are very common, so that there are millions of users. These are not as likely to support the development of new hospital product lines (where the profit-per-user has to be very high) but make a lot of money for the manufacturers. In the past these have included anti-anxiety drugs of the benzodiazepine class (eg., Valium ®, Librium ®), non-steroidal anti-inflammatory drugs (NSAIDs) for arthritis pain (including a few taken off the market for major side effects like Vioxx ®), and most recently “statin” drugs that reduce cholesterol. These drugs not only work for that purpose, they seem to have other beneficial effects in prevention of heart disease, the reasons for which are not entirely understood, so they are very popular. While selling such heavily-used drugs is always profitable, the greatest profit comes in the first decade (or so) when it is under patent and there are no generic competitors.

In a recent Perspective, “Generic atorvastatin and health care costs”,  in the New England Journal of Medicine, Jackevicius and colleagues look at the impact of the costs of statin drugs on health care costs by examining the projected savings on atorvastatin, initially sold as Lipitor®, which became generic this last November.[1] They used the data on the gradual price reduction that followed simvastatin (Zocor®) becoming generic in 2006. There are some differences; atorvastatin is more potent than simvastatin and less likely to cause muscle pain (myopathy), so it may be preferable to many. When neither was generic, Lipitor® had by far the biggest share of the market, but when simvastatin became generic in 2006, it became the biggest seller, with Lipitor® dropping precipitously and brand name Zocor® almost disappearing. Because of its two advantages (greater potency, less myopathy) generic atorvastatin should become the number one statin in the near future. The savings are projected to be enormous: “The overall cost savings from the availability of generic atorvastatin are projected to reach $4.5 billion annually by 2014, equivalent to 23% of total expenditures on statins in that year.”

That’s a lot of money. It is good to be saving it. However, that “saving” means that we have been spending it for the last decade or more. Yes, drug companies deserve to make a profit. Yes, there are investments made that need to be recouped. But this – like, if perhaps not quite so egregious as what we have seen lately in the financial sector – seems to be excessive.

We should not use drugs that harm us or are unnecessary. The question is can we, as individuals or a society, afford to pay so much for the drugs we need in order for their profits to be so high?

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[1] Jackevicius CA, Chou MM, Ross JS, Shah ND, Krumholz HM, “Generic atorvastatin and health care costs”, NEJM 19Jan2012;366(3):201-3.