Sunday, July 26, 2015

Chemotherapy, Quality of Life, and Corporate Profit

“In reality, only 2 major reasons exist for administering chemotherapy to most patients with metastatic cancer: to help them live longer and/or to help them live better.”

So begins “Chemotherapy Near the End of Life: First—and Third and Fourth (Line)—Do No Harm”[1], an editorial by Charles D. Blanke and Erik K. Fromme in JAMA Oncology commenting on an important new study in the same issue by Prigerson and colleagues, Chemotherapy Use, Performance Status, and Quality of Life at the End of Life”.[2]  The study, a fairly large randomized controlled trial, discovered that giving last-ditch chemotherapy for “solid tumors” in patients estimated to have less than 6 months to live did neither. Not only was survival time not increased (although the editorialists note that this study was not designed to look at survival), but quality of life (QOL) was not improved. Indeed, and incredibly important, the group that had the best quality of life before receiving this final round of chemotherapy had the greatest drop in QOL, ending up pretty much as bad as the rest of the group. Blanke and Fromme observe that that this may be because they had “further to fall”. This is likely true, but surely the goal is not to give “treatment” that facilitates that fall.

So why do we do it? Were “we”, doctors especially, ignorant of this? Certainly the strength of the results – especially the fact that those whose pre-treatment QOL was the best were those who were most harmed – was a surprise in that it had never been published before, but that “palliative” chemotherapy at the end of life, intended entirely to improve QOL, often does the opposite – is something that every doctor who cares for patients with cancer, including but not limited to oncologists, has seen. Many of us, including many palliative care specialists, usually recommend against such treatment to patients and their families, often to have our voices drowned out by the encouragement from others (particularly some oncologists).

The truth is that the answer, as with so many things involving people, is complex. People do not usually want to die, and frequently grasp at any straw offered to them. Even when they themselves are not sure that they wish to go on, even when their disease makes them unable to make a decision, their family members often take on the role of demanding more treatment. This rarely if ever comes from a desire to cause more suffering for a loved one, but rather hoping that a miracle will occur. When this is encouraged by the physician who offers some sort of hope it is more likely to happen. The distinction between the outcomes of palliation and longer life is not always clear to patients or their families, and indeed “improvement” and “longer life” may mean different things to the doctor saying it (tumor gets smaller, life expectancy extended by weeks) and those hearing it.

The results of this study showing the decrease in QOL for those who were “best off” prior to treatment should be sobering and decrease the use of end-of-life chemotherapy, but there continue to be critics of the work. Some oncologists, typified by the one quoted by Pam Belluck in the New York Times article on the study (“Benefit of End-Stage Chemotherapy Is Questioned”, July 23, 2015) who “noted that patients were seen between 2002 and 2008, before some newer chemotherapy drugs with fewer side effects or the ability to directly target certain tumors or cancer-causing mutations,” still hold out hope. He may be right, but, of course, all studies are done in the past, and the “things are better now than then” refrain is almost always the one we hear from people unhappy with the results; in all probability, things, for end-of-life cancer patients, are not really better now.

The one clearly unacceptable reason for doing such therapy is the financial benefit to the manufacturers of these chemotherapeutic agents, but also to a lesser degree the providers – mainly the hospitals but also sometimes the doctors – who administer them. This is a major consideration, not generally addressed in the articles about this study. “Costs aside,” Blanke and Fromme write, “we feel the last 6 months of life are not best spent in an oncology treatment unit or at home suffering the toxic effects of largely ineffectual therapies for the majority of patients.” The costs that they are holding aside are the costs of the drugs, the implication is that it is the cost to the patient (or their insurer), a negative to be weighed against the potential benefit (or not) of the therapy. In this sense, it is one item on the scale. But the cost to the patient or insurer is the source of enormous profits to the pharmaceutical companies that make these incredibly expensive drugs, and they are heavily marketed to physicians by those multi-billion-dollar corporations. Their marketing campaigns push the slightest, least-convincingly-demonstrated-by-research potential benefits, and almost never talk (audibly) about the possible, probable, likely negative effects of treatment. 

While these companies are the greatest financial beneficiaries, so are the hospitals and cancer centers that administer them. The reason that there are so many cancer centers is only in part because cancer is a bad disease; it is largely because it is a very profitable disease to treat because the markup paid by insurers (led by Medicare) for administering chemotherapy is very high. Doctors (particularly oncologists) benefit most directly when they are owners of such cancer centers, but to a lesser degree when they receive high salaries from their employer that are made possible by the huge profits on cancer treatment.

It is an ugly thought that your receiving cancer drugs may be in large part because the manufacturers stand to make a lot of money from it, but there it is. And it is not just cancer treatment; a recent article in the Business section of the NY Times from July 24, 2015 by Andrew Pollack, “New Drug Sharply Lowers Cholesterol, but It’s Costly”,  describes the introduction of a new “recombinant DNA” drug called alirocumab (Praluent) that dramatically lowers cholesterol levels, but will cost $14,600 a year! This may be a wonder drug for the relatively small number of people who have familial hypercholesterolemia, but the indications will unquestionably be pushed by physicians with encouragement from the manufacturer. Every time there is the least evidence that a drug, initially intended for the most severely affected patient, can be used for a larger group, there is more potential for enormous profit.  The evidence that just lowering cholesterol as much as can be done is linearly linked to reducing heart attack and stroke is limited. “’This is treating a lab value,’ said Dr. Rita Redberg, a cardiologist at the University of California, San Francisco, referring to lowering cholesterol for its own sake. ‘I don’t think we should rush into it.’

“’We came to a price that is reflective of value, not what the market will bear,’ said Elias Zerhouni, head of research and development at Sanofi [one of the two companies that make alirocumab], who said his own brother had suffered three heart attacks and needed new options to control cholesterol.” I am sorry about his brother, but if you believe that, I’ve got a bridge to sell you. It is absolutely about the price that the market will bear. The sad part is that there may be some who are more willing to believe this because Dr. Zerhouni used to be the head of the National Institutes of Health (NIH), a higher-profile but undoubtedly less well-paid position. Revolving door, anyone?

Alirocumab is likely to be beneficial to some patients but will undoubtedly be used in many more and is unconscionably priced. It’s fine for a company to make profit on its drugs, but predatory pricing and rapacious profit is not. Most disturbing is the thought that people who do not need and will not benefit from a drug, and may even be harmed by it, may receive it mainly so these companies can profit.

The line I quote from Blanke and Fromme at the start of this piece refers to chemotherapy for metastatic cancer, but in fact can be applied far more generally: 

In reality, only 2 reasons exist for administering therapy to patients: to help them live longer and/or to help them live better.

Let’s keep that, and not corporate profit, as our touchstone.

[1] Blanke CD, Fromme EK, “Chemotherapy Near the End of Life: First—and Third and Fourth (Line)—Do No Harm”, JAMA Oncology, published online 7/23/15, doi: 10.1001/jamaoncol.2015.2379
[2] Prigerson HG, et al., “Chemotherapy Use, Performance Status, and Quality of Life at the End of Life”, JAMA Oncol. Published online July 23, 2015. doi:10.1001/jamaoncol.2015.2378

Sunday, July 19, 2015

Tax policy, drug companies and the public's health

Tax policy is complicated. You have to figure out who to tax and how much, and how much revenue it will bring in and what you (the government) needs to spend the money on and figure out how to match it up. People of different political stripes differ with regard to how much money to spend on what, and also who to tax. For example, is it better to have more graduated income tax (a “progressive” tax, where the more you make the higher percent you pay on the incremental amount), or more “regressive” tax where everyone, regardless of income pays the same amount, like a sales tax, or a “proportional tax” where everyone pays the same percent but not the same amount, like some variations of “flat tax”?

In Kansas, for example, our Governor and Legislature have made that decision. Faced with enormous budget deficits as a result of 2012 massive tax cuts on corporations and wealthy individuals, and unable to make it all up with one-time fixes such as raiding the state highway fund (hope those corporations don’t need to transport goods on our roads), they have gone for big sales tax increases. This is because, to them, the 2012 tax cuts are sacrosanct, because they believe that this will stimulate the economy and create jobs. They believe this even though such a strategy has not worked so far in Kansas and has in fact not worked anywhere. They even brought in Arthur Laffer, the trickle-down guru economist, to address the legislature. Nonetheless, owners of “S” corporations (usually small businesses, like lawyer’s offices, or the few remaining private practice doctors’ offices) do not pay state tax on the income they make from being the owners. Their employees -- nurses and secretaries and legal assistants – do, along with the new higher sales taxes. The Governor and Legistlature have other plans as well; faced by a State Supreme Court decision to increase public school funding by a half-billion dollars or so that they don’t have (vide supra), they are thinking about not funding the State Supreme Court. Could be a solution, if they can get around the constitutional issue.

The Federal Government also has to deal with such issues. In the last 50 years our income tax policy has become less progressive, with a top rate of 35% rather than 90% when I was taking civics in junior high school. (Please note that this is not a flat tax of 90% on all of top-earners’ income, but on the marginal amount above the next lower tax rate; everyone paid the same percent on earnings up to each next bracket.) Also in that civics class, we saw that corporate income tax made up more income for the feds than personal tax. Not any more. Corporations are getting away with paying very low taxes, and with the new “global economy” taking more and more of their profits abroad, where they can avoid paying tax until they are re-patriated. To encourage them to do so, the Congress is considering legislation to create a “tax holiday”; this is where corporations are rewarded for bringing their profits home by paying a lower tax rate on them. This has been done before, and been amazingly unsuccessful. So let’s try it again. Like Kansas, why learn from experience? Why not, for example, tax those international earnings? After all, if they are creating jobs, it is not in the US.

Also like Kansas, the US has a problem with roads and other infrastructure, and the Federal Government funds much of the cost of repairs, which are unfortunately not being done. A study by the Center for Effective Government, “Burning our Bridges” notes that “To modernize our infrastructure, the American Society of Civil Engineers estimated it would cost $3.6 trillion by 2020. They warned that if we fail to make these investments, American citizens and businesses will face costs of $1.8 trillion a year in travel delays, water leaks, and power failures.” How has Congress responded? It's slashed infrastructure spending to the lowest levels since the post-WWII era.
 But where could we get the money? Is the amount of money not being paid by US corporations on international earnings that big? Well, there is $2.1 trillion in untaxed international income, so that could be a chunk of change. About half of it is held by 26 corporations. Apple has the most, and GE is #2. The enormously profitable pharmaceutical industry (I have previously noted that it is, each year, either #1 or, well, #1 in profit among US industries) has about $82 billion among its 7 largest companies. Given that the report is called “Burning our Bridges”, it is of interest to note that this is enough money to pay for all US bridge repair and maintenance needs.

I guess this is where the public health and medical part of this post comes in. Let’s just think about that. We have drug companies charging “whatever the market will bear” for their products; for some of the recent recombinant DNA treatments for autoimmune diseases, Hepatitis C, and cancer this can range into 5 digits (before the decimal point) a month. They try every trick in the book to keep their prices high and patents in place to prevent generic competition. Some I have addressed before include changing the formulation of the drug -- the FDA mandated elimination of fluorocarbons as propellants in inhalers was a bonanza because changing to non-fluorocarbon propellants was a “new formulation” allowing them to extend their patents. Or taking drugs used by, but not previously tested and approved for use by, children and testing them (when already, via practice, shown to be safe) in children, also extending their patents. Or in some the most offensive practices, testing drugs that have been used for generations and patenting them, thus jacking up their prices. The prime example is the gout treatment colchicine, formerly available for about 10 cents a pill and now available for $355 for 60 (about $5.20 a pill!).

In Canada, there are price controls on drugs, so they cost less. Thus pharmaceutical manufacturers try to block import (and Internet sale) of drugs from Canada. The Medicare drug benefit, (Part D) passed in the GW Bush administration, forbid Medicare from using its purchasing clout to negotiate lower prices. The new Trans-Pacific Partnership (TPP) pushed through by the Obama administration will offer more protections; corporations will be able to sue governments to ensure their profits, not in real courts but in specialized TPP pro-business “courts”. I wonder how long the price restrictions on drugs in Canada and elsewhere, not to mention the manufacture of affordable generic equivalents of high-priced HIV drugs in Brazil, India, and Thailand, will continue?

I personally am rooting for the success of the Brownback tax cuts to create jobs in Kansas. Not because I think they were good or even close to moral, or even because I think that they have a prayer of being successful, but as long as they are in place it would be nice to see some new jobs. It’s not going to happen with this state government. TPP passed, and there is no meaningful effort to either tax the international profits of pharmaceutical and other corporations, or to force drug manufacturers to make their products affordable in the US.

In their recent paper “Fantasy paradigms of health inequalities: Utopian thinking?”, Alex Scott-Samuel and Kathleen Smith note that "In a capitalist society, where liberal macroeconomic policies position virtually all economic activity – including unhealthy activity – as beneficial, there is an inbuilt incentive to ‘blame the victim’ rather than to tackle the corporate and economic causes of the problem."[1] We prefer not to regulate unhealthy activity (when we have done so, such as with making cars safer and limiting smoking, it took intensive, long-term campaigns by public health advocates), and we allow corporations such as drug companies to profiteer from our trying to repair the damage to our health. And we also let them not pay taxes, which we really need.

It's time to get serious, and hold them responsible and make them responsive.

[1] Scott-Samuel, A. & Smith, K. E. (2015).Fantasy paradigms of health inequalities: Utopian thinking? Social Theory & Health, advance online publication, 1 July 2015; doi: 10.1057/sth.2015.12

Sunday, July 12, 2015

Prostate Screening and the Public’s Health

For the first time in several years, I am writing about prostate cancer screening. I had hoped that this was sufficiently covered in 2009, with PSA Screening: What is the value? (March 21) and the excellent guest piece by Robert Ferrer, PSA Screening: “One of Medicine's Great Success Stories"? (October 27), and finally a bit of celebration in 2011 with PSA redux: The USPSTF finally recommends NOT getting it! (October 14). However, like the proverbial bad penny (or to use a more au courant analogy, zombie), this issue continues to return from the dead. The most recent effort is “Bring Back Prostate Screening”, a NY Times op-ed piece by Deepak A. Kapoor on July 6, 2015.

What Dr. Kapoor is suggesting is obvious from the title, but the question is “is there some new information, some new research, that now makes such screening more reasonable or appropriate?" The answer, unfortunately (because it makes more work for the zombie hunters) is “no”. Dr. Kapoor suggests that there is. He notes research is this field is “... now paying off.” He says that the decision to recommend against prostate screening by the US Preventive Services Task Force “…didn’t take into account adaptations that urologists have made to help better identify patients likely to develop deadly prostate cancers.” He cites the increased sensitivity of PSA screening, the individualization of it to the risks of different men, and the use of PSA trajectory (its rate of increase, or not), as well as new methods of assessing cancer like MRI. However, his assertion is incorrect; all of this information was available to the USPSTF when it made its recommendations, and was taken into account. It is not new.

“At the time,” Dr. Kapoor notes, “I and many other urologists warned of public health repercussions. Our fears have materialized. Since 2010, fewer biopsies have been performed and fewer prostate cancers found. But studies show an increase in the risk that a cancer, when found, will be more aggressive.” This sounds scary, but it is to be expected; when you stop screening everyone you won’t find the cancers early. A big part of recommending against PSA screening was that so many of the cancers it identified were indolent and not going anywhere; the aggressive cancers will be the ones that eventually show up. Indeed, he actually acknowledges that “No increase in cancer mortality has been observed,” but continues to raise the alarm with “…that may be a matter of time; aggressive cancers are less treatable.” So maybe we should be scared.

Well, in fact all prostate cancer is treatable. All cancer is; in fact all conditions are. The question is how effective is the treatment? Does it cure? Does it prolong life? Does it improve the quality of remaining life? This is the area that Dr. Kapoor and his colleagues do not address, because, for prostate cancer, the answer is basically no. If you have the more common kind of prostate cancer, it is slow-growing (indolent) and may even disappear itself; you will die with it, rather than from it. If you have the less-common aggressive form, you may well die from it, and unpleasantly; prostate cancer metastases go to bone and cause a lot of pain. Sadly, however, treatment does not seem to impact this. The “cures” from treatment of prostate cancer are of the ones that would have “cured” themselves, or at least not have manifested with symptoms. The mortality from aggressive deadly cancers is not changed by treatment. This is the critical point that discussions of the sensitivity and specificity of PSA or any other kind of screening often ignores. Not only can they not reliably distinguish between the indolent and aggressive types of cancer well, even if they could and we had a test to reliably tell which one you had, it is only of importance if treatment can make a difference. And in terms of mortality, it doesn’t. What about the other results from treatment? Improved quality of life? Well, here even Dr. Kapoor notes that “cancer treatment can reduce quality of life.” If you consider impotence, urinary incontinence, and the many unpleasant and painful effects of radiation on the rectum to lower quality of life, you betcha.

We can dismiss Dr. Kapoor’s comments by saying he is a urologist, and they make their money treating prostate cancer; can you imagine the impact on their income if we didn’t treat it? But this misses the far bigger issue, which is that we are enamored with – and, more important, spend huge amounts of money on-- high-technology interventions rather than the prosaic, low-tech interventions that have actually been demonstrated to improve the public’s health. Screening for prostate cancer, and overuse and reliance on mammographic screening for breast cancer, are huge industries which (even in breast cancer) have had relatively little impact on mortality. Providing good prenatal care and preventing unwanted pregnancy, ensuring treatment of common diseases like hypertension and diabetes, ensuring that children are not only immunized against infectious disease but are well-fed, well-housed, and well-educated, and free from poisoning by environmental toxins (including bullets) – the basic components of public health and primary care -- may seem less sexy and stimulate our collective psyches less, but they are the things that actually increase population health.

One of the newer fascinations is genomics, the identification of each person’s sequence of DNA. The promise of “precision medicine” is that we will find out who has the risk gene for which disease, and treat it directly and appropriately; treatment for cancer will be based on the genes you have just as treatment for bacterial infections is based on the organism identified by culturing it in a microbiology laboratory. It is so exciting! It is so “sci-fi today”! The American Board of Family Medicine, for example, is planning to create a new self-assessment module (“SAM”, tests that family doctors have to complete one of each year to maintain their Board certification) on genomics. On the other hand, it doesn’t think we need one on contraception, which is too small an area (isn’t it just part of “women’s health”? Oh, do men have a role in contraception also?), unlike genomics, which could affect EVERYTHING!

Except, so far, it hasn’t and there is little evidence to suggest that it will anytime soon. I wrote a blog on the topic on February 1, 2015 (“Precision medicine, trade policy and the cost of drugs: benefiting people or profit for business?) after the appearance of a Times op-ed by Mayo Clinic cancer expert Michael Joyner (“’Moonshot’ medicine will let us down”, January 15, 2015); Dr. Joyner has more recently contributed more comprehensive articles on the topic to JAMA (“Seven questions for personalized medicine[1]) and The Lancet (“Is precision medicine the route to a healthy world?”[2]) in which he makes the important point that most disease is not the result of a single gene, but rather the result of a complex interplay of different genes and the environment. Indeed, the only cancer-specific genes that have been identified so far are the breast cancer genes BRCA1 and BRCA2, and no treatment has emerged; we simply say “get mammograms more often and consider prophylactic mastectomy”.

Spending all this money on precision medicine, on high-tech interventions, expensive drugs and devices is like blowing your house budget on art for the walls before you have built it. Some art is great, some is mediocre, and some is poor, but none will hang well on a jerry-rigged house made poorly of shoddy materials because there was no money left. Some high-tech, expensive interventions are worthwhile but what we really need to increase the population’s health is public health nurses making home visits to pregnant and recently delivered women, and their children; public health nurses or community health workers or even doctors making visits to people’s homes to assess the real risk factors to their health and reasons that they might not be able to comply with treatment plans. We need more primary care, not more interventionalists. But most important, we need to apply what we know works, what we know how to do, to everyone.

That is how we move the needle on population health.

[1] Joyner MJ, Paneth N, Seven Questions for Personalized Medicine, JAMA. 2015 Jun 22. doi: 10.1001/jama.2015.7725. [Epub ahead of print]
[2] Coote, John H, Joyner, Michael J. Is precision medicine the route to a healthy world?. The Lancet385.9978 (Apr 25, 2015): 1617.

Total Pageviews