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.

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[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

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.