Tuesday, August 29, 2017

"Blockbuster" drug or slanted reporting: never forget "cui bono"

‘Drug Aimed at Inflammation May Lower Risk of Heart Disease and Cancer’, by Denise Grady in the New York Times, August 27, 2017, reports on a study in the New England Journal of Medicine, Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease’ by Paul M. Ricker, et al. The study, funded by the drug’s manufacturer, Novartis, examined the impact of the use of canakinumab (brand name: Ilaris) on heart attack survivors. The drug is in a class called “monoclonal antibody inhibitors” (as is almost anything ending in “…mab”); in its case, it inhibits antibodies known as “interleukin 1β”. The main effect is anti-inflammatory, which is why it was originally developed for treatment of juvenile rheumatoid arthritis, an inflammatory disease. However, research showing that inflammation plays a major role in coronary artery disease (the cause of heart attacks) stimulated this large multi-center, drug-company sponsored, trial.

So what did the study show? Of the over 10,000 people in the study, those who were treated with canakinumab had lower rates of what the study designers defined as the “primary end point”, the main thing that they were looking for, “nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death.” That is, did patients have another heart attack or stroke, whether they lived or died. The lower rates in the canakinumab groups were statistically significant, with the group that did the best, the middle-dose (they tested 3 different dosages), having 3.86 “events” per 100 person-years, compared to 4.50 for the placebo group. In absolute terms, there were, thus, 0.64 fewer “events” for each 100 person-years (which is a valid concept, one person taking a drug for 100 years, or 100 people for one year, or any combination in between).

There was, however, no significant difference in “all cause” mortality between the treated and untreated groups, mainly because of the increase in deaths from infections in those treated.  This is not surprising because the anti-inflammatory effect of canakinumab also decreases the body’s immune response. It is also not surprising that the people most likely to die of infection were those who were oldest and sickest in the first place. Six people developed tuberculosis.

Given that the cost of the drug is about $200,000 a year (think about that!), 100 person-years of treatment would cost $20,000,000. And for this price, 0.64 fewer people have a cardiac “event”, and no fewer people die. And some untold number suffering serious side effects from canakinumab, including the infections that occurred that didn’t kill them (not reported). These could be really serious – long hospitalizations for sepsis or pneumonia or cellulitis, non-fatal but significant events like amputations, etc. No wonder the Times article quotes Dr. David J. Maron, the director of preventive cardiology at Stanford University School of Medicine, as saying “This is fantastic”! Dr. Maron, I imagine, has terrific insurance.

Of course, it didn’t cost Novartis $200,000 a year for the drug for the study; that is the retail price that it plans to charge hospitals, insurers, and patients. We have no idea what the drug actually costs Novartis to manufacture; the price they will charge is based on the highly scientific formula called “what the market will bear”. For their own bizarre reasons (see Elizabeth Rosenthal’s “An American Sickness” and this commentary by Jacob Hacker) insurers may gladly pay for this drug (they get to keep a percent, and a higher price means a higher percent, and they just raise rates). Or they may get a discounted charge. Certainly, many poor and uninsured people are not likely to get it. Maybe – probably – Novartis will have a program for giving the drug for little or no money to poor people. But, given how common coronary heart disease (CHD) is, they are incredibly unlikely to give it for free to every uninsured person who has CHD. Maybe they’ll give them a discount, say 90%. Then the poor person would only have to pay $20,000 a year out of pocket. To reduce their risk of another coronary event by 0.0064 per year. And have no lower likelihood of dying. And a greater likelihood of severe infection. Maybe this is, after all, a boon to the poor and uninsured, as they are unlikely to get this terrific opportunity.

The other amazing thing is the actual story in the Times, and what that says about health journalism. As noted by the insightful Howard A. Rodman, the
·        Headline says: "Drug... May Lower Risk of Heart Disease and Cancer"
·        The 2nd paragraph tells us it is a "major milestone"
·        The 3rd paragraph quotes Dr. Maron saying "This is fantastic."
But then you have to scroll down to find
·        In the 5th paragraph, that the drug costs $200,000 per year. It's available only from Novartis, and that Novartis paid for the study.
·        And in the 7th paragraph, that the drug suppresses immune response. In the study, the number of deaths from drug-caused infections equaled the number of lives saved.
Lead with the positives, and then let us down later, maybe after those of us scanning the article have stopped reading.

Is the Times trying to mislead us? I don’t think so. I think that they want, however, to get our attention, get us reading, show us blockbusters. Blockbusters are good for getting attention. It is a big article for the New England Journal of Medicine also. This is why there is a built-in prejudice in medical journals for publishing articles with positive results, and why the authors do their best to “spin” results to positive. As if the incredible amount of work they have put in to the study, not to mention the interest of the sponsor, in this case, a pharmaceutical company that makes the drug in question, was not sufficient impetus. After all, getting our attention is what it is all about; it is why reality TV is so big, and why a reality TV star is now POTUS; see Matt Taibbi’s piece “The Media Is the Villain – for Creating a World Dumb Enough for Trump”. He notes that “If a meteor crashes into jello night at the Playboy mansion, it doesn't matter if you send Edward R. Murrow to do the standup. Some things sell themselves.” Maybe a drug that treats a disease that treats heart disease isn’t that big, but it is big; after all, as Grady notes, “Cardiovascular disease is the leading cause of death worldwide and in the United States, where it killed nearly 634,000 people in 2015. Globally, it killed 15 million,” (paragraph 4, if you’re tracking it).

Neither does this mean that published scientific research is unreliable. Some of it is very good science (even this study is generally good science, despite the published report in NEJM and the coverage in the Times being unconscionably skewed to the positive). Some of it actually reports on drugs or other interventions that make a difference. Sadly, however, in addition to the “blockbuster” effect that the media (including medical journals) want to cover, those interventions that will make a lot of money for a company get more publicity. Especially when the company funds the research. Aspirin, by the way, is still cheap, and it is more effective than this drug, recommended by the US Preventive Services Task Force (USPSTF) for prevention of CHD in adults with greater than a 10% 10-year risk.

I tell medical and other health professions students (at all levels) that, although the Introduction and Discussion sections of the article may seem most interesting, the important parts to read are the Methods and Results, which have the meat (or soy, if you’re vegan) and from which you should draw your own conclusions, without the authors’ spin. If you’re not a health professional, and depend on the mass media for coverage, then you better read the whole article and not stop after the fanfare. It is the reporter’s job to provide the necessary information, but your job to read it wisely.

Certainly, health professional or reporter or consumer, look at who is funding the study. It is important information. And think about conflict of interest. And think, of course, about cui bono. It is likely to be the manufacturers, and maybe the researchers, and sometimes those who are wealthy or well-insured enough to get the drug or intervention (when it is of benefit).

And, surprise, it is never likely to be the poor, uninsured, or those most in need.

Monday, August 7, 2017

The frustration of actually trying to get health care: the other meaning of access

I have written about the quality of care that people in the US receive, and about access to and the cost of care, but another very important issue is the actual process of obtaining appropriate care. This is a major source of frustration for patients and their families, and can drive anger against the system, against doctors, against insurers, against the government. People who experience this frustration and anger want it to change, and sometimes want to lash out, offering an opportunity to be intentionally misled by influential others for their political ends. The demonization of the Affordable Care Act (“Obamacare”) is a good example. Obamacare actually did lots of good things, starting with insuring tens of millions who did not previously have coverage; it also forbid insurers from charging more to those with pre-existing conditions, and allowed children to stay on their parents’ plans until they are 26. Actually, it did little or nothing bad, if the criterion is access to care. A few people saw increased premiums, mainly the healthy young and those who previously had such terrible policies that they were both cheap and essentially worthless. While the Republican congress tried to repeal it, it turned out that, surprise, people would be worse off without it.

On the other hand, frustration with the obstacles to obtaining appropriate care are real, every day, and in-your-face for patients and their families. I have recently been experiencing these from the perspective of the patient (or family) rather than that of the provider, as I work at getting care for my 92-year-old father. My experience with the provider perspective helps me to understand the situation from both sides, and hopefully to try to figure out which obstacles are rational and which are simply unnecessary.

Let me start by largely absolving any of my father’s individual providers; all those involved with him – physicians both general and specialist, physical therapists, and more recently the nurses, social workers, and nurse practitioners through the palliative care agency – are committed, caring and hard-working. They do their best to help him, to be available, to respond when a problem, minor or urgent, arises. However, there are obstacles in the way. Many services require a referral from a physician, from calling in prescriptions, to ordering lab tests or x-rays (and getting the results), to getting physical or occupational therapy, to enrolling in palliative care. While none of these individually may seem to be burdensome for the doctor, there can be many for any individual patient, multiplied by the number of patients a physician sees who need these services. While it is sometimes the specialist who makes such a referral or fills out such a form, it most often “rolls downhill” to the primary care provider. That provider has to have a very large number of patients to get by and make a living, so the phone messages and faxes and lab results pile up while s/he is spending all day actually seeing his/her patients. Rationalizing the delivery of care means trying to get nurses or other staff to deal with as many as possible, but lots of these require a doctor (or other licensed provider, such as a nurse practitioner) to interpret, approve, or sign off on.  And having more staff costs more money, and means (particularly for the primary care provider, whose reimbursement is much lower than for many specialists) having more patients. Thus, a vicious circle, often compared (from the provider’s point of view) to running on a hamster wheel; for patients, this often seems like obstructionism.

Of course, it often is obstructionism, but rarely on the part of the individual provider. The reason is, unsurprisingly, money. For the providers of care, or more usually the companies for which they work (whether for-profit or not), the issue is reimbursement by insurers, including Medicare and Medicaid. There are rules that must be followed, forms that must be filled out, referrals that must be signed, and procedures to go through, or payment will not be forthcoming. And then the provider, whether physician, nurse practitioner, physical therapist, pharmacist, or social worker, whether self-employed or working for a company, doesn’t get paid. And, depending on how often this occurs, will make less, fire staff, or go broke. In addition, insurance companies themselves often create obstacles to payment (such as the time-honored one of just refusing to pay the first time or two, because maybe the provider will give up), but this is more often true for costly surgeries than lower-cost preventive and treatment services. And sometimes the practices seem almost incomprehensible as in insurers requiring patients to use brand-name rather than generic drugs and thus have to pay more out of pocket (“Take the generic, patients are told. Until they are not”, NY Times, August 6, 2017); one word, not used in the article but clearly described: kickback.

To be fair, many of the rules that seem to be obstructions are not only about saving money; they are about both preventing fraud and even patient safety. There absolutely are major fraudsters out there, doctors and home-health companies and nursing homes and every sort of medical support provider (even hospitals), who try to and often succeed in bilking Medicare (and other insurers) out of millions of dollars in inappropriate (“do you want a scooter at no cost to you?” – but someone else is paying!) or truly fraudulent (there is no patient) care. In fact, some care, even if you want it, even if someone is willing to provide it (if they get paid), is not appropriate for you, or your family member. Medicare and other insurers do set criteria, and require that it be documented. This can actually be good, not only for all of us as taxpayers but for our health and safety.

But often it isn’t good. It sometimes makes care that is appropriate, evidence-based, and desired, hard to get. It takes a long time. It takes lots of phone calls, and hours on hold or waiting for calls back. It has messages lost in piles, or over the weekend. It should not happen, but it does. And it is frustrating. The “Triple Aim” guiding progressive health care has received a lot of attention. It is to deliver high-quality care in a cost effective manner that is satisfying to patients. To document the last, many hospitals, provider groups, and companies send out “patient satisfaction” surveys, which are at best cosmetic and at worst destructive. People don’t fill them out “right”; they tend to reflect an overall impression that leads people to mark each of the ostensibly-separate questions “great” or “terrible”. Also, in forming this global impression, folks understandably often overvalue the things that they can assess (like the quality of food or attractiveness of the facility) compared to things that they cannot (such as the actual quality of care). This is, by the way, where providing good customer service makes a big difference, and while some places are getting better, the medical care industry is generally weak in this critical area.

As in almost everything, those with the least get the least. The uninsured, the poorly insured, and the just poor, provide the least incentive to providers (getting paid) to meet their needs. Government regulations that require certain services for Medicare or Medicaid without paying for them result in greater strain on those providers who provide care to people in these groups. Many providers, especially in some fields or medical specialties or geographic areas, try to avoid them. They locate in wealthier neighborhood, don’t take folks who are uninsured (or on Medicaid, and sometimes even Medicare), or offer indulgent, wonderful “concierge” services for those who can pay a significant retainer. Thus works the “market” in health care. A terrible way to go.

A universal health insurance system won’t make all these problems go away; even with it, systems can still be poor, providers can be uncaring. But it will help a lot. Because everyone is covered, there is no “vendor lock”; the market can function well because people choose their providers based on service, not because they are forced to because they are locked in to a limited pool. Information flows between primary care and specialists and therapists and labs and imaging because if it doesn’t folks are free to take their business elsewhere. The way competition should work; competition on providing the best product and service.

And, because we would all be in it together, in the same system, the most empowered will make sure it works for them, and thus, hopefully, for us all.

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