"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 2^nd paragraph tells us it is a "major milestone"

·        The 3^rd paragraph quotes Dr. Maron saying "This is fantastic."

But then you have to scroll down to find

·        In the 5^th 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 7^th 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.

Private Profit and the Public's Health: Which is More Important?

Health care is pretty complicated, and insurance coverage is even harder to understand.This is the message that comes through clearly from the interviews being done by Dr. Paul Gordon and recorded on his blog, https://bikelisteningtour.wordpress.com. Dr. Gordon is taking a unique sabbatical, riding his bicycle across the country from Washington (DC) to Washington (state), interviewing regular people, mostly in cafés and such, about their take on Obamacare. 

The economic status of these people varies from poor to pretty well-off (but none really wealthy), from well insured to uninsured. Their political perspectives range from “everyone should be covered” to “benefits just make people lazy”. Three recent quotes: ‘People use Medicaid as a crutch’, ‘You can’t penalize someone for not having health insurance when it’s so expensive and the economy is doing so poorly’, ‘Here’s my take on it – everyone should have insurance’. What they share with each other, and with most of us, is a general lack of understanding of how Obamacare works (or doesn’t) and why. The flaws in Obamacare are the result of the political tradeoffs that allowed insurance companies to continue to have control and make huge profits, but this is often not clear to most people.

Here is something that is easy to understand, however: when you call “911” as you have been trained to do in an emergency, and they don’t come. Or they don’t come for a long time. Or they come with inadequate supplies. Who do you get angry with when you, or your loved one, dies? The government? They are surely in part at fault, even though they probably contracted the service out, to save money, probably because voters want to pay less tax. But there is another reason, explained in an excellent special article in the New York Times, “When you dial 911 and Wall St. answers” (June 26, 2016). The piece, by Danielle Ivory, Ben Protess, and Kitty Bennett, details how many city services, including ambulance services, are provided by companies that are owned by “private equity firms”. These are companies whose investment capital comes from wealthy individuals and particularly from pension funds, unlike banks whose money comes from depositors. They are even lessregulated than banks, and thus more able to pursue their core mission, making profit:

Unlike other for-profit companies, which often have years of experience making a product or offering a service, private equity is primarily skilled in making money. And in many of these businesses, The Times found, private equity firms applied a sophisticated moneymaking playbook: a mix of cost cuts, price increases, lobbying and litigation.

Whoa. This is starting to get complicated again. Banks vs. “private equity” vs. just plain old for-profit businesses? They are really just different forms of for-profit, and provide a stepwise progression, from public services operated by government for the benefit of the people, to private companies that are contracted by government to do a service but might care about doing it well, to having those companies owned by banks who really just want to make a profit, to having them owned by private equity companies who care about nothing but making a profit. The photo accompanying the Times article is of Lynn Tilton, owner of Patriarch Partners (an ironic name, given that she is a woman), which owned the emergency services company TransCare that served many East Coast communities. TransCare went bankrupt, leaving those communities without emergency medical services. Ms. Tilton’s picture is accompanied by the quote from her reality television stint “It’s only men I strip and flip.” As a poster child, she could become the Martin Shkreli of ripping off necessary public services the way he was of ripping off consumers of life-saving drugs.

“The business of America,” Calvin Coolidge is often paraphrased as saying, “is business.” This perspective, that it is not about doing things that are best for the American people, is based in a belief that capitalism – “business” – will, through the magic of the market, eventually meet those needs. OK, maybe not those of people at the margins, people too poor to buy, so maybe we need a safety net. But most people. A similar statement appeared today in the print edition of the Kansas City Star from KC Mayor Sly James, discussing the controversy over replacing the terminals at Kansas City International Airport with one big, new terminal. Surveys consistently show that the large majority of Kansas Citians (84% in this article, “Regarding KCI’s future, city ponders a new flight path”) like the current arrangement, with short security lines and easy access in and out from one story terminals, but the airlines and big businesses do not. In the large-type quote accompanying his picture in the print edition (but, along with the photo, left out of the online edition), Mayor James said “The people of this city need to be convinced of what I believe is a basic reality, that this airport is about a lot more than ‘how fast can you get out of your car and get to your gate?’” Right. Business interests first. Take that, 84% of Kansas Citians!

Because they most obviously involve life and death, emergency medical services and firefighting (yes, firefighting too has been contracted out to companies owned by private equity firms!) get the greatest play in the Times article, but many other services (like water!) are in the same situation: controlled by companies whose goal is to make a profit rather than to provide effective service for people. This is what happens when municipalities are starved of funds because people vote to cut taxes.

Whether it is health insurance or emergency medical services or municipal water, the system becomes very complicated and hard to understand when it is trying to meet conflicting agendas. When the need for people to receive critical, health-producing service (fire and police protection, clean water, garbage collection, ambulances) is compromised by provisions built into contracts (or the law) for companies (insurance companies, banks, private equity firms) to make profit. I guess it is fine if these services can be effectively and reliably provided by for-profit companies, but when their pursuit of profit through “a mix of cost cuts, price increases, lobbying and litigation” conflict with actually providing services, there is a big problem. In the case of emergency medical services, the problem was that “…many newly insured Americans turned out to be on Medicaid, according to the Kaiser Family Foundation. Medicaid restrictssome of the most aggressive billing tactics.”

A variety of other difficult to understand strategies are also employed at the macro level to place the interests of wealthy corporations above those of the people. These include the unlimited political contributions permitted by the Supreme Court’s Citizen’s United decision, incredible gerrymandering of congressional districts so that we have states where the majority of voters vote for Democrats but most districts are solidly Republican (see the New York Times Book Review “Where votes go to die”, June 26, 2016), and the provisions of the Trans-Pacific Partnership (TPP) that prevent national governments from regulating multi-national corporations.

We could solve this if there was a single, over-arching principle, always codified into law, that the interests of the people as a whole always trumps the profit potential of corporations. I vote for that.

Giving Thanks in a scary world

Let us give thanks.

Let us give thanks that we are not the parents of Michael Brown. One of the more thoughtful and moving pieces on this subject among the thousands to appear is by Charles Blow, Fury after Ferguson.

Let us give thanks, if we do not live in Missouri, that we won’t see the St. Louis County District Attorney running for Governor. Or, if we are, that we can vote against him.

Let us give thanks that we are not in prison, victims of the four-decade old policy of mass incarceration in the US, addressed as a major public health epidemic by the New York Times, “Mass Imprisonment and Public Health”, which details the reasons why

…people in prison are among the unhealthiest members of society. Most come from impoverished communities where chronic and infectious diseases, drug abuse and other physical and mental stressors are present at much higher rates than in the general population. Health care in those communities also tends to be poor or nonexistent.

The experience of being locked up — which often involves dangerous overcrowding and inconsistent or inadequate health care — exacerbates these problems, or creates new ones. Worse, the criminal justice system has to absorb more of the mentally ill and the addicted. The collapse of institutional psychiatric care and the surge of punitive drug laws have sent millions of people to prison, where they rarely if ever get the care they need. Severe mental illness is two to four times as common in prison as on the outside, while more than two-thirds of inmates have a substance abuse problem, compared with about 9 percent of the general public.

Common prison-management tactics can also turn even relatively healthy inmates against themselves. Studies have found that people held in solitary confinement are up to seven times more likely than other inmates to harm themselves or attempt suicide.

The report also highlights the “contagious” health effects of incarceration on the already unstable communities most of the 700,000 inmates released each year will return to. When swaths of young, mostly minority men are put behind bars, families are ripped apart, children grow up fatherless, and poverty and homelessness increase. Today 2.7 million children have a parent in prison, which increases their own risk of incarceration down the road.

Oh, yes. Or their children.

Most of us are not. Some of us are. It is simply not ok. And it is not ok to be selfish, arrogant, so-greedy-it-is-not-to-be-believed multi-billionaires. Be successful, yes. Be rich, yes. Do not be obscenely so wealthy that it requires the destruction of the lives of millions of others.

Blow notes that

Even long-suffering people will not suffer forever. Patience expires. The heart can be broken only so many times before peace is broken. And the absence of peace doesn’t predicate the presence of violence. It does, however, demand the troubling of the comfortable

Nick Hanauer, a multi-billionaire, is less sanguine. He warns his fellow 0.01%ers in a post on Politico.com that “The Pitchforks are coming for us…Plutocrats”. It’s a nice thought, that they would get what is coming to them, but I am less than confident that he is correct. It is a nice thought for Thanksgiving, though.

If we have jobs, let us be thankful. If, even better, they are good jobs, let us be more thankful.

If we have family, let us be thankful. If we have lost family, let us be thankful for the time that we had them. If we can still imagine a world with peace and justice, let us be thankful, although it may be just in our imagination.

And then, let us take a deep breath and realize that it is not just going to come, that we are going to have to work for it. Hard, and tirelessly.

Happy Thanksgiving.