Longevity, life expectancy, premature mortality: Are they lions and tigers and bears?

Before I set up the context for this post, I am going to throw this out to you. Think of putting rocks on a scale to achieve the weight of, let's say, 1,000 lb. And let's say that you are required to use rocks of similar size. You have a bunch of bricks -- these are your biggest "rocks," and you have a bunch of pebbles like the ones I have in my driveway (perhaps you have them in yours too). In order to get to 1,000 lb, will you need more bricks or more pebbles? I am not trying to trick you. This is just an illustration of the fact that you can get to the same magnitude of a variable (in this case weight) by either using a smaller number of more weighty components (bricks) or a larger number of lighter ones (pebbles). Keep this in mind as you read on below.

I got an interesting comment from Brad F. on my post from yesterday regarding the 10% number for the premature death avoidance attributed to access to medical care. He pointed me to a blog post on the always-informative The Incidental Economist web site which called this a "zombie statistic." Despite having a fifteen-year-old who is an avid fan of zombie fiction and film, I was not familiar with this term, but inferred its meaning pretty easily.

The gist was that when people started to look for the origins of this number, the evidence was difficult to find, and, when discovered, was at best shaky:

Thus, as Austin and Adrianna had found, the 35-year old CDC paper seems to be at the root of the often-cited 10% number; it’s “paper 0,” if you will. But those that continue to reference 10% as an estimate for health care’s contribution to health should know that the only evidence they are referencing is a survey of 40 people, done when Jimmy Carter was president. It’s not evidence-based except by the weakest notions of “evidence.” It’s really a zombie statistic.

My obvious next question was whether a more trustworthy estimate existed for the medical care's contribution to life extension in the US. In my search for a better estimate, I continued to go down the rabbit hole of links, arriving here, the AcademyHealth Blog, landing on the article called "Half of longevity gains due to health care." It was a summary of the attempt by the authors of The Incidental Economist to answer this very question. And what did they find? First, they quoted a NEJM citation from 2006, where it was claimed that 90% of the increases in life expectancy since the 1960s was due to reduction in cardiovascular and neonatal deaths. After meandering through several other sources, the authors concluded that we can attribute about 50% of the responsibility for extending our life to medical interventions.

And that's when I really confused myself. I started thinking about whether premature death and longevity are related, and how they may be related, and are we even talking about the same thing when we invoke each of them.

Premature mortality can be quantified in several ways -- 1). percentage of all deaths that are considered premature, or 2). proportion of people in a population whose death is considered premature (that would be so many cases per 100,000 population). Longevity, on the other hand, is a measure of the average life span of a population. The current life expectancy in the US is 78.8 years. This begs the question of how these two, premature deaths and life expectancy, are numerically related to each other. And can the latter go up without the former going down?

Well, if the language here is consistent with how we speak it, "premature" implies that we know what "timely" means. The definition of a "timely" death must be based on the average life expectancy in a population. This number varies according to certain characteristics of a population, of course, so different subgroups would have a different life expectancy. For example, at any given age, the life expectancy of a person with heart disease should be lower than that for a person who is perfectly healthy. If we can reduce the risk of a premature death in people with heart disease, their life expectancy should edge closer to that of a healthy individual. And, in fact, according to the literature, this has happened in cardiovascular patients, partly due to better treatment of blood pressure, and partly due to fewer people smoking and other healthful lifestyle modifications.

So, it's clear that when death due to a disease is postponed, longevity increases and, ergo, premature deaths drop. It's a bit circular, I know. But here is one interesting detail to consider. Longevity or life expectancy (I use them interchangeably) is an age average. So here is one question: Does the impact on the magnitude of life expectancy gains vary with the age of the population in which premature deaths are avoided? I know, its a clunky question. What I mean is, would you expect life expectancy to go up more, less or same amount if we manage to reduce premature deaths in infancy versus old age? If you consider that life expectancy is an average, then infant mortality attenuates this average severely (think adding a whole bunch of numbers into the denominator without contributing anything to the numerator). So you can imagine, if infant mortality goes down a lot (a big reduction in premature deaths), overall population life expectancy spikes decisively. Reducing premature deaths among the elderly, clearly, by this same calculation, will not result in nearly the same increase in life expectancy.

Another way of looking at this is to consider that a much larger reduction in premature deaths among the elderly (think driveway pebbles) than among infants (those sizable bricks) would be needed in order to reach a similar degree of longevity improvement. A less intuitive corollary of this is that we indeed can have an increase in premature mortality in a group that contributes little to longevity (the elderly) and still witness a large bump in life expectancy with a much smaller reduction in premature deaths within a group with an outsized contribution to longevity (infants). So that answers the second question I posed about these measures -- they can diverge.

Now, on to the estimated contribution of medical care to either or both of these. We have, in fact, witnessed a dramatic reduction in infant mortality. I found this report from Health Resources and Services Administration that infant mortality has dropped from 55.7 per 1,000 live births in 1935 to 6.8 per 1,000 live births in 2007. And here is what the authors cite as reasons:

...dramatic declines in infant mortality rates over the long term were due to large declines in mortality from pneumonia and influenza, birth defects, prematurity and low birthweight, respiratory distress syndrome (RDS), sudden infant death syndrome (SIDS), and injuries. Improvements in living conditions, advances in neonatal medicine and infant heath care, reductions in smoking during pregnancy, and increased access to and use of prenatal care have been suggested as factors responsible for decreases in infant mortality over the past several decades...  

 

And here is an interesting detail: the pace of this drop was a dizzying 3.1% per year on average between 1935 and 2000. However, between 2000 and 2007, the rate went down only from 6.9 to 6.8 per 1,000 live births, a staggering deceleration in this steep decline. A further detail indicates that "much of the statistically significant decline [occurred] in the neonatal period." The implication of this is that the latest declines are due to technology use, most likely among the very premature infants upon delivery. This is the very definition of access to medical care, and falls completely outside of the domain of public health.

Just one more random thought. Reductions in infant and cardiovascular mortality, each a product of both medical and public health interventions, are one side of the life expectancy equation. The other, darker, side is the fact that in some groups and locations in the US, the overall longevity is waning. Much of this phenomenon can be attributed to poverty, environmental factors and poor health behaviors, or, in sum, a reflection of our dismal investment in public health. And, sure, there is a component of access here too. And what about this calculus: Between 1990 and 2010, mortality from cardiovascular disease dropped by about 150,000 per year. That would be an awesome contribution to increased longevity and reduced premature deaths, if it weren't offset by all the deaths (presumably premature) related to the healthcare system itself.

I know that none of this gets to the crux of the matter: What is a reliable estimate of what proportion of the increases in life expectancy can be attributed to access to medical care? But what it does make me appreciate is the complexity of each and every term, every definition, every estimate that we confront daily. This devil, as always, is in the details.


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"Lifesaving": I don't think it means what you think it means

Transparency, I think that is what pissed me off so much. Or rather the opaqueness. Got me to post again, though, right? Well, don't get used to it.

           

The message was clear: We are heroes, we are giving you lifesaving nuggets of information. And Gina Kolata swallowed it, hook, line and sinker. No pushback, no critical thinking, just drooly awe. I get pissed about stuff like that. Yes, I do. Am I the only one who sees the hypocrisy? The comments would suggest otherwise, but my reasons are a bit different from some of what I saw: we cannot scapegoat pharma for this one, folks.  

The headline read "Lower Blood Pressure Guidelines Could Be ‘Lifesaving,’ Federal Study Says.” There has been a lot on triggers and trigger warnings these days in the press. Well, let me contribute to the discussion. If you know me, you know there are multiple “triggers” in that title for me; there really should have been a trigger warning. "If you have seen through cherry-picked data before, if you have seen through disease mongering, if sensationalized medical headlines induce vomiting in you, beware of triggers in this headline." And, by the way, the study will not be published for another couple of months, so who has vetted these data? The investigators who are so incredibly invested in the results? Their PR office? Journalists hungry for a story? Laughable!

So, "triggers."

First: Lifesaving. Very few things in life are lifesaving. Under the right circumstances, a parachute is indispensable for saving a life. A surgery can save the life of a traumatized human. An EpiPen can be lifesaving. There are just not that many circumstances in which medicine can really claim saving lives. Most of the strides we have made in extending life expectancy did not come through pills, contrary to breathless reports. We owe them to public health interventions – clean water, sewage treatment, vaccination. Even if you look at the current causes of premature death in the US, it’s largely unrelated to medicine. Believe it or not, only 10% of premature death can be attributed to not having access to medicine. The remaining 90% is just what you would think: genetics, behavior, environment and economics. Yes, money, or its flip side, poverty, contributes generously to early mortality in the US. So if you invoke “lifesaving” in a headline in the context of a medical intervention, the burden of proof in on you. But I guess the public bears the burden of credulity. And that pisses me off.

           

Second: "Lower blood pressure guidelines." So what they are telling me is that they have found evidence that getting one's blood pressure into a lower range (systolic 120 mmHg or below in this study) than what is currently recommended (systolic 140 in people 30-59, and150 mmHg in those over 60) will save lives. OK, what is the next obvious question? If you are me, there are several. One: Is this true for everyone over 50 (this study’s population) with high blood pressure? Is it true for my 80-year-old mother just as much as for a 55-year-old African American man who also has diabetes? And what about that 62-year-old executive whose stressful job occasionally throws her into a hypertensive paroxysm? Two: How much does it reduce any given person's risk for dying and over what period of time? To say that it reduces the risk of death is meaningless. We will all die eventually. As much as we like to split hairs about pre-diebetes, we prefer to remain silent on that much more prevalent chronic condition of humanity – pre-death. So, in the case of my 80-year-old mother, how much will it reduce her risk of dying, and over how long – 10 years, 20 years, more? Does it even make sense to ask these questions given that age puts us at risk for death from many causes at the same time? The question is much more relevant for the 55-year-old African American man, of course, but the headline, and, alas, the story fail to tell me this detail. Three: Was the observed mortality benefit even due to the blood pressure difference? That is, how well did they succeed in treating each group to their designated blood pressure target? These answers can only come once the paper becomes available. Right now we just have to take their word for it. And you know how much that appeals to me, right?

           

Third: The story made a reference to a 25% reduction in mortality. If it meant that everyone has a 100% chance of dying, and now this risk is down to 75%, well, that may be lifesaving. However, even the most optimistic among us surely cannot think that this is what this number means. In fact, what this number means is that whatever your risk is today of dying in the next 5 years, say, by keeping your blood pressure at or below 120 will reduce it by 25%. Someone like me, I would guess, has an under 5% risk of dying over the next 5 years. Reducing this risk by 25% gets me into a 3% range. Some may say that this is substantial. Others, me included, will ask another question.

           

Fourth: At what cost? And I have to say, the investigators along with Kolata thought of that. They indicated that these drugs are pretty cheap, as 90% of them are generic. Boom! All set, right? Wrong. Side effects are costly (the article skirts this issue). And not just in dollars, but in quality of life, in whether or not you can get out of bed to take care of your children, whether or not you can give a 30-minute talk at a conference without either running out to the bathroom or wetting yourself, in whether you increase your risk of passing out or even of having a stroke by dropping your blood pressure too much, in whether you injure your kidneys by the same mechanism. And to be fair, as a part of the study, the researchers are looking at least at some of these important questions. But here is the kicker: those data are still being analyzed. So even the investigators don’t know what is on the other side of the risk-benefit scale. It means that in essence, they are touting something as “lifesaving” without telling us in whom, how lifesaving, and what the trade-offs may be.

           

And oh, here is one last question that comes to mind for me:

Fifth: Did GSK sponsor this study? I ask that with my tongue firmly in my cheek, because I know that this study had federal funding. It was our tax dollars, on the order of $10-20 million, I am guessing, that picked up the tab. Why is my tongue in cheek? Because if GSK had put out a news release like this, not even the East Podunk Times, let alone The New York Times, the paper of record, would have been stupid enough to print it. Because pharma, right?

           

So what is the moral? There is more than one, take away what you will. What stands out for me is that we have become blind. I am not an industry apologist – there is history there, which I am not interested in rewriting. I am also quite realistic about investment in pharmaceutical business as a vehicle for wealth in the US. However, in this hunt for lies and liars, another head has popped up on the hydra. While we weren't looking, academic researchers somehow became more interested in their 15 minutes of fame than in the integrity of what they present to the world. And, as far as we think we have come away from accepting paternalism in medicine, we are right there to worship them.

Why does this piss me off so much? I don't know. Perhaps the arrogance. Perhaps because it makes me sad to see that my fellow researchers can be either so blind or so ambitious as to push out something so unfinished to media vultures looking for "lifesaving" meat. Perhaps I feel for my former colleagues in their offices, who will now need to deal with spikes in anxiety and even blood pressure in their already hypertensive elderly patients, and are now in a position to leave that anxiety unaddressed in this age of the incredible shrinking appointment that has done away with nuanced relationship-nurturing conversations. Perhaps I feel for them even more because they too will feel more anxiety in this unforgiving world of 21st century medicine in America, where their hides depend on meeting "quality metrics" built on half-baked data like those reported in Kolata's story. And finally, and most importantly, I feel for the patients, who, without knowing it, are the true subjects of this experiment in American medicine, where docs are beholden less and less to the individuals in front of them and more and more to the gluttonous bureaucratic machine that is swallowing their humanity. It is beyond time to stop this madness.

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The slow work of healing

I just finished reading "Tattoos on the Heart" by Gregory Boyle. I came to it partly via Krista Tippett's conversation with him last summer at the Chautauqua Institute, and partly through other sources. It is a far-ranging account of his work over the last 20 years with the members of toughest Latino gangs in LA through his non-profit Homeboy Industries. The book is suffused with love for these societal outcasts and peppered with wisdom, some in the Christian and some in other traditions, including secular.

What does a book like this have to do with healthcare? Well, a lot. There are many points that might help rehumanize clinical medicine. But this passage on page 179 really made me stop in my tracks:

Funders sometimes say, "We don't fund efforts; we fund outcomes." We all hear this and think how sensible, practical, realistic, hard-nosed, and clear-eyed it is. But maybe Jesus doesn't know why we are nodding so vigorously. Without wanting to, we sometimes allow our preference for the poor to morph into a preference for the well-behaved and the most likely to succeed, even if you get better outcomes when you work with those folks. If success is our engine, we sidestep the difficult and belligerent and eventually abandon "the slow work of God."

Now, I am not Christian or even particularly religious. I am, however, a fan of the Jesus persona who merged with the poor and the hungry and the downtrodden, who became the change he wanted to see. And I had to re-read this paragraph several times, particularly the last sentence. Is this not exactly what we are seeing in medicine? We have told ourselves a lie that by chasing only those outcomes that are quantifiable we are pursuing only that which is important. But wasn't it Einstein who said that not everything that counts can be counted, and not everything that can be counted counts?

Is this gaming of the system that Father Boyle talks about in the paragraph above not exactly what we are seeing as the end-result of the perversion of the idea of evidence-based medicine? What if we change a few of the words in the above paragraph (and stick to secular language)? Will it fit what is happening in medicine today?

Payors Funders sometimes say, "We don't fund efforts; we fund outcomes." We all hear this and think how sensible, practical, realistic, hard-nosed, and clear-eyed it is. But maybe Jesus doesn't know why we are nodding so vigorously. Without wanting to, we sometimes allow our preference to help the sick for the poor to morph into a preference to take care of for the well-behaved and the most likely to succeed, even if you get better outcomes when you work with those folks. If success is our engine, we sidestep the difficult and belligerent and sickest and eventually abandon "the slow work of healing God."

I don't have the answers to how to solve our fiscal and quality crises in medicine. Well, I do, but they involve a cultural overhaul of the entire US of A. But this paragraph sure is making me think.

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The New York Times, aspirin and melanoma, oh my!

One of the reasons my blogging has fallen off lately is because I hate sounding like a broken record. Yet here I am again calling this time the New York Times Well blog on its reporting of, yes, you guessed it, another cancer study.

The story this time is about a paper coming out of the humongous Women's Health Initiative study that examines the relationship between aspirin and melanoma development, hypothesizing that aspirin may help prevent this skin cancer. The paper was published in the journal Cancer and is, of course, behind a paywall. And the abstract, as always, tells me very little.

So I did a little guessing and left this comment on the blog:

So, an absolute risk reduction would have been a much more helpful number to cite, and because the full paper is behind a paywall I cannot get that number. But I can do a little educated estimating:

There were 548 incident melanomas among 59,806 women, amounting to a 0.9% risk of developing this cancer over 12 years. Let's just call it 1%, shall we? Understanding that this 1% is a hybrid of the risk with and the risk without aspirin, the baseline risk must be a little bit higher. Let's give aspirin a huge break and assign the risk without it to the entire group -- let's call it 1.25% over 12 years. Reducing this 1.25% risk by 21% relatively give us roughly 1% risk of melanoma in 12 years in this age group. So, really we are going from 1.25% to 1% risk by using aspirin. This means that 400 women need to take aspirin regularly to avoid 1 case of melanoma (if we believe that this relationship is causal). Mind you, we are not talking about death from melanoma, but just a diagnosis of melanoma. And let's remember that early melanomas are just excised without further treatment. 

Now, among these 400 women daily aspirin can be expected to cause roughly 1 major bleeding event per year. So, over 12 years there would be up to 12 major bleeds. All to save 1 person from a melanoma diagnosis. Why not report the full story?

We'll see if it gets accepted. And by the way the aspirin and bleeding numbers came from a recent large study published in JAMA and covered here at Forbes.

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Healing medicine's moral injuries and spiritual violations

This, from the On Being blog:

Dr. Shay has his own name for the thing the clinical definition of PTSD leaves out. He calls it “moral injury” — and the term is catching on with both the VA and the Department of Defense.

[...] 

“Whether it breaks the bone or not,” he says, “that wound is the uncomplicated — or primary — injury. That doesn’t kill the soldier; what kills him are the complications — infection or hemorrhage.”

Post-traumatic stress disorder, Dr. Shay explains, is the primary injury, the “uncomplicated injury.” Moral injury is the infection; it’s the hemorrhaging.

And a parallel quote from Abe Verghese's The Tennis Partner:

It's important that you realize that every illness, whether a broken bone, or a bad pneumonia, comes with a spiritual violation that parallels the physical ailment.

As I was commenting on the Facebook page of On Being, I started to think about our constant pursuit of precision medicine, which just misleads us into a delusion of certainty, and how far we have drifted from the humanistic goals of medicine -- healing the soul along with the body.

Yesterday I listened to a podcast of Krista Tippett's conversation with Natalie Batalha, an astronomer who discovered the first rock planet outside of our solar system. Dr. Batalha, the ultimate scientist, reminded me that poetry and imagination are essential ingredients of science. She said something like "I am the universe looking at myself through the eyes of this sentient being." This is poetry and spirituality, and every component of this statement is grounded in scientific fact.

The science of medicine needs to regain its soul. It can do this only through the admission of our great uncertainties at the intersection of the "uncomplicated injury" and "moral injury." And even more than admit, we need to embrace and revel in these uncertainties -- this is where poetry and imagination reside. If we fail to do this, we risk compounding this "spiritual violation" instead of easing it. I know this isn't anywhere in the PPACA, and it is not a quality metric that anyone will monitor so as to reward/punish. And it's uncharted territory to boot. Yet this is precisely what is needed to heal medicine.

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ACOG's dysmenorrhea FAQs: Evidence of propaganda?

I have been looking up information on endometriosis for a friend of mine, and came upon this from the American College of Obstetricians and Gynecologists:

So I bit and started reading. And about half way through my reading it I realized that this really reminds me of how they taught literature in the my native USSR. The teaching consisted of stock interpretations of the great authors' works through the prism of Communist Party propaganda. In this interpretation all of the writers' messages railed against the monarchy, and all exhortations were for the purpose of freeing the proletariat. No teacher ever dared to disagree, and no student was expected to question.

Why, you ask, do these ACOG FAQs on dysmenorrhea remind me of my schooling in the old country? Well, glad you asked. Check out this gem, for example:

That's it. No follow-up questions? Good!

But really let's take it from the top. So, OK, there is the pelvic exam. I can deal with that because I am used to that as the default for anything going on "down there." Then there is the ultrasounds exam. I guess I can deal with that too because there has been so much in the news about pelvic ultrasound, and that seems to be what is done to get a better look at what is down there. A laparoscopy? Wait, isn't that a surgical procedure? Yeah, they even say it's a surgery, and it's done to get a "look inside the pelvic region." Hmmm, this sounds pretty serious. How come they don't say anything here, in these FAQs, about what they are looking for, how good this surgery is at finding it, what the chances that what they find is responsible for my dysmenorrhea, what is the treatment and how successful it is at alleviating my symptoms of dysmenorrhea, and whether or not there are alternative interventions?

(Does anyone really ask the patients what their FAQs are or are they generated by the clinicians based on what they think should be important to the patient? Or even worse, based on what they think they can give a perfunctory answer to? Just from reading these Qs and As I think it's the latter.)

You get my point. This formulation of information is beyond useless. It seems paternalistic in its "there there, dear, we will take care of everything" attitude. Perhaps I am out of touch. Perhaps women, patients in general, don't want to go beyond what their doctor tells them to do. But I happen to think that it is these FAQs that are out of touch. Granted, I am a "difficult" patient, as even a pelvic exam, let alone ultrasound and surgery, meets with questions around the evidence of its effectiveness. But even if you have only completed ePatient 101, you should know enough to ask about something as serious as a laparoscopy! How can anyone be expected to just acquiesce and, sighing, say "yes, I guess I have to have surgery." This "FAQ" is completely absurd in its willful lack of useful information. And if you read the rest of the document, you will find many places where this is true as well.

I know that some of you will read this and click away saying "oh, there she goes again." But I think you need to rethink your apathy. After all, there are well over 200,000 deaths (and possibly even more than 400,000) annually in the US that happen unnecessarily just from contact with our "healthcare" system. If you can avoid the avoidable, is it not incumbent upon you to be fully informed? You may think that all these recommendations are evidence-based, and there is not a whole lot of wiggle room in how to proceed. Well you are wrong if you think so, since the evidence, even when it is available, is rarely, if ever, unequivocal. And furthermore, in medicine no benefit comes without a risk. Are you sure you want your doctor to make these decisions for you? How is it that people who are not even willing to take wardrobe advice from their mothers wade so enthusiastically into these high-risk medical adventures with their eyes and ears closed?

I wrote Between the Lines to show just how imprecise and uncertain the science of clinical medicine is. But beyond that, I wanted to provide you with tools at least to ask the right questions. So, please, go and ask. And insist that you be included in the FAQ processes. Otherwise, we are just wasting terabytes on propaganda.            

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What does $750 billion in wasted spending look like?

Here is an infographic (I know) from the Institute of Medicine who just released this report. According to it, we are wasting $750 billion annually in unnecessary healthcare costs, and here is the breakdown. Note the ~$250 billion on overdiagnosis and overtreatment. Now,what are we going to do about it?

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BTL reader question: How do you get to 2%?

I have started a FAQ page on the BTL book web site here, and I will cross-post the discussion here on the blog. This will give us an opportunity to have a more interactive discussion, if necessary, with additional comments and questions.

Here is the inaugural installment.

On August 13, 2012, this question came in via Twitter:

Well, here is the answer (and thank you for the question, Tia!)

First the problem. At the bottom of page 74 and going on to the top of page 75 I discuss the question posed in a 1978 New England Journal of Medicine paper by Casscells and colleagues to 60 physicians and physicians-in-training at Harvard Medical School. The problem went like this:
 
"If a test to detect a disease whose prevalence is 1/1000 has a false positive rate of 5 per cent, what is the chance that a person found to have a positive result actually has the disease, assuming that you know nothing about the person's symptoms or signs?"

The question clearly mimics a disease screening situation. The answer is simple yet elusive. Let us assume that 1,000 people are tested. Among them only 1 person has the actual disease. However, given that the false positive rate is 5%, we also know that out of the 1,000 people tested, 50 will have a false positive test. Assuming that the single person with the disease also has a positive test, we can expect 51 people to test positive. But since only 1 out of these 51 people with a positive test has the disease, the answer to the question above is 1/51=2%. This is a pretty shocking realization, given that a large plurality of the Harvard doctors and trainees chose 95% as their answer. 

So, be careful not to let your intuition override the data when making medical decisions!

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Medicine as the trolley problem

Are you familiar with the trolley problem? It is an ethics dilemma first formulated by the great Philippa Foot as a part of a series of such dilemmas. Her formulation goes roughly like this. Imagine there is a tram hurtling down a track. If it keeps going straight, it will hit and kill 5 people who are working on that track. The conductor is able to throw a switch and divert the train to another part of the track, where 1 single worker will be killed by the trolley. The question is what should the conductor do? Most people when asked respond that yes, he should throw the switch and sacrifice 1 life to save 5. After all, the net benefit is n=4.

There are literally thousands of alternative formulations of this problem, but one of them from the philosopher Judith Jarvis Thomson merits special consideration. The problem starts out similarly, with 5 lives on a track in potential peril. The vantage point and the solution are quite different, though. Now there is a bridge over the rail track, and a very large man is looking at the tracks from the bridge. One way to stop the train is to throw a heavy object in its path, like this large man, for example. You are on the bridge standing behind the man. Would you be justified in pushing him off the bridge in front of the tram to meet his death in order to spare the 5 workers down the tracks? Most people when faced with this formulation say an emphatic "no." This is somehow puzzling, since the net benefit is the same, n=4, as in the original Foot formulation.

Philosophy professors have puzzled over this difference for decades, and there are several potential explanations for why we respond differently to the two scenarios. One explanation has to do with the proximity of the operator (conductor in the first case and the person doing the pushing in the second) to the sacrificial lamb -- in the first case one is enough removed from the action of killing by merely redirecting the tram, whereas in the second the action is, well, more active, and the operator is actually pushing an innocent person to his death.

Though in some ways the scenarios seem to bear no practical distinction from one another, we see the morals and ethics of each differently. This difference in the view point is instructive to the field of medicine, where it has implications to how policy relates to the individual patient encounter. Here is what I mean.

Suppose you are a policy maker, and you recommend that every woman at age 40 start to receive an annual screening mammogram to reduce deaths from breast cancer. At the population level, if we screen 1,000 women for about 30 years, we will save approximately 8 of them from a breast cancer death. (Yes, it's 8, not 80, and not 800). At the same time, among these 1,000 women, there will be over 2,000 false alarms, and over 150 of these will result in an unnecessary biopsy. Some of these biopsies will incur further complications, though currently we  do not seem to have the data to quantify this risk. But what if even one of these biopsies were to lead to death of or another dire lasting complication in a woman who turned out not to have cancer? And by the way the accounting is not all that different when applying the new USPSTF mammography screening recommendations. Well, then we have the trolley problem, don't we? We are potentially sacrificing 1 individual to save 8. And who does the sacrificing is where the variations of the trolley problem come in.

Payers levy financial penalties on primary care physicians when they fail to comply with screening recommendations in their patient panels. The payer certainly sees this issue as the original formulation of the problem: Why not throw this financial switch to achieve net life savings? But for a clinician who deals with the individual patient this may be akin to pushing her over the bridge toward a potentially fatal event. Because we don't have a crystal ball, we cannot say which woman will die or incur a terrible complication. But the same population data that tell us about benefits must also give us pause when reflecting on the risks. Add the ubiquitous uncertainty (and lack of data) into this equation, and the implications are even more shocking. So, while making policy recommendations based on population data is sensible, policing uniform application of these recommendations to individual patients is fraught: of course, clinicians and patients need to be cautious about making individual decisions even when in population data benefits outweigh risks.

On the surface risk-benefit equations for many interventions may appear favorable, leading to blanket policy recommendations to employ them on everyone who qualifies. In the office, the clinician, caught in a tug of war between mountains of new literature and the ever-shrinking appointment times, is hard-pressed to take the time to consider these recommendations in the context of the individual patient. And furthermore, financial incentives from payers act as a short-hand justification, a "nudge," for doing as recommended rather than for giving it thought. So, who must look out for the patient's interest? The patient, that's who. Who understands the patient's attitude toward the risks and the benefits? The patient, that's who. Who now has to be responsible for making the ultimate informed decision about which track to stand on? The patient, that's who.

For me the trolley problem gives clarity to the reservations that I walk around with every day. I have done a lot of soul searching about why it is that, even if the benefits seem to outweigh the risks, I am still more often than not skeptical about whether a particular intervention is right for me. And since every intervention in medicine has a real risk, though mostly quite low, of going terribly awry, my skepticism is justified. This is my approach to evaluating these risks and benefits, based on my values and my understanding of the data as it is today.

What's the answer to this ethical conundrum in medicine? I cannot see that policy makers will stop throwing the switch in the near future, and so as a society we will be forced to accept the tram's collateral damage. And while this may make sense in an area such as vaccination, where thousands of lives can be saved by sacrificing a very few by throwing the switch, in most everyday less clear-cut medical decisions the answer is less clear-cut. Will doctors rebel against being forced to throw some patients on the tracks in order to save some marginally larger number of others? I don't think that they have the time or the energy or the incentive to do this, since the framing of the switch-throwing is through the rhetoric of "evidence." Right or wrong, doctors are shackled by the stigma of ignorance that comes with not following evidence-based guidelines, and this may act to perpetuate blind compliance. This leaves the patients, for some of whom the right thing will be just to get themselves off the tracks altogether, far away from the hurtling trolley until its brakes are fixed.                        

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Early radical prostatectomy trial: Does it mean what you think it means?

Another study this week added to the controversy about early prostate cancer treatment. The press, as usual, stopped at citing the conclusion: Early prostatectomy does not reduce all-cause mortality. But the really interesting stuff is buried in the paper. Let's deconstruct.

This was a randomized controlled trial of early radical prostatectomy versus observation. The study was done mostly within the Veterans' Affairs system and took 8 years to enroll a little over 700 men. This alone should give us pause. Figure 1 of the paper gives the breakdown of the enrollment process: 5,023 men were eligible for the study, yet 4,292 declined participation, leaving 731 (15% of those who were eligible) to participate. This is a problem, since there is no way of knowing whether these 731 men are actually representative of the 5,023 that were eligible. Perhaps there was something unusual about them that made them and their physicians agree to enroll in this trial. Perhaps they were generally sicker than those who declined and were apprehensive about the prospect of observation. Or perhaps it was the opposite, and they felt confident in either treatment. We can make up all kinds of stories about those who did and those who did not agree to participate, but the reality is that we just don't know. This creates a problem with the generalizability of the data, raising the question of who are the patients that these data actually apply to.

The next issue was what might be called "protocol violation," though I don't believe the investigators actually called it that. Here is what I mean. 364 men were randomized to the prostatectomy group, and of them only 281 actually underwent a prostatectomy, leaving nearly one-quarter of the group free of the main exposure of interest. Similarly, of the 367 men randomized to observation, 36 (10%) underwent a radical prostatectomy. We might call this inadvertent cross-over, which does tend to happen in RCTs, but needs to be minimized in order to get at the real answer. What this type of cross-over does is, as is pretty intuitively obvious, blend the groups' differences in exposure, resulting in a smaller difference in the outcome, if there is in fact a difference. So, when you don't get a difference, as happened in this trial, you don't know if it is because of these protocol violations or because these treatments are essentially equivalent.

And indeed, the study results indicated that there is really no difference between the two approaches in terms of the primary endpoint (all-cause mortality over a substantially long follow-up period was 47% in the prostatectomy and 50% in the control groups [hazard ratio 0.88, 95% confidence interval 0.71 to 1.08, p=0.22]). This means that the 12% relative difference in this outcome between the groups was more likely due to chance than to any benefit of the surgery. "But how can cancer surgery impact all-cause mortality?" you say. "It only claims to alter what happens to the cancer, no?" Well, yes that is true. However, can you really call a treatment like that successful if all it does is give you the opportunity to die of something else within the same period of time? I thought not. And anyway, looking at the prostate cancer mortality, there really was no difference there either: 5.8% attributable mortality in surgery group compared to 8.4% in the observation group (hazard ratio 0.63, 95% confidence interval 0.36 to 1.09, p=0.09).  

The editorial accompanying this study raised some very interesting points (thanks to Dr. Bradley Flansbaum for pointing me to it). He and I both puzzled over this one particularly unclear statement:

...only 15% of the deaths were attributed to prostate cancer or its treatment. Although overall mortality is an appealing end point, in this context, the majority of end points would be noninformative for the comparison of interest. The expectation of a 25% relative reduction in mortality when 85% of the events are noninformative implies an enormous treatment effect with respect to the informative end points.

Huh? What does "noninformative" mean in this context? After thinking about it quite a bit, I came to the conclusion that the editorialists are saying that, since prostate cancer caused such a small proportion of all deaths, one cannot expect this treatment to impact all-cause mortality (certainly not the 25% relative reduction that the investigators targeted), the majority of the causes being non-prostate cancer related. Yeah, well, but then see my statement above about the problematic aspects of disease-specific mortality as an outcome measure.

The editorial authors did have a valid point, though, when it came to evaluating the precision of the effects. Directionally, there certainly seemed to be a reduction in both all-cause and prostate cancer mortality in the group randomized to surgery. On the other hand, the confidence intervals both crossed unity (I have an in-depth discussion of this in the book). On the third hand (erp!) the portion of the 95% CI below 1.0 was far greater than that above 1.0. This may imply that with a study that could have achieved greater precision (that is, narrower confidence intervals) we might have gotten a statistical difference between the groups. But to get at higher precision we would have needed either 1) a larger sample size (which the investigators were unable to obtain even over an 8-year enrollment period), or 2) fewer treatment cross-overs (which is clearly a difficult proposition, even in the context of a RCT), or 3) both. On the other hand (the fourth?), the 3% absolute reduction in all-cause mortality amounts to the number needed to treat of roughly 33, which may be clinically acceptable.

So what does this study tell us? Not a whole lot, unfortunately. It throws an additional pinch of confusion into the cauldron already boiling over with contradiction and uncertainty. Will we ever get the definitive answer to the question raised in this work? I doubt it, given the obvious difficulties implementing this RCT.  

                  

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House appropriations bill to terminate AHRQ and prohibit funding patient-centered research

Update 7/18/12, 3:30 PM eastern:

The Hill has reported here that the bill has cleared the subcommittee. It will be going to the full committee next week.

The $150 billion bill cuts $6.3 billion from current levels of spending in the Labor, Health and Human Services and Education Departments and is part of Republican efforts to rein in government spending – an important message for the GOP on the campaign trail. [...] But other areas are slashed. The bill ends President Obama’s signature Race to the Top education initiative and cuts millions from advanced appropriations for the Corporation for Public Broadcasting, which funds NPR and PBS. The agency that monitors child labor abroad is cut by 68 percent and the agency that distributes Social Security payments gets cut by $764 million. It also would cut funding for Planned Parenthood if the organization continued to provide abortions. (Hat tip to Michael Millenson for the above link)

Yes, folks, you read that right: The House of Representatives has drafted an appropriations bill that will dissolve the AHRQ and prohibit any funding for patient-centered outcomes research (PCOR). The AHRQ is an agency that spearheads and funds healthcare safety and quality research, as well as ways to rein in the costs while expanding access. If it is eliminated, there will be no one to focus on these critical issues. This bill is truly anti-patient and the reps must be informed that they have gone too far.

Here are the names of the Appropriations Committee members, with the subcommittee members responsible for this bill in bold (via STFM):

Democratic Members

• Norman D. Dicks, Washington
• Marcy Kaptur, Ohio
• Peter J. Visclosky, Indiana
• Nita M. Lowey, New York
• José E. Serrano, New York
• Rosa L. DeLauro, Connecticut
• James P. Moran, Virginia
• John W. Olver, Massachusetts
• Ed Pastor, Arizona
• David E. Price, North Carolina
• Maurice D. Hinchey, New York
• Lucille Roybal-Allard, California
• Sam Farr, California
• Jesse L. Jackson, Jr., Illinois
• Chaka Fattah, Pennsylvania
• Steven R. Rothman, New Jersey
• Sanford D. Bishop, Jr., Georgia
• Barbara Lee, California
• Adam B. Schiff, California
• Michael M. Honda, California
• Betty McCollum, Minnesota

• Republican Members

• Harold Rogers, Kentucky, Chairman
• C.W. Bill Young, Florida
• Jerry Lewis, California
• Frank R. Wolf, Virginia
• Jack Kingston, Georgia
• Rodney P. Frelinghuysen, New Jersey
• Tom Latham, Iowa
• Robert B. Aderholt, Alabama
• Jo Ann Emerson, Missouri
• Kay Granger, Texas
• Michael K. Simpson, Idaho
• John Abney Culberson, Texas
• Ander Crenshaw, Florida
• Denny Rehberg, Montana
• John R. Carter, Texas
• Rodney Alexander, Louisiana
• Ken Calvert, California
• Jo Bonner, Alabama
• Steven C. LaTourette, Ohio
• Tom Cole, Oklahoma
• Jeff Flake, Arizona
• Mario Diaz-Balart, Florida
• Charles W. Dent, Pennsylvania
• Steve Austria, Ohio
• Cynthia M. Lummis, Wyoming
• Tom Graves, Georgia
• Kevin Yoder, Kansas
• Steve Womack, Arkansas
• Alan Nunnelee, Mississippi

 Call yours at 202-225-3121!

Here are some pertinent links, courtesy of Kenny Lin, MD, and others:
-The House press release (note they brag about defunding ObamaCare and "protecting" life in the same breath)
-The draft of the bill (see page 90)
-AcademyHealth announcement (where I learned about the PCOR prohibition)
-Statement from Mary Wooley, the President of Research!America about why this is a stupid move
-The Incidental Economist blog is compiling a list of useful projects funded by the AHRQ here

So please please please call your reps to stop this insanity!


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DHHS: Does this lie make me look stupid?

Update, July 12, 4:30 PM Eastern:
Just got this extra lame reply from healthfinder:

Dear Ms. Zilberberg, Thank you for contacting healthfinder.gov.  healthfinder is a government Web site featuring prevention and wellness information and tools to help you and those you care about stay healthy. At healthfinder.gov, you will find:
 ·         interactive tools like menu planners and health calculators
·         online checkups
·         printable information that you can share with a family member or take to the doctor.
 healthfinder.gov is coordinated by the Office of Disease Prevention and Health Promotion (ODPHP), U.S. Department of Health and Human Services and the National Health Information Center (NHIC). NHIC links people to organizations that provide reliable health information. All of healthfinder.gov’s topics and tools go through subject matter expert reviews. As a result of these reviews, sentences and wording sometimes get updated and/or changed. This particular topic has already been reviewed, and the content team will be rewording the language; the word “best” will be removed from that sentence. This change will be reflected on the site in the next scheduled healthfinder.gov update. Sincerely, 
healthfinder.gov TeamNational Health Information Centerhealthfinder.gov is coordinated by the Office of Disease Prevention and Health Promotion (ODPHP), U.S. Department of Health and Human Services and the National Health Information Center (NHIC).

HOW ABOUT INCLUDING A DISCUSSION OF SAFE SEX?!!!!!!! Idiotic.




Update July 11, 10:50 AM Eastern: 
I have just sent the following e-mail to healthfinder.gov at the address healthfinder@nhic.org. I urge everyone who reads this to send them the same or a similar message. And if you do, please, leave a comment below to let everyone know.

Hello, 

I wanted to let you know that the information you posted on this web page on Pap testing is erroneous and misleading. Telling women that the "best" way to prevent cervical cancer is through a regular Pap test is not supported by evidence. The "best" way is to prevent HPV infection by engaging in safe sexual intercourse. As a public health communicator you are doing a tremendous disservice to the public.  

I urge you to change this message to reflect reality. 

Thank you. 

Marya Zilberberg, MD, MPH, FCCP 

There is pounding in my temples, my back muscles are in a spasm, and I might even be turning green and busting out of my clothes. What caused all this? This innocent-looking tweet from the Department of Health and Human Services:

I had to do a double take. My blood started to boil almost immediately. But I persisted, clicked on the link, and saw this:

The first sentence really says "The best way to prevent cervical cancer is to get regular Pap tests." Jaw, meet floor. What does the word "prevent" really mean? I went to The Free Dictionary for enlightenment:

Just as I had suspected: to avert, to keep from happening. And how does a Pap test keep the cancer away? It finds "abnormal cells before they turn into cancer." And where do abnormal cells come from? God, right? Well, no, they are mostly associated with an HPV infection, which comes from exposing yourself to unprotected sexual intercourse, usually with someone whose HPV status you don't know. You see where I am going with this? The message here is that there is nothing more effective at preventing cervical cancer than having a Pap test to detect early changes and lop out the misbehaving piece of your cervix. Are they serious? Is this really the "best way"? Let's examine the meaning of "best":

   
I guess beauty (and value) are in the eye of the beholder. Does subjecting yourself to a surgical procedure that may leave your cervix unable to help your uterus to maintain a pregnancy qualify as "surpassing all others in excellence" or as "most desirable"? Not in my book, not when a little advanced planning and a nickel for a condom could could keep that horse from leaving the barn in the first place. True prevention does not take place in a doctor's office, and it is a mistake to equate screening to prevention.

Come on, DHHS, who writes your stuff? Fire them! You are risking your credibility. What's next? "Bulimia is the best way to prevent obesity"?    

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Drugs and devices: expensive. Hubris: priceless.

This morning I was listening to the Morning Edition on NPR, and heard a story about the tax on medical devices that is written into the healthcare law. As you can imagine, there is opposition to such a tax by the manufacturers, as they are concerned about the usual, "stifling innovation" (yawn). It's hard to be amused by anything to do with healthcare these days, but here is a part of the conversation that had me in LOLZ (my 14-yo's expression):

ARNOLD: Okay. So here's how this new tax works. When a medical device gets sold, there will be a 2.3 percent sales or excise tax. Now, people who support this tax say that the medical device makers are exaggerating about the impact. Paul Van de Water is an economist with the left-leaning Center on Budget and Policy Priorities. He says that this tax is basically the same as a sales tax that you pay at the grocery store.

PAUL VAN DE WATER: The grocery store is collecting the tax. The grocery store is the institution that sends the tax to the state government, just the way the medical device manufacturer is going to write the check to the Treasury.

ARNOLD: Van de Water says that the tax doesn't really target the medical device makers that much. They'll just pass most of the cost along to their customers, who are mostly big hospitals, the same way a grocery store charges their customers. But the industry disagrees. David Nexon is with the medical device trade group called AdvaMed.

DAVID NEXON: There's a difference between a tax that, you know, an individual consumer pays as opposed to one that you're negotiating a price with a large, sophisticated buyer.

ARNOLD: In other words, Nexon says a hospital chain will push back and resist paying anything extra.

NEXON: In this very competitive market, it's extremely difficult for our members to raise prices.

Hah! Is he saying what I think he is saying? That because individual consumers are too dumb to understand about externalizing additional expenses, such as taxes, it is easier to put one over on them than on the savvy hospitals? Could he possibly mean that only "large, sophisticated buyers," and not ordinary consumers, would never stand for the information asymmetry they thrive on? That the individual consumers just don't have the power that hospitals do to push up against potentially predatory pricing? 

The last time I heard or read anything this blatant was in this New York Times piece from December 2009. This is a company executive talking about the rationale for the company's cancer drug's disproportionately steep price:

Mr. Caruso also said the price of Folotyn was not out of line with that of other drugs for rare cancers. Patients, moreover, are likely to use the drug for only a couple of months because the tumor worsens so quickly, he said. So the total cost of using Folotyn will be less than for many other drugs with lower monthly prices.

Wow, do these people get paid to advance their organizations' agendas? For my money they are not doing such a hot job at anything other than confirming all the societal views of them. Are they too stupid to realize that, even if you think stuff like this, you shouldn't say it out loud? How embarrassing.

Bottom line? Their drugs and devices: expensive. Their hubris: priceless.


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