Wednesday, September 16, 2015

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.

If you like Healthcare, etc., please consider a donation (button in the right margin) to support development of this content. But just to be clear, it is not tax-deductible, as we do not have a non-profit status. And I post when I feel like it. Thank you for your support!

Tuesday, September 15, 2015

"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.

If you like Healthcare, etc., please consider a donation (button in the right margin) to support development of this content. But just to be clear, it is not tax-deductible, as we do not have a non-profit status. And I only post when I feel like it. Thank you for your support!