Showing posts with label risk. Show all posts
Showing posts with label risk. Show all posts

Thursday, April 26, 2012

Fast science: No time for uncertainty

Reading Barbara Ehrenreich's "Bright-Sided" has been liberating in that is has given me permission to let my pessimistic nature out of the closet. Well, it's not exactly that I am pessimistic, but certainly I am not given over to brightness and cheer all the time. My poison is worry. Yes, I am a worrier, in case you had not noticed. So, imagine how satisfying it is for me to find new things to worry about. As if climate change were not enough, lately I started to worry about science.

No, my anxiety about how we do clinical science overall is not new; this blog is overrun with it. However, the new branch of that anxiety relates to something I have termed "fast science." Like fast food it fills us up, but the calories are at best empty and at worst detrimental. What I mean is that science is a process more than it is a result, and this process cannot and should not be microwaved. Don't believe me? Let me give you a couple of instances where slow science may be the answer to our woes.

1. Lies and damned lies
Remember this story in the Atlantic that rattled us with its incendiary message? Researcher John Ioannidis has been making headlines with his assertion that most, if not all, of what we know in medicine is in doubt, given how we do and publish research. And how we do and publish research has everything to do with the speed of "progress." Academic careers are made with positive results, to sell news the media demand positive results, and to respond to this demand academic journals prefer only to publish positive results (this last phenomenon is referred to as "publication bias," and is something Ben Goldacre rails against at length). A further manifestation of this fast science is that "no replicators need apply." I am, of course, referring to an extension of the publications bias, whereby journals are not interested in publishing even a positive study that replicates a previous finding -- this is simply not sexy. Thus, results have to be quick and positive to grab a share of our attention and sell academic prestige, journals and news.

2. Science output to drive business profits
In his book Supercapitalism, Robert Reich describes the growing demand by investors over the last several decades to squeeze ever-growing profits. It is clear that this chase after short-term profits has resulted in job loss in the US through outsourcing, the widening of the economic gap, and even the crash of the world economy following the collapse of the mortgage-backed securities house of cards. Much of the profit can be counted on to come through scientific innovations which may or may not improve our quality of life.
In medicine, where scientific progress is applied to our fragile being, being reasonably sure of our findings seems pretty important. Yet speed is once again the order of the day. I will grant you that speed is of importance in such diseases as advanced cancer, for example, where we may and should accept a level of uncertainty that we would ordinarily run away from in other circumstances. But doesn't it make sense to be much more cautious before broadly accepting an intervention that happens before one gets sick, one that is meant to diagnose either early disease or a precursor to one? Should we not demand slower science before we allow anyone to medicalize such normal events in life as menopause and aging? Should this caution also not apply to screening for diseases that may or may not impact us in the long term, yet the chase could hurt us substantially in the immediate future?
But this is not the way to stimulate the economy or to make a profit. The half-life of a medical device, for example, is less than 1 year. After that a new "improved" version of the device is expected, whether it does or does not improve outcomes. For decades we were told to get screening mammography after the age of 40, only to find out now that the risks of this may well outweigh its benefits for many. The American Lung Association has just endorsed CT screening for lung cancer among current or former heavy smokers, yet the jury on its risk-benefit-uncertainty equation should still be in the thick of deliberations.

3. Science denialism
We hear a lot about how people are turning away from science. The state of Tennessee is about to descend back into the dark ages when superstitions instead of scientific theories dominated the classroom. A strong and largely anti-scientific lobby wants to bury any mention of human-driven climate change; fortunately, it looks like they are not succeeding. The anti-vaccination groups are getting more instead of less vocal following repeated debunking of any link between vaccination and autism. Science denialism is so rampant that there was even a need for a conference on how to address it. What gives?
While blaming everything on fast science alone may be reductionist, fast science in the setting of our growing societal innumeracy is a recipe for disaster, as we are seeing unfold. Our schools have failed spectacularly in their duty to educate kids about the process of science, while at the same time arming them with the "single-right-answer-to-every-question" attitude toward knowledge. This pernicious combination, along with the publication and reporting of sexy science at the expense of the more thorough analytic and introspective approach, seals the impression that the roller coaster of scientific knowledge represents not the very essence of how science should be done, but that science (and scientists) has failed.
Is slow science the answer to this fiasco? Only in part, I am afraid. Without altering fundamentally how we teach science at all levels, it would not be the cure, even if it were possible to execute. No, I am afraid that without teaching what science is, it is not even possible to get it to slow down.

Let me reiterate: the pace of scientific discovery is slow. This does not mean that we need to hide every step of it from view until we get the results that we deem worthy of sharing. On the contrary, I agree with those who think that sharing at the more interim steps can only improve what we do. Yet the innumeracy, fame and fortune are forces that put such free sharing in peril by misrepresenting it as the final answer to everything. And when the answer is changed, which is not only expected, but indeed desired in scientific pursuits, the public opinion punishes science.

Let me end with a quote I read on one of my favorite web sites, Brain Pickings, in a review of the book boldly entitled Ignorance: How It Drives Science:
Are we too enthralled with the answers these days? Are we afraid of questions, especially those that linger too long? We seem to have come to a phase in civilization marked by a voracious appetite for knowledge, in which the growth of information is exponential and, perhaps more important, its availability easier and faster than ever.
[...]There are a lot of facts to be known in order to be a professional anything — lawyer, doctor, engineer, accountant, teacher. But with science there is one important difference. The facts serve mainly to access the ignorance… Scientists don’t concentrate on what they know, which is considerable but minuscule, but rather on what they don’t know…. Science traffics in ignorance, cultivates it, and is driven by it. Mucking about in the unknown is an adventure; doing it for a living is something most scientists consider a privilege. 
So, let's celebrate uncertainty. Let's take time to question, answer and question again. Slow down, take a deep breath, cook a slow meal and think.

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Monday, April 9, 2012

Five ways to tame the risk-benefit-uncertainty troika

There was a story on NPR this morning that sent me in a radical direction. It discussed the increase in use of brachytherapy for localized breast cancer. The idea is that this is a concentrated dose delivered much more locally and rapidly (over 5 days) than the conventional external beam radiation (over 6 weeks). The issue is that it has not been tested rigorously in a randomized controlled trial yet, and some oncologists are concerned about its outcomes as they compare to the conventional approach. One of the concerns stems from an increase in the rates of subsequent mastectomies, which are double in brachytherapy relative to conventional. At the same time, there are clear benefits, not the least of which is the period of exposure and the hassle associated with daily trips for radiation for 6 weeks.

Several points popped up in my head in response to the story:
1. When discussing this predominantly women's disease, the expert voices mostly heard from were male (5 of the 6 doctors quoted). Does this matter? Not sure.
2. The priorities addressed by the experts were the traditional outcomes -- survival, recurrence, metastasis. The priorities described by the patient were about her time and convenience today.
3. The concern about the procedure stems from the observed doubling of the need for mastectomy within 5 years among patients treated with brachytherapy, an event "rare no matter what what kind of radiation women got."

So what's my point? Do I think that more rigorous testing is not indicated? Not at all; we need a more rigorous evaluation of the technique. No, what I am wondering is at what point should a procedure like this (or any intervention, for that matter) become available to patients as an option to be considered? Should its availability be determined in a dark room by bespectacled men around a conference table, or should it be put on the menu of choices, along with its risks, benefits and uncertainties, as soon as it looks safe enough, whatever that looks like?

The larger question this raises is what is the degree of uncertainty that we are willing to accept around interventions that become available, be it a drug or a procedure or a device? How do we incorporate patients' priorities for outcomes that are important to them into these decisions? Remember ACT-UP and how they moved the FDA to make more rapid decisions about treatments for HIV/AIDS? Have we swung too far in the opposite direction today, whereby we want a virtual guarantee of safety before a technology is approved?

I offer these 5 potential question to help with making these decisions:
1. How severe/deadly is the disease in question?
2. What is (are) the known potential benefit(s) of the intervention?
3. What is (are) the known potential risk(s) of the intervention?
4. What uncertainties bracket this risk-benefit equation?
5. How does the patient feel about the extent of this risk-benefit-uncertainty balance in the context of her condition?

I think that the first four are the questions that the FDA struggles with every day. They are the gatekeepers for the availability of new technologies, and, therefore, for the relevance of the fifth question. What I am wondering is whether it is not better to start bringing a lot more of the public perspective to the discussion much earlier, so that the patient can have the option of evaluating more choices sooner. I know I may be treading on thin ice here, but I am ignoring any market forces or special interests for the moment. The question I am asking is "In the best of all possible worlds, where no one is trying to sell you anything, when is the best time to give the patient an opportunity to accept or reject an intervention, given the risk-benefit-uncertainty profile?"

Bottom line: There are no guarantees. Just because something is available on the market does not mean that it is completely safe or completely effective. Most importantly, it does not mean that we come even close to being certain about these attributes. As a corollary, just because there are uncertainties about the risks and benefits of an intervention, does it mean that it should not be available as an option for a patient? My guess is that there is a balance of this troika of properties that may be optimal on average, but I am also guessing that that this average balance will miss a substantial volume of outliers. Just as some people thrive on the thrill of bungee jumping while others clamp down just at the mere thought of it, so some patients may surprise us with their position on this risk-benefit-uncertainty continuum.

I apologize if my argument is not clear -- I am definitely thinking about this stuff actively. The one thing I am absolutely sure of is this: Unless the public and clinicians are educated about how to have these conversations, we will always have to rely on and, consequently, blame someone else for making decisions for us.

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. 


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