Pediatrics and Scare Tactics: From Rock-n-Play to Car Safety Seats

Is sleeping in a car seat dangerous?

Earlier this year, the Fisher-Price company relented to pressure from the AAP (American Academy of Pediatrics) and recalled 4.7 million of Rock 'n Play (RnP) baby rockers, which now presumably occupy landfills.  This recommendation stemmed from an "investigation" by consumer reports showing that since 2011, 32 babies died while sleeping in the RnP.  These deaths are tragic, but what does it mean?  In order to make sense of this "statistic" we need to determine a rate, based on the exposure period, something like "the rate of infant death in the RnP is 1 per 10 million RnP occupied hours" or something like that.  Then we would compare it to the rate of infant death sleeping in bed.  If it was higher, we would have a starting point for considering whether ceteris paribus, maybe it's the RnP that is causing the infant deaths.  We would want to know the ratio of observed deaths in the RnP to expected deaths sleeping in some other arrangement for the same amount of time.  Of course, even if we found the observed rate was higher than the expected rate, other possibilities exist, i.e., it's an association, a marker for some other factor, rather than a cause of the deaths.  A more sophisticated study would, through a variety of methods, try to control for those other factors, say, socioeconomic status, infant birth weight, and so on.  The striking thing to me and other evidence minded people was that this recall did not even use the observed versus expected rate, or any rate at all!  Just a numerator!  We could do some back of the envelope calculations with some assumptions about rate ratios, but I won't bother here.  Suffice it to say that we had an infant son at that time and we kept using the RnP until he outgrew it and then we gave it away.

Last week, the AAP was at it again, playing loose with the data but tight with recommendations based upon them.  This time, it's car seats.  In an article in the August, 2019 edition of the journal Pediatrics, Liaw et al present data showing that, in a cohort of 11,779 infant deaths, 3% occurred in "sitting devices", and in 63% of this 3%, the sitting device was a car safety seat (CSS).  In the deaths in CSSs, 51.6% occurred in the child's home rather than in a car.  What was the rate of infant death per hour in the CSS?  We don't know.  What is the expected rate of death for the same amount of time sleeping, you know, in the recommended arrangement?  We don't know!  We're at it again - we have a numerator without a denominator, so no rate and no rate to compare it to.  It could be that 3% of the infant deaths occurred in car seats because infants are sleeping in car seats 3% of the time!

The Therapeutic Paradox: What's Right for the Population May Not Be Right for the Patient

Bad for the population, good for me

An article in this week's New York Times called Will This Treatment Help Me?  There's a Statistic for that highlights the disconnect between the risks (and risk reductions) that epidemiologists, researchers, guideline writers, the pharmaceutical industry, and policy wonks think are significant and the risks (and risk reductions) patients intuitively think are significant enough to warrant treatment.

The authors, bloggers at The Incidental Economist, begin the article with a sobering look at the number needed to treat (NNT).  For the primary prevention of myocardial infarction (MI), if 2000 people with a 10% or higher risk of MI in the next 10 years take aspirin for 2 years, one MI will be prevented.  1999 people will have gotten no benefit from aspirin, and four will have an MI in spite of taking aspirin.  Aspirin, a very good drug on all accounts, is far from a panacea, and this from a man (me) who takes it in spite of falling far below the risk threshold at which it is recommended.

One problem with NNT is that for patients it is a gratuitous numerical transformation of a simple number that anybody could understand (the absolute risk reduction  - "your risk of stroke is reduced 3% by taking coumadin"), into a more abstract one (the NNT - "if we treat 33 people with coumadin, we prevent one stroke among them") that requires retransformation into examples that people can understand, as shown in pictograms in the NYT article.  A person trying to understand stroke prevention with coumadin could care less about the other 32 people his doctor is treating with coumadin, he is interested in himself.  And his risk is reduced 3%.  So why do we even use the NNT, why not just use ARR?

The enemy of good evidence is better evidence: Aspirin, colorectal cancer, and knowing when enough is enough

An epidemiological study of the impact of aspirin (ASA) on outcomes from colorectal carcinoma (CRCA) in JAMA has made quite a splash which has extended to the lay press (see Chan et al: http://jama.ama-assn.org/cgi/content/short/302/6/649?home ; and http://www.nytimes.com/2009/08/12/health/research/12aspirin.html ). I read this study, which normally would not have been of interest to me, because I knew that it was an epidemiological study and suspected that numerous methodological flaws would limit the conclusions that one could draw from it. And I admit that I was surprised that it has all the trappings of a methodologically superb study, complete in almost every way, including reporting of the Wald test for the assumption of proportional hazards, reporting of assessment for collinearity and overfitting of the model etc. It's all there, everything that one could want.


I should start by stating that there is biological plausibility of the hypothesis that ASA might influence the course of these cancers which express COX-2. I am no expert in this area, so I will take it as granted that the basic science evidence is sound enough to inflate the pre-test probability of an effect of ASA to a non-negligible level. Moreover, as pointed out by the authors, other smaller epidemiological investigations have suggested that ASA might improve outcomes from CRCA. The authors of the current investigation found a [marginally] statistically significant reduced hazards of death of approximately 0.3 in patients who took ASA after a diagnosis of CRCA, but not before.

Without delving into the details (knowing that one might find the devil there), I found the conclusions the authors made interesting, namely that additional investigations and randomized controlled trials will be needed before we can recommend ASA to patients diagnosed with CRCA. This caught me as a bit odd, depending upon what our goals are. If our goal is to further study the mechanisms of this disease in pursuit of the truth of the EFFICACY of ASA (see previous blog entry on vertebroplasty for the distinctions between efficacy and effectiveness research), then fine, we need a randomized controlled trial to eliminate all the potential confounding that is inherent in the current study, most notably the possibility that patients who took ASA are different from those who didn't in some important way that also influences outcome. But I'm prepared to accept that there is ample evidence that ASA benefits this condition and that if I had CRCA, the risks of not taking ASA far exceed the risks of taking it, and I would shun participation in any study in which I might be randomized to placebo. This may sound heretical, but allow me to explain my thinking.

I do worry that something that "makes sense" biologically and which is bolstered by epidemiological data might prove to be spurious, as happened in the decades-long saga of Premarin-prevention which came to a close with the Women's Health Initiative (WHI) study. But there are important differences here. Premarin had known side effects (clotting, increased risk of breast cancer) and it was being used long-term for the PREVENTION of remote diseases that would afflict women in the [distant] future. ASA has a proven safety profile spanning over a century, and patients with CRCA have a near-term risk of DEATH from it. So, even though both premarin and ASA might be used on the basis of fallible epidemiological data, there are important differences that we must consider. (I am also reminded of the ongoing debates and study of NAC for prevention of contrast nephropathy, which I think has gone on for far too long. There is ample evidence that it might help, and no evidence of adverse effects or excessive cost. When is enough enough?)

I just think we have become too beholden to certain mantras (like RCTs being the end-all-be-all or mortality being the only acceptable outcome measure), and we don't look at different situations with an independently critical eye. This is not low tidal volume ventilation where the critical care community needs unassailable evidence of efficacy to be convinced to administer it to patients who will have little say in the tidal volume their doctor uses to ventilate them. These are cognizant patients with cancer, this is a widely available over-the-counter drug, and this is a disease which makes people feel desperate, desperate enough to enroll in trials of experimental and toxic therapies. The minor side effects of ASA are the LEAST of their worries, especially considering that most of the patients in the cohort examined in this trial were using ASA for analgesia! If they are generally not concerned about side effects when it is used for arthritis, how can we justify withholding or not recommending it for patients with CANCER whose LIVES may be saved by it?

I were a patient with CRCA, I would take ASA (in fact I already take ASA!) and I would scoff at attempts to enroll me into a trial where I might receive placebo. The purists in pursuit of efficacy and mechanisms and the perfect trial be damned. I would much rather have a gastrointestinal hemorrhage than an early death from CRCA. That's just me. Others may appraise the risks and values of the various outcomes differently. And if they want to enroll in a trial, more power to them, so long as the investigators have adequately and accurately informed them of the existing data and the risks of both ASA and placebo, in the specific context of their specific disease and given the epidemiological data. Otherwise, their enrollment is probably ethically precarious, especially if they would go home and take an ASA for a more benign condition without another thought about it.