Enrolling Bad Patients After Good: Sunk Cost Bias and the Meta-Analytic Futility Stopping Rule

Four (relatively) large critical care randomized controlled trials were published early in the NEJM in the last week.  I was excited to blog on them, but then I realized they're all four old news, so there's nothing to blog about.  But alas, the fact that there is no news is the news.

In the last week, we "learned" that more transfusion is not helpful in septic shock, that EGDT (the ARISE trial) is not beneficial in sepsis, that simvastatin (HARP-2 trial) is not beneficial in ARDS, and that parental administration of nutrition is not superior to enteral administration in critical illness.  Any of that sound familiar?

I read the first two articles, then discovered the last two and I said to myself "I'm not reading these."  At first I felt bad about this decision, but then that I realized it is a rational one.  Here's why.

It All Hinges on the Premises: Prophylactic Platelet Transfusion in Hematologic Malignancy

A quick update before I proceed with the current post:  The Institute of Medicine has met and they agree with me that sodium restriction is for the birds.  (Click here for a New York Times summary article.)  In other news, the oh-so-natural Omega-3 fatty acid panacea did not improve cardiovascular outcomes as reported in the NEJM on May 9th, 2013.

An article by the TOPPS investigators in the May 9th NEJM is very useful to remind us not to believe everything we read, to always check our premises, and that some data are so dependent on the perspective from which they're interpreted or the method or stipulations of analysis that they can be used to support just about any viewpoint.

The authors sought to determine if a strategy of withholding prophylactic platelet transfusions for platelet counts below 10,000 in patients with hematologic malignancy was non-inferior to giving prophylactic platelet transfusions.  I like this idea, because I like "less is more" and I think the body is basically antifragile.  But non-inferior how?  And what do we mean by non-inferior in this trial?

Falling to Pieces: Hemolysis of the Hemoglobin Hypothesis

A paramount goal of this blog is to understand the evidence as it applies to the epistemology of medical knowledge, hypothesis testing, and overarching themes in the so-called evidence based medicine movement.  Swedberg et al report the results of a large[Amgen funded] randomized controlled trial of darbepoetin [to normalize hemoglobin values] in congestive heart failure (published online ahead of print this weekend) which affords us the opportunity to explore these themes afresh in the context of new and prior data.

The normalization heuristic, simply restated, is the tendency for all healthcare providers including nurses, respiratory therapists, nutritionists, physicians, and pharmacists among others, to believe intuitively or explicitly that values and variables that can be measured should be normalized if interventions to this avail are at their disposal.  As an extension, modifiable variables should be measured so that they can be normalized.  This general heuristic is deeply flawed, and indeed practically useless as a guide for clinical care.