Is There a Baby in That Bathwater? Status Quo Bias in Evidence Appraisal in Critical Care

"But we are not here concerned with hopes and fears, only the truth so far as our reason allows us to discover it."  -  Charles Darwin, The Descent of Man

Status quo bias is a cognitive decision making bias that leads to decision makers' preference for the choice represented by the current status quo, even when the status quo is arbitrary or irrelevant.  Decision makers tend to perceive a change from the status quo as a loss and therefore their decisions are biased toward the status quo.  This can lead to preference reversals when the status quo reference frame is changed.  The status quo can be debiased using a reversal test, i.e., manipulating the status quo either experimentally or via thought experiment to consider a change in the opposite direction.  If reluctance to change from the status quo exists in both directions, status quo bias is likely to exist.

My collaborators Peter Terry, Hal Arkes and I reported in a study published in 2006 that physicians were far more likely to abandon a therapy that was status quo or standard therapy based on new evidence of harm than they were to adopt an identical therapy based on the same evidence of benefit from a fictitious RCT (randomized controlled trial) presented in the vignette.  These results suggested that there was an asymmetric status quo bias - physicians showed a strong preference for the status quo in the adoption of new therapies, but a strong preference for abandoning the status quo when a standard of care was shown to be harmful.  Two characteristics of the vignettes used in this intersubject study deserve attention.  First, the vignettes described a standard or status quo therapy that had no support from RCTs prior to the fictitious one described in the vignette.  Second, this study was driven in part by what I perceived at the time was a curious lack of adoption of drotrecogin-alfa (Xigris), with its then purported mortality benefit and associated bleeding risk.  Thus, our vignettes had very significant trade-offs in terms of side effects in both the adopt and abandon reference frames.  Our results seemed to explain s/low uptake of Xigris, and were also consistent with the relatively rapid abandonment of hormone replacement therapy (HRT) after publication of the WHI, the first RCT of HRT.

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.

Sepsis Bungles: The Lessons of Early Goal Directed Therapy

On March 18th, the NEJM published early online three original trials of therapies for the critically ill that will serve as fodder for several posts.  Here, I focus on the ProCESS trial of protocol guided therapy for early septic shock.  This trial is in essence a multicenter version of the landmark 2001 trial of Early Goal Directed Therapy (EGDT) for severe sepsis by Rivers et al.  That trial showed a stunning 16% absolute reduction in mortality in sepsis attributed to the use of a protocol based on physiological goals for hemodynamic management.  That absolute reduction in mortality is perhaps the largest for any therapy in critical care medicine.  If such a reduction were confirmed, it would make EGDT the single most important therapy in the field.  If such reduction cannot be confirmed, there are several reasons why the Rivers results may have been misleading:

• As I have blogged in the case of intensive insulin therapy, Single center studies inflate treatment effects when compared to multicenter studies for reasons that are unclear, but which may be related to bias especially in unblinded studies.  (The revelation that Rivers was an investor in one of the devices used in the trial raised additional concerns about bias.)
• Regression to the mean may lead to reduced effect sizes when trials are repeated, especially when the index trial has a very large effect size.  In a similar vein, since large absolute mortality reductions are statistically unlikely in critical care medicine, Bayesian inference means that trials reporting large reductions are likely to represent type I statistical errors.

There were other concerns about the Rivers study and how it was later incorporated into practice, but I won't belabor them here.  The ProCESS trial randomized about 1350 patients among three groups, one simulating the original Rivers protocol, one to a modified Rivers protocol, and one representing "standard care" that is, care directed by the treating physician without a protocol.  The study had 80% power to demonstrate a mortality reduction of 6-7%.  Before you read further, please wager, will the trial show any statistically significant differences in outcome that favor EGDT or protocolized care?