Tuesday, March 27, 2012

Surrogate markers: reflections of efficacy or only graven images?

I ran across this article the other day, in which Richard Lehman, a British physician and blogger for BMJ, reviews highlights from several popular medical journals.  At the end, he cites an article entitled The Idolatry of the Surrogate [2], where Yudkin, et al present an excellent discussion of the controversies surrounding the use of surrogate markers of efficacy versus hard clinical outcomes.  The article by Yudkin, et al uses diabetes as an example, but the same argument could be made for many of the markers commonly used in cardiovascular clinical practice (e.g., low-density lipoprotein, carotid intima media thickness, etc).

One of the best parts of Lehman's piece is his citation of Yudkin's Ten Commandments, a section that did not actually make it into the Idolatry piece due to concern over potential religious sensitivities.  I found its omission unfortunate, as it is one of the best anecdotes on clinical practice I have read in a while and one I wanted to share:

The New Therapeutics: Ten Commandments
  1. Thou shalt treat according to level of risk rather than level of risk factor.
  2. Thou shalt exercise caution when adding drugs to existing polypharmacy.
  3. Thou shalt consider benefits of drugs as proven only by hard endpoint studies.
  4. Thou shalt not bow down to surrogate endpoints, for these are but graven images.
  5. Thou shalt not worship Treatment Targets, for these are but the creations of Committees.
  6. Thou shalt apply a pinch of salt to Relative Risk Reductions, regardless of P values, for the population of their provenance may bear little relationship to thy daily clientele.
  7. Thou shalt honour the Numbers Needed to Treat, for therein rest the clues to patient-relevant information and to treatment costs.
  8. Thou shalt not see detailmen, nor covet an Educational Symposium in a luxury setting.
  9. Thou shalt share decisions on treatment options with the patient in the light of estimates of the individual’s likely risks and benefits.
  10. Honour the elderly patient, for although this is where the greatest levels of risk reside, so do the greatest hazards of many treatments.

Those of you who follow my blog regularly know that this topic is one of my favorite to debate, as I think it is one of the most controversial in all of professional practice. In the vast majority cases, I tend to side with Yudkin's arguments -- I believe the above considerations lead one to think more critically about a patient's overall risk and the potential for benefit (or additional risk) with any given intervention.  Unfortunately, this is often met with some initial resistance, as these arguments rarely fall in line with recognized practice guidelines.

But, as the analysis by Smith, et al in 2009 pointed out, only about a tenth of the recommendations made in cardiology guidelines are based on randomized controlled trials -- the remaining majority are based on small or limited patient populations and over half from expert consensus or standards of care [2].

... which only makes this topic worth debating again and again.

  1. Yudkin JS, et al. The idolatry of the surrogate. BMJ. 2011 Dec 28;343:d7995.
  2. Tricoci P, Allen JM, Smith SC Jr, et al. Scientific evidence underlying the ACC/AHA clinical practice guidelines. JAMA. 2009 Feb 25;301(8):831-41.

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