Tuesday, December 28, 2004

The random and the deterministic in medicine

Forty years ago pathophysiological concerns were stressed in medical education and statistics and epidemiology were little more than John Snow and the Broad St. Pump and the mean and standard deviations and t tests.The landscape has changed. Logistic regressions, Markow simulations, and even more obscure statistical tools populate the methods sections of medical articles.There is much "black box" output.
There is a theme in the history of medicine of an affection for determinisitic thinking and an antipathy for statistics. Statistics, after all, to a large degree began in the study of gambling. Coin flips, and rolls of dice were not the stuff that physicians were concerned with. When did the pendulum swing so far to the data side ? When did concerns with aggregate data begin to push out thoughts about what exactly is going on?.
The following is an example how how what at first seemed to be a random occurence was determined to a large degree by a SNP or single nucleotide polymorphism. The small percent of children treated with thioprine type drugs who developed a serious leukopenia did appear random until it was learned than about 1/300 Caucasians are deficient in TPMT (Thiopurine methyl transferase) which in turn was caused by a single misplaced nucelotide. Now testing for that enzyme deficiency or for the genetic variation allows for downward adjustment of the chemotherapy dose for those patients with TPMT deficiency and the previously random serious marrow damage is avoided.
Of course, every situation with bad clinical outcomes that can be described in aggregate numbers is not that simple. But, at least some of the time what appears at first to be random is shown to be determined by a describable -and often controlable -mechanism. At least some of the time and and at some level random is simply ignorance.


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