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Thrombolytic Agents: The Science of the Art of Choosing the Better Treatment
- Michael E. Farkouh, MD;
- Jeff D. Lang, MD; and
- David L. Sackett, MD, MSc
- Departments of Medicine and Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada. Requests for Reprints: David L. Sackett, MD, Nuffield Department of Medicine, University of Oxford, John Radcliffe Hospital, Level 5, Headington, Oxford OX3 9DU, United Kingdom.
The current dispute about whether the thrombolytic agent of choice for patients with suspected heart attacks should be tissue plasminogen activator (tPA) or streptokinase is succulent. It invokes arguments across the spectrum of health research, from bench to bedside to cost–benefit. Its combatants (and many of their defenders and detractors) are informed, articulate, and proud. The financial stakes are colossal. Reputations and fortunes are on the line. There is enough science and show-biz for every interest and taste. Somewhere, William Osler and H. L. Mencken are exchanging winks.
But how ought a clinician decide which of these two treatments, each with its competing claims for superiority, is the best one for her to use in her practice? There should be a science to the art of making such clinical judgments, and it should go beyond special pleading, polemics, and appeals to authority. What are some of the elements of that science? How might they apply to the current controversy?
Methodology Should Serve Biology
These elements begin with biology and the mechanisms of disease, cross-fertilized by epidemiology and tempered by humility. Thus, we seek the same, single biological mechanism to explain the superiority of one treatment and the inferiority of its competitor. This mechanism, if found, both provides the intellectual comfort of coherence and identifies the intermediate end points and responses that we should seek in therapeutic reports comparing these treatments. If superior treatment #1 produces its ultimate therapeutic benefit through a biological mechanism that generates the intermediate response R, then even patients receiving the inferior treatment #2 who exhibit this intermediate response R should likewise exhibit the ultimate therapeutic benefit.
Moreover, if this relation holds, it also argues against pooling trial results in meta-analyses or overviews of regimens that produce qualitatively different rates of the intermediate response (that is, high rates with one regimen …
