Save the baby: reviving deduction and refocusing induction in clinical research.

Evidence-based medicine is rapidly gaining ground as the gold-standard tool for medical decision making. The consensus "grade-A" evidence format is the supersized version of the workhorse of clinical validation: the randomized controlled trial (RCT). As authors struggle to give voice to their work, prospective, randomized, double-blind, placebo-controlled trials with mega-populations have become the order of the day. Because of the hierarchical nature implied by the grading system, any deviation from this format will be downgraded accordingly. Journals will be hard-pressed to publish anything but highly graded studies, but is this the only form of medical evidence that should be published?

Clinicians seeking therapeutic endpoint evidence will likely rely on the RCT for the foreseeable future. However, the speed of discovery of important, clinically relevant knowledge is increasing so rapidly that reliance on the present method of generating RCT data may prove unable to keep pace. Some specific questions need to be addressed:

* How will translational research be developed, discussed, and utilized to generate hypotheses central to the RCT process?

* How will we disseminate the bench research findings that redefine and clarify clinically relevant cellular mechanisms that form the foundation of how cells, organs, and systems function in health and disease?

* How do we share rapidly evolving research discoveries--without which clear, concise, and clinically significant RCT studies cannot be effectively designed?

A century ago, another highly regarded field of science was experiencing a rush of fresh and revolutionary ideas. From the time of the light bulb to the atom bomb, the body of knowledge in physics surged. Electromagnetism, light theory, quantum mechanics, subatomic particles, atomic energy, and the most famous discovery of that era, Einstein's theory of relativity, were just a few topics that caught the popular imagination and stimulated the scientific community, as well.

One of the most amazing feats central to the tsunami of ground-breaking discoveries in physics was Einstein's ability to do "thought experiments." It was this technique of interpreting existing knowledge in terms of what was "known" and then identifying contradictions, deducing resolutions, and creating unifying theories, which were then validated experimentally, that changed the face of physics forever.

In a 1919 article, Einstein addressed the dynamics of the dualism of scientific thought and discovery, induction versus deduction:

      The simplest picture one can form about the creation of an
   empirical science is along the lines of an inductive method.
   Individual facts are selected and grouped together so that the laws
   that connect them become apparent.... However, the big advances in
   scientific knowledge originated in this way only to a small
   degree.... The truly great advances in our understanding of nature
   originated in a way almost diametrically opposed to induction. The
   intuitive grasp of the essentials of a large complex of facts leads
   the scientist to the postulation of a hypothetical basic law or
   laws. From these laws, he derives his conclusions. (1)

To think that the revolution in physics was due to one man, however, would do a disservice to a cadre of distinguished scientists. During this period, many were involved in the quest for the discovery of fundamental unifying theories capable of explaining observable outcomes. Together, this group began the field of theoretical physics, a discipline that has generated a rich heritage of prodding research and remains vital today and essential to future scientific success. Theoretical papers were readily accessible and widely read, and they drove the inductive process in physics: the experiment that was often independently designed to evaluate the theories.

Medicine now faces a similar knowledge explosion. Unfortunately, discovery by induction alone via the RCT frequently requires 5 to 10 years, one question at a time--placing the medical discovery system at risk of being perceived as slow, cumbersome, and inefficient by an impatient public. Clinical journals could reenergize the process by encouraging publication of papers based on well-reasoned deductions from peer-reviewed basic and/or translational research, or even logically generated "thought experiments" that spur the RCT process.

A concerted effort to disseminate novel, yet "unproven," concepts may overcome the inertia associated with the present RCT system and avoid delays when controversial ideas must fight through a wall of naysayers. Such was the case with the discovery of Helicobacter pylori's role in gastritis and peptic ulcer disease. The idea proved correct. The proponents received the 2005 Nobel Prize in Medicine. Yet it took years, self-infection, and cure to gain any ground. In much the same way, the tomato was introduced to Europe hundreds of years ago.

There are many similar ideas that should be given voice. Hopefully, evidence-based medicine will revive deduction to rejuvenate and expedite the RCT process. Throwing out deduction by giving it a "low" grade places nascent ideas at risk of being drowned out and lost.

Reference

(1.) Einstein A. Induction and deduction in physics. Berliner Tageblatt, Dec 25, 1919; Collected Papers of Albert Einstein 7:28.

Thomas A. Kwyer, MD, FAPWCA

AmmunoMed, Inc., and

Toledo ENT, PC

Toledo, Ohio