The critical resource of D G Altman's "Practical Statistics for Medical Research" was also available at Google Books. Various search terminologies were used which include "Evolution/History/Review of Clinical Trials", "Ethical issues of clinical trials", "Nazi medical war crimes", "Nuremberg/Helsinki/Belmont" codes. Formulae for the sample size calculations were also accessed from journal publications and some power point presentation slides which have been cited and calculations were performed manually.
Owing to the practical significance of implications of therapeutic interventions for patients, historians have shown an active interest in the charting out of evolution of clinical trials. Histories of clinical trials have been recorded and they have analysed the development of quantification in therapeutic evaluation, the emergence of probabilistic thinking, the application of statistical methods and theory and the sociology, ethics and politics of clinical trials as succinctly summarized by Chalmers (1) in 2001.
The basic concept behind the modern day clinical trial is not a new one. In fact, the earliest recorded reference to something resembling a clinical trial can be found in none other than the Bible. The extract, which is found in the Book of Daniel, describes the efforts of the Babylonian king, Nebuchadnezzar II (605-562 BCE), to compare his recommended diet, consisting of meat and wine, with one of legumes and water over a 10 day period. At the end of the trial the king noted that those on the legumes and water diet were fitter than those who had been fed meat and wine and switched the latter to legumes as well.
Inclusion of blinding and placebos to reduce observer biases comprise an important factor in planning an effective RCT. Records of these point out to as early as eighteen century when Dr.Benjamin Franklin was appointed by King of France in the Royal Commission to judge the authenticity of "Animal Magnetism" which alleged that sicknesses were caused by some apparent "obstacle" in the flow of body fluids and could be removed by the touch of a physicians finger or by pointing an iron rod. In a retort to the small percentage of success, Franklin replied, " the Spirits given by the Hope of Success them to exert more Strength in moving their Limbs " Clearly, Franklin was aware of what we now call 'the placebo effect' as described by Huth (2) in 2006
Further, Booth (3) in his book in 2005 documented the role of Physician John Haygarth in 1810-1820 attacked the widespread quack of Perkinism which involved "redirecting the natural body electricity" by using bi-material rods and was the first physician to carry out a single blind clinical trial using a placebo.
May it be the instance of the challenge put forth by Flemish physician Jean Baptist Von Helmont of ensuring that like is compared with like in the case of people suffering from fevers, pleurisies without bloodletting in the 1700's or Amberson flipping a coin for unbiased allocation for assigning treatment in the Tuberculosis trial in 1938; medical practitioners have considered the ethical aspects of fair allocation and avoidance of undue advantage since a long time now. Unbiased comparison groups according to Chalmers (1) in those times would result either from "schedules (coin tosses, selection of different coloured beads from an urn, reference to