Trial By Fire

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How I came across this book: A freebie from the University of Edinburgh.

Favorite Line from the book: Those who cannot remember the past are condemned to repeat it. In the field of clinical trials, as in any other human endeavor, it is always useful to look back in time in order to make sense of the world we live and work in now.

Cleopatra VII in ancient Egypt is reported to design a trial to find out the sex of the baby by examining human subjects (her female servants) at different stages of pregnancy – examination in this case meant vivisection, and certain death of both fetus and the mother!

A randomized controlled trial has been recognized as the ‘gold-standard’ method in health research. Data generated from randomized controlled trials are considered the epitome of evidence in medical research. An impact factor is a measure of the frequency with which the average article in a journal has been cited in a particular year. If you pick up a copy of ‘New England Journal of Medicine’, which has one of the highest impact factor for any medical journal, the usual title of some of the featured articles in the journal would have these words – ‘Double Blind Randomized Placebo-Controlled Trial of…..’.

A controlled trial is a systematic study which compares an already available ‘standard of care’ treatment with the new intervention in question. To compare the two treatments (‘standard of care’ vs. new intervention), we need two groups which are identical to each other so we can compare ‘apples to apples’ instead of ‘apples to oranges.’ If a researcher tries to match the groups using their best guess, then it will lead to bias as a researcher can only match for known factors but not for the unknown factors. If a researcher will assign the treatment to a patient, then there is again potential for bias being introduced in the study. To eliminate all these biases, groups and treatment are assigned by a chance procedure called ‘Randomization’. During the process of investigation, both patients and investigators should not know the treatment assignment to reduce any further bias. This process is called ‘Blinding’. When either the patient or the investigator is aware of the treatment then it becomes a single-blind study. If there is no ‘standard of care’ already available, then investigators use a placebo in the comparison arm. A placebo is an inactive pill, which should look and taste the same as the active pill or a placebo (sham) operation may be used in trials of surgery.

After reading some ‘clinical trials’ papers, it will soon appear that these words, ‘Randomization,’ ‘Double Blind,’ and ‘Placebo’ are generic to some of the highly cited articles and the importance of these words may get diluted after some time. However, there is a history behind each word. Dr. Allan Gaw has carefully chosen six different examples from 2500 years of medical history to connect the dots and explain how clinical trials came into play and applied as we know it today. In modern medicine, we assume an informed, voluntary consent is taken from every patient before they are enrolled in a clinical trial. Some of the dark histories of humanity such as Cleopatra’s experiment will tell us a different story!