History of biostatistics J. Rosser Matthews University of Maryland, College Park, MD, USA Correspondence to: J. Rosser Matthews Professional Writing Program English Department 1220 Tawes Hall University of Maryland College Park, MD, USA +1 (301) 405-3762 [email protected] Abstract The history of biostatistics could be viewed as an ongoing dialectic between continuity and change. Although statistical methods are used in current clinical studies, there is still ambivalence towards its application when medical practitioners treat individual patients. This article illustrates this dialectic by highlighting selected historical episodes and methodological innovations – such as debates about inoculation and blood - letting, as well as how randomisation was introduced into clinical trial design. These historical episodes are a catalyst to consider assistance of non-practitioners of medicine such as statisticians and medical writers. Methodologically, clinical trials and dialectic by discussing examples from different types of diseases.1 While basically epidemiological studies are united by a antiquity to the emergence of the clinical qualitative, the work is historically population-based focus; they privilege the trial in the mid-20th century. significant because it looked beyond the group (i.e., population) over the clinically individual to suggest a role for larger unique individual. Over time, this pop - Ancient sources: Hippocratic geographic and environmental factors. ulation-based thinking has remained writings and the bible Furthermore, it relied on naturalistic constant; however, the specific statistical Although the Hippocrates writers (active in explanations rather than invoking various techniques to measure and assess group the 5th century BCE) did not employ deities to account for illness and therefore characteristics have evolved. Consequently, statistical methods, one treatise does stand anticipated a modern scientific outlook. the history of biostatistics could be viewed out as a pioneering example of an environ - Another ancient forerunner of contemp - as an ongoing dialectic between continuity mental epidemiological study– the treatise orary clinical trials is discussed in the Bible’s and change. The continuity derives from On Airs, Waters, and Places (c. 400 BCE). 1 Book of Daniel. King Nebuchadnezzar of focusing on the group rather than the Relying on a view of disease as based on an Babylon wanted all of his subjects to eat a clinically distinct individual. The change imbalance in bodily fluids– known as diet of only meat and wine. However, Daniel derives from developments in statistical humours – the work emphasised how and some of the other Jewish children theory that have led to more sophisticated climatic changes throughout the seasons of wanted to eat a diet of legumes and water. analyses. In this article, I will illustrate this the year contributed to the spread of The King permitted them this diet for 10 8 | September 2016 Medical Writing | Volume 25 Number 3 Matthews – History of Biostatistics days – after which it was determined that probability math ematics to contrast life 1872) (Figure 1). By collecting data on they were indeed healthier. Consequently, expectancies for inoculated and non- patients admitted to hospitals, Louis argued they were allowed to continue on this diet.2 inoculated individuals; also, he calculated that the practice of bloodletting was actually Although not having the “apparatus” of a the benefits of inocu lation broken down by doing more harm than good. In his 1835 modern clinical trial (e.g., statistical tests to age. D’Alembert challenged Bernoulli’s treatise Recherches sur les effets de la saignée, determine p-values, confidence intervals assumptions and said that Bernoulli’s model Louis pointed out that 18 patients died out etc.), it does illustrate the use of a had not accurately captured the psychology of the 47 who had been bled (approximately comparison to test the efficacy of a dietary of human decision making – would an 3:7) whereas only nine died out of the 36 intervention. individual accept the risk of death now patients not bled – producing a lower (from inoculation) for an expected “pay-off” mortality rate of approximately 1:4.4 Eighteenth century of additional years of life when one was old Louis justified his approach by claiming developments and feeble?3 that the difference between numbers and In the 18th century, one prominent example While the debates about inoculation words (such as “more or less” and “rarely or of using statistical methods to resolve relied on mortality statistics, the individual frequently”) is “the difference of truth and therapeutic debates centred on the practice that is more often credited with designing a error; of a thing clear and truly scientific on of smallpox inoculation. This involved controlled clinical trial (i.e., intentionally the one hand, and of something vague and inserting actual smallpox pustules under an dividing the participants into two or more worthless on the other.” Furthermore, Louis individual’s skin in the hope of creating a comparable groups to test hypotheses) is prophesied that, with the widespread mild (i.e., non-disfiguring) case of the James Lind (1716-1794). In 1757, Lind (a introduction of numerical reasoning, “we disease that would induce later immunity. ship’s surgeon) had to deal with an outbreak shall hear no more of medical tact, of a kind Since this actually put patients at risk of of scurvy. He selected 12 of the sailors and of divining power of physicians.”4 In contracting a potentially fatal form of the divided them into six groups of twos. All were language that foreshadows contemporary disease, this became the subject of much given the same diet – except for a key discussions of “evidence-based medicine,” controversy. different ingredient for each of the distinct six Louis was basically saying that the key to Some argued against this procedure groups. For the two sailors who received transform medicine into a science was to based on the Hippocratic injunction “first, oranges and limes as supplement, there was rely on population-based thinking rather do not harm.” However, many writers one complete and one near recovery; none of than individual expertise. justified the procedure based on arguments the other five groups improved as much. Some of Louis’ contemporaries criticised that today would be called “risk-benefit Despite some obvious structural similarities his approach for failing to acknowledge that analysis.” For example, the London physician to the Biblical account, Lind is today the physician had to treat the John Arburthnot (1665-1735) published an regarded as the (modern) individual as a patient rather than anonymous pamphlet in 1722, in which he “father” of the controlled clinical a statistical construct. For examined the London Bills of Mortality from trial.2 instance, the phys ician Benigno earlier years and estimated that the chance Risueño d’Amador (1802- of dying from naturally-occurring smallpox Nineteenth century 1849) used an analogy to was 1:10. He then asserted (without developments maritime insurance. Although past evidence) that the chance of dying from In several areas of 19th century experience might tell you that 100 inoculation-induced smallpox was 1:100. scientific end eavour, stat istical vessels would perish for each 1,000 This ten-fold reduction made him conclude reason ing was introd uc ed – that embarked, these pop ul at ion- that inoculation made sense: “A Practice and the field of medi - based regularities could not which brings the Mortality of the Small Pox cine was no except - tell you which specific ships from one in ten to one in a hundred, if it ion. In the 1830s, obtain’d universally would save the City of one of the most London at least 1,500 People Yearly; and the pro m inent Figure 1. same Odds wou’d be a sufficient prudential advoc ates for Pierre-Charles- Motive to any private Person to proceed applying the Alexandre Louis upon.”3 In 1760, a more mathematically “numer ical (1787-1872) was sophisticated version of this type of analysis method” to a pioneer of the took place in a debate between the Swiss medicine was “numerical mathematician Daniel Bernoulli (1700- the French clinician method” in 1782) and the French mathematician Jean Pierre-Charles- medicine. d’Alembert (1717-1783). Bernoulli drew on Alexandre Louis (1787- www.emwa.org Volume 25 Number 3 | Medical Writing September 2016 | 9 History of Biostatistics – Matthews would be destroyed. Analogously, Risueño followers committed to Gavarret’s specific interest in developing statistics derived from d’Amador argued that the calculus of the mathe matical approach emerged. As a a desire to make explicit the statistical math em aticians “cannot be used to forecast result, the meaning of statistical evidence implications of Darwin’s theory of natural a determined event, but only to establish the remained contentious throughout the 19th selection, he also advocated the extension of probability of a certain num er ical prop - century. For example, the famous surgeon, these methods into medicine. To that end, ortion between two classes of possible Joseph Lister (1827-1912), argued for his he often contributed to the British Medical events. But it is precisely this fact which particular method of antiseptic surgery Journal, the Lancet, and The Royal Society of makes it completely useless in medicine.”5 based on statistical studies; however, his Medicine as attempts to “educate” the Drawing a different