The Emperor of All Maladies: A Biography of Cancer

by Siddhartha Mukherjee

To ration streptomycin, an objective experiment to determine its efficacy in human tuberculosis was needed. But what sort of experiment? An English statistician named Bradford Hill (a former victim of TB himself) proposed an extraordinary solution. Hill began by recognizing that doctors, of all people, could not be entrusted to perform such an experiment without inherent biases. Every biological experiment requires a “control” arm—untreated subjects against whom the efficacy of a treatment can be judged. But left to their own devices, doctors were inevitably likely (even if unconsciously so) to select certain types of patients upfront, then judge the effects of a drug on this highly skewed population using subjective criteria, piling bias on top of bias. Hill’s proposed solution was to remove such biases by randomly assigning patients to treatment with streptomycin versus a placebo. By “randomizing” patients to each arm, any doctors’ biases in patient assignment would be dispelled. Neutrality would be enforced—and thus a hypothesis could be strictly tested. Hill’s randomized trial was a success. The streptomycin arm of the trial clearly showed an improved response over the placebo arm, enshrining the antibiotic as a new anti-TB drug. But perhaps more important, it was Hill’s methodological invention that was permanently enshrined. For medical scientists, the randomized trial became the most stringent means to evaluate the efficacy of any intervention in the most unbiased m...