Paul Meier, who died on August 7 aged 87, was a statistician who championed the idea of testing new medical treatments through randomised trials, so helping to lead a revolution in clinical research and saving, albeit indirectly, millions of lives.
The idea of assigning subjects in medical trials solely on the basis of random selection might now seem obvious. But, like many medical innovations, it did not seem so at the time Meier proposed it in the 1950s. Indeed, it met with some resistance.
Before then, researchers tended to hand-pick their “guinea pigs” from among groups of people they believed were likely to benefit most from a new treatment – often healthier or younger patients. Many physicians were horrified at the idea that their selection should be random, together with an equally randomly-selected “control” group of patients who were given the standard treatment or a placebo.
Meier argued that the old way of doing things made it difficult if not impossible to tell whether a given treatment was effective or not. Individual characteristics of the patients — including age, lifestyle and other illnesses — could, he argued, be equally responsible for what happened to them during a trial. But when patients are randomly assigned to get one treatment or another, such “confounding variables” tend to cancel each other out, making it easier to detect the real effects of the treatment being studied.
At first Meier’s arguments met with incomprehension: “When I said 'randomise’ in breast cancer trials,” he recalled in 2004, “I was looked at with amazement by my medical colleagues: 'Randomise? We know that this treatment is better than that one.’ I said, 'Not really!’”. The Oxford epidemiologist Sir Richard Peto has said that Meier, perhaps more than any other individual, was the person who influenced drug regulatory agencies to insist on the central importance of randomised evidence.
Meier was also well known as the co-developer of a statistical method called the Kaplan-Meier estimator, now a standard tool for estimating survival rates from clinical trial data. In a paper published in the Journal of the American Statistical Association in June 1958, he and his collaborator, Edward Kaplan, set out a series of equations for estimating survival rates, taking into account the fact that some patients die during clinical trials; some do not complete the trials; and others survive beyond the trials. The method allows every patient’s experience to contribute to the ultimate calculation of survival rates and enables the construction of an X- and Y-axis graph which shows the proportion of patients alive at any point in a curved line known as the Kaplan-Meier Curve.
Although it took some time to catch on, Kaplan and Meier’s paper has become one of the most cited in any scientific discipline. The Kaplan-Meier estimator and curve are now used in virtually every clinical study into diseases ranging from cancer to Aids and heart disease to diabetes. As a result of the curve, patients undergoing chemotherapy and other unpleasant treatments can be informed of the effect on their estimated chances of survival over five, 10 or even 15 years, so that they can make an informed decision about whether to go ahead or not.
Paul Meier was born in Newark, New Jersey, on July 24 1924. His father was an industrial chemist, his mother a secondary school headmistress. During the Second World War they sponsored a number of Jewish refugees from Europe, including Carl Djerassi, who developed the contraceptive pill. After studying at Oberlin College, Ohio, Paul took a degree in Mathematical Logic and a doctorate in Statistics at Princeton University.
From 1948 to 1952 he taught at Lehigh University. Then, after five years at Johns Hopkins University, in 1957 he moved to the University of Chicago, where he became chairman of the Statistics department.
Meier first came to public notice following a botched trial of a polio vaccine which, because it inadvertently contained live virus, killed 10 people, paralysed 164 and left 70,000 others with muscle weakness. In 1957 Meier published a paper in the journal Science in which he described deficiencies in the production of vaccines by several pharmaceutical companies and castigated those who had funded the research: “Perhaps the most disturbing element of the entire programme has been the disparity between the risks that were known to be involved and the repeated assurances of safety,” he wrote.
Meier left Chicago in 1992 and moved to Columbia University, New York. He frequently worked as an adviser to the American Food and Drug Administration and the Centres for Disease Control and Prevention. In recent years he had been involved in designing a randomised trial for a treatment for toxoplasmosis, a parasitic disease often carried by cats that is thought to be carried widely in the world’s human population and can result in a wide variety of health problems for those with weakened immune systems, including newborns.
Paul Meier, who was a proficient sailor and musician, married Louise Goldstone in 1948. She survives him with three daughters.
Paul Meier was born in Newark, New Jersey, on July 24 1924. His father was an industrial chemist, his mother a secondary school headmistress. During the Second World War they sponsored a number of Jewish refugees from Europe, including Carl Djerassi, who developed the contraceptive pill. After studying at Oberlin College, Ohio, Paul took a degree in Mathematical Logic and a doctorate in Statistics at Princeton University.
From 1948 to 1952 he taught at Lehigh University. Then, after five years at Johns Hopkins University, in 1957 he moved to the University of Chicago, where he became chairman of the Statistics department.
Meier first came to public notice following a botched trial of a polio vaccine which, because it inadvertently contained live virus, killed 10 people, paralysed 164 and left 70,000 others with muscle weakness. In 1957 Meier published a paper in the journal Science in which he described deficiencies in the production of vaccines by several pharmaceutical companies and castigated those who had funded the research: “Perhaps the most disturbing element of the entire programme has been the disparity between the risks that were known to be involved and the repeated assurances of safety,” he wrote.
Meier left Chicago in 1992 and moved to Columbia University, New York. He frequently worked as an adviser to the American Food and Drug Administration and the Centres for Disease Control and Prevention. In recent years he had been involved in designing a randomised trial for a treatment for toxoplasmosis, a parasitic disease often carried by cats that is thought to be carried widely in the world’s human population and can result in a wide variety of health problems for those with weakened immune systems, including newborns.
Paul Meier, who was a proficient sailor and musician, married Louise Goldstone in 1948. She survives him with three daughters.
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