st: Paul Meier 1924-2011

[Nick Cox <njcoxstata@gmail.com>]

Biostatisticians and anyone who has ever used the Kaplan-Meier
estimator may be interested in this obituary of Paul Meier from the
New York Times.

http://www.nytimes.com/2011/08/13/health/13meier.html

Paul Meier, Statistician Who Revolutionized Medical Trials, Dies at 87

DENNIS HEVESI

August 12, 2011

Paul Meier, a leading medical statistician who had a major influence on
how the federal government assesses and makes decisions about new
treatments that can affect the lives of millions, died on Sunday at his
home in Manhattan. He was 87.

The cause was complications of a stroke, his daughter Diane Meier said.

As early as the mid-1950s, Dr. Meier was one of the first and most vocal
proponents of what is called "randomization".

Under the protocol, researchers randomly assign one group of patients to
receive an experimental treatment and another to receive the standard
treatment. In that way, the researchers try to avoid unintentionally
skewing the results by choosing, for example, the healthier or younger
patients to receive the new treatment.

If the number of subjects is large enough, the two groups will be the
same in every respect except the treatment they receive. Such randomized
controlled trials are considered the most rigorous way to conduct a
study and the best way to gather convincing evidence of a treatment’s
effects.

Before randomization, the science of clinical trials was imprecise.
Researchers, for example, would give a new treatment to patients who
they thought might benefit and compare the outcomes to those of previous
patients who were not treated, a method that could introduce serious
bias.

The Food and Drug Administration requires randomized trials before
approving new drugs, and the National Institutes of Health spend large
parts of their budget conducting randomized clinical trials.

Among the other leading advocates of randomization was Sir Richard Peto,
a renowned researcher at Oxford University. In an e-mail, Mr. Peto said
that Dr. Meier, "perhaps more than any other U.S. statistician, was the
one who influenced U.S. drug regulatory agencies, and hence clinical
researchers throughout the U.S. and other countries, to insist on the
central importance of randomized evidence".

"That strategic decision half a century ago has already saved millions
of lives," Mr. Peto continued, "and those millions should be attributed
to Paul".

Perhaps as significant to the field of medical statistics was Dr.
Meier’s cooperation with Edward L. Kaplan, a researcher at the
University of California Radiation Laboratory, in formulating a now
widely accepted standard for estimating patient survival. (Dr. Kaplan
died in 2006.)

In a paper published in the Journal of the American Statistical
Association in June 1958, the collaborators put forth a new, efficient
method for estimating patient survival rates, taking into account the
fact that some patients die during research trials while others survive
beyond the trials. The method, called the Kaplan-Meier estimator, is
based on a complex mathematical formula using information from those who
died and those who survived to estimate (depicted in a curve) the
proportion of patients alive at any point during the trial.

"If you have a patient with breast cancer receiving a particular
treatment or drug, you can estimate her 5-, 10- or 15-year survival
rate," Theodore Karrison, a researcher at the University of Chicago,
said Thursday. "It has become the standard tool used by medical
researchers for determining the duration of survival in thousands of
studies, ranging from cancer to AIDS to cardiovascular disease to
diabetes, to name just a few."

Today, almost every medical study includes Kaplan-Meier curves. And the
original paper is one of the most widely quoted in medical literature,
having been cited more than 35,000 times, according to the Thomson
Reuters Web of Knowledge, a Web site that maintains citation databases.

Born in Newark on July 24, 1924, Paul Meier was one of two sons of Frank
and Clara Meier. His father was a chemist; his mother, a school
principal.

Besides his daughter Diane, Dr. Meier is survived by his wife of 63
years, the former Louise Goldstone; two other daughters, Karen Meier and
Joan Meier; and five grandchildren.

Dr. Meier received his bachelor’s degree in physics and mathematics from
Oberlin in 1945, then earned his master’s in mathematical logic in 1947
and his doctorate in statistics in 1951, both at Princeton. He taught at
Lehigh from 1948 to 1952, at Johns Hopkins until 1957 and then joined
the faculty at the University of Chicago, where he became chairman of
the statistics department. He later taught at Columbia.

Researchers were not always attuned to Dr. Meier’s advocacy. "When I
said ‘randomize’ in breast cancer trials," he recalled in a 2004
interview for Clinical Trials, the publication of the Society for
Clinical Trials, "I was looked at with amazement by my medical
colleagues: ‘Randomize? We know that this treatment is better than that
one.’ I said, ‘Not really!’ "

On Thursday, Robert T. O’Neill, director of the Office of Biostatistics
at the Federal Drug Administration’s Center for Drug Evaluation and
Research, said that as a member of the agency’s advisory committee, Dr.
Meier "forcefully expressed the statistical principles that we follow
today, particularly randomization and the follow-up of patients".

"When Paul spoke, people listened, and few could spar with him."

A version of this article appeared in print on August 14, 2011, on page
A18 of the New York edition with the headline: Paul Meier, 87,
Statistician Who Revolutionized Drug Trials.

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