RIP Statistician Paul Meier. Proponent not Father of the RCT.

14 08 2011

This headline in Boing Boing caught my eye today:  RIP Paul Meier, father of the randomized trial

Not surprisingly, I knew that Paul Meier (with Kaplan) introduced the Kaplan-Meier estimator (1958), a very important tool for measuring how many patients survive a medical treatment. But I didn’t know he was “father of the randomized trial”….

But is he really?:Father of the randomized trial and “probably best known for the introduction of randomized trials into the evaluation of medical treatments”, as Boing Boing states?

Boing Boing’s very short article is based on the New York Times article: Paul Meier, Statistician Who Revolutionized Medical Trials, Dies at 87. According to the NY Times “Dr. Meier was one of the first and most vocal proponents of what is called “randomization.” 

Randomization, the NY-Times explains, is:

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.

(for a more detailed explanation see my previous posts The best study designs…. for dummies and #NotSoFunny #16 – Ridiculing RCTs & EBM)

Meier was a very successful proponent, that is for sure. According to Sir Richard Peto, (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.”

But an advocate need not be a father, for advocates are seldom the inventors/creators. A proponent is more of a nurse, a mentor or a … foster-parent.

Is Meier the true father/inventor of the RCT? And if not, who is?

Googling “Father of the randomized trial” won’t help, because all 1.610  hits point to Dr. Meier…. thanks to Boing Boing careless copying.

What I read so far doesn’t point at one single creator. And the RCT wasn’t just suddenly there. It started with comparison of treatments under controlled conditions. Back in 1753, the British naval surgeon James Lind published his famous account of 12 scurvy patients, “their cases as similar as I could get them” noting that “the most sudden and visible good effects were perceived from the uses of the oranges and lemons and that citrus fruit cured scurvy [3]. The French physician Pierre Louis and Harvard anatomist Oliver Wendell Holmes (19th century) were also fierce proponents of supporting conclusions about the effectiveness of treatments with statistics, not subjective impressions.[4]

But what was the first real RCT?

Perhaps the first real RCT was The Nuremberg salt test (1835) [6]. This was possibly not only the first RCT, but also the first scientific demonstration of the lack of effect of a homeopathic dilution. More than 50 visitors of a local tavern participated in the experiment. Half of them received a vial  filled with distilled snow water, the other half a vial with ordinary salt in a homeopathic C30-dilution of distilled snow water. None of the participants knew whether he got the “actual medicine or not” (blinding). The numbered vials were coded and the code was broken after the experiment (allocation concealment).

The first publications of RCT’s were in the field of psychology and agriculture. As a matter of fact one other famous statistician, Ronald A. Fisher  (of the Fisher’s exact test) seems to play a more important role in the genesis and popularization of RCT’s than Meier, albeit in agricultural research [5,7]. The book “The Lady Tasting Tea: How Statistics Revolutionized Science in the Twentieth Century” describes how Fisher devised a randomized trial at the spot to test the contention of a lady that she could taste the difference between tea into which milk had been poured and tea that had been poured into milk (almost according to homeopathic principles) [7]

According to Wikipedia [5] the published (medical) RCT appeared in the 1948 paper entitled “Streptomycin treatment of pulmonary tuberculosis”. One of the authors, Austin Bradford Hill, is (also) credited as having conceived the modern RCT.

Thus the road to the modern RCT is long, starting with the notions that experiments should be done under controlled conditions and that it doesn’t make sense to base treatment on intuition. Later, experiments were designed in which treatments were compared to placebo (or other treatments) in a randomized and blinded fashion, with concealment of allocation.

Paul Meier was not the inventor of the RCT, but a successful vocal proponent of the RCT. That in itself is commendable enough.

And although the Boing Boing article was incorrect, and many people googling for “father of the RCT” will find the wrong answer from now on, it did raise my interest in the history of the RCT and the role of statisticians in the development of science and clinical trials.
I plan to read a few of the articles and books mentioned below. Like the relatively lighthearted “The Lady Tasting Tea” [7]. You can envision a book review once I have finished reading it.

Note added 15-05 13.45 pm:

Today a more accurate article appeared in the Boston Globe (“Paul Meier; revolutionized medical studies using math”), which does justice to the important role of Dr Meier in the espousal of randomization as an essential element in clinical trials. For that is what he did.

Quote:

Dr. Meier published a scathing paper in the journal Science, “Safety Testing of Poliomyelitis Vaccine,’’ in which he described deficiencies in the production of vaccines by several companies. His paper was seen as a forthright indictment of federal authorities, pharmaceutical manufacturers, and the National Foundation for Infantile Paralysis, which funded the research for a polio vaccine.

  1. RIP Paul Meier, father of the randomized trial (boingboing.net)
  2. Paul Meier, Statistician Who Revolutionized Medical Trials, Dies at 87 (nytimes.com)
  3. M L Meldrum A brief history of the randomized controlled trial. From oranges and lemons to the gold standard. Hematology/ Oncology Clinics of North America (2000) Volume: 14, Issue: 4, Pages: 745-760, vii PubMed: 10949771  or see http://www.mendeley.com
  4. Fye WB. The power of clinical trials and guidelines,and the challenge of conflicts of interest. J Am Coll Cardiol. 2003 Apr 16;41(8):1237-42. PubMed PMID: 12706915. Full text
  5. http://en.wikipedia.org/wiki/Randomized_controlled_trial
  6. Stolberg M (2006). Inventing the randomized double-blind trial: The Nuremberg salt test of 1835. JLL Bulletin: Commentaries on the history of treatment evaluation (www.jameslindlibrary.org).
  7. The Lady Tasting Tea: How Statistics Revolutionized Science in the Twentieth Century Peter Cummings, MD, MPH, Jama 2001;286(10):1238-1239. doi:10.1001/jama.286.10.1238  Book Review.
    Book by David Salsburg, 340 pp, with illus, $23.95, ISBN 0-7167-41006-7, New York, NY, WH Freeman, 2001.
  8. Kaptchuk TJ. Intentional ignorance: a history of blind assessment and placebo controls in medicine. Bull Hist Med. 1998 Fall;72(3):389-433. PubMed PMID: 9780448. abstract
  9. The best study design for dummies/ (http://laikaspoetnik.wordpress.com: 2008/08/25/)
  10. #Notsofunny: Ridiculing RCT’s and EBM (http://laikaspoetnik.wordpress.com: 2010/02/01/)
  11. RIP Paul Meier : Research Randomization Advocate (mystrongmedicine.com)
  12. If randomized clinical trials don’t show that your woo works, try anthropology! (scienceblogs.com)
  13. The revenge of “microfascism”: PoMo strikes medicine again (scienceblogs.com)
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