The Randomized Clinical Trial

By Harrington, David P. | Journal of the American Statistical Association, March 2000 | Go to article overview

The Randomized Clinical Trial

Harrington, David P., Journal of the American Statistical Association


The randomized clinical trial is among the most important methodological tools in biostatistics. Some have conjectured that it could be the most significant advance in scientific medicine in the twentieth century (Smith 1998). In the statistical community, it is the method of choice for controlling confounding in medical studies where two or more interventions are compared and where the choice of intervention by either the subject or the study investigator could lead to selection bias. Among physicians, it is central to evidence-based medicine and is the major step along the way from treatment choice based on opinion and experience to that based on scientific finding.

Randomization in experimental designs is, of course, not limited to studies of human subjects. Fisher (1926, 1935) advocated it in the study of biological problems, and randomization became widely used in agricultural experiments. But randomized clinical trials in medicine have special features that set them apart from other experimental designs: the experimental units are human subjects, sometimes diagnosed with a potentially fatal disease, and the study subjects and their physicians cede treatment choice to a random allocation scheme. A methodologic device for statisticians supplants one of the central aspects of the patient--physician relationship--personal choice of treatment. This intrusion into the caregiving role in medicine will always spark controversy (Hellman and Hellman 1991).

It is impossible to estimate the frequency with which randomized trials have been used in medicine, but some estimate that the number of randomized trials runs into the hundreds of thousands (Chalmers 1998). The Cochrane Collaboration (1999) lists review teams in more than 50 diseases that maintain libraries of reviews of published trials, and that archive now indexes more than 250,000 trials.

Close relatives of the randomized clinical trial were conducted as early as 1747 (Lind 1753), when James Lind studied six strategies for treating scurvy on the British ship HMS Salisbury. Although Lind appears to not have assigned his treatments randomly, he recognized that bias can result when responses are correlated more with, disease characteristics or environmental features than with a putatively successful treatment. He surely sought to avoid the shoals described by his contemporary, Thomas Jefferson, in an 1807 letter to Dr. Caspar Wistar: "The patient, treated on the fashionable theory, sometimes gets well in spite of the medicine. The medicine therefore restored him, and the young doctor receives new courage to proceed in his bold experiments on the lives of his fellow creatures" (Jefferson 1984). Lind's study design attempted to hold constant the factors within the control of the investigator (other aspects of diet, the environment of the patient) while varying only the treatment. By today's standa rds, Lind's study was flawed for two reasons: He assigned only two patients to each treatment (he would not be the last investigator to conduct an underpowered study), and he apparently failed to recognize that unmeasured patient characteristics beyond his observation and control could influence results.

The modern randomized trial emerged in the midtwentieth century. Some believe that the 1948 report in the British Medical Journal (Medical Research Council 1948) of a randomized trial comparing streptomycin with a no-treatment control is the first detailed published account of randomized treatment assignments. The use of randomization in that trial was due in large part to the pioneering work of Bradford Hill. In addition to controlling possible confounding, randomization apparently also provided an acceptable way to ration the small supply of streptomycin (Doll 1998). Within 20 years, randomization in medical research had become widely adopted.

In one of the delightful ironies of modern science, the randomized trial "adjusts" for both observed and unobserved heterogeneity in a controlled experiment by introducing chance variation into the study design. …

The rest of this article is only available to active members of Questia

Sign up now for a free, 1-day trial and receive full access to:

  • Questia's entire collection
  • Automatic bibliography creation
  • More helpful research tools like notes, citations, and highlights
  • A full archive of books and articles related to this one
  • Ad-free environment

Already a member? Log in now.

Notes for this article

Add a new note
If you are trying to select text to create highlights or citations, remember that you must now click or tap on the first word, and then click or tap on the last word.
One moment ...
Default project is now your active project.
Project items

Items saved from this article

This article has been saved
Highlights (0)
Some of your highlights are legacy items.

Highlights saved before July 30, 2012 will not be displayed on their respective source pages.

You can easily re-create the highlights by opening the book page or article, selecting the text, and clicking “Highlight.”

Citations (0)
Some of your citations are legacy items.

Any citation created before July 30, 2012 will labeled as a “Cited page.” New citations will be saved as cited passages, pages or articles.

We also added the ability to view new citations from your projects or the book or article where you created them.

Notes (0)
Bookmarks (0)

You have no saved items from this article

Project items include:
  • Saved book/article
  • Highlights
  • Quotes/citations
  • Notes
  • Bookmarks
Cite this article

Cited article

Citations are available only to our active members.
Sign up now to cite pages or passages in MLA, APA and Chicago citation styles.

(Einhorn, 1992, p. 25)

(Einhorn 25)


1. Lois J. Einhorn, Abraham Lincoln, the Orator: Penetrating the Lincoln Legend (Westport, CT: Greenwood Press, 1992), 25,

Cited article

The Randomized Clinical Trial


Text size Smaller Larger Reset View mode
Search within

Search within this article

Look up

Look up a word

  • Dictionary
  • Thesaurus
Please submit a word or phrase above.
Print this page

Print this page

Why can't I print more than one page at a time?

Full screen

matching results for page

    Questia reader help

    How to highlight and cite specific passages

    1. Click or tap the first word you want to select.
    2. Click or tap the last word you want to select, and you’ll see everything in between get selected.
    3. You’ll then get a menu of options like creating a highlight or a citation from that passage of text.

    OK, got it!

    Cited passage

    Citations are available only to our active members.
    Sign up now to cite pages or passages in MLA, APA and Chicago citation styles.

    "Portraying himself as an honest, ordinary person helped Lincoln identify with his audiences." (Einhorn, 1992, p. 25).

    "Portraying himself as an honest, ordinary person helped Lincoln identify with his audiences." (Einhorn 25)

    "Portraying himself as an honest, ordinary person helped Lincoln identify with his audiences."1

    1. Lois J. Einhorn, Abraham Lincoln, the Orator: Penetrating the Lincoln Legend (Westport, CT: Greenwood Press, 1992), 25,

    Cited passage

    Thanks for trying Questia!

    Please continue trying out our research tools, but please note, full functionality is available only to our active members.

    Your work will be lost once you leave this Web page.

    For full access in an ad-free environment, sign up now for a FREE, 1-day trial.

    Already a member? Log in now.