Chapter 3-3. Hill’s Causal Criteria
In 1965, Austin Bradford Hill published a paper presenting a list of nine aspects of an empirical
association to consider when deciding whether an association is causal. (Hill, 1965; reprinted in
Greenland, 1987).
In his paper, Hill stated,
“None of my nine viewpoints can bring indisputable evidence for or against the causeand-effect hypothesis and none can be required as a sine qua non.”1
Even though Hill did not claim the criteria established a causation conclusion, and even though
the criteria have been convincingly discredited, except for perhaps temporality (putative cause
precedes the effect) (Rothman and Greenland, 1998, pp.24-28; Rothman, 2002, pp.18-20), the
criteria are still frequently quoted, paraphrased, and applied in research papers.
For example, the epidemiologist, Jos Twisk, states in his recent textbook (Twisk, 2003),
“Table 1.1 shows the most important criteria for causality, which can be found in every
epidemiological textbook (e.g. Rothman and Greenland, 1998).”
Twisk’s table 1.1 lists seven of Hill’s nine criteria.
It is useful to review these criteria, so that when they appear as arguments in published papers,
you will recognize the source from which the “reasoning” become popular.
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1
sine qua non (si-ni-,kwä-`nän) something absolute indispensable or essential
Source: Stoddard GJ. Biostatistics and Epidemiology Using Stata: A Course Manual [unpublished manuscript] University of Utah
School of Medicine, 2010.
Chapter 3-3 (revision 1 Aug 2010)
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Hill’s Causal Criteria (Rothman and Greenland, 1998, pp.24-28)
___________________________________________________________________________
1. Strength.
Strong associations are more likely to be causal than weak associations.
2. Consistency.
The association is repeatedly observed in different populations under
different circumstances.
3. Specificity.
The cause leads to a single effect, not multiple effects.
4. Temporality.
The cause precedes the effect in time.
5. Biologic gradient. The presence of a monotonic (consistently increasing or decreasing)
dose-response curve.
6. Plausibility.
The causal hypothesis has biologic plausibility.
7. Coherence.
The cause-and-effect interpretation for an association does not conflict
with what is known of the natural history and biology of the disease.
8. Experimental evidence. Experimental , or semi-experimental, evidence exists to support the
causation hypothesis.
9. Analogy.
Judgment from analogy, such as observing what effect a similar drug has
on a disease.
Problems with Hill’s Causal Criteria (Rothman, 2002, p.19, Table 2-2)
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“1. Strength
Strength depends on the prevalence of other causes and, thus, is not a
biologic characteristic; could be confounded
2. Consistency
Exceptions are understood best with hindsight
3. Specificity
A cause can have many effects
4. Temporality
It may be difficult to establish the temporal sequence between cause and
effect
5. Biologic gradient Could be confounded; threshold phenomena would not show a progressive
relation
6. Plausibility
Too subjective
7. Coherence
How does it differ from consistency or plausibility?
8. Experimental evidence
Not always available
9. Analogy
Analogies abound”
Chapter 3-3 (revision 1 Aug 2010)
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Example of Applying Hill’s Causal Criteria
Procter & Gamble spent about 25 years and more than $200 million dollars developing a
synthetic chemical (brand name: Olean), which tastes and cooks like fat but passes through the
body undigested because its molecules are too big. Snack products prepared with Olean were
introduced in 1996 by its subsidary company, Frito Lay. The product had a strike against it from
the beginning, as the FDA required every package be labeled with the warning that Olestra may
cause abdominal cramping and loose stools.
This label warning stems from two clinical studies where stubjects were required to consume
olestra at every meal for 56 consecutive days, which resulted in increased mild to moderate GI
symptoms (Cheskin, et al, 1998).
Michael Jacobson, a Ralph Nader protégé, went after the product and devestated its imagine on
television, with sensationalization along the lines of the label warning (Levine, 1997).
By the next day, he'd lined up at least seven victims willing to tell their disturbing tales at the
Indiana Press Club. The victims of what Jacobson called "olestra poisoning" then came to the
lectern to tell their not-for-the-squeamish stories. First up was Nancy Sixsmith, a Noblesville,
Ind., publishing executive, who shyly recounted, "I ate 10 or 12 chips, and I didn't make it
back to the office: It's embarrassing to say, but I just didn't have any control. The cramping
started and I actually soiled myself in the car." A retiree named Harold Chapman recalled in a
broad twang: "I was carrying on so bad, they had to call 911 and take me to the hospital. They
gave me two shots of morphine--two shots--and it never stopped the pain."
In a move to recover the product’s credibility, Procter & Gamble sponsored a comparative trial of
Olestra and regular potatoe chips, using a researcher from The Johns Hopkins University School
of Medicine. The results were published in JAMA, concluding that no increase in GI symptoms
with Olestra were observed (Cheskin, et al, 1998).
See if you can identify instances in the Cheskin article where Hill’s Causal Criteria was used in
reverse to support the conclusion of no increase in GI symptoms.
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References
Cheskin LJ, Miday R, Zorich N, Filloon T. (1998). Gastrointestinal symptoms following
consumption of Olestra or regular triglyceride potato chips. JAMA 279(2):150-152.
Hill AB. (1965). The environment and disease: association or causation? Proceedings of the
Royal Society of Medicine. 58:295-300. Reprinted in Greenland S, editor (1987).
Evolution of Epidemiologic Ideas: Annotated Readings on Concepts and Methods.
Chestnut Hill, Massachusetts, Epidemiology Resources, Inc. pp. 14-20.
Levine A. (1997). Food fight in Indianapolis. US News & World Report. May 5:53-54.
Rothman KJ. (2002). Epidemiology: An Introduction. Oxford, Oxford University Press.
Rothman KJ, Greenland S. (1998). Modern Epidemiology, 2nd ed. Philadelphia, PA,
Lippincott-Raven Publishers.
Twisk JWR. (2003). Applied Longitudinal Data Analysis for Epidemiology: A Practical
Guide. Cambridge, Cambridge University Press.
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