J ClinEpidemiol Vol. 45, No. 8, pp. 923-924, 1992
0895-4356/92%5.00+ 0.00 Copyright @$1992Pergamon PressLtd
Printed in Great Britain. All rights reserved
Second Thoughts COLON CANCER AND ULCERATIVE COLITIS: EPIDEMIOLOGIC EXERCISE REVISITED J. P. Department
AN
VANDENBROUCKE
of Clinical Epidemiology, L&den University Hospital, Building 1, CO-P, P.O. Box 9600, 2300 RC Leiden, The Netherlands (Received 5 March 1992)
Severe criticisms of the methodologic shortcomings of a study on colon cancer occurrence in patients with ulcerative colitis were published in 1980 [l], They led to the development of one of the nicest class exercises in clinical epidemiology on “How to read clinical journals, to learn the clinical course and prognosis of disease” [2,3]. Although it originated at McMaster’s, the exercise is now used world-wide with some variations. In my personal opinion it is one of the greatest epidemiologic exercises, and vies for attractiveness with “Smoking and Lung-cancer” as originally drafted by Milton Terris, and with “John Snow”, which originated with Wade Hampton Frost. After the original much criticized publication [2], the debate on colon cancer and colitis continued [4-6]. An almost final paper was published in 1990 [7]: a completely population-based study, as these can only be performed in Scandinavia. The logic of the class exercise on “colon cancer and colitis” leads inexorably to the conclusion that both the estimates of overall colon cancer incidence and the incidence of high”. universal colitis were “spuriously Although generally taking a sober view of the impact of methodology myself, I was still surprised to read how the results of the recent Swedish study were rather close to this notorious “black sheep” of epidemiology. The study confirmed the huge incidence of colon cancer in patients with universal colitis over three to four decades [7]. In my teaching, even before 1990, I had already incorporated some caution. At the end of the exercise, I used to warn the students that
we had now collectively “destroyed” the original paper, but that this did not mean that its message was necessarily untrue. Quite often students wondered why this paper had ever been accepted by an editor. I told them that clinicians had already “known” since the 1920s that colitis caused colon cancer, especially if long standing and generalized. I also emphasized a less noted “methodologic error” of the original study, i.e. that the person-years were “counted backwards” to the date of the first symptoms-far out of the relatively limited time frame of the study. The main things which remained uncertain, I proposed to the students, were the estimates, because on the one hand the numerators were too high (colitis patients with cancer at presentation were included), but so were the denominators (as person-years had been counted back)---a really nice solution to this problem was published in 1989 by Kurtzke [8]. What happened? A caustic view would hold that clinical epidemiology leads only to delays in the progress of medicine because it throws up hurdles consisting of armchair ruminations on bias. A more benign view might have it that strong associations, like the one between colon cancer and colitis, are extremely robust to defects of study design, and can be picked up quite easily by the acumen of the astute observer. Perhaps the original authors were lucky that the errors in the numerators and denominators more or less canceled out. The situation is not unique. In the beginning of the “Smoking and Lung-cancer” exercise, I pointed out to the students that the original case-control studies were methodologically 923
924
Second Thoughts
quite defective-by present standards-and yet found truth. At the end of the exercise, I confessed to the students that a single randomized controlled trial of smoking cessation had not confirmed the rosy expectations of the British doctors who spontaneously quitted their cigarettes [9]. Apparently, voluntary quitters are not the same as random ones. Likewise, at the end of the John Snow exercise, I told students that John Snow’s magnificent rebuttal of William Farr’s hypothesis that cholera in London districts was related to the district’s height above sea level (such a nice example of confounding “avant la lettre”, showing that even Farr was subject to miasmatic fantasies), was somewhat redressed by a recent geographic analysis which included the factor of water drainage, raising the possibility that Farr was partially right [lo]. I continue to use the colitis exercise as a prime example of epidemiologic reasoning about the study of prognosis, but now incorporate the 1990 publication in my teaching, and tell students that in judging medical science they should retain a healthy balance between subject matter insight and methodological criticism-I hastily add that this is no blank cheque for
sloppy studies, but should guard us against too much reliance on methodology alone. REFERENCES 1. Sackett DL, Whelan G. Cancer risk in ulcerative colitis: scientific requirements for the study of prognosis. Glstroeaterology 1980; 78: 1632-1635. 2. Greenstein AJ, Sachar DB, Smith H, Pucillo A, Papatestas AE, Kreel I, Geller SA, Janowitz HD, Aufses AH. Cancer in universal and left-sided ulcerative colitis: factors determining risk. Gastroenterology 1979; 77: 290-294. 3. Tugwell PX. How to read clinical journals: III. To learn the clinical course and prognosis of disease.. CM Med Assoc 1981; 124: 869-872. 4. Katzka I, Brody RS, Morris E, Katz S. Assessment of colorectal cancer risk in patients with ulcerative colitis: experience from a private practice. Gastroenterology 1983; 85: 22-29. 5. Yardley JH, Ransohoff DF, Riddell RH, Goldman H. Cancer in inflammatory bowel disease: how serious is the problem and what should be done about it? Gastroenterology 1983; 85: 197-200. 6. Katzka I, Brody B. Cancer risk in ulceractive colitis. Gastroenterology 1983; 85: 787-788. I. Ekbom A, Helmick C, Zack M, Adami H. Ulcerative colitis and colorectal cancer. A population-based studv. N Ennl J Med 1990: 323: 1228-1233. 8. Ku&ke JFPOn estimating survival; a tale of two censors. J CIla Epidemiol 1989; 42: 169-175. 9. Rose G, Hamilton PJ, Colmell L et al. A randomized controlled trial of anti-smoking advice: IO-year results. J Epidemiol Comm Health 1982; 36: 102-108. 10. Cliff AE, Haggett P. Atlas of Msease Distributions. Oxford: Blackwell; 1988: 4446.
0895-4356/92%5.00+ 0.00 Copyright @$1992Pergamon PressLtd
Printed in Great Britain. All rights reserved
Second Thoughts COLON CANCER AND ULCERATIVE COLITIS: EPIDEMIOLOGIC EXERCISE REVISITED J. P. Department
AN
VANDENBROUCKE
of Clinical Epidemiology, L&den University Hospital, Building 1, CO-P, P.O. Box 9600, 2300 RC Leiden, The Netherlands (Received 5 March 1992)
Severe criticisms of the methodologic shortcomings of a study on colon cancer occurrence in patients with ulcerative colitis were published in 1980 [l], They led to the development of one of the nicest class exercises in clinical epidemiology on “How to read clinical journals, to learn the clinical course and prognosis of disease” [2,3]. Although it originated at McMaster’s, the exercise is now used world-wide with some variations. In my personal opinion it is one of the greatest epidemiologic exercises, and vies for attractiveness with “Smoking and Lung-cancer” as originally drafted by Milton Terris, and with “John Snow”, which originated with Wade Hampton Frost. After the original much criticized publication [2], the debate on colon cancer and colitis continued [4-6]. An almost final paper was published in 1990 [7]: a completely population-based study, as these can only be performed in Scandinavia. The logic of the class exercise on “colon cancer and colitis” leads inexorably to the conclusion that both the estimates of overall colon cancer incidence and the incidence of high”. universal colitis were “spuriously Although generally taking a sober view of the impact of methodology myself, I was still surprised to read how the results of the recent Swedish study were rather close to this notorious “black sheep” of epidemiology. The study confirmed the huge incidence of colon cancer in patients with universal colitis over three to four decades [7]. In my teaching, even before 1990, I had already incorporated some caution. At the end of the exercise, I used to warn the students that
we had now collectively “destroyed” the original paper, but that this did not mean that its message was necessarily untrue. Quite often students wondered why this paper had ever been accepted by an editor. I told them that clinicians had already “known” since the 1920s that colitis caused colon cancer, especially if long standing and generalized. I also emphasized a less noted “methodologic error” of the original study, i.e. that the person-years were “counted backwards” to the date of the first symptoms-far out of the relatively limited time frame of the study. The main things which remained uncertain, I proposed to the students, were the estimates, because on the one hand the numerators were too high (colitis patients with cancer at presentation were included), but so were the denominators (as person-years had been counted back)---a really nice solution to this problem was published in 1989 by Kurtzke [8]. What happened? A caustic view would hold that clinical epidemiology leads only to delays in the progress of medicine because it throws up hurdles consisting of armchair ruminations on bias. A more benign view might have it that strong associations, like the one between colon cancer and colitis, are extremely robust to defects of study design, and can be picked up quite easily by the acumen of the astute observer. Perhaps the original authors were lucky that the errors in the numerators and denominators more or less canceled out. The situation is not unique. In the beginning of the “Smoking and Lung-cancer” exercise, I pointed out to the students that the original case-control studies were methodologically 923
924
Second Thoughts
quite defective-by present standards-and yet found truth. At the end of the exercise, I confessed to the students that a single randomized controlled trial of smoking cessation had not confirmed the rosy expectations of the British doctors who spontaneously quitted their cigarettes [9]. Apparently, voluntary quitters are not the same as random ones. Likewise, at the end of the John Snow exercise, I told students that John Snow’s magnificent rebuttal of William Farr’s hypothesis that cholera in London districts was related to the district’s height above sea level (such a nice example of confounding “avant la lettre”, showing that even Farr was subject to miasmatic fantasies), was somewhat redressed by a recent geographic analysis which included the factor of water drainage, raising the possibility that Farr was partially right [lo]. I continue to use the colitis exercise as a prime example of epidemiologic reasoning about the study of prognosis, but now incorporate the 1990 publication in my teaching, and tell students that in judging medical science they should retain a healthy balance between subject matter insight and methodological criticism-I hastily add that this is no blank cheque for
sloppy studies, but should guard us against too much reliance on methodology alone. REFERENCES 1. Sackett DL, Whelan G. Cancer risk in ulcerative colitis: scientific requirements for the study of prognosis. Glstroeaterology 1980; 78: 1632-1635. 2. Greenstein AJ, Sachar DB, Smith H, Pucillo A, Papatestas AE, Kreel I, Geller SA, Janowitz HD, Aufses AH. Cancer in universal and left-sided ulcerative colitis: factors determining risk. Gastroenterology 1979; 77: 290-294. 3. Tugwell PX. How to read clinical journals: III. To learn the clinical course and prognosis of disease.. CM Med Assoc 1981; 124: 869-872. 4. Katzka I, Brody RS, Morris E, Katz S. Assessment of colorectal cancer risk in patients with ulcerative colitis: experience from a private practice. Gastroenterology 1983; 85: 22-29. 5. Yardley JH, Ransohoff DF, Riddell RH, Goldman H. Cancer in inflammatory bowel disease: how serious is the problem and what should be done about it? Gastroenterology 1983; 85: 197-200. 6. Katzka I, Brody B. Cancer risk in ulceractive colitis. Gastroenterology 1983; 85: 787-788. I. Ekbom A, Helmick C, Zack M, Adami H. Ulcerative colitis and colorectal cancer. A population-based studv. N Ennl J Med 1990: 323: 1228-1233. 8. Ku&ke JFPOn estimating survival; a tale of two censors. J CIla Epidemiol 1989; 42: 169-175. 9. Rose G, Hamilton PJ, Colmell L et al. A randomized controlled trial of anti-smoking advice: IO-year results. J Epidemiol Comm Health 1982; 36: 102-108. 10. Cliff AE, Haggett P. Atlas of Msease Distributions. Oxford: Blackwell; 1988: 4446.
