Affiliations of authors: N. Segnan, C. Senore, Centro Prevenzione Oncologica-Piemonte, Turin, Italy; L. Bonelli, Istituto Nazionale Ricerca sul Cancro, Genoa, Italy.
Correspondence to: Nereo Segnan, M.D., M.S. Epi, Unita di Epidemiologia, Centro Prevenzione Oncologica-Piemonte, Azienda Sanitaria Ospedaleira, "S Giovanni Battista," Via S Francesco da Paola 31, 10123 Torino, Italy (e-mail: nereo. segnan{at}cpo.it).
Dr. Hoff et al. raised interesting issues, which we address by describing in more detail the rationale for the design of the SCORE trial.
Study population. The trial aims to estimate the magnitude and the duration of the preventive effect of a single sigmoidoscopy screen at approximately age 60 years. The design choices adopted (including, in one center, randomizing only those responders definitely interested) were aimed at optimizing the efficiency of the study. Although the compliance rates were consistent among the trial centers (range = 54%64%), we believe that it is not appropriate to extrapolate the compliance achieved in this study to that which would pertain if screening were offered directly to the population. Another study (SCORE 2), with a different design, is ongoing in Italy (1) to assess compliance with different screening strategies. As mentioned in our article, we plan to assess the impact of the low response rate to the questionnaire on the generalizability of the trial findings by following up all subjects targeted for recruitment for colorectal cancer incidence and mortality.
Exclusions. Our goal was to examine the effect of a single screen in individuals who had had no prior screening or endoscopic examination; we were not suggesting that people with a past history of colorectal polyps should be excluded from screening. The proportion of subjects excluded who reported a previous negative endoscopy or a diagnosis of polyps, colorectal cancer, or inflammatory bowel disease ranged from 2.1% to 3.7% and from 2.5% to 7.1%, respectively, among the different centers. Therefore, few patients in the subgroup who responded to the mail questionnaire had had an endoscopy.
Polyp prevalence at age 5564 years is much higher in the Norwegian trial mentioned by Dr. Hoff (50% at age 5564 years) (2) than in the SCORE trial (18%). Nevertheless, the prevalence of adenomas appears more consistent in Norway and Italy (16% [calculated from (2)] and 11%, respectively), suggesting systematic differences between the two countries in the criteria for resection of diminutive polyps. The progression rate of diminutive polyps to cancer can affect the efficacy of screening. Because the probability of progression appears small (3), the benefit of follow-up of persons with this type of lesion is undefined.
Random assignment to control group. In Italy, all patients in the National Health Service (NHS) can have an endoscopy at the request of their general physician (GP). A regimen of such open-access randomization of GPs, which was done in centers where candidate screenees had been selected through preliminary GP sampling, should be even more effective than household randomization at reducing contamination because 1) household members generally share the same GP and will therefore tend to be assigned to the same arm, and 2) GPs are not required to behave differently with their patients, having all intervention or all control patients. In two centers, the GPs were not directly involved in the study, and the necessary information to perform household randomization was not available from the NHS register. Therefore, individual randomization was used in those centers. In Milan, all GPs agreed to a household randomization procedure.
If an intervention such as sigmoidoscopy is available as part of usual care, some degree of contamination is unavoidable during recruitment and follow-up in the control group and among non-responders in the intervention group (4). From this perspective, cluster randomization is expected to reduce contamination compared with individual randomization. However, the adoption of both individual and cluster randomization in our trial should not affect the validity of the trial because of the large number of clusters (507 GPs were involved), and because only eligible responders were randomized.
We agree with Dr. Hoff about the need to implement quality controls for endoscopy-based screening programs targeting the general population.
REFERENCES
1 Segnan N, Andreoni B, Bisanti L, Castiglione G, Ferrari A, Gasperoni S, et al. Comparing different strategies for colorectal cancer. Gastroenterology 2002;122(4S):1572.
2 Bretthauer M, Hoff G, Grotmol T, Gondal G, Hofstad B, Hupperts-Hauss G, et al. Quality control in colorectal screening: differences in detection rates of colorectal lesions among endoscopists. 18th Union Internationale Contre le Cancer (UICC) Cancer Congress, Abstract O 89. Int J Cancer 2002;Suppl 13.
3 Kronborg O, Fenger C. Clinical evidence of the adenoma-carcinoma sequence. Eur J Cancer Prev 1999;8 Suppl 1:S7386.[ISI][Medline]
4 Cuzick J, Edwards R, Segnan N. Adjusting for non-compliance and contamination in randomized clinical trials. Stat Med 1997;16:101729.[CrossRef][ISI][Medline]
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