Clarifying Enrollment Procedures in the Trial of CT Screening for Lung Cancer

Abstract

correspondence n engl j med 359;8 www.nejm.org august 21, 2008 871 ria exist for evaluating the serotonin syndrome, these criteria may have varying usefulness when applied to different databases. The Hunter crite-ria were developed at a toxicology service using a data set of overdoses in which medical staff used a preformatted form that prompted staff to eval-uate specific overdose symptoms. 3 The criteria can be used for adverse drug reactions but have not been validated for that purpose. 4 Because the serotonin syndrome reflects a clinical spectrum (mild, moderate, or severe), such strict criteria may lack appropriate sensitivity when applied to data-bases containing spontaneously reported adverse drug events from the public, such as the AERS. 1. of 5-HT1B/D ligands with recombinant h 5-HT1A receptors: in-trinsic activity and modulation by G-protein activation state. Naunyn Schmiedebergs Arch Pharmacol 1998;357:490-9. Boyer EW, Shannon M. The serotonin syndrome. N Engl J 2. Med 2005;352:1112-20. [Erratum, N Engl J Med 2007;356:2437.] Dunkley EJ, Isbister GK, Sibbritt D, Dawson AH, Whyte IM. 3. The Hunter Serotonin Toxicity Criteria: simple and accurate diag-nostic decision rules for serotonin toxicity. QJM 2003;96:635-42. Isbister GK, Buckley NA, Whyte IM. Serotonin toxicity: a 4. practical approach to diagnosis and treatment. Med J Aust 2007;187:361-5. To the Editor: I would like to clarify the selec-tion process leading to the inclusion of the pa-tients in the previous report on survival in the trial of computed tomographic (CT) screening for lung cancer (Oct. 26, 2006, issue). 1 The pro-cess at 37 of the 38 participating sites was as follows. People interested in participating in the trial were first interviewed and were adminis-tered a precoded questionnaire by the study staff. The data from the questionnaires were entered, and data entry was checked, according to the standard protocol used at each center. The data were then transmitted electronically to the coor-dinating center. There, eligibility was assessed by means of a computer algorithm, and those who did not meet the eligibility criteria were excluded (Fig. 1). At the 38th site, the questionnaire was not administered, and therefore all the needed data were not recorded before enrollment. For participants who received a diagnosis of lung cancer after baseline screening, study rec-ords were reviewed by the steering committee at one of its twice-yearly meetings. This review included confirmation of eligibility for the study — that is, asymptomatic status at the time of enrollment. If the symptoms resulting in exclu-sion had been present at enrollment but had not been recorded, the participant was excluded post hoc. This was the case for three patients among the 37 sites. Other features relevant to overall survival or survival itself were not used as a basis for exclusion. At the 38th site, at which symp-toms at enrollment had not been documented, eight participants were excluded on the basis of preexisting disqualifying symptoms, and one was excluded because pathological confirmation of lung cancer was not received by the coordinat-ing center (Fig. 1). The symptomatic status of participants who did not receive a diagnosis of lung cancer was not reviewed, since this infor-mation had no bearing on the research question addressed by the study. Except for the 12 patients excluded after en-rollment (the 3 from the 37 sites at which the screening questionnaire had been administered and the 9 from the 38th site, at which the ques-tionnaire was not administered), no patients were excluded from the study after they had been enrolled on the basis of the computer algo-rithm. Inclusion of these 12 patients changes the 10-year survival rate for patients with lung can-cer from the 80% (95% confidence interval [CI], 74 to 85) reported previously for 484 patients to 81% (95% CI, 75 to 86) for 496 patients. The other reported findings are not changed. The article also reported that eight patients with clinical stage I lung cancer remained un-treated and died within 5 years after diagnosis. However, only three had a pathological diagno-sis of stage I lung cancer. Another four had stage I disease confirmed on CT, but further