Defecation

Data for this study were acquired from a recently completed placebo-controlled randomized trial of rosiglitazone for mild to moderately active ulcerative colitis (clinicaltrials.gov #NCT00065065) which has been described in greater detail previously.7 (link) The trial used a slight modification of the Mayo score to assess disease activity (Table 1). Specifically, the bleeding component as described in the Mayo index was modified such that a score of 3 required both visible blood in 50% or more of bowel movements and at least some bowel movements with blood alone.
The study included 105 patients with mild to moderately active disease defined as a total DAI score of 4 to 10, inclusively. Patients were randomized in a 1:1 ratio to receive either rosiglitazone 4 mg or placebo twice daily for 12 weeks. Disease activity was measured at randomization and every four weeks thereafter until week 12, however lower endoscopy was only completed at week 0 and week 12, such that only a partial Mayo score (9 point scale that excludes the endoscopic appearance of the mucosa) could be calculated at the interim visits. In the very early accrual period of the study, a follow-up visit was included at week 2. Without knowledge of the response rates in either arm, the Data and Safety Monitoring Board (DSMB) requested that the week 2 follow-up evaluation be eliminated with the hopes of minimizing the placebo response rate and maximizing recruitment and retention.6 (link), 8 (link), 9 (link) Eighteen patients completed the week 2 follow-up visit.
During the course of the study, patients could be treated with other conventional medications used to treat active ulcerative colitis including mesalamine, oral corticosteroids, immunomodulators, or topical therapies (mesalamine or corticosteroids) at stable doses. Use of corticosteroids at doses greater than 20mg per day of prednisone or the equivalent was an exclusion criterion. Steroid tapering was not permitted during the study.
In anticipation of this sub-study, at each visit we also included questions about change in disease activity compared to the previous visit and compared to the randomization visit on a global seven-point scale (Table 2). The choices included much better, moderately better, a little better, unchanged, a little worse, moderately worse, and much worse. Patients also graded their current disease activity at each visit on a 6 point Likert scale – perfect, very good (minimal symptoms), good (only mild symptoms), moderately active, moderately severe, or severe. Data on quality of life were measured with the Inflammatory Bowel Disease Questionnaire (IBDQ) authored by Dr. Jan Irvine under license from McMaster University, Hamilton, Canada.10 (link)

All analyses were conducted pooling patients in both arms of the clinical trial. Descriptive statistics were used to describe patients included in the study. Continuous variables are reported as medians and interquartile ranges and categorical variables as proportions. Correlations were measured using Spearman correlation coefficients (rho). Except where noted, only data for patients who completed the week 12 study visit were analyzed; this allowed for greater variation in disease activity than at baseline, since at randomization all patients were required to have DAI scores between 4 and 10, inclusive.
To assess sensitivity and specificity for clinical remission and clinical response, we relied on the patient’s assessment of disease activity in the preceding 24 hours at randomization and at the week 12 visit. Clinical remission was defined as a self-assessment of perfect or very good (minimal disease activity). Clinical response required improvement by at least two points on the 6 point Likert scale. Receiver operating characteristics (ROC) curves were generated and the C-statistic was calculated as a summary measure of the discriminative properties of the indices. Optimal cut points were identified by the highest sensitivity × specificity product. Area under the ROC curves for different disease indices were compared using the roccomp command in Stata v10 (Stata Corp, College Station, TX).
Because neither the patient rating nor the Mayo score are a pure gold standard for disease activity, we also calculated kappa statistics across a range of cut points to assess the impact of changing cut points on the agreement between the patient ratings and partial Mayo score. The kappa statistic measures the degree of agreement between the two measures beyond that which would be expected by chance. The kappa statistic can have values ranging from −1 to 1, with values of .41–.60 representing moderate agreement, .61–.80 representing substantial agreement, and values greater than .80 representing almost perfect agreement.11 (link)
Finally, because the physician’s global assessment is likely greatly driven by the patient’s report of bowel movement frequency and bleeding, we examined whether a score composed exclusively of these two factors would perform as well as the modified DAI. This six-point scale was compared to the patient’s self report in the same manner described for the full and partial Mayo scores. We refer to this as the “6 point scale” in this report.