The Multi-Crossover Model for Classifying Patients as Responders to a Given Treatment

Abstract

The strength and the validity of the multi-crossover model (MCO model) were investigated to optimalize the procedure for correctly classifying individual responders to a given therapy. One hundred and fifteen patients with non-ulcer dyspepsia from seven Norwegian hospitals were included in a 6-week double-blind MCO-designed trial with alternating weekly treatments with ranitidine and placebo. An individual effect score (X score) was calculated on the basis of the number of times the active drug was associated with less symptoms than the preceding or following placebo period. Patients categorized as responders (X score greater than or equal to 4) or unclassifiables (X scores = 2 or 3) after the MCO period continued single-blind active treatment for 4 weeks and were then reclassified by means of cross-tabulation of efficacy and adverse effects. Eighty-five per cent of the MCO responders and 62% of the 42 MCO unclassifiables were reclassified as responders. The reclassified responders were then included in a single-blind follow-up placebo period until relapse or for a maximum of 8 weeks. The relapse rate was significantly greater (p less than 0.01) and the time to relapse significantly shorter (p less than 0.01) in the group of MCO responders than in the MCO unclassifiables. The large response and relapse rates in the group of MCO responders verify that the MCO model is a reliable method for correctly classifying responders to treatment. Our results indicate that by including patients with an X score of 3 in the definition of 'responder', the MCO model could be modified to optimalize the procedure for correct classification.

Ranitidine for Non-Ulcer Dyspepsia: A Clinical Study of the Symptomatic Effect of Ranitidine and a Classification and Characterization of the Responders to Treatment

“…They received single-blind treatment with placebo for 8 weeks and were requested to contact the hospital immediately if symptoms recurred before the scheduled visit. (16).…”

“…Patients with Xs = 0-1 were classified as 'nonresponders'; Xs = 2-3 as 'unclassified', and Xs = 4 5 as 'responders' to ranitidine treatment (12). Two efficacy indices (Ei) (16) were also calculated; one was based on the differences between the recorded degree of symptoms on the VAS (measured in centimetres) and the other on differences in the use of antacids in each ranitidine period and the preceding and following placebo period. The difference was positive when active treatment was superior to placebo, and vice versa (16).…”

“…Two efficacy indices (Ei) (16) were also calculated; one was based on the differences between the recorded degree of symptoms on the VAS (measured in centimetres) and the other on differences in the use of antacids in each ranitidine period and the preceding and following placebo period. The difference was positive when active treatment was superior to placebo, and vice versa (16). The mean of these five differences between Part I1 (the treatment period) was a 4-week single-blind treatment with ranitidine of the MCO-classified groups unclassified and responders.…”

“…The study was carried out as a block randomized, double-blind, placebo-controlled, multicentre trial with a multi-crossover (MCO) design (16). A family history of gastrointestinal disease was taken, and previous diseases, NUD symptoms, and other gastrointestinal symptoms were recorded in detail.…”

“…Differences were considered significant if the p value was less than or equal to 5%. The Student test for specified hypotheses was used for analysis of the results from the MCO period based on the efficacy index (Ei) (16). Comparison between groups was carried out by using analysis of variance (17).…”