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The “Definite Improvement Level” (DIL) as a determinant of drug efficacy

      Patients have different expressions for clinically meaningful relief, “it works” and “it’s better” being phrases frequently used to communicate improvement. Cepeda et al reported “much improvement” in responder analyses for patients with acute post-operative pain.1 In our study we specified a higher level, “definite improvement”, as the patient-defined endpoint2 for analyzing drug efficacy. To determine the definite improvement level (DIL) for a common type of non-surgical acute pain, we interviewed patients with acute pharyngitis after they had used a 100-mm visual analog scale (VAS) to rate pain intensity in a randomized, double-blind trial comparing the use of 1 sugar-based flurbiprofen 8.75 mg lozenge and 1 sugar-based (placebo) lozenge.3 We asked patients to indicate which cut-off point meant definite improvement relative to his/her own pre-treatment VAS rating. For the 119 patients in this study, the DIL ranged from 19-97% pain intensity difference (PID), and on average 55% PID was indicative of definite improvement (analogous to the classic “pain half-gone” criterion of efficacy). Significantly more patients using flurbiprofen 8.75 mg than placebo over 6 hours reported ≥ his/her own DIL (p<0.05), confirmed by results from mean treatment group analyses.3,4 Because this method is derived from words patients use to assess drug performance in clinical practice, it makes sense to analyze drug activity similarly in clinical trials. We recommend that other investigators apply patients’ own determinants of drug efficacy (patient-defined endpoints) in responder analyses. One method is to use the individual patient’s criterion for definite improvement. Ongoing research is developing similar and standardized efficacy measurement instruments for this and other study models. (1. Cepeda et al, Pain, 2003; 2. Schachtel et al, Clin Pharmacol Ther, 2005; 3. Schachtel et al, J Pain, 2012; 4. Schachtel et al, Clin Pharmacol Drug Dev, 2012.) Supported by a grant from Reckitt Benckiser.