This presentation is part of: Poster Session - Public Health; Methodological Advances
IS THERE A SPECIAL AWARD FOR THE EXPERIMENTAL DRUG IN RANDOMIZED CONTROLLED TRIALS? THE CASE OF INTERFERON FOR CHRONIC HEPATITIS C
Fabio A. Tinč, MD1, Luigi Pagliaro, MD1, and Massimo Attanasio, PhD2. (1) V. Cervello Hospital, Gastroenterology, Palermo, Italy, (2) University of Palermo, Metodi Quantitativi per le Scienze Umane, Palermo, Italy
Purpose: an association between the experimental drug and benefit has been reported from RCTs of Fluoxetine. We searched for the same relationship 69 RCTs of Interferon alpha for Chronic Hepatitis C (CHC) that used the same dose of 9 MU/week at least in one of the arms. Methods: ALT normalization sustained for at least 6 months was the abstracted measure of benefit; such effect was analysed in experimental vs control group for association with a set of variables of design and reporting. A fixed effects, arm level, logistic meta-regression accounted for the sources of heterogeneity reported in the individual studies (PROC LOGISTIC-SAS Institute, Cary, NC). Results: main characteristics of arms were mean age 46 years, male 65%, cirrhotics 21%, genotype-1 61%, yearly schedule 28%, high quality score (Jadad > 3) 28%, multicenter RCT 52%, unblind RCT 72%, oriental country 17%, large trial (> 200 pts) 19%, funding for profit 51%, no-profit 19%, not declared 30%. Arms used as experimental included older patients, more cirrhotics, almost all originated from monocentric RCTs and were published mainly before 1995. Overall, 826 out of 4936 patients were sustained responders (benefit 17%). Only four variables maintained statistical significance after forward selection: mono vs multicentric trial (OR 1.9, 95%CI 1.5-2.5), experimental vs control arm (OR 1.5, 95%CI 1.1-1,9), yearly vs six-months schedule (OR 1.3, 95% CI 1.1-1.9) and trial’ first author from Asia (OR 1.4, 95%CI 1.0-1.9). The Model Chi-square was 89.8, df 4, p< 0.0001. Conclusion: arms wherein Interferon was used as experimental drug obtained higher rates of benefit. Methodological issues (local randomization procedure in the monocentric RCT or absence of double blind in all) or other factors might account for or contribute to the association between experimental role and likelihood of benefit. If present in other set of trials, this association might suggest a sort of special award for the experimental drug.
