PURPOSE: To describe a method for quantitatively dealing with drug dose in comparative effectiveness reviews. Second-generation antidepressants are used as an example to illustrate this method and to determine whether dose influences conclusions on comparative effectiveness. METHODS: Studies previously identified in a systematic review of second-generation antidepressants were included if data on drug dose were available. The usual dosing range for each drug was defined and then used to create 2- and 3-level dose categories. Placebo-controlled data were used to calculate overall effect sizes for the drug class and effect sizes stratified by drug dose. Meta-regression tested the impact of dose on effect size. Weighted mean differences and risk ratios were calculated for comparative studies, stratifying by whether compared doses were equivalent. RESULTS: The dose classification method was able to identify dose-response trends in the context of meta-analysis. Compared to low-dose studies, medium- and high-dose studies had a 1- to 2-point greater differential in mean Hamilton Depression Rating Scale (HAM-D) change (P < 0:001). Dose was not a statistically significant predictor of categorical HAM-D response. Among comparative trials with nonequivalent doses, trends favored higher dose categories but generally were not statistically significant. CONCLUSIONS: A structured method for quantitatively dealing with drug dose in comparative effectiveness reviews is described, with application to the second-generation antidepressants. Dose-dependent reductions in HAM-D scores were identified, although differences did not translate into better response rates for higher doses. Dose equivalency was not a significant factor among comparative studies in second-generation antidepressants.
PURPOSE: To describe a method for quantitatively dealing with drug dose in comparative effectiveness reviews. Second-generation antidepressants are used as an example to illustrate this method and to determine whether dose influences conclusions on comparative effectiveness. METHODS: Studies previously identified in a systematic review of second-generation antidepressants were included if data on drug dose were available. The usual dosing range for each drug was defined and then used to create 2- and 3-level dose categories. Placebo-controlled data were used to calculate overall effect sizes for the drug class and effect sizes stratified by drug dose. Meta-regression tested the impact of dose on effect size. Weighted mean differences and risk ratios were calculated for comparative studies, stratifying by whether compared doses were equivalent. RESULTS: The dose classification method was able to identify dose-response trends in the context of meta-analysis. Compared to low-dose studies, medium- and high-dose studies had a 1- to 2-point greater differential in mean Hamilton Depression Rating Scale (HAM-D) change (P < 0:001). Dose was not a statistically significant predictor of categorical HAM-D response. Among comparative trials with nonequivalent doses, trends favored higher dose categories but generally were not statistically significant. CONCLUSIONS: A structured method for quantitatively dealing with drug dose in comparative effectiveness reviews is described, with application to the second-generation antidepressants. Dose-dependent reductions in HAM-D scores were identified, although differences did not translate into better response rates for higher doses. Dose equivalency was not a significant factor among comparative studies in second-generation antidepressants.
Authors: Gerald Gartlehner; Barbara Nussbaumer-Streit; Bradley N Gaynes; Catherine A Forneris; Laura C Morgan; Amy Greenblatt; Jörg Wipplinger; Linda J Lux; Megan G Van Noord; Dietmar Winkler Journal: Cochrane Database Syst Rev Date: 2019-03-18
Authors: Carolyn S Sterke; Gijsbertus Ziere; Ed F van Beeck; Caspar W N Looman; Tischa J M van der Cammen Journal: Br J Clin Pharmacol Date: 2012-05 Impact factor: 4.335
Authors: Barbara Nussbaumer-Streit; Amy Greenblatt; Angela Kaminski-Hartenthaler; Megan G Van Noord; Catherine A Forneris; Laura C Morgan; Bradley N Gaynes; Jörg Wipplinger; Linda J Lux; Dietmar Winkler; Gerald Gartlehner Journal: Cochrane Database Syst Rev Date: 2019-06-17
Authors: Barbara Nussbaumer-Streit; Catherine A Forneris; Laura C Morgan; Megan G Van Noord; Bradley N Gaynes; Amy Greenblatt; Jörg Wipplinger; Linda J Lux; Dietmar Winkler; Gerald Gartlehner Journal: Cochrane Database Syst Rev Date: 2019-03-18
Authors: Barbara Nussbaumer-Streit; Kylie Thaler; Andrea Chapman; Thomas Probst; Dietmar Winkler; Andreas Sönnichsen; Bradley N Gaynes; Gerald Gartlehner Journal: Cochrane Database Syst Rev Date: 2021-03-04
Authors: Yoshihiro Noda; Zafiris J Daskalakis; Jonathan Downar; Paul E Croarkin; Paul B Fitzgerald; Daniel M Blumberger Journal: Neuropsychiatr Dis Treat Date: 2014-10-31 Impact factor: 2.570