title: A users' guide to understanding therapeutic substitutions.
abstract: Therapeutic substitutions are common at the level of ministries of health, clinicians, and pharmacy dispensaries. Guidance in determining whether drugs offer similar risk-benefit profiles is limited. Those making decisions on therapeutic substitutions should be aware of potential biases that make differentiating therapeutic agents difficult. Readers should consider whether the biological mechanisms and doses are similar across agents, whether the evidence is sufficiently valid across agents, and whether the safety and therapeutic effects of each drug are similar. This article uses a problem-based format to address the biological mechanism, validity, and results of a scenario in which therapeutic substitutions may be considered.
authors.affiliation: Faculty of Health Sciences, University of Ottawa, 43 Templeton Street, Ottawa, Canada K1N6X1; Centre for Clinical Epidemiology and Evaluation (C2E2), University of British Columbia, 828 West 10th Ave, Research Pavilion, Vancouver, Canada, V5Z 1M9. Electronic address: edward.mills@uottawa.ca.
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Mills
authors.affiliation: College of Pharmacy, Faculty of Health Professions, Dalhousie University, 5968 College St, Halifax, Nova Scotia, Canada, B3H 4R2.
authors.forename: David
authors.initials: D
authors.lastname: Gardner
authors.affiliation: Centre for Clinical Epidemiology and Evaluation (C2E2), University of British Columbia, 828 West 10th Ave, Research Pavilion, Vancouver, Canada, V5Z 1M9; Department of Clinical Epidemiology & Biostatistics, McMaster University, 1280 Main St. West, Hamilton, Ontario, Canada, L8S 4K1.
authors.forename: Kristian
authors.initials: K
authors.lastname: Thorlund
authors.affiliation: Department of Clinical Epidemiology & Biostatistics, McMaster University, 1280 Main St. West, Hamilton, Ontario, Canada, L8S 4K1; Basel Institute for Clinical Epidemiology and Biostatistics, University Hospital Basel, CH-4031, Basel, Switzerland.
authors.forename: Matthias
authors.initials: M
authors.lastname: Briel
authors.affiliation: Centre for Clinical Epidemiology and Evaluation (C2E2), University of British Columbia, 828 West 10th Ave, Research Pavilion, Vancouver, Canada, V5Z 1M9.
authors.forename: Stirling
authors.initials: S
authors.lastname: Bryan
authors.affiliation: Clinical Epidemiology Program, Ottawa Hospital Research Institute, 725 Parkdale Ave, Ottawa, Ontario, Canada, K1Y 4E9.
authors.forename: Brian
authors.initials: B
authors.lastname: Hutton
authors.affiliation: Department of Clinical Epidemiology & Biostatistics, McMaster University, 1280 Main St. West, Hamilton, Ontario, Canada, L8S 4K1.
authors.forename: Gordon H
authors.initials: GH
authors.lastname: Guyatt
mesh_terms: D015982:Bias; D003657:Decision Making; D057915:Drug Substitution / Q000379:methods* / Q000592:standards*; D019317:Evidence-Based Medicine; D005260:Female; D006801:Humans; D008297:Male; D055553:Prescription Drugs / Q000008:administration & dosage* / Q000592:standards*; D016032:Randomized Controlled Trials as Topic; D018570:Risk Assessment; D013810:Therapeutic Equivalency
chemical_list: D055553:Prescription Drugs
keywords: Class effects; Evidence-based medicine; Generic substitutions; Network meta-analysis; Statins; Therapeutic substitutions