title: Issues in the assessment of non-inferiority: perspectives drawn from case studies.
abstract: Superiority claims for improved efficacy are the backbone of clinical development of new therapies. However, not every new therapy in development allows for such a claim. Some therapies per se do not try to improve efficacy further but concentrate on important aspects in safety or convenience. Such improvements can be equally important to patients, and development strategies should be available for such compounds. A three-arm design with placebo, active control and experimental treatment may be viewed as the golden standard for such compounds; however, it may be difficult if not impossible to add a placebo arm in certain diseases. In such situations, non-inferiority designs are the only development option left. This paper will highlight some of the key issues with such designs in practice and will report experience from two studies from different therapeutic areas intended for regulatory submission.
authors.affiliation: F. Hoffmann-La Roche, Basel, Switzerland. hans_ulrich.burger@roche.com
authors.forename: H Ulrich
authors.initials: HU
authors.lastname: Burger
authors.forename: Ulrich
authors.initials: U
authors.lastname: Beyer
authors.forename: Markus
authors.initials: M
authors.lastname: Abt
mesh_terms: D000740:Anemia / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D002986:Clinical Trials as Topic / Q000379:methods*; D017326:Clinical Trials, Phase III as Topic; D015179:Colorectal Neoplasms / Q000188:drug therapy; D016001:Confidence Intervals; D035061:Control Groups; D003956:Dialysis / Q000009:adverse effects; D018450:Disease Progression; D018572:Disease-Free Survival; D017277:Drug Approval / Q000379:methods / Q000706:statistics & numerical data*; D015507:Drugs, Investigational / Q000009:adverse effects / Q000378:metabolism; D005069:Evaluation Studies as Topic; D006801:Humans; D007674:Kidney Diseases / Q000150:complications / Q000188:drug therapy; D015233:Models, Statistical; D017060:Patient Satisfaction; D010919:Placebos; D016032:Randomized Controlled Trials as Topic; D012107:Research Design; D018570:Risk Assessment / Q000706:statistics & numerical data; D016896:Treatment Outcome
chemical_list: D015507:Drugs, Investigational; D010919:Placebos