title: Providing evidence of efficacy for a new drug.
abstract: There are many issues to consider when designing an efficacy package for drug registration. Generally in Europe and the United States, two or more confirmatory trials demonstrating efficacy (p < 0.025, one-tailed) of the test treatment versus a suitable control group must be conducted with a priori definition of a primary efficacy endpoint. Exceptions are possible, and there is always extensive discussion whenever less is proposed or more is required. Every aspect of the basic requirement can be questioned: number of trials; choice of control groups; selection of primary efficacy variables(s); levels of significance; one-tailed versus two-tailed test. These issues will be discussed, and justification is given when proposals are made for deviations from standard practice. Differences between Europe and the U.S. are discussed for certain disease entities. Because the assessment of the weight of evidence in favour of a drug effect is difficult to quantitate, if not impossible, no definitive guidance can be given that is suitable for all circumstances and countries.
authors.affiliation: Hoechst Marion Roussel, Inc., Kansas City, MO 64137, USA. stephen.ruberg@hmrag.com
authors.forename: S
authors.initials: S
authors.lastname: Ruberg
authors.forename: V
authors.initials: V
authors.lastname: Cairns
mesh_terms: D015982:Bias; D002986:Clinical Trials as Topic / Q000592:standards*; D003627:Data Interpretation, Statistical; D004305:Dose-Response Relationship, Drug; D004341:Drug Evaluation / Q000592:standards*; D015987:Effect Modifier, Epidemiologic; D005060:Europe; D017408:Guidelines as Topic; D006801:Humans; D007391:International Cooperation; D015203:Reproducibility of Results; D012107:Research Design / Q000592:standards*; D016896:Treatment Outcome; D014481:United States