title: Clinical research and methodology: What usage and what hierarchical order for secondary endpoints?
abstract: In a randomised clinical trial, when the result of the primary endpoint shows a significant benefit, the secondary endpoints are scrutinised to identify additional effects of the treatment. However, this approach entails a risk of concluding that there is a benefit for one of these endpoints when such benefit does not exist (inflation of type I error risk). There are mainly two methods used to control the risk of drawing erroneous conclusions for secondary endpoints. The first method consists of distributing the risk over several co-primary endpoints, so as to maintain an overall risk of 5%. The second is the hierarchical test procedure, which consists of first establishing a hierarchy of the endpoints, then evaluating each endpoint in succession according to this hierarchy while the endpoints continue to show statistical significance. This simple method makes it possible to show the additional advantages of treatments and to identify the factors that differentiate them.
authors.affiliation: Inserm UMR1059, unité de recherche clinique, innovation, pharmacologie, université Jean-Monnet, CHU Saint-Etienne, 42055 Saint-Étienne, France. Electronic address: silvy.laporte@chu-st-etienne.fr.
authors.forename: Silvy
authors.initials: S
authors.lastname: Laporte
authors.affiliation: Laboratoire Amgen, 92650 Boulogne-Billancourt, France.
authors.forename: Marine
authors.initials: M
authors.lastname: Diviné
authors.affiliation: Société Denelia, 92110 Clichy, France.
authors.forename: Danièle
authors.initials: D
authors.lastname: Girault
mesh_terms: D035843:Biomedical Research; D023381:Endpoint Determination; D006801:Humans; D012107:Research Design; D018401:Sample Size
keywords: Endpoint; Hierarchical test procedure; Inflation of type I error; Secondary endpoints