Grobler, Anna Christina.Matthews, Glenda Beverley.Molenberghs, Geert.2016-10-242016-10-2420142014Grobler, A.C., Matthews, G. and Molenberghs, G. 2014. The impact of missing data on clinical trials: a re-analysis of a placebo controlled trial of Hypericum perforatum (St Johns wort) and sertraline in major depressive disorder. Psychopharmacology 231(9), 1987-1999.http://dx.doi.org/10.1007/s00213-013-3344-xhttp://hdl.handle.net/10413/13538CAPRISA, 2013.Rationale and objective Hypericum perforatum (St John's wort) is used to treat depression, but the effectiveness has not been established. Recent guidelines described the analysis of clinical trials with missing data, inspiring the reanalysis of this trial using proper missing data methods. The objective was to determine whether hypericum was superior to placebo in treating major depression. Methods A placebo-controlled, randomized clinical trial was conducted for 8 weeks to determine the effectiveness of hypericum or sertraline in reducing depression, measured using the Hamilton depression scale. We performed sensitivity analyses under different assumptions about the missing data process. Results Three hundred forty participants were randomized, with 28 % lost to follow-up. The missing data mechanism was not missing completely at random. Under missing at random assumptions, some sensitivity analyses found no difference between either treatment arm and placebo, while some sensitivity analyses found a significant difference from baseline to week 8 between sertraline and placebo (−1.28, 95 % credible interval [−2.48; −0.08]), but not between hypericum and placebo (0.56, [−0.64;1.76]). The results were similar when the missing data process was assumed to be missing not at random. Conclusions There is no difference between hypericum and placebo, regardless of the assumption about the missing data process. There is a significant difference between sertraline and placebo with some statistical methods used. It is important to conduct an analysis that takes account of missing data using valid statistically principled methods. The assumptions about the missing data process could influence the results.enSt John's wort.Hypericum perforatum.Herbal medicine.Antidepressant.Sertraline.Hamilton depression scale.Multiple imputation.Missing at random.Missing not at random.Peer reviewed journal article