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.
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 armand 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.
Anneke C
AC
Grobler
Glenda
G
Matthews
Geert
G
Molenberghs
D000928:Antidepressive Agents / Q000627:therapeutic use*; D003865:Major Depressive Disorder / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D020902:Hypericum; D008137:Longitudinal Studies; D008297:Male; D015233:Models, Statistical; D010352:Patient Dropouts; D008517:Phytotherapy; D010936:Plant Extracts / Q000627:therapeutic use*; D011569:Psychiatric Status Rating Scales; D012680:Sensitivity and Specificity; D020280:Sertraline / Q000627:therapeutic use*; D016896:Treatment Outcome
D000928:Antidepressive Agents; D010936:Plant Extracts; D020280:Sertraline