title: Prevalence of primary outcome changes in clinical trials registered on ClinicalTrials.gov: a cross-sectional study.
abstract: BACKGROUND
  An important principle in the good conduct of clinical trials is that a summary of the trial protocol, with a pre-defined primary outcome, should be freely available before the study commences. The clinical trials registry ClinicalTrials.gov provides one method of doing this, and once the trial is registered, any changes made to the primary outcome are documented. The objectives of this study were: to assess the proportion of registered trials on ClinicalTrials.gov that had the primary outcome changed; to assess when the primary outcome was changed in relation to the listed study start and end dates and to assess whether the primary outcome change had any relation to the study sponsor.
  
  
  METHODS
  A cross-sectional analysis of all interventional clinical trials registered on ClinicalTrials.gov as of 25 October 2012 was performed. The main outcome was any change made to the initially listed primary outcome and the time of the change in relation to the trial start and end date.
  
  
  RESULTS
  Our analysis showed that 28229 of 89204 (31.7%) registered studies had their primary outcome changed.  Industry funding was associated with all primary outcome changes, odds ratio (OR)= 1.36, 95% confidence interval (CI)=1.31-1.41, p<0.001; with primary outcome changes after study start date OR=1.37, 95% CI=1.32-1.42, p<0.001; with primary outcome changes after primary completion date OR=1.84, 95% CI=1.75-1.94, p<0.001 and with primary outcome changes after study completion date OR=1.82, 95% CI=1.73-1.91, p<0.001.  Conclusions A significant proportion of interventional trials registered on ClinicalTrials.gov have their primary outcomes altered after the listed study start and completion dates. These changes are associated with funding source.
authors: Medical Research Council Functional Genomics Unit and Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, OX1 3PT, UK.
authors: Sreeram
authors: S
authors: Ramagopalan
authors: London School of Hygiene and Tropical Medicine, London, WC1E 7HT, UK.
authors: Andrew P
authors: AP
authors: Skingsley
authors: Medical Research Council Functional Genomics Unit and Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, OX1 3PT, UK.
authors: Lahiru
authors: L
authors: Handunnetthi
authors: London School of Hygiene and Tropical Medicine, London, WC1E 7HT, UK.
authors: Michelle
authors: M
authors: Klingel
authors: London School of Hygiene and Tropical Medicine, London, WC1E 7HT, UK.
authors: Daniel
authors: D
authors: Magnus
authors: Medical Research Council Functional Genomics Unit and Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, OX1 3PT, UK.
authors: Julia
authors: J
authors: Pakpoor
authors: London School of Hygiene and Tropical Medicine, London, WC1E 7HT, UK.
authors: Ben
authors: B
authors: Goldacre