“Prospective registration of a randomised controlled trial (RCT) based on a protocol with formal ethics approval is a benchmark for transparent medical research. The reporting of the primary results of the study should correspond to the design, analysis, and reporting specified in the protocol and trial registration. However, modifications to various aspects of the trial are often made after registration, ranging from administrative updates to substantial protocol amendments. To track the history of revisions, the protocol and registry entry should be updated, and the documentation trail should support an independent appraisal of whether any biases have been introduced that could affect interpretation of trial results.
In this issue of the MJA, Coskinas and colleagues report their investigation of changes to 181 phase 3 RCTs registered with the Australian New Zealand Clinical Trials Registry (ANZCTR) during 1 September 2007 – 31 December 2013.1 The authors compared protocol documents (including ANZCTR registration information) with subsequent journal publications for any changes to the primary outcome, treatment comparisons, analysis set definition, eligibility criteria, sample size, or primary analysis method. They found that protocols were available for only 124 trials (69%); it could be determined that no major changes had been made to eleven of these trials (9%), while 78 had definitely been modified (63%). By comparing publications with trial registration information, it was found that no changes were made to five of the 57 trials without available protocols (9%), and it could not be determined whether changes had been made to a further ten (18%)….”