Consistency of protocol and safety data reporting in clinical trial registrations and corresponding publications of interventions involving 3,4-methylenedioxymethamphetamine (MDMA)
2Department of Pharmacology, School of Medicine, University of Split, Croatia
Background: The efficacy of 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy for patients with post-traumatic stress disorder has been demonstrated in clinical trials, although this remains controversial due to the classified status of the substance in most countries and the vulnerability of patients during dosing sessions. Pre-registration of clinical trials is one way to increase their credibility and transparency.
Objectives: Our aim was to evaluate registration data for clinical trials on MDMA to see whether any significant methodological modifications were made to the protocol registration over time that could imply possible bias within the study.
Methods: Using ClinicalTrials.gov advanced search on 21 February 2023, we retrieved all trials that had MDMA under the field “Intervention”. For all included trials, we analysed the CT.gov “Archive” field and searched whether any primary outcome and participants’ eligibility criteria were quantitatively (changes in number of parameters or timing of measurement) or qualitatively changed. This was considered a major change. We also recorded any addition of information or formatting as a minor change which does not significantly impact the content. Our next step is to screen PubMed/MEDLINE and Scopus databases for scientific articles of all studies noted as “Completed”. We will evaluate protocol amendments that could justify major changes and also the level of congruence between the data on adverse events recorded in the registry and corresponding publications.
Results: We identified 78 registered trials, of which 59.0% were classified as “Completed”. Out of those, only 15 trials (32.6%) had their study results posted in the CT.gov results database. Considering all 78 trials, minor changes to the eligibility criteria were found in 23.1% trials, whilst 20.5% trials had major changes. For primary outcome reporting, 24.4% trials had minor changes, while 11.5% changes were classified as major.
Conclusions: Our findings raise awareness on the need for consistency of protocol reporting in MDMA trial registrations, especially in terms of modifying eligibility criteria once the registration has already been submitted.
Patient, public and/or healthcare consumer involvement: Our findings and recommendations help increase the trustworthiness of the clinical trial findings for PTSD patients and for informing any potential policy changes.