Clinical trial discontinuation and non-publication for the pharmacologic treatment of Post-Traumatic Stress Disorder among military veterans

Abstract

Background: Failures by researchers and clinicians to understand, confront, and overcome barriers in veteran-health research may result in the waste of finite resources. Research waste includes clinical trial discontinuation and non-publication which have been shown to be substantial among several fields of medicine. It is the ethical responsibility of researchers, as scientists, to contribute their findings to the existing literature as supported by the International Committee of Medical Journal Editors and the National Institute for Health Research and the Declaration of Helsinki regarding human subjects. Given the rates of discontinuation and non-publication of clinical trials among other fields of medicine and the lack of evidence demonstrating publication rates of clinical trials (CTs) among veterans, our primary objective was to determine rates of discontinuation and non-publication among post traumatic stress disorder (PTSD) focused CTs with pharmaceutical interventions specific to the veteran population.

Methods: We performed a systematic search of registered trials using ClinicalTrials.gov for pharmaceutical interventions for the treatment of PTSD. Studies were screened in a duplicate masked fashion and extracted study characteristics including sample size, study design, trial status, phase, and funding source. We then searched the trials designation ID and title to identify publications associated with the study. If no study was found, and the study was not prematurely terminated, the study’s primary contact was emailed to identify potential publications. Studies were classified as completed or discontinued based on the status category provided from ClinicalTrials.gov. Descriptive statistics of trials will be reported and associations of trial termination and non-publication will be assessed using logistic regression.

Results: Our search returned 351 studies, 54 of which met inclusion criteria. Among these 54 studies 11 were discontinued and 15 were not published. The median enrollment among all trials was 37 (IQR). Among the terminated studies, 0 participants were enrolled. Among the non-published trials, 12 were enrolled. Reasons for study termination included low enrollment, withdrawn funding, and deployment of the principal investigator overseas. We found a statistically significant association between sample size and discontinuation, but not among any other examined study characteristic.

Conclusion: We found that a combined 29% of trials of medications for PTSD among veterans were either discontinued or not-published. Engaging in clinical trials research without publication of results wastes the finite resources available to investigators. This may also lead to limitations and bias within the existing medical literature. Further, it is not only the ethical responsibility of researchers to publish results, but a legal requirement under Section 801 of the FDA Amendments Act (FDAAA) of 2007 to report study results which has been reaffirmed and strengthened in 2017 and the first preliminary litigation was announced. In light of the dedication of our service men and women to serving the United States, sometimes at great personal cost, it is the ethical responsibility of researchers to advance clinical knowledge via CT publication as it relates to improving treatments for veterans diagnosed with PTSD is greater than ever before.