A Retrospective Analysis of Clinical Research Misconduct Using FDA-Issued Warning Letters and Clinical Investigator Inspection List From 2010 to 2014

Abstract

The overall decrease in violations is encouraging. But, the high proportion of violations related to failure to follow the investigational plan is concerning as the complexity of trials increases. We conclude that more detailed information is necessary to accurately evaluate these violations. The current study provides a model for creating more granular data of violations to better inform clinical investigators and improve clinical trials.

An audit of US FDA warning letters issued to sponsors, institutional review boards and investigators over a six-year period

“…Deviation from the investigational plan turned out to be the most frequent violation theme. The reason this theme recurs and has not changed over time (7), is because the [3] investigators who are more experienced could be shouldering a greater burden of studies leaving them with inadequate time for supervision. Additionally, pressure from the pharmaceutical industry to meet stringent timelines may lead investigators to take short cuts or buckle under pressure.…”

Online but unlawful sales of unapproved and misbranded prescription drugs: Internet pharmacy compliance with Food and Drug Administration warning letters

“…Untitled letters serve as initial notices of violation, which are issued for violations that are less significant than those triggering warning letters and, thus, contain no statement of potential enforcement action (Food and Drug Administration, 2022b). Research on drug‐related warning letters has been conducted in many contexts, such as pharmaceutical advertising and promotion (Benson & Alfors, 2007; Chatterjee et al, 2012; Kamal et al, 2009; Limbu et al, 2019; Mohite et al, 2021; Nguyen et al, 2013; Salas et al, 2008; Symonds et al, 2014); online pharmaceutical advertising (Hoy & Park, 2014; Kim, 2015); OTC promotion (Salas et al, 2008); clinical investigators researching drugs and devices as well as their institutional review boards and/or research sponsors (Bramstedt, 2004; Bramstedt & Kassimatis, 2004; O'Reilly et al, 2013; Romano et al, 2018; Shetty & Saiyed, 2015); OTC drug manufacture and labelling (Bai et al, 2021); and COVID‐19‐related drugs, devices, biologics, and dietary supplements (Bramstedt, 2020; Sridharan & Sivaramakrishnan, 2021).…”

“…No previous studies of state regulatory agency or FDA warning letters directed to brick‐and‐mortar or online pharmacies were uncovered in our review of the literature. Of research into FDA warning letters related to drugs in other contexts, most examined warning letters exclusively from 2015 or earlier (Benson & Alfors, 2007; Bramstedt, 2004; Bramstedt & Kassimatis, 2004; Chatterjee et al, 2012; Hoy & Park, 2014; Kamal et al, 2009; Kim, 2015; Nguyen et al, 2013; O'Reilly et al, 2013; Romano et al, 2018; Salas et al, 2008; Shetty & Saiyed, 2015; Stewart & Neumann, 2002; Symonds et al, 2014) with a few notable exceptions (Bai et al, 2021; Bramstedt, 2020; Limbu et al, 2019; Mohite et al, 2021; Sridharan & Sivaramakrishnan, 2021). None of these previous investigations of FDA warning letters examined consequences, such as compliance, despite warning letters' position as the FDA's primary means to achieve voluntary compliance from violators of its consumer protection regulations.…”

Blockchain’s potential to improve clinical trials—an essay by Leeza Osipenko

“…Clinical trials are prone to research misconduct, data falsification, or simply unintended errors 234. Trials often deviate from prespecified protocol or may record inaccurate case histories 5. The extent of these problems is difficult to quantify,3 but—along with inappropriate trial design and data analysis, under-reporting of results, and publication bias—it leads to significant waste in clinical research 67.…”