IMPORTANCE: Every year, the US Food and Drug Administration (FDA) inspects several hundred clinical sites performing biomedical research on human participants and occasionally finds evidence of substantial departures from good clinical practice and research misconduct. However, the FDA has no systematic method of communicating these findings to the scientific community, leaving open the possibility that research misconduct detected by a government agency goes unremarked in the peer-reviewed literature.
OBJECTIVES: To identify published clinical trials in which an FDA inspection found significant evidence of objectionable conditions or practices, to describe violations, and to determine whether the violations are mentioned in the peer-reviewed literature.
DESIGN AND SETTING:Cross-sectional analysis of publicly available documents, dated from January 1, 1998, to September 30, 2013, describing FDA inspections of clinical trial sites in which significant evidence of objectionable conditions or practices was found.
MAIN OUTCOMES AND MEASURES:For each inspection document that could be linked to a specific published clinical trial, the main measure was a yes/no determination of whether there was mention in the peer-reviewed literature of problems the FDA had identified.
RESULTS: Fifty-seven published clinical trials were identified for which an FDA inspection of a trial site had found significant evidence of 1 or more of the following problems: falsification or submission of false information, 22 trials (39%); problems with adverse events reporting, 14 trials (25%); protocol violations, 42 trials (74%); inadequate or inaccurate recordkeeping, 35 trials (61%); failure to protect the safety of patients and/or issues with oversight or informed consent, 30 trials (53%); and violations not otherwise categorized, 20 trials (35%). Only 3 of the 78 publications (4%) that resulted from trials in which the FDA found significant violations mentioned the objectionable conditions or practices found during the inspection. No corrections, retractions, expressions of concern, or other comments acknowledging the key issues identified by the inspection were subsequently published.
CONCLUSIONS AND RELEVANCE:When the FDA finds significant departures from good clinical practice, those findings are seldom reflected in the peer-reviewed literature, even when there is evidence of data fabrication or other forms of research misconduct.
We are having pharma making excessive profits, just like the bankers and just like the bankers, who are doing some dodgey practises, so are pharma and neuros and likewise the government is turning a blind eye to report anything sounds familiar
The FDA inspections uncovered one or more violations in the 57 published clinical trials identified including:
- 22 trials with falsified information.
- 14 trials where researchers failed to report adverse events.
- 42 trials with violations of the trials protocols.
- 35 trials with record-keeping errors.
- 30 trials in which researchers failed to protect patient safety or acquire informed consent.
A patient in a trial had a foot amputated two weeks after receiving stem cells to treat poor blood flow in a leg. Despite this, the article from the stem cell trial claimed that ALL of the patients reported improvement in their limbs.
A patient died in a chemotherapy trial due to a researcher’s falsification of documents, and the researcher ended up in prison after pleading guilty to fraud and criminally negligent homicide. None of the articles published from this clinical trial mention either the fraud or the subsequent homicide case.
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.
FINDINGS: 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.