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Credit: CDC
Patient safety violations emerged as a common theme in a review of “first warning” letters issued to clinical trial sponsors, investigators, and internal review boards (IRBs).
The US Food and Drug Administration (FDA) issued the 84 warning letters in response to trial violations uncovered during site visits.
The review of these letters showed that 55% of investigators failed to protect subjects’ safety and report adverse events to the IRB, 24% of sponsors failed to submit adverse event data to the FDA, and 22% of IRBs failed to “address risk minimization and protect vulnerable study subjects.”
Yashashri C. Shetty and Aafreen A. Saiyed, both of King Edward Memorial Hospital in Mumbai, detailed these findings in the Journal of Medical Ethics.
The researchers reviewed the content of 84 first-warning letters issued by the FDA following site visits between 2005 and 2012.
Sponsor violations
Forty-six warning letters were issued to trial sponsors. Their most common violations were failure to follow the monitoring schedule (58.69%) and failure to obtain investigator agreement (34.78%).
The same proportion of sponsors (30.43%) failed to secure investigators’ compliance and failed to maintain records, both of study data and for shipping product to the investigator.
Other violations included failure to submit an Investigational Device Exemption or Investigational New Drug application to the FDA (28.26%) and failure to review, evaluate, and submit adverse drug event reports to the FDA (23.91%). Two sponsors did not allow FDA inspection, and 1 did not obtain IRB approval.
Investigator infractions
Twenty warning letters were issued to investigators. Ninety-five percent of the letters said investigators were guilty of deviating from the investigational plan. Fifty-five percent of letters said the researchers failed to protect subject safety and report adverse events to the IRB.
Violations regarding records—largely, the failure to maintain and produce them for inspection—were documented in 40% of the letters. And informed consent issues were highlighted in 35%.
Other violations included those related to the product under investigation (15%), failure to obtain IRB approval (10%), and failure to personally supervise the study (30%).
IRB transgressions
Eighteen warning letters were issued to IRBs. The most common violation (61.11%) was failure to follow written procedures for continuing review.
Other common violations (55.56%) were those related to membership and meetings—failure to maintain minutes, inappropriate membership, quorum issues, misuse of expedited review, and the lack of a layperson in meetings.
The remaining violations included failure to follow regulatory requirements (44.4%), failure to follow standard operating procedures and maintain documentation (44.44%), failure to address risk minimization and protect vulnerable subjects (22.22%), conflicts of interest and informed consent issues (27.78%), and failure to appoint a qualified investigator (5.55%).
Comparing past and present
The study authors compared their findings with previously published research in the same arena, dating back as far as 1997. They found that regulatory compliance generally improved over the years, but supervision worsened.
And 2 new serious violations cropped up in the interim: failure to get the green light from an IRB before pressing ahead and submitting false data to the FDA and/or sponsors.
In a bid to boost compliance with good clinical practice, the authors suggest that every regulatory agency charged with overseeing clinical trials should pay main participating centers a visit and regularly publish the details of their findings. 
Credit: CDC
Patient safety violations emerged as a common theme in a review of “first warning” letters issued to clinical trial sponsors, investigators, and internal review boards (IRBs).
The US Food and Drug Administration (FDA) issued the 84 warning letters in response to trial violations uncovered during site visits.
The review of these letters showed that 55% of investigators failed to protect subjects’ safety and report adverse events to the IRB, 24% of sponsors failed to submit adverse event data to the FDA, and 22% of IRBs failed to “address risk minimization and protect vulnerable study subjects.”
Yashashri C. Shetty and Aafreen A. Saiyed, both of King Edward Memorial Hospital in Mumbai, detailed these findings in the Journal of Medical Ethics.
The researchers reviewed the content of 84 first-warning letters issued by the FDA following site visits between 2005 and 2012.
Sponsor violations
Forty-six warning letters were issued to trial sponsors. Their most common violations were failure to follow the monitoring schedule (58.69%) and failure to obtain investigator agreement (34.78%).
The same proportion of sponsors (30.43%) failed to secure investigators’ compliance and failed to maintain records, both of study data and for shipping product to the investigator.
Other violations included failure to submit an Investigational Device Exemption or Investigational New Drug application to the FDA (28.26%) and failure to review, evaluate, and submit adverse drug event reports to the FDA (23.91%). Two sponsors did not allow FDA inspection, and 1 did not obtain IRB approval.
Investigator infractions
Twenty warning letters were issued to investigators. Ninety-five percent of the letters said investigators were guilty of deviating from the investigational plan. Fifty-five percent of letters said the researchers failed to protect subject safety and report adverse events to the IRB.
Violations regarding records—largely, the failure to maintain and produce them for inspection—were documented in 40% of the letters. And informed consent issues were highlighted in 35%.
Other violations included those related to the product under investigation (15%), failure to obtain IRB approval (10%), and failure to personally supervise the study (30%).
IRB transgressions
Eighteen warning letters were issued to IRBs. The most common violation (61.11%) was failure to follow written procedures for continuing review.
Other common violations (55.56%) were those related to membership and meetings—failure to maintain minutes, inappropriate membership, quorum issues, misuse of expedited review, and the lack of a layperson in meetings.
The remaining violations included failure to follow regulatory requirements (44.4%), failure to follow standard operating procedures and maintain documentation (44.44%), failure to address risk minimization and protect vulnerable subjects (22.22%), conflicts of interest and informed consent issues (27.78%), and failure to appoint a qualified investigator (5.55%).
Comparing past and present
The study authors compared their findings with previously published research in the same arena, dating back as far as 1997. They found that regulatory compliance generally improved over the years, but supervision worsened.
And 2 new serious violations cropped up in the interim: failure to get the green light from an IRB before pressing ahead and submitting false data to the FDA and/or sponsors.
In a bid to boost compliance with good clinical practice, the authors suggest that every regulatory agency charged with overseeing clinical trials should pay main participating centers a visit and regularly publish the details of their findings.
Credit: CDC
Patient safety violations emerged as a common theme in a review of “first warning” letters issued to clinical trial sponsors, investigators, and internal review boards (IRBs).
The US Food and Drug Administration (FDA) issued the 84 warning letters in response to trial violations uncovered during site visits.
The review of these letters showed that 55% of investigators failed to protect subjects’ safety and report adverse events to the IRB, 24% of sponsors failed to submit adverse event data to the FDA, and 22% of IRBs failed to “address risk minimization and protect vulnerable study subjects.”
Yashashri C. Shetty and Aafreen A. Saiyed, both of King Edward Memorial Hospital in Mumbai, detailed these findings in the Journal of Medical Ethics.
The researchers reviewed the content of 84 first-warning letters issued by the FDA following site visits between 2005 and 2012.
Sponsor violations
Forty-six warning letters were issued to trial sponsors. Their most common violations were failure to follow the monitoring schedule (58.69%) and failure to obtain investigator agreement (34.78%).
The same proportion of sponsors (30.43%) failed to secure investigators’ compliance and failed to maintain records, both of study data and for shipping product to the investigator.
Other violations included failure to submit an Investigational Device Exemption or Investigational New Drug application to the FDA (28.26%) and failure to review, evaluate, and submit adverse drug event reports to the FDA (23.91%). Two sponsors did not allow FDA inspection, and 1 did not obtain IRB approval.
Investigator infractions
Twenty warning letters were issued to investigators. Ninety-five percent of the letters said investigators were guilty of deviating from the investigational plan. Fifty-five percent of letters said the researchers failed to protect subject safety and report adverse events to the IRB.
Violations regarding records—largely, the failure to maintain and produce them for inspection—were documented in 40% of the letters. And informed consent issues were highlighted in 35%.
Other violations included those related to the product under investigation (15%), failure to obtain IRB approval (10%), and failure to personally supervise the study (30%).
IRB transgressions
Eighteen warning letters were issued to IRBs. The most common violation (61.11%) was failure to follow written procedures for continuing review.
Other common violations (55.56%) were those related to membership and meetings—failure to maintain minutes, inappropriate membership, quorum issues, misuse of expedited review, and the lack of a layperson in meetings.
The remaining violations included failure to follow regulatory requirements (44.4%), failure to follow standard operating procedures and maintain documentation (44.44%), failure to address risk minimization and protect vulnerable subjects (22.22%), conflicts of interest and informed consent issues (27.78%), and failure to appoint a qualified investigator (5.55%).
Comparing past and present
The study authors compared their findings with previously published research in the same arena, dating back as far as 1997. They found that regulatory compliance generally improved over the years, but supervision worsened.
And 2 new serious violations cropped up in the interim: failure to get the green light from an IRB before pressing ahead and submitting false data to the FDA and/or sponsors.
In a bid to boost compliance with good clinical practice, the authors suggest that every regulatory agency charged with overseeing clinical trials should pay main participating centers a visit and regularly publish the details of their findings.