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Drug manufacturers did not report about 10% of serious and unexpected adverse events to the U.S. Food and Drug Administration within the required time period, investigators reported online in JAMA Internal Medicine.
Moreover, manufacturers were more likely to delay reporting serious and unexpected drug-related deaths than other AEs, said Paul Ma, Ph.D., of the University of Minnesota, Minneapolis, and his associates.
“As the FDA uses this information to update drug warnings, delays in reporting can have important public health consequences, particularly if manufacturers selectively delay reporting based on relevant patient outcomes,” the researchers said. “While increased enforcement may decrease violations, a simple alternative would be to recommend direct submission of reports to the FDA rather than via the manufacturer.”
Health providers and consumers can report adverse events to either drug manufacturers or the FDA under current regulations. Manufacturers have 15 days to forward reports of “expedited” events, defined as both unexpected (not included in the current FDA label) and serious (deaths, life-threatening drug reactions, new or prolonged inpatient hospitalizations, persistent or major disabilities, or birth defects). Although the extent to which drug manufacturers followed the 15-day requirement was unknown, there had been media reports of delays, the researchers noted (JAMA Intern. Med. 2015 July 27 [doi: 10.1001/jamainternmed.2015.3565]).
To better quantify the problem, Dr. Ma and his associates studied expedited AEs reported to the FDA Adverse Event Reporting System between 2004 and June 2014. Among 1.6 million reports, manufacturers failed to report 9.94% within the 15-day window, including more than 40,000 deaths. “Strikingly, AEs with patient death were more likely to be delayed,” added the investigators. “It is possible that manufacturers spend additional time in verifying reports concerning deaths, but this discretion is outside the scope of the current regulatory regime.”
Manufacturers reported about 90% of AEs that did not involve death on time, compared with 88% of those that did involve death. Furthermore, patient death remained linked to delayed reporting after accounting for multiple concurrent prescriptions; who reported the AE to the manufacturer; whether reported electronically or on paper; and the age, sex, and weight of patients.
“Further research is needed to better understand the mechanisms behind the manufacturers’ delayed reporting and the optimal regulatory policy toward mandatory disclosures of AEs,” the researchers concluded.
The Minnesota Accounting Research Center and the National Institute of Aging helped fund the research. The investigators disclosed no conflicts of interest.
“Our awareness of the potential adverse effects (AEs) of newly approved drugs and devices is limited. Premarket trials are often small and of limited duration, and the patients in clinical trials are healthier than unselected patients in routine clinical practice. Thus, the public and physicians rely on the U.S. Food and Drug Administration (FDA) Adverse Event Reporting System to inform us of unknown or unsuspected risks associated with use of drugs and devices.”
“Such reporting delays [as those found in the study] should never occur, as they mean that more patients are exposed to potentially avoidable serious harm, including death. However, no disciplinary actions have been taken when companies fail to submit reports to the FDA in the time frame required. Clearly, the lack of consequences contributes to a lack of deterrence for these illegal and dangerous delays.
“There is another enforcement tool that the FDA could begin to deploy immediately: suspending drug sales or withdrawing drug approval. Federal regulations give the FDA the power to withdraw drug approval ‘if an applicant fails to establish and maintain records and make [timely] reports [as] required under this section.’ One improvement would be for AE reports to go directly to the FDA instead of via the manufacturer, as recommended by” Dr. Ma and his associates.
Dr. Rita F. Redberg is director of women’s cardiovascular services at the Philip R. Lee Institute for Health Policy Studies at the University of California, San Francisco. She reported no conflicts of interest. These comments were taken from her accompanying editorial (JAMA Intern. Med. 2015 July 27 [doi:10.1001/jamainternmed.2015.356]).
“Our awareness of the potential adverse effects (AEs) of newly approved drugs and devices is limited. Premarket trials are often small and of limited duration, and the patients in clinical trials are healthier than unselected patients in routine clinical practice. Thus, the public and physicians rely on the U.S. Food and Drug Administration (FDA) Adverse Event Reporting System to inform us of unknown or unsuspected risks associated with use of drugs and devices.”
“Such reporting delays [as those found in the study] should never occur, as they mean that more patients are exposed to potentially avoidable serious harm, including death. However, no disciplinary actions have been taken when companies fail to submit reports to the FDA in the time frame required. Clearly, the lack of consequences contributes to a lack of deterrence for these illegal and dangerous delays.
“There is another enforcement tool that the FDA could begin to deploy immediately: suspending drug sales or withdrawing drug approval. Federal regulations give the FDA the power to withdraw drug approval ‘if an applicant fails to establish and maintain records and make [timely] reports [as] required under this section.’ One improvement would be for AE reports to go directly to the FDA instead of via the manufacturer, as recommended by” Dr. Ma and his associates.
Dr. Rita F. Redberg is director of women’s cardiovascular services at the Philip R. Lee Institute for Health Policy Studies at the University of California, San Francisco. She reported no conflicts of interest. These comments were taken from her accompanying editorial (JAMA Intern. Med. 2015 July 27 [doi:10.1001/jamainternmed.2015.356]).
“Our awareness of the potential adverse effects (AEs) of newly approved drugs and devices is limited. Premarket trials are often small and of limited duration, and the patients in clinical trials are healthier than unselected patients in routine clinical practice. Thus, the public and physicians rely on the U.S. Food and Drug Administration (FDA) Adverse Event Reporting System to inform us of unknown or unsuspected risks associated with use of drugs and devices.”
“Such reporting delays [as those found in the study] should never occur, as they mean that more patients are exposed to potentially avoidable serious harm, including death. However, no disciplinary actions have been taken when companies fail to submit reports to the FDA in the time frame required. Clearly, the lack of consequences contributes to a lack of deterrence for these illegal and dangerous delays.
“There is another enforcement tool that the FDA could begin to deploy immediately: suspending drug sales or withdrawing drug approval. Federal regulations give the FDA the power to withdraw drug approval ‘if an applicant fails to establish and maintain records and make [timely] reports [as] required under this section.’ One improvement would be for AE reports to go directly to the FDA instead of via the manufacturer, as recommended by” Dr. Ma and his associates.
Dr. Rita F. Redberg is director of women’s cardiovascular services at the Philip R. Lee Institute for Health Policy Studies at the University of California, San Francisco. She reported no conflicts of interest. These comments were taken from her accompanying editorial (JAMA Intern. Med. 2015 July 27 [doi:10.1001/jamainternmed.2015.356]).
Drug manufacturers did not report about 10% of serious and unexpected adverse events to the U.S. Food and Drug Administration within the required time period, investigators reported online in JAMA Internal Medicine.
Moreover, manufacturers were more likely to delay reporting serious and unexpected drug-related deaths than other AEs, said Paul Ma, Ph.D., of the University of Minnesota, Minneapolis, and his associates.
“As the FDA uses this information to update drug warnings, delays in reporting can have important public health consequences, particularly if manufacturers selectively delay reporting based on relevant patient outcomes,” the researchers said. “While increased enforcement may decrease violations, a simple alternative would be to recommend direct submission of reports to the FDA rather than via the manufacturer.”
Health providers and consumers can report adverse events to either drug manufacturers or the FDA under current regulations. Manufacturers have 15 days to forward reports of “expedited” events, defined as both unexpected (not included in the current FDA label) and serious (deaths, life-threatening drug reactions, new or prolonged inpatient hospitalizations, persistent or major disabilities, or birth defects). Although the extent to which drug manufacturers followed the 15-day requirement was unknown, there had been media reports of delays, the researchers noted (JAMA Intern. Med. 2015 July 27 [doi: 10.1001/jamainternmed.2015.3565]).
To better quantify the problem, Dr. Ma and his associates studied expedited AEs reported to the FDA Adverse Event Reporting System between 2004 and June 2014. Among 1.6 million reports, manufacturers failed to report 9.94% within the 15-day window, including more than 40,000 deaths. “Strikingly, AEs with patient death were more likely to be delayed,” added the investigators. “It is possible that manufacturers spend additional time in verifying reports concerning deaths, but this discretion is outside the scope of the current regulatory regime.”
Manufacturers reported about 90% of AEs that did not involve death on time, compared with 88% of those that did involve death. Furthermore, patient death remained linked to delayed reporting after accounting for multiple concurrent prescriptions; who reported the AE to the manufacturer; whether reported electronically or on paper; and the age, sex, and weight of patients.
“Further research is needed to better understand the mechanisms behind the manufacturers’ delayed reporting and the optimal regulatory policy toward mandatory disclosures of AEs,” the researchers concluded.
The Minnesota Accounting Research Center and the National Institute of Aging helped fund the research. The investigators disclosed no conflicts of interest.
Drug manufacturers did not report about 10% of serious and unexpected adverse events to the U.S. Food and Drug Administration within the required time period, investigators reported online in JAMA Internal Medicine.
Moreover, manufacturers were more likely to delay reporting serious and unexpected drug-related deaths than other AEs, said Paul Ma, Ph.D., of the University of Minnesota, Minneapolis, and his associates.
“As the FDA uses this information to update drug warnings, delays in reporting can have important public health consequences, particularly if manufacturers selectively delay reporting based on relevant patient outcomes,” the researchers said. “While increased enforcement may decrease violations, a simple alternative would be to recommend direct submission of reports to the FDA rather than via the manufacturer.”
Health providers and consumers can report adverse events to either drug manufacturers or the FDA under current regulations. Manufacturers have 15 days to forward reports of “expedited” events, defined as both unexpected (not included in the current FDA label) and serious (deaths, life-threatening drug reactions, new or prolonged inpatient hospitalizations, persistent or major disabilities, or birth defects). Although the extent to which drug manufacturers followed the 15-day requirement was unknown, there had been media reports of delays, the researchers noted (JAMA Intern. Med. 2015 July 27 [doi: 10.1001/jamainternmed.2015.3565]).
To better quantify the problem, Dr. Ma and his associates studied expedited AEs reported to the FDA Adverse Event Reporting System between 2004 and June 2014. Among 1.6 million reports, manufacturers failed to report 9.94% within the 15-day window, including more than 40,000 deaths. “Strikingly, AEs with patient death were more likely to be delayed,” added the investigators. “It is possible that manufacturers spend additional time in verifying reports concerning deaths, but this discretion is outside the scope of the current regulatory regime.”
Manufacturers reported about 90% of AEs that did not involve death on time, compared with 88% of those that did involve death. Furthermore, patient death remained linked to delayed reporting after accounting for multiple concurrent prescriptions; who reported the AE to the manufacturer; whether reported electronically or on paper; and the age, sex, and weight of patients.
“Further research is needed to better understand the mechanisms behind the manufacturers’ delayed reporting and the optimal regulatory policy toward mandatory disclosures of AEs,” the researchers concluded.
The Minnesota Accounting Research Center and the National Institute of Aging helped fund the research. The investigators disclosed no conflicts of interest.
FROM JAMA INTERNAL MEDICINE
Key clinical point: Drug manufacturers delayed reporting about 10% of serious unexpected adverse events to the FDA.
Major finding: Manufacturers broke the 15-day deadline for about 10% of such events, and those involving deaths were more likely to be delayed than others.
Data source: Analysis of 1.6 million serious and unexpected AEs reported to the FDA Adverse Event Reporting System between 2004 and June 2014.
Disclosures: The Minnesota Accounting Research Center and the National Institute of Aging helped fund the research. The investigators disclosed no conflicts of interest.
