Survey shows mixed AED safety knowledge among neurologists

SAN DIEGO – Most neurologists are aware of recent Food and Drug Administration safety warnings regarding the use of antiepileptic medications, but about 20% do not recognize these risks, results from a large membership survey demonstrated.

"FDA drug safety warnings are not systematically delivered to neurologists," Dr. Susan Shaw said at the annual meeting of the American Academy of Neurology. "The sources of information are numerous and varied. We also feel that the FDA drug safety warnings are not effectively delivered to neurologists."

Courtesy Dr. Susan Shaw

She based her remarks on an Internet-based survey distributed to 4,627 AAN members in 2012. Although the FDA issues drug safety communications and MedWatch alert e-mails, "these are only sent to those who are registered to receive the notifications," explained Dr. Shaw, a neurologist who is director of the epilepsy service line at Rancho Los Amigos National Rehabilitation Center, Downey, Calif., and is with the department of neurology at the University of Southern California, Los Angeles. The FDA may send alerts to physician specialty organizations such as the AAN, "which may then transmit the information to their members, but not all neurologists are members of the AAN," she noted. "The FDA may require drug manufacturers to update product inserts or highlight severe actions with ‘black box’ warnings or ‘dear health care provider’ letters. Still other neurologists rely on published articles or continuing medical education. Therefore, it is unknown whether the FDA’s alerts are effectively reaching neurologists."

Dr. Shaw and her associates set out to determine whether neurologists are aware of four recent FDA warnings regarding antiepileptic drugs (AEDs) and to determine whether neurologists are implementing recommended screening. Safety alert No. 1 was issued by the FDA on Dec. 12, 2007, and recommended screening for HLA-B*1502 in patients of Asian descent prior to treatment with carbamazepine, because of the risk of Stevens-Johnson syndrome and toxic epidermal necrolysis. "The risk of this haplotype is up to 10 times higher in some Asian countries than in countries with mostly Caucasian populations," Dr. Shaw said.

Safety alert No. 2 was the FDA announcement on Dec. 16, 2008, that required makers of AEDs to add labeling information warning that their use increases the risk of suicidal thoughts and behaviors. Safety alert No. 3 was the FDA healthcare provider notice released on Dec. 3, 2009, which recommended counseling for women of childbearing age who are taking valproate and labeling change for the drug because of the risk of congenital malformations in offspring of women treated with the drug during pregnancy. Safety alert No. 4 was the FDA drug safety communication and labeling change released on June 30, 2011, regarding the risk of impaired cognitive development in children exposed to valproate in utero.

"We do know that some of the FDA warnings, especially regarding suicidality, are controversial, but we think that it is important for providers to be aware of warnings and recommendations made by the FDA," Dr. Shaw said.

Of the 4,627 neurologists queried, 605 (13%) responded, which Dr. Shaw noted is a typical response rate for these types of surveys. The researchers excluded 100 who did not care for patients with epilepsy, which left a final survey sample size of 505 respondents from all 50 states and the District of Columbia. Their average age was 49 years and they had been in practice for an average of 22 years. The majority (96%) were board-certified in neurology, 40% worked in an academic hospital clinic, 32% worked in group practice, 18% worked in solo practice, and the remainder worked in other settings.

For each of the four safety alerts, "we asked questions to see if respondents had a general awareness of this risk," Dr. Shaw said. "We also asked questions to see if they knew more specific details regarding the risk."

Overall, about 80% of respondents did know about the four FDA safety alerts. "However, that does mean that approximately one-fifth of neurologists are not aware at all of the safety risks for these drugs," Dr. Shaw said. Knowledge of the specific details for each safety alert varied widely, from 34% to 74%.

The researchers also found that 29% of respondents had initiated carbamazepine in patients of Asian descent, but only 23% conducted the recommended haplotype testing for these patients. Most providers (93%) counseled women regarding birth defect risks while taking valproate, but only 34% could identify the specific risk of congenital malformations. Similarly, only 49% knew the degree to which scores on the Differential Ability Scale declined with in utero valproate exposure, compared with other AED monotherapy. In fact, 31% incorrectly believed that cognitive and developmental risks have not been established in offspring exposed to divalproex in utero.

The sources of drug safety alerts used by the respondents "were numerous, and there was no one universal source, which suggests that the safety information delivery is not done so systematically," Dr. Shaw said. The only characteristic of survey respondents associated with better knowledge of AED safety alerts was treating more epilepsy patients per year.

"We feel that a better system of doing risk notification may be warranted," she concluded. "In fact, when we asked the survey respondents, less than 5% of them wanted to continue the current system the way it is."

Most survey respondents preferred implementing a formal warning process via specialty organizations or e-mails of product insert warnings.

Dr. Shaw said that she had no relevant financial conflicts to disclose.

dbrunk@frontlinemedcom.com

SAN DIEGO – Most neurologists are aware of recent Food and Drug Administration safety warnings regarding the use of antiepileptic medications, but about 20% do not recognize these risks, results from a large membership survey demonstrated.

"FDA drug safety warnings are not systematically delivered to neurologists," Dr. Susan Shaw said at the annual meeting of the American Academy of Neurology. "The sources of information are numerous and varied. We also feel that the FDA drug safety warnings are not effectively delivered to neurologists."

Courtesy Dr. Susan Shaw

She based her remarks on an Internet-based survey distributed to 4,627 AAN members in 2012. Although the FDA issues drug safety communications and MedWatch alert e-mails, "these are only sent to those who are registered to receive the notifications," explained Dr. Shaw, a neurologist who is director of the epilepsy service line at Rancho Los Amigos National Rehabilitation Center, Downey, Calif., and is with the department of neurology at the University of Southern California, Los Angeles. The FDA may send alerts to physician specialty organizations such as the AAN, "which may then transmit the information to their members, but not all neurologists are members of the AAN," she noted. "The FDA may require drug manufacturers to update product inserts or highlight severe actions with ‘black box’ warnings or ‘dear health care provider’ letters. Still other neurologists rely on published articles or continuing medical education. Therefore, it is unknown whether the FDA’s alerts are effectively reaching neurologists."

Dr. Shaw and her associates set out to determine whether neurologists are aware of four recent FDA warnings regarding antiepileptic drugs (AEDs) and to determine whether neurologists are implementing recommended screening. Safety alert No. 1 was issued by the FDA on Dec. 12, 2007, and recommended screening for HLA-B*1502 in patients of Asian descent prior to treatment with carbamazepine, because of the risk of Stevens-Johnson syndrome and toxic epidermal necrolysis. "The risk of this haplotype is up to 10 times higher in some Asian countries than in countries with mostly Caucasian populations," Dr. Shaw said.

Safety alert No. 2 was the FDA announcement on Dec. 16, 2008, that required makers of AEDs to add labeling information warning that their use increases the risk of suicidal thoughts and behaviors. Safety alert No. 3 was the FDA healthcare provider notice released on Dec. 3, 2009, which recommended counseling for women of childbearing age who are taking valproate and labeling change for the drug because of the risk of congenital malformations in offspring of women treated with the drug during pregnancy. Safety alert No. 4 was the FDA drug safety communication and labeling change released on June 30, 2011, regarding the risk of impaired cognitive development in children exposed to valproate in utero.

"We do know that some of the FDA warnings, especially regarding suicidality, are controversial, but we think that it is important for providers to be aware of warnings and recommendations made by the FDA," Dr. Shaw said.

Of the 4,627 neurologists queried, 605 (13%) responded, which Dr. Shaw noted is a typical response rate for these types of surveys. The researchers excluded 100 who did not care for patients with epilepsy, which left a final survey sample size of 505 respondents from all 50 states and the District of Columbia. Their average age was 49 years and they had been in practice for an average of 22 years. The majority (96%) were board-certified in neurology, 40% worked in an academic hospital clinic, 32% worked in group practice, 18% worked in solo practice, and the remainder worked in other settings.

For each of the four safety alerts, "we asked questions to see if respondents had a general awareness of this risk," Dr. Shaw said. "We also asked questions to see if they knew more specific details regarding the risk."

Overall, about 80% of respondents did know about the four FDA safety alerts. "However, that does mean that approximately one-fifth of neurologists are not aware at all of the safety risks for these drugs," Dr. Shaw said. Knowledge of the specific details for each safety alert varied widely, from 34% to 74%.

The researchers also found that 29% of respondents had initiated carbamazepine in patients of Asian descent, but only 23% conducted the recommended haplotype testing for these patients. Most providers (93%) counseled women regarding birth defect risks while taking valproate, but only 34% could identify the specific risk of congenital malformations. Similarly, only 49% knew the degree to which scores on the Differential Ability Scale declined with in utero valproate exposure, compared with other AED monotherapy. In fact, 31% incorrectly believed that cognitive and developmental risks have not been established in offspring exposed to divalproex in utero.

The sources of drug safety alerts used by the respondents "were numerous, and there was no one universal source, which suggests that the safety information delivery is not done so systematically," Dr. Shaw said. The only characteristic of survey respondents associated with better knowledge of AED safety alerts was treating more epilepsy patients per year.

"We feel that a better system of doing risk notification may be warranted," she concluded. "In fact, when we asked the survey respondents, less than 5% of them wanted to continue the current system the way it is."

Most survey respondents preferred implementing a formal warning process via specialty organizations or e-mails of product insert warnings.

Dr. Shaw said that she had no relevant financial conflicts to disclose.

dbrunk@frontlinemedcom.com

SAN DIEGO – Most neurologists are aware of recent Food and Drug Administration safety warnings regarding the use of antiepileptic medications, but about 20% do not recognize these risks, results from a large membership survey demonstrated.

"FDA drug safety warnings are not systematically delivered to neurologists," Dr. Susan Shaw said at the annual meeting of the American Academy of Neurology. "The sources of information are numerous and varied. We also feel that the FDA drug safety warnings are not effectively delivered to neurologists."

Courtesy Dr. Susan Shaw

She based her remarks on an Internet-based survey distributed to 4,627 AAN members in 2012. Although the FDA issues drug safety communications and MedWatch alert e-mails, "these are only sent to those who are registered to receive the notifications," explained Dr. Shaw, a neurologist who is director of the epilepsy service line at Rancho Los Amigos National Rehabilitation Center, Downey, Calif., and is with the department of neurology at the University of Southern California, Los Angeles. The FDA may send alerts to physician specialty organizations such as the AAN, "which may then transmit the information to their members, but not all neurologists are members of the AAN," she noted. "The FDA may require drug manufacturers to update product inserts or highlight severe actions with ‘black box’ warnings or ‘dear health care provider’ letters. Still other neurologists rely on published articles or continuing medical education. Therefore, it is unknown whether the FDA’s alerts are effectively reaching neurologists."

Dr. Shaw and her associates set out to determine whether neurologists are aware of four recent FDA warnings regarding antiepileptic drugs (AEDs) and to determine whether neurologists are implementing recommended screening. Safety alert No. 1 was issued by the FDA on Dec. 12, 2007, and recommended screening for HLA-B*1502 in patients of Asian descent prior to treatment with carbamazepine, because of the risk of Stevens-Johnson syndrome and toxic epidermal necrolysis. "The risk of this haplotype is up to 10 times higher in some Asian countries than in countries with mostly Caucasian populations," Dr. Shaw said.

Safety alert No. 2 was the FDA announcement on Dec. 16, 2008, that required makers of AEDs to add labeling information warning that their use increases the risk of suicidal thoughts and behaviors. Safety alert No. 3 was the FDA healthcare provider notice released on Dec. 3, 2009, which recommended counseling for women of childbearing age who are taking valproate and labeling change for the drug because of the risk of congenital malformations in offspring of women treated with the drug during pregnancy. Safety alert No. 4 was the FDA drug safety communication and labeling change released on June 30, 2011, regarding the risk of impaired cognitive development in children exposed to valproate in utero.

"We do know that some of the FDA warnings, especially regarding suicidality, are controversial, but we think that it is important for providers to be aware of warnings and recommendations made by the FDA," Dr. Shaw said.

Of the 4,627 neurologists queried, 605 (13%) responded, which Dr. Shaw noted is a typical response rate for these types of surveys. The researchers excluded 100 who did not care for patients with epilepsy, which left a final survey sample size of 505 respondents from all 50 states and the District of Columbia. Their average age was 49 years and they had been in practice for an average of 22 years. The majority (96%) were board-certified in neurology, 40% worked in an academic hospital clinic, 32% worked in group practice, 18% worked in solo practice, and the remainder worked in other settings.

For each of the four safety alerts, "we asked questions to see if respondents had a general awareness of this risk," Dr. Shaw said. "We also asked questions to see if they knew more specific details regarding the risk."

Overall, about 80% of respondents did know about the four FDA safety alerts. "However, that does mean that approximately one-fifth of neurologists are not aware at all of the safety risks for these drugs," Dr. Shaw said. Knowledge of the specific details for each safety alert varied widely, from 34% to 74%.

The researchers also found that 29% of respondents had initiated carbamazepine in patients of Asian descent, but only 23% conducted the recommended haplotype testing for these patients. Most providers (93%) counseled women regarding birth defect risks while taking valproate, but only 34% could identify the specific risk of congenital malformations. Similarly, only 49% knew the degree to which scores on the Differential Ability Scale declined with in utero valproate exposure, compared with other AED monotherapy. In fact, 31% incorrectly believed that cognitive and developmental risks have not been established in offspring exposed to divalproex in utero.

The sources of drug safety alerts used by the respondents "were numerous, and there was no one universal source, which suggests that the safety information delivery is not done so systematically," Dr. Shaw said. The only characteristic of survey respondents associated with better knowledge of AED safety alerts was treating more epilepsy patients per year.

"We feel that a better system of doing risk notification may be warranted," she concluded. "In fact, when we asked the survey respondents, less than 5% of them wanted to continue the current system the way it is."

Most survey respondents preferred implementing a formal warning process via specialty organizations or e-mails of product insert warnings.

Dr. Shaw said that she had no relevant financial conflicts to disclose.

dbrunk@frontlinemedcom.com