Heidi Splete

Patients at risk for gastric ulcers from long-term, low-dose aspirin regimens who received a novel aspirin therapy had significantly less ulceration, compared with those who received standard low-dose aspirin in a randomized, single-blind trial. The findings were published in the February issue of the American Journal of Gastroenterology.

Preclinical studies have shown that the noncovalent association of aspirin and phosphatidylcholine helps aspirin travel across the gastrointestinal mucosa with less risk for bleeding, said Dr. Byron Cryer of the University of Texas Southwestern Medical Center and Veterans Affairs North Texas Health Care System, Dallas, and his colleagues. This is important, the authors wrote, because "45% of patients with cardiovascular risk factors are not treated with antiplatelet agents because their risks of gastrointestinal (GI) bleeding outweigh [the] vascular benefit."

After 7 days of daily treatment, only 22% of patients randomized to an aspirin-phosphatidylcholine complex known as PL2200 developed six or more gastrointestinal erosions or an ulcer, compared with 42% of those randomized to immediate-release low-dose aspirin alone, a significant difference (P = .0027). Endoscopy was used to evaluate the upper-GI mucosa.

In addition, significantly fewer patients developed gastroduodenal ulcers in the PL2200 group, compared with the low-dose aspirin group (5% vs. 18%, respectively, P = .0069); this amounted to a 71% lower incidence of ulcers in the PL2200 group. The intent-to-treat population included 99 patients in the PL2200 group and 102 patients in the low-dose aspirin group. The patients were healthy and ranged in age from 50 to 74 years; they were considered at risk for GI injury because of their age (Am. J. Gastroenterol. 2011 [doi:10.1038/ajg.2010.436]).

For 7 days, the low-dose aspirin group received 325 mg of aspirin orally once a day, and the PL2200 patients received one PL2200 capsule that contained 325 mg of aspirin once a day. A total of 7 patients in the PL2200 group and 11 in the low-dose aspirin group were excluded because of baseline GI erosion, and 1 patient in each group was excluded for taking a prohibited medication during the study period. These exclusions left a per-protocol population of 91 subjects in the PL2200 group and 90 in the low-dose aspirin group. The percentages of patients that developed ulcers in the per-protocol analysis were similar to those in the intent-to-treat population.

No treatment-related discontinuations or serious adverse events were reported in either group.

"The study suggests that local effects that disrupt the gastric barrier to acid are an important component of aspirin-induced gastropathy," the researchers wrote. The relative contributions of local and systemic mechanisms that induce GI injury are not well understood, they added.

The study was limited by the short-term follow-up, and larger, longer-term studies are needed. However, the findings suggest that PL2200 is associated with significantly better GI safety than low-dose aspirin. Consequently, PL2200 might improve compliance in at risk patients who are likely to discontinue aspirin due to GI side effects, the researchers added.

All study authors, endoscopists, and investigators were blinded until database lock.

The study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases and by PLx Pharma Inc., which is developing PL2200. Dr. Cryer has served as a consultant for multiple pharmaceutical companies including PLx Pharma, AstraZeneca Pharmaceuticals, and Cogentus Pharmaceuticals, and has served on advisory and review committees for Pfizer. Several study coauthors have received research support from or are employed by PLx Pharma or disclosed relationships with other pharmaceutical companies.

Patients at risk for gastric ulcers from long-term, low-dose aspirin regimens who received a novel aspirin therapy had significantly less ulceration, compared with those who received standard low-dose aspirin in a randomized, single-blind trial. The findings were published in the February issue of the American Journal of Gastroenterology.

Preclinical studies have shown that the noncovalent association of aspirin and phosphatidylcholine helps aspirin travel across the gastrointestinal mucosa with less risk for bleeding, said Dr. Byron Cryer of the University of Texas Southwestern Medical Center and Veterans Affairs North Texas Health Care System, Dallas, and his colleagues. This is important, the authors wrote, because "45% of patients with cardiovascular risk factors are not treated with antiplatelet agents because their risks of gastrointestinal (GI) bleeding outweigh [the] vascular benefit."

After 7 days of daily treatment, only 22% of patients randomized to an aspirin-phosphatidylcholine complex known as PL2200 developed six or more gastrointestinal erosions or an ulcer, compared with 42% of those randomized to immediate-release low-dose aspirin alone, a significant difference (P = .0027). Endoscopy was used to evaluate the upper-GI mucosa.

In addition, significantly fewer patients developed gastroduodenal ulcers in the PL2200 group, compared with the low-dose aspirin group (5% vs. 18%, respectively, P = .0069); this amounted to a 71% lower incidence of ulcers in the PL2200 group. The intent-to-treat population included 99 patients in the PL2200 group and 102 patients in the low-dose aspirin group. The patients were healthy and ranged in age from 50 to 74 years; they were considered at risk for GI injury because of their age (Am. J. Gastroenterol. 2011 [doi:10.1038/ajg.2010.436]).

For 7 days, the low-dose aspirin group received 325 mg of aspirin orally once a day, and the PL2200 patients received one PL2200 capsule that contained 325 mg of aspirin once a day. A total of 7 patients in the PL2200 group and 11 in the low-dose aspirin group were excluded because of baseline GI erosion, and 1 patient in each group was excluded for taking a prohibited medication during the study period. These exclusions left a per-protocol population of 91 subjects in the PL2200 group and 90 in the low-dose aspirin group. The percentages of patients that developed ulcers in the per-protocol analysis were similar to those in the intent-to-treat population.

No treatment-related discontinuations or serious adverse events were reported in either group.

"The study suggests that local effects that disrupt the gastric barrier to acid are an important component of aspirin-induced gastropathy," the researchers wrote. The relative contributions of local and systemic mechanisms that induce GI injury are not well understood, they added.

The study was limited by the short-term follow-up, and larger, longer-term studies are needed. However, the findings suggest that PL2200 is associated with significantly better GI safety than low-dose aspirin. Consequently, PL2200 might improve compliance in at risk patients who are likely to discontinue aspirin due to GI side effects, the researchers added.

All study authors, endoscopists, and investigators were blinded until database lock.

The study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases and by PLx Pharma Inc., which is developing PL2200. Dr. Cryer has served as a consultant for multiple pharmaceutical companies including PLx Pharma, AstraZeneca Pharmaceuticals, and Cogentus Pharmaceuticals, and has served on advisory and review committees for Pfizer. Several study coauthors have received research support from or are employed by PLx Pharma or disclosed relationships with other pharmaceutical companies.

Patients at risk for gastric ulcers from long-term, low-dose aspirin regimens who received a novel aspirin therapy had significantly less ulceration, compared with those who received standard low-dose aspirin in a randomized, single-blind trial. The findings were published in the February issue of the American Journal of Gastroenterology.

Preclinical studies have shown that the noncovalent association of aspirin and phosphatidylcholine helps aspirin travel across the gastrointestinal mucosa with less risk for bleeding, said Dr. Byron Cryer of the University of Texas Southwestern Medical Center and Veterans Affairs North Texas Health Care System, Dallas, and his colleagues. This is important, the authors wrote, because "45% of patients with cardiovascular risk factors are not treated with antiplatelet agents because their risks of gastrointestinal (GI) bleeding outweigh [the] vascular benefit."

After 7 days of daily treatment, only 22% of patients randomized to an aspirin-phosphatidylcholine complex known as PL2200 developed six or more gastrointestinal erosions or an ulcer, compared with 42% of those randomized to immediate-release low-dose aspirin alone, a significant difference (P = .0027). Endoscopy was used to evaluate the upper-GI mucosa.

In addition, significantly fewer patients developed gastroduodenal ulcers in the PL2200 group, compared with the low-dose aspirin group (5% vs. 18%, respectively, P = .0069); this amounted to a 71% lower incidence of ulcers in the PL2200 group. The intent-to-treat population included 99 patients in the PL2200 group and 102 patients in the low-dose aspirin group. The patients were healthy and ranged in age from 50 to 74 years; they were considered at risk for GI injury because of their age (Am. J. Gastroenterol. 2011 [doi:10.1038/ajg.2010.436]).

For 7 days, the low-dose aspirin group received 325 mg of aspirin orally once a day, and the PL2200 patients received one PL2200 capsule that contained 325 mg of aspirin once a day. A total of 7 patients in the PL2200 group and 11 in the low-dose aspirin group were excluded because of baseline GI erosion, and 1 patient in each group was excluded for taking a prohibited medication during the study period. These exclusions left a per-protocol population of 91 subjects in the PL2200 group and 90 in the low-dose aspirin group. The percentages of patients that developed ulcers in the per-protocol analysis were similar to those in the intent-to-treat population.

No treatment-related discontinuations or serious adverse events were reported in either group.

"The study suggests that local effects that disrupt the gastric barrier to acid are an important component of aspirin-induced gastropathy," the researchers wrote. The relative contributions of local and systemic mechanisms that induce GI injury are not well understood, they added.

The study was limited by the short-term follow-up, and larger, longer-term studies are needed. However, the findings suggest that PL2200 is associated with significantly better GI safety than low-dose aspirin. Consequently, PL2200 might improve compliance in at risk patients who are likely to discontinue aspirin due to GI side effects, the researchers added.

All study authors, endoscopists, and investigators were blinded until database lock.

The study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases and by PLx Pharma Inc., which is developing PL2200. Dr. Cryer has served as a consultant for multiple pharmaceutical companies including PLx Pharma, AstraZeneca Pharmaceuticals, and Cogentus Pharmaceuticals, and has served on advisory and review committees for Pfizer. Several study coauthors have received research support from or are employed by PLx Pharma or disclosed relationships with other pharmaceutical companies.

Eribulin monotherapy achieved "a significant and clinically meaningful improvement" in overall survival, compared with other treatments of choice in women with heavily pretreated metastatic breast cancer, according to pivotal EMBRACE trial data published online by the Lancet on March 3.

Median overall survival rate reached 13.1 months in women treated with eribulin (Halaven), compared with 10.6 months in the control group (P = .041). Median progression-free survival was 3.7 months and 2.2 months, respectively (P = .137) based on an independent review of the intent-to-treat population. Fatal adverse events occurred in 4% of the eribulin patients vs. 7% of the control group.

"To our knowledge, EMBRACE is the first major single-agent study of a cytotoxic or biological agent to show significantly increased survival in patients with such heavily pretreated metastatic breast cancer," said Dr. Javier Cortes of Vall d’Hebron University Hospital and Institute of Oncology in Barcelona and colleagues (Lancet 2011 March 3 [doi: 10.1016/S0140-6736(11)60070-6]).

A non-taxane microtubule inhibitor, eribulin is a synthetic analogue of halichondrin B, a natural product isolated from a sea sponge. The U.S. Food & Drug Administration based its approval of eribulin for women who had received at least two prior treatments, including a taxane and an anthracycline, for metastatic breast cancer on results of the EMBRACE (Eisai Metastatic Breast Cancer Study Assessing Physician’s Choice vs. E7389) study. Findings were originally presented at the American Society of Clinical Oncology annual meeting in 2010.

The open-label study randomized 508 women to eribulin and 254 to a control group; 6 patients in each group discontinued before starting treatment, leaving 503 in the eribulin group and 247 in the control group. The women were aged 18 years and older, with confirmed breast cancer and a history of 2-5 previous chemotherapy regimens.

Patients in the eribulin group received 1.4 mg/m² eribulin mesylate intravenously for 2-5 minutes on days 1 and 8 of a 21-day cycle. The control group received the physician’s treatment of choice, which could be any single-agent chemotherapy, hormonal therapy, or biologic therapy approved for cancer, and administered according to the local practice.

The researchers assessed tumor response every 8 weeks. Treatment continued until disease progression, serious noncompliance with protocol, unacceptable toxicity, or a doctor’s or patient’s request to stop treatment. The patients had a median of four previous chemotherapy regimens, of which capecitabine was the most common (73%). A total of 16% had HER2-positive disease, and 19% had triple-negative breast cancer.

The most common overall adverse event was asthenia or fatigue of all grades, which occurred in 54% in the eribulin group and 40% of the control group. The most common hematologic adverse event was neutropenia of all grades in 52% of the eribulin group and 30% of the control group.

About a fourth of both groups experienced serious adverse events. Peripheral neuropathy was the most common cause for discontinuing eribulin, occurring in 5% of 503 patients.

The findings were limited by the range of the therapies in the control group and by the use of overall survival as a primary end point, the researchers noted. But the diversity of the control group might make the findings more generalizable to clinical practice, they added.

"The benefit that eribulin had shown as a single agent in this setting suggests that this drug could become a new standard of care; further evaluation earlier in the natural history of breast cancer is warranted," the researchers wrote.

In an accompanying editorial, Dr. Nancy U. Lin and Dr. Harold J. Burstein wrote that he results of the EMBRACE study raise many questions, including whether some patients or tumor subtypes would benefit from ongoing therapy (Lancet 2011 March 3 [doi: 10.1016/S0140-6736(11)60280-8]).

Dr. Lin and Dr. Burstein, both of Harvard Medical School and the Dana-Farber Cancer Institute, Boston, noted that the relatively modest clinical improvements suggest the need for more information on how the treatment affects symptom control and quality of life.

"In the meantime, EMBRACE provides much-needed, high-level evidence for chemotherapy use in patients with heavily pretreated breast cancer," they wrote. "And that evidence suggests that the methods to treat advanced breast cancer are growing," they wrote.

The study was funded by Eisai, maker of eribulin, and Eisai employees were involved in the study design, data collection, and data analysis. Dr. Cortes has received consultant fees from Eisai and Roche.

Dr. Lin and Dr. Burstein said they had no conflicts of interest.

Eribulin monotherapy achieved "a significant and clinically meaningful improvement" in overall survival, compared with other treatments of choice in women with heavily pretreated metastatic breast cancer, according to pivotal EMBRACE trial data published online by the Lancet on March 3.

Median overall survival rate reached 13.1 months in women treated with eribulin (Halaven), compared with 10.6 months in the control group (P = .041). Median progression-free survival was 3.7 months and 2.2 months, respectively (P = .137) based on an independent review of the intent-to-treat population. Fatal adverse events occurred in 4% of the eribulin patients vs. 7% of the control group.

"To our knowledge, EMBRACE is the first major single-agent study of a cytotoxic or biological agent to show significantly increased survival in patients with such heavily pretreated metastatic breast cancer," said Dr. Javier Cortes of Vall d’Hebron University Hospital and Institute of Oncology in Barcelona and colleagues (Lancet 2011 March 3 [doi: 10.1016/S0140-6736(11)60070-6]).

A non-taxane microtubule inhibitor, eribulin is a synthetic analogue of halichondrin B, a natural product isolated from a sea sponge. The U.S. Food & Drug Administration based its approval of eribulin for women who had received at least two prior treatments, including a taxane and an anthracycline, for metastatic breast cancer on results of the EMBRACE (Eisai Metastatic Breast Cancer Study Assessing Physician’s Choice vs. E7389) study. Findings were originally presented at the American Society of Clinical Oncology annual meeting in 2010.

The open-label study randomized 508 women to eribulin and 254 to a control group; 6 patients in each group discontinued before starting treatment, leaving 503 in the eribulin group and 247 in the control group. The women were aged 18 years and older, with confirmed breast cancer and a history of 2-5 previous chemotherapy regimens.

Patients in the eribulin group received 1.4 mg/m² eribulin mesylate intravenously for 2-5 minutes on days 1 and 8 of a 21-day cycle. The control group received the physician’s treatment of choice, which could be any single-agent chemotherapy, hormonal therapy, or biologic therapy approved for cancer, and administered according to the local practice.

The researchers assessed tumor response every 8 weeks. Treatment continued until disease progression, serious noncompliance with protocol, unacceptable toxicity, or a doctor’s or patient’s request to stop treatment. The patients had a median of four previous chemotherapy regimens, of which capecitabine was the most common (73%). A total of 16% had HER2-positive disease, and 19% had triple-negative breast cancer.

The most common overall adverse event was asthenia or fatigue of all grades, which occurred in 54% in the eribulin group and 40% of the control group. The most common hematologic adverse event was neutropenia of all grades in 52% of the eribulin group and 30% of the control group.

About a fourth of both groups experienced serious adverse events. Peripheral neuropathy was the most common cause for discontinuing eribulin, occurring in 5% of 503 patients.

The findings were limited by the range of the therapies in the control group and by the use of overall survival as a primary end point, the researchers noted. But the diversity of the control group might make the findings more generalizable to clinical practice, they added.

"The benefit that eribulin had shown as a single agent in this setting suggests that this drug could become a new standard of care; further evaluation earlier in the natural history of breast cancer is warranted," the researchers wrote.

In an accompanying editorial, Dr. Nancy U. Lin and Dr. Harold J. Burstein wrote that he results of the EMBRACE study raise many questions, including whether some patients or tumor subtypes would benefit from ongoing therapy (Lancet 2011 March 3 [doi: 10.1016/S0140-6736(11)60280-8]).

Dr. Lin and Dr. Burstein, both of Harvard Medical School and the Dana-Farber Cancer Institute, Boston, noted that the relatively modest clinical improvements suggest the need for more information on how the treatment affects symptom control and quality of life.

"In the meantime, EMBRACE provides much-needed, high-level evidence for chemotherapy use in patients with heavily pretreated breast cancer," they wrote. "And that evidence suggests that the methods to treat advanced breast cancer are growing," they wrote.

The study was funded by Eisai, maker of eribulin, and Eisai employees were involved in the study design, data collection, and data analysis. Dr. Cortes has received consultant fees from Eisai and Roche.

Dr. Lin and Dr. Burstein said they had no conflicts of interest.

Eribulin monotherapy achieved "a significant and clinically meaningful improvement" in overall survival, compared with other treatments of choice in women with heavily pretreated metastatic breast cancer, according to pivotal EMBRACE trial data published online by the Lancet on March 3.

Median overall survival rate reached 13.1 months in women treated with eribulin (Halaven), compared with 10.6 months in the control group (P = .041). Median progression-free survival was 3.7 months and 2.2 months, respectively (P = .137) based on an independent review of the intent-to-treat population. Fatal adverse events occurred in 4% of the eribulin patients vs. 7% of the control group.

"To our knowledge, EMBRACE is the first major single-agent study of a cytotoxic or biological agent to show significantly increased survival in patients with such heavily pretreated metastatic breast cancer," said Dr. Javier Cortes of Vall d’Hebron University Hospital and Institute of Oncology in Barcelona and colleagues (Lancet 2011 March 3 [doi: 10.1016/S0140-6736(11)60070-6]).

A non-taxane microtubule inhibitor, eribulin is a synthetic analogue of halichondrin B, a natural product isolated from a sea sponge. The U.S. Food & Drug Administration based its approval of eribulin for women who had received at least two prior treatments, including a taxane and an anthracycline, for metastatic breast cancer on results of the EMBRACE (Eisai Metastatic Breast Cancer Study Assessing Physician’s Choice vs. E7389) study. Findings were originally presented at the American Society of Clinical Oncology annual meeting in 2010.

The open-label study randomized 508 women to eribulin and 254 to a control group; 6 patients in each group discontinued before starting treatment, leaving 503 in the eribulin group and 247 in the control group. The women were aged 18 years and older, with confirmed breast cancer and a history of 2-5 previous chemotherapy regimens.

Patients in the eribulin group received 1.4 mg/m² eribulin mesylate intravenously for 2-5 minutes on days 1 and 8 of a 21-day cycle. The control group received the physician’s treatment of choice, which could be any single-agent chemotherapy, hormonal therapy, or biologic therapy approved for cancer, and administered according to the local practice.

The researchers assessed tumor response every 8 weeks. Treatment continued until disease progression, serious noncompliance with protocol, unacceptable toxicity, or a doctor’s or patient’s request to stop treatment. The patients had a median of four previous chemotherapy regimens, of which capecitabine was the most common (73%). A total of 16% had HER2-positive disease, and 19% had triple-negative breast cancer.

The most common overall adverse event was asthenia or fatigue of all grades, which occurred in 54% in the eribulin group and 40% of the control group. The most common hematologic adverse event was neutropenia of all grades in 52% of the eribulin group and 30% of the control group.

About a fourth of both groups experienced serious adverse events. Peripheral neuropathy was the most common cause for discontinuing eribulin, occurring in 5% of 503 patients.

The findings were limited by the range of the therapies in the control group and by the use of overall survival as a primary end point, the researchers noted. But the diversity of the control group might make the findings more generalizable to clinical practice, they added.

"The benefit that eribulin had shown as a single agent in this setting suggests that this drug could become a new standard of care; further evaluation earlier in the natural history of breast cancer is warranted," the researchers wrote.

In an accompanying editorial, Dr. Nancy U. Lin and Dr. Harold J. Burstein wrote that he results of the EMBRACE study raise many questions, including whether some patients or tumor subtypes would benefit from ongoing therapy (Lancet 2011 March 3 [doi: 10.1016/S0140-6736(11)60280-8]).

Dr. Lin and Dr. Burstein, both of Harvard Medical School and the Dana-Farber Cancer Institute, Boston, noted that the relatively modest clinical improvements suggest the need for more information on how the treatment affects symptom control and quality of life.

"In the meantime, EMBRACE provides much-needed, high-level evidence for chemotherapy use in patients with heavily pretreated breast cancer," they wrote. "And that evidence suggests that the methods to treat advanced breast cancer are growing," they wrote.

The study was funded by Eisai, maker of eribulin, and Eisai employees were involved in the study design, data collection, and data analysis. Dr. Cortes has received consultant fees from Eisai and Roche.

Dr. Lin and Dr. Burstein said they had no conflicts of interest.

Eribulin monotherapy achieved "a significant and clinically meaningful improvement" in overall survival, compared with other treatments of choice in women with heavily pretreated metastatic breast cancer, according to pivotal EMBRACE trial data published online by the Lancet on March 3.

Median overall survival rate reached 13.1 months in women treated with eribulin (Halaven), compared with 10.6 months in the control group (P = .041). Median progression-free survival was 3.7 months and 2.2 months, respectively (P = .137) based on an independent review of the intent-to-treat population. Fatal adverse events occurred in 4% of the eribulin patients vs. 7% of the control group.

"To our knowledge, EMBRACE is the first major single-agent study of a cytotoxic or biological agent to show significantly increased survival in patients with such heavily pretreated metastatic breast cancer," said Dr. Javier Cortes of Vall d’Hebron University Hospital and Institute of Oncology in Barcelona and colleagues (Lancet 2011 March 3 [doi: 10.1016/S0140-6736(11)60070-6]).

A non-taxane microtubule inhibitor, eribulin is a synthetic analogue of halichondrin B, a natural product isolated from a sea sponge. The U.S. Food & Drug Administration based its approval of eribulin for women who had received at least two prior treatments, including a taxane and an anthracycline, for metastatic breast cancer on results of the EMBRACE (Eisai Metastatic Breast Cancer Study Assessing Physician’s Choice vs. E7389) study. Findings were originally presented at the American Society of Clinical Oncology annual meeting in 2010.

The open-label study randomized 508 women to eribulin and 254 to a control group; 6 patients in each group discontinued before starting treatment, leaving 503 in the eribulin group and 247 in the control group. The women were aged 18 years and older, with confirmed breast cancer and a history of 2-5 previous chemotherapy regimens.

Patients in the eribulin group received 1.4 mg/m² eribulin mesylate intravenously for 2-5 minutes on days 1 and 8 of a 21-day cycle. The control group received the physician’s treatment of choice, which could be any single-agent chemotherapy, hormonal therapy, or biologic therapy approved for cancer, and administered according to the local practice.

The researchers assessed tumor response every 8 weeks. Treatment continued until disease progression, serious noncompliance with protocol, unacceptable toxicity, or a doctor’s or patient’s request to stop treatment. The patients had a median of four previous chemotherapy regimens, of which capecitabine was the most common (73%). A total of 16% had HER2-positive disease, and 19% had triple-negative breast cancer.

The most common overall adverse event was asthenia or fatigue of all grades, which occurred in 54% in the eribulin group and 40% of the control group. The most common hematologic adverse event was neutropenia of all grades in 52% of the eribulin group and 30% of the control group.

About a fourth of both groups experienced serious adverse events. Peripheral neuropathy was the most common cause for discontinuing eribulin, occurring in 5% of 503 patients.

The findings were limited by the range of the therapies in the control group and by the use of overall survival as a primary end point, the researchers noted. But the diversity of the control group might make the findings more generalizable to clinical practice, they added.

"The benefit that eribulin had shown as a single agent in this setting suggests that this drug could become a new standard of care; further evaluation earlier in the natural history of breast cancer is warranted," the researchers wrote.

In an accompanying editorial, Dr. Nancy U. Lin and Dr. Harold J. Burstein wrote that he results of the EMBRACE study raise many questions, including whether some patients or tumor subtypes would benefit from ongoing therapy (Lancet 2011 March 3 [doi: 10.1016/S0140-6736(11)60280-8]).

Dr. Lin and Dr. Burstein, both of Harvard Medical School and the Dana-Farber Cancer Institute, Boston, noted that the relatively modest clinical improvements suggest the need for more information on how the treatment affects symptom control and quality of life.

"In the meantime, EMBRACE provides much-needed, high-level evidence for chemotherapy use in patients with heavily pretreated breast cancer," they wrote. "And that evidence suggests that the methods to treat advanced breast cancer are growing," they wrote.

The study was funded by Eisai, maker of eribulin, and Eisai employees were involved in the study design, data collection, and data analysis. Dr. Cortes has received consultant fees from Eisai and Roche.

Dr. Lin and Dr. Burstein said they had no conflicts of interest.

Eribulin monotherapy achieved "a significant and clinically meaningful improvement" in overall survival, compared with other treatments of choice in women with heavily pretreated metastatic breast cancer, according to pivotal EMBRACE trial data published online by the Lancet on March 3.

Median overall survival rate reached 13.1 months in women treated with eribulin (Halaven), compared with 10.6 months in the control group (P = .041). Median progression-free survival was 3.7 months and 2.2 months, respectively (P = .137) based on an independent review of the intent-to-treat population. Fatal adverse events occurred in 4% of the eribulin patients vs. 7% of the control group.

"To our knowledge, EMBRACE is the first major single-agent study of a cytotoxic or biological agent to show significantly increased survival in patients with such heavily pretreated metastatic breast cancer," said Dr. Javier Cortes of Vall d’Hebron University Hospital and Institute of Oncology in Barcelona and colleagues (Lancet 2011 March 3 [doi: 10.1016/S0140-6736(11)60070-6]).

A non-taxane microtubule inhibitor, eribulin is a synthetic analogue of halichondrin B, a natural product isolated from a sea sponge. The U.S. Food & Drug Administration based its approval of eribulin for women who had received at least two prior treatments, including a taxane and an anthracycline, for metastatic breast cancer on results of the EMBRACE (Eisai Metastatic Breast Cancer Study Assessing Physician’s Choice vs. E7389) study. Findings were originally presented at the American Society of Clinical Oncology annual meeting in 2010.

The open-label study randomized 508 women to eribulin and 254 to a control group; 6 patients in each group discontinued before starting treatment, leaving 503 in the eribulin group and 247 in the control group. The women were aged 18 years and older, with confirmed breast cancer and a history of 2-5 previous chemotherapy regimens.

Patients in the eribulin group received 1.4 mg/m² eribulin mesylate intravenously for 2-5 minutes on days 1 and 8 of a 21-day cycle. The control group received the physician’s treatment of choice, which could be any single-agent chemotherapy, hormonal therapy, or biologic therapy approved for cancer, and administered according to the local practice.

The researchers assessed tumor response every 8 weeks. Treatment continued until disease progression, serious noncompliance with protocol, unacceptable toxicity, or a doctor’s or patient’s request to stop treatment. The patients had a median of four previous chemotherapy regimens, of which capecitabine was the most common (73%). A total of 16% had HER2-positive disease, and 19% had triple-negative breast cancer.

The most common overall adverse event was asthenia or fatigue of all grades, which occurred in 54% in the eribulin group and 40% of the control group. The most common hematologic adverse event was neutropenia of all grades in 52% of the eribulin group and 30% of the control group.

About a fourth of both groups experienced serious adverse events. Peripheral neuropathy was the most common cause for discontinuing eribulin, occurring in 5% of 503 patients.

The findings were limited by the range of the therapies in the control group and by the use of overall survival as a primary end point, the researchers noted. But the diversity of the control group might make the findings more generalizable to clinical practice, they added.

"The benefit that eribulin had shown as a single agent in this setting suggests that this drug could become a new standard of care; further evaluation earlier in the natural history of breast cancer is warranted," the researchers wrote.

In an accompanying editorial, Dr. Nancy U. Lin and Dr. Harold J. Burstein wrote that he results of the EMBRACE study raise many questions, including whether some patients or tumor subtypes would benefit from ongoing therapy (Lancet 2011 March 3 [doi: 10.1016/S0140-6736(11)60280-8]).

Dr. Lin and Dr. Burstein, both of Harvard Medical School and the Dana-Farber Cancer Institute, Boston, noted that the relatively modest clinical improvements suggest the need for more information on how the treatment affects symptom control and quality of life.

"In the meantime, EMBRACE provides much-needed, high-level evidence for chemotherapy use in patients with heavily pretreated breast cancer," they wrote. "And that evidence suggests that the methods to treat advanced breast cancer are growing," they wrote.

The study was funded by Eisai, maker of eribulin, and Eisai employees were involved in the study design, data collection, and data analysis. Dr. Cortes has received consultant fees from Eisai and Roche.

Dr. Lin and Dr. Burstein said they had no conflicts of interest.

Eribulin monotherapy achieved "a significant and clinically meaningful improvement" in overall survival, compared with other treatments of choice in women with heavily pretreated metastatic breast cancer, according to pivotal EMBRACE trial data published online by the Lancet on March 3.

Median overall survival rate reached 13.1 months in women treated with eribulin (Halaven), compared with 10.6 months in the control group (P = .041). Median progression-free survival was 3.7 months and 2.2 months, respectively (P = .137) based on an independent review of the intent-to-treat population. Fatal adverse events occurred in 4% of the eribulin patients vs. 7% of the control group.

"To our knowledge, EMBRACE is the first major single-agent study of a cytotoxic or biological agent to show significantly increased survival in patients with such heavily pretreated metastatic breast cancer," said Dr. Javier Cortes of Vall d’Hebron University Hospital and Institute of Oncology in Barcelona and colleagues (Lancet 2011 March 3 [doi: 10.1016/S0140-6736(11)60070-6]).

A non-taxane microtubule inhibitor, eribulin is a synthetic analogue of halichondrin B, a natural product isolated from a sea sponge. The U.S. Food & Drug Administration based its approval of eribulin for women who had received at least two prior treatments, including a taxane and an anthracycline, for metastatic breast cancer on results of the EMBRACE (Eisai Metastatic Breast Cancer Study Assessing Physician’s Choice vs. E7389) study. Findings were originally presented at the American Society of Clinical Oncology annual meeting in 2010.

The open-label study randomized 508 women to eribulin and 254 to a control group; 6 patients in each group discontinued before starting treatment, leaving 503 in the eribulin group and 247 in the control group. The women were aged 18 years and older, with confirmed breast cancer and a history of 2-5 previous chemotherapy regimens.

Patients in the eribulin group received 1.4 mg/m² eribulin mesylate intravenously for 2-5 minutes on days 1 and 8 of a 21-day cycle. The control group received the physician’s treatment of choice, which could be any single-agent chemotherapy, hormonal therapy, or biologic therapy approved for cancer, and administered according to the local practice.

The researchers assessed tumor response every 8 weeks. Treatment continued until disease progression, serious noncompliance with protocol, unacceptable toxicity, or a doctor’s or patient’s request to stop treatment. The patients had a median of four previous chemotherapy regimens, of which capecitabine was the most common (73%). A total of 16% had HER2-positive disease, and 19% had triple-negative breast cancer.

The most common overall adverse event was asthenia or fatigue of all grades, which occurred in 54% in the eribulin group and 40% of the control group. The most common hematologic adverse event was neutropenia of all grades in 52% of the eribulin group and 30% of the control group.

About a fourth of both groups experienced serious adverse events. Peripheral neuropathy was the most common cause for discontinuing eribulin, occurring in 5% of 503 patients.

The findings were limited by the range of the therapies in the control group and by the use of overall survival as a primary end point, the researchers noted. But the diversity of the control group might make the findings more generalizable to clinical practice, they added.

"The benefit that eribulin had shown as a single agent in this setting suggests that this drug could become a new standard of care; further evaluation earlier in the natural history of breast cancer is warranted," the researchers wrote.

In an accompanying editorial, Dr. Nancy U. Lin and Dr. Harold J. Burstein wrote that he results of the EMBRACE study raise many questions, including whether some patients or tumor subtypes would benefit from ongoing therapy (Lancet 2011 March 3 [doi: 10.1016/S0140-6736(11)60280-8]).

Dr. Lin and Dr. Burstein, both of Harvard Medical School and the Dana-Farber Cancer Institute, Boston, noted that the relatively modest clinical improvements suggest the need for more information on how the treatment affects symptom control and quality of life.

"In the meantime, EMBRACE provides much-needed, high-level evidence for chemotherapy use in patients with heavily pretreated breast cancer," they wrote. "And that evidence suggests that the methods to treat advanced breast cancer are growing," they wrote.

The study was funded by Eisai, maker of eribulin, and Eisai employees were involved in the study design, data collection, and data analysis. Dr. Cortes has received consultant fees from Eisai and Roche.

Dr. Lin and Dr. Burstein said they had no conflicts of interest.

Women are underrepresented in safety and efficacy studies for high-risk cardiovascular devices, based on a review of 123 studies for 78 devices. The results were published online March 1 in Circulation: Cardiovascular Quality and Outcomes.

"There have been no analyses of gender bias in studies submitted for [Food and Drug Administration] approval of medical devices," despite a 1994 requirement to do so, said Dr. Sanket S. Dhruva of the University of California, San Francisco, and colleagues.

The researchers reviewed data involving high-risk cardiovascular devices that received premarket approval from the FDA from 2000 through 2007.

Overall, 34 studies (28%) did not report the sex of the study participants, and 67% of the participants in the studies that reported gender were male. The number of women enrolled in the studies remained stable over the 8-year study period, the researchers noted (Circ. Cardiovasc. Qual. Outcomes 2011;4:165-71.

Of the 123 studies, 107 were reviewed for gender bias comments or analysis. One study that included such a comment and 15 studies that did not include gender bias comments were excluded because they had fewer than 50 patients.

The FDA requires gender bias comments and analyses for all studies, but only 50 (41%) of the studies in this review included a gender bias comment or analysis. Of these, 47 (94%) included analysis of the findings by gender, and 12 (26%) of these described any gender-based difference in device safety or efficacy.

Of the 57 studies without a gender bias comment, 6 (11%) reported sex-specific data or analysis.

In 36 (29%) of the studies, the researchers wrote that the gender distribution in the study reflected the disease distribution or the referral population for the device.

In addition, 22 of 123 studies (18%) included a statement citing a random selection of men vs. women or that no gender selection bias occurred.

In 80 studies, the total number of patients and the percentage of men were identified, and the researchers found discrepancies in 38 (48%) of these. Most (84%) of the discrepancies were due to larger numbers of men included in the study than the percentage suggested.

Few studies provided raw data or statistical analyses in the FDA Summaries of Safety and Effectiveness Data (SSEDs), the researchers noted.

The study findings were limited by the inclusion of only publicly available SSEDs and meeting materials from the Circulatory System Devices Panel. However, the FDA held workshops in 2008 on "the study and analysis of sex/gender differences in cardiovascular medical device trials reviewed by the FDA," which suggests efforts to enroll more women in cardiovascular device studies and to report gender-specific data, the researchers noted.

Dr. Dhruva had no financial conflicts to disclose.

Women are underrepresented in safety and efficacy studies for high-risk cardiovascular devices, based on a review of 123 studies for 78 devices. The results were published online March 1 in Circulation: Cardiovascular Quality and Outcomes.

"There have been no analyses of gender bias in studies submitted for [Food and Drug Administration] approval of medical devices," despite a 1994 requirement to do so, said Dr. Sanket S. Dhruva of the University of California, San Francisco, and colleagues.

The researchers reviewed data involving high-risk cardiovascular devices that received premarket approval from the FDA from 2000 through 2007.

Overall, 34 studies (28%) did not report the sex of the study participants, and 67% of the participants in the studies that reported gender were male. The number of women enrolled in the studies remained stable over the 8-year study period, the researchers noted (Circ. Cardiovasc. Qual. Outcomes 2011;4:165-71.

Of the 123 studies, 107 were reviewed for gender bias comments or analysis. One study that included such a comment and 15 studies that did not include gender bias comments were excluded because they had fewer than 50 patients.

The FDA requires gender bias comments and analyses for all studies, but only 50 (41%) of the studies in this review included a gender bias comment or analysis. Of these, 47 (94%) included analysis of the findings by gender, and 12 (26%) of these described any gender-based difference in device safety or efficacy.

Of the 57 studies without a gender bias comment, 6 (11%) reported sex-specific data or analysis.

In 36 (29%) of the studies, the researchers wrote that the gender distribution in the study reflected the disease distribution or the referral population for the device.

In addition, 22 of 123 studies (18%) included a statement citing a random selection of men vs. women or that no gender selection bias occurred.

In 80 studies, the total number of patients and the percentage of men were identified, and the researchers found discrepancies in 38 (48%) of these. Most (84%) of the discrepancies were due to larger numbers of men included in the study than the percentage suggested.

Few studies provided raw data or statistical analyses in the FDA Summaries of Safety and Effectiveness Data (SSEDs), the researchers noted.

The study findings were limited by the inclusion of only publicly available SSEDs and meeting materials from the Circulatory System Devices Panel. However, the FDA held workshops in 2008 on "the study and analysis of sex/gender differences in cardiovascular medical device trials reviewed by the FDA," which suggests efforts to enroll more women in cardiovascular device studies and to report gender-specific data, the researchers noted.

Dr. Dhruva had no financial conflicts to disclose.

Women are underrepresented in safety and efficacy studies for high-risk cardiovascular devices, based on a review of 123 studies for 78 devices. The results were published online March 1 in Circulation: Cardiovascular Quality and Outcomes.

"There have been no analyses of gender bias in studies submitted for [Food and Drug Administration] approval of medical devices," despite a 1994 requirement to do so, said Dr. Sanket S. Dhruva of the University of California, San Francisco, and colleagues.

The researchers reviewed data involving high-risk cardiovascular devices that received premarket approval from the FDA from 2000 through 2007.

Overall, 34 studies (28%) did not report the sex of the study participants, and 67% of the participants in the studies that reported gender were male. The number of women enrolled in the studies remained stable over the 8-year study period, the researchers noted (Circ. Cardiovasc. Qual. Outcomes 2011;4:165-71.

Of the 123 studies, 107 were reviewed for gender bias comments or analysis. One study that included such a comment and 15 studies that did not include gender bias comments were excluded because they had fewer than 50 patients.

The FDA requires gender bias comments and analyses for all studies, but only 50 (41%) of the studies in this review included a gender bias comment or analysis. Of these, 47 (94%) included analysis of the findings by gender, and 12 (26%) of these described any gender-based difference in device safety or efficacy.

Of the 57 studies without a gender bias comment, 6 (11%) reported sex-specific data or analysis.

In 36 (29%) of the studies, the researchers wrote that the gender distribution in the study reflected the disease distribution or the referral population for the device.

In addition, 22 of 123 studies (18%) included a statement citing a random selection of men vs. women or that no gender selection bias occurred.

In 80 studies, the total number of patients and the percentage of men were identified, and the researchers found discrepancies in 38 (48%) of these. Most (84%) of the discrepancies were due to larger numbers of men included in the study than the percentage suggested.

Few studies provided raw data or statistical analyses in the FDA Summaries of Safety and Effectiveness Data (SSEDs), the researchers noted.

The study findings were limited by the inclusion of only publicly available SSEDs and meeting materials from the Circulatory System Devices Panel. However, the FDA held workshops in 2008 on "the study and analysis of sex/gender differences in cardiovascular medical device trials reviewed by the FDA," which suggests efforts to enroll more women in cardiovascular device studies and to report gender-specific data, the researchers noted.

Dr. Dhruva had no financial conflicts to disclose.

Women are underrepresented in safety and efficacy studies for high-risk cardiovascular devices, based on a review of 123 studies for 78 devices. The results were published online March 1 in Circulation: Cardiovascular Quality and Outcomes.

"There have been no analyses of gender bias in studies submitted for [Food and Drug Administration] approval of medical devices," despite a 1994 requirement to do so, said Dr. Sanket S. Dhruva of the University of California, San Francisco, and colleagues.

The researchers reviewed data involving high-risk cardiovascular devices that received premarket approval from the FDA from 2000 through 2007.

Overall, 34 studies (28%) did not report the sex of the study participants, and 67% of the participants in the studies that reported gender were male. The number of women enrolled in the studies remained stable over the 8-year study period, the researchers noted (Circ. Cardiovasc. Qual. Outcomes 2011;4:165-71.

Of the 123 studies, 107 were reviewed for gender bias comments or analysis. One study that included such a comment and 15 studies that did not include gender bias comments were excluded because they had fewer than 50 patients.

The FDA requires gender bias comments and analyses for all studies, but only 50 (41%) of the studies in this review included a gender bias comment or analysis. Of these, 47 (94%) included analysis of the findings by gender, and 12 (26%) of these described any gender-based difference in device safety or efficacy.

Of the 57 studies without a gender bias comment, 6 (11%) reported sex-specific data or analysis.

In 36 (29%) of the studies, the researchers wrote that the gender distribution in the study reflected the disease distribution or the referral population for the device.

In addition, 22 of 123 studies (18%) included a statement citing a random selection of men vs. women or that no gender selection bias occurred.

In 80 studies, the total number of patients and the percentage of men were identified, and the researchers found discrepancies in 38 (48%) of these. Most (84%) of the discrepancies were due to larger numbers of men included in the study than the percentage suggested.

Few studies provided raw data or statistical analyses in the FDA Summaries of Safety and Effectiveness Data (SSEDs), the researchers noted.

The study findings were limited by the inclusion of only publicly available SSEDs and meeting materials from the Circulatory System Devices Panel. However, the FDA held workshops in 2008 on "the study and analysis of sex/gender differences in cardiovascular medical device trials reviewed by the FDA," which suggests efforts to enroll more women in cardiovascular device studies and to report gender-specific data, the researchers noted.

Dr. Dhruva had no financial conflicts to disclose.

Women are underrepresented in safety and efficacy studies for high-risk cardiovascular devices, based on a review of 123 studies for 78 devices. The results were published online March 1 in Circulation: Cardiovascular Quality and Outcomes.

"There have been no analyses of gender bias in studies submitted for [Food and Drug Administration] approval of medical devices," despite a 1994 requirement to do so, said Dr. Sanket S. Dhruva of the University of California, San Francisco, and colleagues.

The researchers reviewed data involving high-risk cardiovascular devices that received premarket approval from the FDA from 2000 through 2007.

Overall, 34 studies (28%) did not report the sex of the study participants, and 67% of the participants in the studies that reported gender were male. The number of women enrolled in the studies remained stable over the 8-year study period, the researchers noted (Circ. Cardiovasc. Qual. Outcomes 2011;4:165-71.

Of the 123 studies, 107 were reviewed for gender bias comments or analysis. One study that included such a comment and 15 studies that did not include gender bias comments were excluded because they had fewer than 50 patients.

The FDA requires gender bias comments and analyses for all studies, but only 50 (41%) of the studies in this review included a gender bias comment or analysis. Of these, 47 (94%) included analysis of the findings by gender, and 12 (26%) of these described any gender-based difference in device safety or efficacy.

Of the 57 studies without a gender bias comment, 6 (11%) reported sex-specific data or analysis.

In 36 (29%) of the studies, the researchers wrote that the gender distribution in the study reflected the disease distribution or the referral population for the device.

In addition, 22 of 123 studies (18%) included a statement citing a random selection of men vs. women or that no gender selection bias occurred.

In 80 studies, the total number of patients and the percentage of men were identified, and the researchers found discrepancies in 38 (48%) of these. Most (84%) of the discrepancies were due to larger numbers of men included in the study than the percentage suggested.

Few studies provided raw data or statistical analyses in the FDA Summaries of Safety and Effectiveness Data (SSEDs), the researchers noted.

The study findings were limited by the inclusion of only publicly available SSEDs and meeting materials from the Circulatory System Devices Panel. However, the FDA held workshops in 2008 on "the study and analysis of sex/gender differences in cardiovascular medical device trials reviewed by the FDA," which suggests efforts to enroll more women in cardiovascular device studies and to report gender-specific data, the researchers noted.

Dr. Dhruva had no financial conflicts to disclose.

Women are underrepresented in safety and efficacy studies for high-risk cardiovascular devices, based on a review of 123 studies for 78 devices. The results were published online March 1 in Circulation: Cardiovascular Quality and Outcomes.

"There have been no analyses of gender bias in studies submitted for [Food and Drug Administration] approval of medical devices," despite a 1994 requirement to do so, said Dr. Sanket S. Dhruva of the University of California, San Francisco, and colleagues.

The researchers reviewed data involving high-risk cardiovascular devices that received premarket approval from the FDA from 2000 through 2007.

Overall, 34 studies (28%) did not report the sex of the study participants, and 67% of the participants in the studies that reported gender were male. The number of women enrolled in the studies remained stable over the 8-year study period, the researchers noted (Circ. Cardiovasc. Qual. Outcomes 2011;4:165-71.

Of the 123 studies, 107 were reviewed for gender bias comments or analysis. One study that included such a comment and 15 studies that did not include gender bias comments were excluded because they had fewer than 50 patients.

The FDA requires gender bias comments and analyses for all studies, but only 50 (41%) of the studies in this review included a gender bias comment or analysis. Of these, 47 (94%) included analysis of the findings by gender, and 12 (26%) of these described any gender-based difference in device safety or efficacy.

Of the 57 studies without a gender bias comment, 6 (11%) reported sex-specific data or analysis.

In 36 (29%) of the studies, the researchers wrote that the gender distribution in the study reflected the disease distribution or the referral population for the device.

In addition, 22 of 123 studies (18%) included a statement citing a random selection of men vs. women or that no gender selection bias occurred.

In 80 studies, the total number of patients and the percentage of men were identified, and the researchers found discrepancies in 38 (48%) of these. Most (84%) of the discrepancies were due to larger numbers of men included in the study than the percentage suggested.

Few studies provided raw data or statistical analyses in the FDA Summaries of Safety and Effectiveness Data (SSEDs), the researchers noted.

The study findings were limited by the inclusion of only publicly available SSEDs and meeting materials from the Circulatory System Devices Panel. However, the FDA held workshops in 2008 on "the study and analysis of sex/gender differences in cardiovascular medical device trials reviewed by the FDA," which suggests efforts to enroll more women in cardiovascular device studies and to report gender-specific data, the researchers noted.

Dr. Dhruva had no financial conflicts to disclose.

Women are underrepresented in safety and efficacy studies for high-risk cardiovascular devices, based on a review of 123 studies for 78 devices. The results were published online March 1 in Circulation: Cardiovascular Quality and Outcomes.

"There have been no analyses of gender bias in studies submitted for [Food and Drug Administration] approval of medical devices," despite a 1994 requirement to do so, said Dr. Sanket S. Dhruva of the University of California, San Francisco, and colleagues.

The researchers reviewed data involving high-risk cardiovascular devices that received premarket approval from the FDA from 2000 through 2007.

Overall, 34 studies (28%) did not report the sex of the study participants, and 67% of the participants in the studies that reported gender were male. The number of women enrolled in the studies remained stable over the 8-year study period, the researchers noted (Circ. Cardiovasc. Qual. Outcomes 2011;4:165-71.

Of the 123 studies, 107 were reviewed for gender bias comments or analysis. One study that included such a comment and 15 studies that did not include gender bias comments were excluded because they had fewer than 50 patients.

The FDA requires gender bias comments and analyses for all studies, but only 50 (41%) of the studies in this review included a gender bias comment or analysis. Of these, 47 (94%) included analysis of the findings by gender, and 12 (26%) of these described any gender-based difference in device safety or efficacy.

Of the 57 studies without a gender bias comment, 6 (11%) reported sex-specific data or analysis.

In 36 (29%) of the studies, the researchers wrote that the gender distribution in the study reflected the disease distribution or the referral population for the device.

In addition, 22 of 123 studies (18%) included a statement citing a random selection of men vs. women or that no gender selection bias occurred.

In 80 studies, the total number of patients and the percentage of men were identified, and the researchers found discrepancies in 38 (48%) of these. Most (84%) of the discrepancies were due to larger numbers of men included in the study than the percentage suggested.

Few studies provided raw data or statistical analyses in the FDA Summaries of Safety and Effectiveness Data (SSEDs), the researchers noted.

The study findings were limited by the inclusion of only publicly available SSEDs and meeting materials from the Circulatory System Devices Panel. However, the FDA held workshops in 2008 on "the study and analysis of sex/gender differences in cardiovascular medical device trials reviewed by the FDA," which suggests efforts to enroll more women in cardiovascular device studies and to report gender-specific data, the researchers noted.

Dr. Dhruva had no financial conflicts to disclose.

Women are underrepresented in safety and efficacy studies for high-risk cardiovascular devices, based on a review of 123 studies for 78 devices. The results were published online March 1 in Circulation: Cardiovascular Quality and Outcomes.

"There have been no analyses of gender bias in studies submitted for [Food and Drug Administration] approval of medical devices," despite a 1994 requirement to do so, said Dr. Sanket S. Dhruva of the University of California, San Francisco, and colleagues.

The researchers reviewed data involving high-risk cardiovascular devices that received premarket approval from the FDA from 2000 through 2007.

Overall, 34 studies (28%) did not report the sex of the study participants, and 67% of the participants in the studies that reported gender were male. The number of women enrolled in the studies remained stable over the 8-year study period, the researchers noted (Circ. Cardiovasc. Qual. Outcomes 2011;4:165-71.

Of the 123 studies, 107 were reviewed for gender bias comments or analysis. One study that included such a comment and 15 studies that did not include gender bias comments were excluded because they had fewer than 50 patients.

The FDA requires gender bias comments and analyses for all studies, but only 50 (41%) of the studies in this review included a gender bias comment or analysis. Of these, 47 (94%) included analysis of the findings by gender, and 12 (26%) of these described any gender-based difference in device safety or efficacy.

Of the 57 studies without a gender bias comment, 6 (11%) reported sex-specific data or analysis.

In 36 (29%) of the studies, the researchers wrote that the gender distribution in the study reflected the disease distribution or the referral population for the device.

In addition, 22 of 123 studies (18%) included a statement citing a random selection of men vs. women or that no gender selection bias occurred.

In 80 studies, the total number of patients and the percentage of men were identified, and the researchers found discrepancies in 38 (48%) of these. Most (84%) of the discrepancies were due to larger numbers of men included in the study than the percentage suggested.

Few studies provided raw data or statistical analyses in the FDA Summaries of Safety and Effectiveness Data (SSEDs), the researchers noted.

The study findings were limited by the inclusion of only publicly available SSEDs and meeting materials from the Circulatory System Devices Panel. However, the FDA held workshops in 2008 on "the study and analysis of sex/gender differences in cardiovascular medical device trials reviewed by the FDA," which suggests efforts to enroll more women in cardiovascular device studies and to report gender-specific data, the researchers noted.

Dr. Dhruva had no financial conflicts to disclose.

Women are underrepresented in safety and efficacy studies for high-risk cardiovascular devices, based on a review of 123 studies for 78 devices. The results were published online March 1 in Circulation: Cardiovascular Quality and Outcomes.

"There have been no analyses of gender bias in studies submitted for [Food and Drug Administration] approval of medical devices," despite a 1994 requirement to do so, said Dr. Sanket S. Dhruva of the University of California, San Francisco, and colleagues.

The researchers reviewed data involving high-risk cardiovascular devices that received premarket approval from the FDA from 2000 through 2007.

Overall, 34 studies (28%) did not report the sex of the study participants, and 67% of the participants in the studies that reported gender were male. The number of women enrolled in the studies remained stable over the 8-year study period, the researchers noted (Circ. Cardiovasc. Qual. Outcomes 2011;4:165-71.

Of the 123 studies, 107 were reviewed for gender bias comments or analysis. One study that included such a comment and 15 studies that did not include gender bias comments were excluded because they had fewer than 50 patients.

The FDA requires gender bias comments and analyses for all studies, but only 50 (41%) of the studies in this review included a gender bias comment or analysis. Of these, 47 (94%) included analysis of the findings by gender, and 12 (26%) of these described any gender-based difference in device safety or efficacy.

Of the 57 studies without a gender bias comment, 6 (11%) reported sex-specific data or analysis.

In 36 (29%) of the studies, the researchers wrote that the gender distribution in the study reflected the disease distribution or the referral population for the device.

In addition, 22 of 123 studies (18%) included a statement citing a random selection of men vs. women or that no gender selection bias occurred.

In 80 studies, the total number of patients and the percentage of men were identified, and the researchers found discrepancies in 38 (48%) of these. Most (84%) of the discrepancies were due to larger numbers of men included in the study than the percentage suggested.

Few studies provided raw data or statistical analyses in the FDA Summaries of Safety and Effectiveness Data (SSEDs), the researchers noted.

The study findings were limited by the inclusion of only publicly available SSEDs and meeting materials from the Circulatory System Devices Panel. However, the FDA held workshops in 2008 on "the study and analysis of sex/gender differences in cardiovascular medical device trials reviewed by the FDA," which suggests efforts to enroll more women in cardiovascular device studies and to report gender-specific data, the researchers noted.

Dr. Dhruva had no financial conflicts to disclose.

Approximately 68 million American adults have high blood pressure and 71 million have high cholesterol, and the conditions are uncontrolled in 37 million and 48 million, respectively, according to a Vital Signs report released by the Centers for Disease Control and Prevention.

“Heart disease is the leading killer in America, and the bottom line is that high blood pressure and high cholesterol are out of control for most Americans who have these conditions,” CDC Director Thomas R. Frieden said in a teleconference accompanying the report's release.

High blood pressure and high cholesterol remain top risk factors for life-threatening conditions such as strokes, heart attacks, and vascular diseases, he added.

Controlling high blood pressure and cholesterol is one of the most important things you can do for your patients, Dr. Frieden said. Know how many of your patients have high blood pressure and high cholesterol, what proportion are controlled, and what can be done to help more patients get these conditions under control, he added.

“We have seen many examples of health systems, health programs, and doctors' offices using information technology to support patients and drastically improve the levels of control, and that's something that is needed throughout health care in this country,” Dr. Frieden said.

The report was based on data from the National Health and Nutrition Examination Survey (NHANES) on adults aged 18 years and older. The findings also indicate that about 20 million U.S. adults with high blood pressure and 37 million with high cholesterol are not being treated for these conditions.

The prevalence of control of high blood pressure was 29% among adults without health insurance, and the control of high cholesterol was less than 15% among those with limited access to health care. But at least 80% of individuals with uncontrolled high blood pressure and high cholesterol have health insurance, Dr. Frieden noted.

For those with health insurance, the characteristics of their specific plans are more likely to affect whether they have high blood pressure or high cholesterol under control than are their personal characteristics, he said.

High blood pressure was defined as BP greater than 140/90 mm Hg or reported use of blood pressure–lowering medication. The national prevalence of high blood pressure remained stable over the past decade, altho ugh 70% of those with hypertension were being treated and 46% were being controlled, according to the report.

The criteria for high cholesterol included the use of cholesterol medication or having an LDL cholesterol level of 100 mg/dL or higher for high-risk individuals, 130 mg/dL or higher for intermediate-risk individuals, and 160 mg/dL for those at low risk.

The proportion of adults treated for high cholesterol increased from 28% to 48% over the past decade, and the proportion of those controlling their high cholesterol increased from less than 20% to more than 30%.

The findings were limited by the lack of data on individuals in nursing homes and institutions not included in NHANES databases, the CDC researchers noted.

About 100,000 deaths [in the U.S.] are preventable by simple, low-cost improvements in our ability to control high blood pressure and high cholesterol, said Dr. Frieden. “Better control can save lives and save money.”

The report is online at www.cdc.gov/vitalsigns

Approximately 68 million American adults have high blood pressure and 71 million have high cholesterol, and the conditions are uncontrolled in 37 million and 48 million, respectively, according to a Vital Signs report released by the Centers for Disease Control and Prevention.

“Heart disease is the leading killer in America, and the bottom line is that high blood pressure and high cholesterol are out of control for most Americans who have these conditions,” CDC Director Thomas R. Frieden said in a teleconference accompanying the report's release.

High blood pressure and high cholesterol remain top risk factors for life-threatening conditions such as strokes, heart attacks, and vascular diseases, he added.

Controlling high blood pressure and cholesterol is one of the most important things you can do for your patients, Dr. Frieden said. Know how many of your patients have high blood pressure and high cholesterol, what proportion are controlled, and what can be done to help more patients get these conditions under control, he added.

“We have seen many examples of health systems, health programs, and doctors' offices using information technology to support patients and drastically improve the levels of control, and that's something that is needed throughout health care in this country,” Dr. Frieden said.

The report was based on data from the National Health and Nutrition Examination Survey (NHANES) on adults aged 18 years and older. The findings also indicate that about 20 million U.S. adults with high blood pressure and 37 million with high cholesterol are not being treated for these conditions.

The prevalence of control of high blood pressure was 29% among adults without health insurance, and the control of high cholesterol was less than 15% among those with limited access to health care. But at least 80% of individuals with uncontrolled high blood pressure and high cholesterol have health insurance, Dr. Frieden noted.

For those with health insurance, the characteristics of their specific plans are more likely to affect whether they have high blood pressure or high cholesterol under control than are their personal characteristics, he said.

High blood pressure was defined as BP greater than 140/90 mm Hg or reported use of blood pressure–lowering medication. The national prevalence of high blood pressure remained stable over the past decade, altho ugh 70% of those with hypertension were being treated and 46% were being controlled, according to the report.

The criteria for high cholesterol included the use of cholesterol medication or having an LDL cholesterol level of 100 mg/dL or higher for high-risk individuals, 130 mg/dL or higher for intermediate-risk individuals, and 160 mg/dL for those at low risk.

The proportion of adults treated for high cholesterol increased from 28% to 48% over the past decade, and the proportion of those controlling their high cholesterol increased from less than 20% to more than 30%.

The findings were limited by the lack of data on individuals in nursing homes and institutions not included in NHANES databases, the CDC researchers noted.

About 100,000 deaths [in the U.S.] are preventable by simple, low-cost improvements in our ability to control high blood pressure and high cholesterol, said Dr. Frieden. “Better control can save lives and save money.”

The report is online at www.cdc.gov/vitalsigns

Approximately 68 million American adults have high blood pressure and 71 million have high cholesterol, and the conditions are uncontrolled in 37 million and 48 million, respectively, according to a Vital Signs report released by the Centers for Disease Control and Prevention.

“Heart disease is the leading killer in America, and the bottom line is that high blood pressure and high cholesterol are out of control for most Americans who have these conditions,” CDC Director Thomas R. Frieden said in a teleconference accompanying the report's release.

High blood pressure and high cholesterol remain top risk factors for life-threatening conditions such as strokes, heart attacks, and vascular diseases, he added.

Controlling high blood pressure and cholesterol is one of the most important things you can do for your patients, Dr. Frieden said. Know how many of your patients have high blood pressure and high cholesterol, what proportion are controlled, and what can be done to help more patients get these conditions under control, he added.

“We have seen many examples of health systems, health programs, and doctors' offices using information technology to support patients and drastically improve the levels of control, and that's something that is needed throughout health care in this country,” Dr. Frieden said.

The report was based on data from the National Health and Nutrition Examination Survey (NHANES) on adults aged 18 years and older. The findings also indicate that about 20 million U.S. adults with high blood pressure and 37 million with high cholesterol are not being treated for these conditions.

The prevalence of control of high blood pressure was 29% among adults without health insurance, and the control of high cholesterol was less than 15% among those with limited access to health care. But at least 80% of individuals with uncontrolled high blood pressure and high cholesterol have health insurance, Dr. Frieden noted.

For those with health insurance, the characteristics of their specific plans are more likely to affect whether they have high blood pressure or high cholesterol under control than are their personal characteristics, he said.

High blood pressure was defined as BP greater than 140/90 mm Hg or reported use of blood pressure–lowering medication. The national prevalence of high blood pressure remained stable over the past decade, altho ugh 70% of those with hypertension were being treated and 46% were being controlled, according to the report.

The criteria for high cholesterol included the use of cholesterol medication or having an LDL cholesterol level of 100 mg/dL or higher for high-risk individuals, 130 mg/dL or higher for intermediate-risk individuals, and 160 mg/dL for those at low risk.

The proportion of adults treated for high cholesterol increased from 28% to 48% over the past decade, and the proportion of those controlling their high cholesterol increased from less than 20% to more than 30%.

The findings were limited by the lack of data on individuals in nursing homes and institutions not included in NHANES databases, the CDC researchers noted.

About 100,000 deaths [in the U.S.] are preventable by simple, low-cost improvements in our ability to control high blood pressure and high cholesterol, said Dr. Frieden. “Better control can save lives and save money.”

The report is online at www.cdc.gov/vitalsigns

Major Finding: Overall, the contingent screening test showed a cost-effectiveness ratio of $26,833 Canadian dollars per case of DS. The next most cost-effective test was the serum integrated screening test, but the incremental cost-effectiveness ratio (ICER) between the serum integrated screening and contingent screening tests was $3,815 Canadian dollars for every DS birth detected.

Data Source: A cost-effective study of Down syndrome screening tests based on a computer model including 110,948 pregnancies.

Disclosures: The journal did not provide any disclosure information.

Contingent screening for prenatal Down syndrome was the most cost-effective stratagem, compared with other screening protocols, based on data from a computer simulation study of 110,948 pregnancies.

Several screening options are available in Canada and the United States, but data to help clinicians choose among the tests are limited, wrote Dr. Jean Gekas of the Centre Hospitalier de l'Université Laval in Quebec City, and colleagues.

The researchers used a computer model to analyze a virtual population of 110,948 pregnant women based on the demographic, genetic, and Down syndrome (DS) phenotype characteristics of the local population in Quebec. The tests included were the combined test, triple test, quadruple test, integrated test, serum integrated test, sequential screening test, contingent screening test, and amniocentesis for women aged 35 years and older (Am. J. Obstet. Gynecol. 2011;204:175.e1-8).

“The contingent strategy seems to be the most cost effective and is associated with an attractive rate of procedure-related euploid miscarriages and unnecessary terminations,” they wrote. “Moreover, this screening option provides a majority of women with reassurance early in gestation and may minimize costs by limiting retesting.”

Overall, the contingent screening test showed a cost-effectiveness ratio of $26,833 Canadian dollars per case of DS. The next most cost-effective test was the serum integrated screening test, but the incremental cost-effectiveness ratio (ICER) between the serum integrated screening and contingent screening tests was $3,815 Canadian dollars for every DS birth detected.

The combined test, currently popular in the United States and Canada, had a slightly higher cost-effectiveness ratio of $47,358 Canadian dollars than does the contingent test, but it allowed 91% of women to be reassured in the first trimester, they said.

Similar results on major outcomes including false positives, unnecessary terminations, and DS pregnancies were observed for contingent tests and several other screening tests. But the contingent screening test was associated with one of the lowest rates of procedure-related miscarriages (10). The contingent test also allowed 78% of patients to be reassured in the first trimester.

The combined test was associated with the highest rate of DS pregnancies in the first trimester (90%), and the highest rates of procedure-related euploid miscarriages (71) and unnecessary terminations (24). The combined test was the most expensive of the tests that followed screening strategies, most likely due to the requirement of a nuchal fold transparency test, and the high rate of false positives and subsequent unnecessary terminations associated with it, Dr. Gekas and associates said.

The computer model showed that the integrated test had the lowest rate of procedure-related miscarriages. However, widespread use of the integrated test would prevent women from being reassured in the first trimester, they noted.

The study was limited by the lack of prospective data and the potential inability to generalize the results across countries, they said. However, “it is unlikely that a large-scale prospective clinical trial comparing these eight screening approaches could rapidly be organized across North America.”

Major Finding: Overall, the contingent screening test showed a cost-effectiveness ratio of $26,833 Canadian dollars per case of DS. The next most cost-effective test was the serum integrated screening test, but the incremental cost-effectiveness ratio (ICER) between the serum integrated screening and contingent screening tests was $3,815 Canadian dollars for every DS birth detected.

Data Source: A cost-effective study of Down syndrome screening tests based on a computer model including 110,948 pregnancies.

Disclosures: The journal did not provide any disclosure information.

Contingent screening for prenatal Down syndrome was the most cost-effective stratagem, compared with other screening protocols, based on data from a computer simulation study of 110,948 pregnancies.

Several screening options are available in Canada and the United States, but data to help clinicians choose among the tests are limited, wrote Dr. Jean Gekas of the Centre Hospitalier de l'Université Laval in Quebec City, and colleagues.

The researchers used a computer model to analyze a virtual population of 110,948 pregnant women based on the demographic, genetic, and Down syndrome (DS) phenotype characteristics of the local population in Quebec. The tests included were the combined test, triple test, quadruple test, integrated test, serum integrated test, sequential screening test, contingent screening test, and amniocentesis for women aged 35 years and older (Am. J. Obstet. Gynecol. 2011;204:175.e1-8).

“The contingent strategy seems to be the most cost effective and is associated with an attractive rate of procedure-related euploid miscarriages and unnecessary terminations,” they wrote. “Moreover, this screening option provides a majority of women with reassurance early in gestation and may minimize costs by limiting retesting.”

Overall, the contingent screening test showed a cost-effectiveness ratio of $26,833 Canadian dollars per case of DS. The next most cost-effective test was the serum integrated screening test, but the incremental cost-effectiveness ratio (ICER) between the serum integrated screening and contingent screening tests was $3,815 Canadian dollars for every DS birth detected.

The combined test, currently popular in the United States and Canada, had a slightly higher cost-effectiveness ratio of $47,358 Canadian dollars than does the contingent test, but it allowed 91% of women to be reassured in the first trimester, they said.

Similar results on major outcomes including false positives, unnecessary terminations, and DS pregnancies were observed for contingent tests and several other screening tests. But the contingent screening test was associated with one of the lowest rates of procedure-related miscarriages (10). The contingent test also allowed 78% of patients to be reassured in the first trimester.

The combined test was associated with the highest rate of DS pregnancies in the first trimester (90%), and the highest rates of procedure-related euploid miscarriages (71) and unnecessary terminations (24). The combined test was the most expensive of the tests that followed screening strategies, most likely due to the requirement of a nuchal fold transparency test, and the high rate of false positives and subsequent unnecessary terminations associated with it, Dr. Gekas and associates said.

The computer model showed that the integrated test had the lowest rate of procedure-related miscarriages. However, widespread use of the integrated test would prevent women from being reassured in the first trimester, they noted.

The study was limited by the lack of prospective data and the potential inability to generalize the results across countries, they said. However, “it is unlikely that a large-scale prospective clinical trial comparing these eight screening approaches could rapidly be organized across North America.”

Major Finding: Overall, the contingent screening test showed a cost-effectiveness ratio of $26,833 Canadian dollars per case of DS. The next most cost-effective test was the serum integrated screening test, but the incremental cost-effectiveness ratio (ICER) between the serum integrated screening and contingent screening tests was $3,815 Canadian dollars for every DS birth detected.

Data Source: A cost-effective study of Down syndrome screening tests based on a computer model including 110,948 pregnancies.

Disclosures: The journal did not provide any disclosure information.

Contingent screening for prenatal Down syndrome was the most cost-effective stratagem, compared with other screening protocols, based on data from a computer simulation study of 110,948 pregnancies.

Several screening options are available in Canada and the United States, but data to help clinicians choose among the tests are limited, wrote Dr. Jean Gekas of the Centre Hospitalier de l'Université Laval in Quebec City, and colleagues.

The researchers used a computer model to analyze a virtual population of 110,948 pregnant women based on the demographic, genetic, and Down syndrome (DS) phenotype characteristics of the local population in Quebec. The tests included were the combined test, triple test, quadruple test, integrated test, serum integrated test, sequential screening test, contingent screening test, and amniocentesis for women aged 35 years and older (Am. J. Obstet. Gynecol. 2011;204:175.e1-8).

“The contingent strategy seems to be the most cost effective and is associated with an attractive rate of procedure-related euploid miscarriages and unnecessary terminations,” they wrote. “Moreover, this screening option provides a majority of women with reassurance early in gestation and may minimize costs by limiting retesting.”

Overall, the contingent screening test showed a cost-effectiveness ratio of $26,833 Canadian dollars per case of DS. The next most cost-effective test was the serum integrated screening test, but the incremental cost-effectiveness ratio (ICER) between the serum integrated screening and contingent screening tests was $3,815 Canadian dollars for every DS birth detected.

The combined test, currently popular in the United States and Canada, had a slightly higher cost-effectiveness ratio of $47,358 Canadian dollars than does the contingent test, but it allowed 91% of women to be reassured in the first trimester, they said.

Similar results on major outcomes including false positives, unnecessary terminations, and DS pregnancies were observed for contingent tests and several other screening tests. But the contingent screening test was associated with one of the lowest rates of procedure-related miscarriages (10). The contingent test also allowed 78% of patients to be reassured in the first trimester.

The combined test was associated with the highest rate of DS pregnancies in the first trimester (90%), and the highest rates of procedure-related euploid miscarriages (71) and unnecessary terminations (24). The combined test was the most expensive of the tests that followed screening strategies, most likely due to the requirement of a nuchal fold transparency test, and the high rate of false positives and subsequent unnecessary terminations associated with it, Dr. Gekas and associates said.

The computer model showed that the integrated test had the lowest rate of procedure-related miscarriages. However, widespread use of the integrated test would prevent women from being reassured in the first trimester, they noted.

The study was limited by the lack of prospective data and the potential inability to generalize the results across countries, they said. However, “it is unlikely that a large-scale prospective clinical trial comparing these eight screening approaches could rapidly be organized across North America.”

Major Finding: Death or the need for a shunt was significantly less likely in the prenatal surgery group, compared with the postnatal surgery group (68% vs. 98%).

Data Source: In the Management of Myelomeningocele Study (MOMS), 183 volunteer women with singleton pregnancies were randomized to prenatal surgery before the 26th week of pregnancy or surgery for their infants after birth.

Disclosures: The study was sponsored by the National Institutes of Health.

Prenatal surgery to repair myelomeningoceles significantly reduced the need for shunts at 1 year of age and improved children's motor function at age 30 months, compared with children who had surgery after birth, based on data from a randomized trial of 183 pregnant women.

The results reflect data from 158 children who were evaluated at 12 months of age and 134 children evaluated at 30 months. Data collection is ongoing.

The surgery to repair the opening in the spine is usually performed after birth, but data from animal studies suggest that prenatal surgery could result in fewer complications, said Dr. N. Scott Adzick of the Children's Hospital of Philadelphia and his colleagues.

In the Management of Myelomeningocele Study (MOMS), 183 volunteer women with singleton pregnancies were randomized to prenatal surgery before the 26th week of pregnancy or surgery for their infants after birth (N. Engl. J. Med. 2011 [doi:10.1056/NEJMoa1014379]).

The children were examined for two primary outcomes. The first outcome, at age 12 months, was patient death or the need for a shunt. The second outcome, at age 30 months, was a composite score of motor function and brain development. The score was based on the Bayley Scales of Infant Development II (BSID-II) Mental Development Index and the difference between each child's actual ability and his or her expected motor function based on the severity of the spinal defects.

Death or the need for a shunt was significantly less likely in the prenatal surgery group, compared with the postnatal surgery group (68% vs. 98%). The rates of shunt placement were significantly lower in the prenatal surgery group, compared with the postnatal surgery group (40% vs. 82%).

All the fetuses in the study suffered from hindbrain herniation, in which the base of the brain is pulled into the spinal canal. But at 12 months, 36% of the children in the prenatal surgery group had no evidence of hindbrain herniation, compared with 4% in the postnatal surgery group. In addition, infants in the prenatal surgery group had lower rates of moderate or severe hindbrain herniation than did the postnatal surgery group (25% vs. 67%).

In addition, infants in the prenatal surgery group scored an average of 21% higher on measures of mental and motor function, compared with the postnatal surgery group, with primary outcome scores of 149 vs. 123, respectively.

Infants who underwent prenatal surgery were born at a mean 34.1 weeks of pregnancy, compared with a mean 37.3 weeks of pregnancy for the postnatal surgery group. Significantly more infants in the prenatal surgery group had respiratory distress syndrome, compared with the postnatal surgery group (21% vs. 6%).

In terms of secondary outcomes, children in the prenatal surgery group were more likely to be able to walk without crutches or other orthotic devices, compared with the postnatal surgery group (21% vs. 42%).

The mean age of the pregnant women was 29 years. Each fetus had a myelomeningocele located between the T1 and S1 vertebrae, evidence of hindbrain herniation, and a gestational age of 19.0-25.9 weeks. Exclusion criteria included body mass index of 35 kg/m

Approximately one-third of the women in the prenatal surgery group showed uterine thinning or an area of dehiscence at the time of delivery. Women undergoing prenatal surgery must understand that they will require a cesarean delivery for the current pregnancy and any future pregnancies, the researchers added.

Myelomeningocele, a severe form of spina bifida in which the backbone and spinal canal do not close completely before birth, occurs in approximately 4 of every 10,000 births in the United States, Dr. Diana L. Farmer, division chief of pediatric surgery at the University of California, San Francisco, said in a teleconference. Dr. Farmer was one of several researchers on the study who took part in a teleconference to present the study findings.

The study was not large enough to show an impact of gestational age on the results, but data collection is ongoing. “This is a priceless cohort of patients that we will follow for a longer period of time,” Dr. Farmer said. She noted that the National Institutes of Health has agreed to fund follow-up of the patients until age 6–9 years. Future studies will include whether the children in the prenatal surgery group remain free of shunts, maintain improved motor function, and require fewer procedures, compared with the postnatal group.

Although the surgery is highly specialized and more research is needed, the results suggest that ob.gyns. can recommend the procedure to appropriate patients at this time, Dr. Farmer said.

“At the present time, it would be responsible to inform families that this represents an additional option in care that they could consider. The decision to undergo fetal surgery is quite individual and different for every patient, but I think families need to know that this is one option in the armamentarium.”

View on The News

Early Results Promising

Although the results are promising, it is important to be cautious in generalizing the success of prenatal surgery for myelomeningoceles to a wider population, Dr. Joe Leigh Simpson and Dr. Michael F. Greene said.

“The study by Adzick and colleagues. is “a major step in the right direction, but the still suboptimal rates of poor neonatal outcome and high maternal risk necessitate the use of less invasive approaches if such procedures are to be widely implemented,” they said.

Results might be less successful for patients treated in centers that are not as experienced in the procedure, Dr. Simpson and Dr. Greene noted.

In addition, more research is needed to determine which fetuses are more likely to benefit from the surgery, and whether performing the procedure earlier in gestation would yield even better outcomes, they added.

DR. SIMPSON is at Florida International University in Miami, and DR. GREENE is at Massachusetts General Hospital in Boston. They made their comments in an accompanying editorial (N. Engl. J. Med. 2011 [doi:10.1056/NEJMe1101228]). Dr. Simpson disclosed that he serves on the advisory boards for Rarecells Diagnostics, Novartis, BioDx, and Bayer HealthCare. Dr. Greene is an associate editor for the New England Journal of Medicine.

Major Finding: Death or the need for a shunt was significantly less likely in the prenatal surgery group, compared with the postnatal surgery group (68% vs. 98%).

Data Source: In the Management of Myelomeningocele Study (MOMS), 183 volunteer women with singleton pregnancies were randomized to prenatal surgery before the 26th week of pregnancy or surgery for their infants after birth.

Disclosures: The study was sponsored by the National Institutes of Health.

Prenatal surgery to repair myelomeningoceles significantly reduced the need for shunts at 1 year of age and improved children's motor function at age 30 months, compared with children who had surgery after birth, based on data from a randomized trial of 183 pregnant women.

The results reflect data from 158 children who were evaluated at 12 months of age and 134 children evaluated at 30 months. Data collection is ongoing.

The surgery to repair the opening in the spine is usually performed after birth, but data from animal studies suggest that prenatal surgery could result in fewer complications, said Dr. N. Scott Adzick of the Children's Hospital of Philadelphia and his colleagues.

In the Management of Myelomeningocele Study (MOMS), 183 volunteer women with singleton pregnancies were randomized to prenatal surgery before the 26th week of pregnancy or surgery for their infants after birth (N. Engl. J. Med. 2011 [doi:10.1056/NEJMoa1014379]).

The children were examined for two primary outcomes. The first outcome, at age 12 months, was patient death or the need for a shunt. The second outcome, at age 30 months, was a composite score of motor function and brain development. The score was based on the Bayley Scales of Infant Development II (BSID-II) Mental Development Index and the difference between each child's actual ability and his or her expected motor function based on the severity of the spinal defects.

Death or the need for a shunt was significantly less likely in the prenatal surgery group, compared with the postnatal surgery group (68% vs. 98%). The rates of shunt placement were significantly lower in the prenatal surgery group, compared with the postnatal surgery group (40% vs. 82%).

All the fetuses in the study suffered from hindbrain herniation, in which the base of the brain is pulled into the spinal canal. But at 12 months, 36% of the children in the prenatal surgery group had no evidence of hindbrain herniation, compared with 4% in the postnatal surgery group. In addition, infants in the prenatal surgery group had lower rates of moderate or severe hindbrain herniation than did the postnatal surgery group (25% vs. 67%).

In addition, infants in the prenatal surgery group scored an average of 21% higher on measures of mental and motor function, compared with the postnatal surgery group, with primary outcome scores of 149 vs. 123, respectively.

Infants who underwent prenatal surgery were born at a mean 34.1 weeks of pregnancy, compared with a mean 37.3 weeks of pregnancy for the postnatal surgery group. Significantly more infants in the prenatal surgery group had respiratory distress syndrome, compared with the postnatal surgery group (21% vs. 6%).

In terms of secondary outcomes, children in the prenatal surgery group were more likely to be able to walk without crutches or other orthotic devices, compared with the postnatal surgery group (21% vs. 42%).

The mean age of the pregnant women was 29 years. Each fetus had a myelomeningocele located between the T1 and S1 vertebrae, evidence of hindbrain herniation, and a gestational age of 19.0-25.9 weeks. Exclusion criteria included body mass index of 35 kg/m

Approximately one-third of the women in the prenatal surgery group showed uterine thinning or an area of dehiscence at the time of delivery. Women undergoing prenatal surgery must understand that they will require a cesarean delivery for the current pregnancy and any future pregnancies, the researchers added.

Myelomeningocele, a severe form of spina bifida in which the backbone and spinal canal do not close completely before birth, occurs in approximately 4 of every 10,000 births in the United States, Dr. Diana L. Farmer, division chief of pediatric surgery at the University of California, San Francisco, said in a teleconference. Dr. Farmer was one of several researchers on the study who took part in a teleconference to present the study findings.

The study was not large enough to show an impact of gestational age on the results, but data collection is ongoing. “This is a priceless cohort of patients that we will follow for a longer period of time,” Dr. Farmer said. She noted that the National Institutes of Health has agreed to fund follow-up of the patients until age 6–9 years. Future studies will include whether the children in the prenatal surgery group remain free of shunts, maintain improved motor function, and require fewer procedures, compared with the postnatal group.

Although the surgery is highly specialized and more research is needed, the results suggest that ob.gyns. can recommend the procedure to appropriate patients at this time, Dr. Farmer said.

“At the present time, it would be responsible to inform families that this represents an additional option in care that they could consider. The decision to undergo fetal surgery is quite individual and different for every patient, but I think families need to know that this is one option in the armamentarium.”

View on The News

Early Results Promising

Although the results are promising, it is important to be cautious in generalizing the success of prenatal surgery for myelomeningoceles to a wider population, Dr. Joe Leigh Simpson and Dr. Michael F. Greene said.

“The study by Adzick and colleagues. is “a major step in the right direction, but the still suboptimal rates of poor neonatal outcome and high maternal risk necessitate the use of less invasive approaches if such procedures are to be widely implemented,” they said.

Results might be less successful for patients treated in centers that are not as experienced in the procedure, Dr. Simpson and Dr. Greene noted.

In addition, more research is needed to determine which fetuses are more likely to benefit from the surgery, and whether performing the procedure earlier in gestation would yield even better outcomes, they added.

DR. SIMPSON is at Florida International University in Miami, and DR. GREENE is at Massachusetts General Hospital in Boston. They made their comments in an accompanying editorial (N. Engl. J. Med. 2011 [doi:10.1056/NEJMe1101228]). Dr. Simpson disclosed that he serves on the advisory boards for Rarecells Diagnostics, Novartis, BioDx, and Bayer HealthCare. Dr. Greene is an associate editor for the New England Journal of Medicine.

Major Finding: Death or the need for a shunt was significantly less likely in the prenatal surgery group, compared with the postnatal surgery group (68% vs. 98%).

Data Source: In the Management of Myelomeningocele Study (MOMS), 183 volunteer women with singleton pregnancies were randomized to prenatal surgery before the 26th week of pregnancy or surgery for their infants after birth.

Disclosures: The study was sponsored by the National Institutes of Health.

Prenatal surgery to repair myelomeningoceles significantly reduced the need for shunts at 1 year of age and improved children's motor function at age 30 months, compared with children who had surgery after birth, based on data from a randomized trial of 183 pregnant women.

The results reflect data from 158 children who were evaluated at 12 months of age and 134 children evaluated at 30 months. Data collection is ongoing.

The surgery to repair the opening in the spine is usually performed after birth, but data from animal studies suggest that prenatal surgery could result in fewer complications, said Dr. N. Scott Adzick of the Children's Hospital of Philadelphia and his colleagues.

In the Management of Myelomeningocele Study (MOMS), 183 volunteer women with singleton pregnancies were randomized to prenatal surgery before the 26th week of pregnancy or surgery for their infants after birth (N. Engl. J. Med. 2011 [doi:10.1056/NEJMoa1014379]).

The children were examined for two primary outcomes. The first outcome, at age 12 months, was patient death or the need for a shunt. The second outcome, at age 30 months, was a composite score of motor function and brain development. The score was based on the Bayley Scales of Infant Development II (BSID-II) Mental Development Index and the difference between each child's actual ability and his or her expected motor function based on the severity of the spinal defects.

Death or the need for a shunt was significantly less likely in the prenatal surgery group, compared with the postnatal surgery group (68% vs. 98%). The rates of shunt placement were significantly lower in the prenatal surgery group, compared with the postnatal surgery group (40% vs. 82%).

All the fetuses in the study suffered from hindbrain herniation, in which the base of the brain is pulled into the spinal canal. But at 12 months, 36% of the children in the prenatal surgery group had no evidence of hindbrain herniation, compared with 4% in the postnatal surgery group. In addition, infants in the prenatal surgery group had lower rates of moderate or severe hindbrain herniation than did the postnatal surgery group (25% vs. 67%).

In addition, infants in the prenatal surgery group scored an average of 21% higher on measures of mental and motor function, compared with the postnatal surgery group, with primary outcome scores of 149 vs. 123, respectively.

Infants who underwent prenatal surgery were born at a mean 34.1 weeks of pregnancy, compared with a mean 37.3 weeks of pregnancy for the postnatal surgery group. Significantly more infants in the prenatal surgery group had respiratory distress syndrome, compared with the postnatal surgery group (21% vs. 6%).

In terms of secondary outcomes, children in the prenatal surgery group were more likely to be able to walk without crutches or other orthotic devices, compared with the postnatal surgery group (21% vs. 42%).

The mean age of the pregnant women was 29 years. Each fetus had a myelomeningocele located between the T1 and S1 vertebrae, evidence of hindbrain herniation, and a gestational age of 19.0-25.9 weeks. Exclusion criteria included body mass index of 35 kg/m

Approximately one-third of the women in the prenatal surgery group showed uterine thinning or an area of dehiscence at the time of delivery. Women undergoing prenatal surgery must understand that they will require a cesarean delivery for the current pregnancy and any future pregnancies, the researchers added.

Myelomeningocele, a severe form of spina bifida in which the backbone and spinal canal do not close completely before birth, occurs in approximately 4 of every 10,000 births in the United States, Dr. Diana L. Farmer, division chief of pediatric surgery at the University of California, San Francisco, said in a teleconference. Dr. Farmer was one of several researchers on the study who took part in a teleconference to present the study findings.

The study was not large enough to show an impact of gestational age on the results, but data collection is ongoing. “This is a priceless cohort of patients that we will follow for a longer period of time,” Dr. Farmer said. She noted that the National Institutes of Health has agreed to fund follow-up of the patients until age 6–9 years. Future studies will include whether the children in the prenatal surgery group remain free of shunts, maintain improved motor function, and require fewer procedures, compared with the postnatal group.

Although the surgery is highly specialized and more research is needed, the results suggest that ob.gyns. can recommend the procedure to appropriate patients at this time, Dr. Farmer said.

“At the present time, it would be responsible to inform families that this represents an additional option in care that they could consider. The decision to undergo fetal surgery is quite individual and different for every patient, but I think families need to know that this is one option in the armamentarium.”

View on The News

Early Results Promising

Although the results are promising, it is important to be cautious in generalizing the success of prenatal surgery for myelomeningoceles to a wider population, Dr. Joe Leigh Simpson and Dr. Michael F. Greene said.

“The study by Adzick and colleagues. is “a major step in the right direction, but the still suboptimal rates of poor neonatal outcome and high maternal risk necessitate the use of less invasive approaches if such procedures are to be widely implemented,” they said.

Results might be less successful for patients treated in centers that are not as experienced in the procedure, Dr. Simpson and Dr. Greene noted.

In addition, more research is needed to determine which fetuses are more likely to benefit from the surgery, and whether performing the procedure earlier in gestation would yield even better outcomes, they added.

DR. SIMPSON is at Florida International University in Miami, and DR. GREENE is at Massachusetts General Hospital in Boston. They made their comments in an accompanying editorial (N. Engl. J. Med. 2011 [doi:10.1056/NEJMe1101228]). Dr. Simpson disclosed that he serves on the advisory boards for Rarecells Diagnostics, Novartis, BioDx, and Bayer HealthCare. Dr. Greene is an associate editor for the New England Journal of Medicine.

Prenatal surgery to repair myelomeningoceles significantly reduced the need for shunts at 1 year of age and improved children's motor function at age 30 months, compared with children who had surgery after birth, based on data from a randomized trial of 183 pregnant women.

The results, published online, reflect data from 158 children who were evaluated at 12 months of age and 134 children evaluated at 30 months. Data collection is ongoing.

Surgery to repair the opening in the spine is usually performed after birth, but data from animal studies suggest that prenatal surgery could result in fewer complications, said Dr. N. Scott Adzick of the Children's Hospital of Philadelphia and his colleagues.

In the Management of Myelomeningocele Study (MOMS), 183 volunteer women with singleton pregnancies were randomized to prenatal surgery before the 26th week of pregnancy or surgery for their infants after birth (N. Engl. J. Med. 2011 Feb. 9 [doi:10.1056/NEJMoa 1014379

The children were examined for two primary outcomes. The first outcome, at age 12 months, was patient death or the need for a shunt. The second outcome, at age 30 months, was a composite score of motor function and brain development. The score was based on the Bayley Scales of Infant Development II (BSID-II) Mental Development Index and the difference between each child's actual ability and their expected motor function based on the severity of their spinal defect.

Death or the need for a shunt was significantly less likely in the prenatal surgery group, compared with the postnatal surgery group (68% vs. 98%). The rates of shunt placement were significantly lower for the prenatal surgery group, compared with the postnatal surgery group (40% vs. 82%).

All the fetuses in the study suffered from hindbrain herniation, in which the base of the brain is pulled into the spinal canal.

But at 12 months, 36% of the children in the prenatal surgery group had no evidence of hindbrain herniation, compared with 4% in the postnatal surgery group. Infants in the prenatal surgery group also had lower rates of moderate or severe hindbrain herniation than did the postnatal surgery group (25% vs. 67%).

In addition, infants in the prenatal surgery group scored an average of 21% higher on measures of mental and motor function, compared with infants in the postnatal surgery group, with primary outcome scores of 149 vs. 123, respectively.

Infants who underwent prenatal surgery were born at a mean 34.1 weeks of pregnancy, compared with a mean 37.3 weeks of pregnancy for the postnatal surgery group.

Significantly more infants in the prenatal surgery group had respiratory distress syndrome, compared with the postnatal surgery group (21% vs. 6%).

In terms of secondary outcomes, children in the prenatal surgery group were more likely to be able to walk without crutches or other orthotic devices, compared with the postnatal surgery group (21% vs. 42%).

The mean age of the pregnant women was 29 years. Each fetus had a myelomeningocele located between the T1 and S1 vertebrae, evidence of hindbrain herniation, and a gestational age of 19.0–25.9 weeks.

Exclusion criteria included a body mass index of 35 kg/m

Approximately one-third of the women in the prenatal surgery group showed uterine thinning or an area of dehiscence at the time of delivery. Women undergoing prenatal surgery must understand that they will require a cesarean delivery for the current pregnancy and any future pregnancies, the authors added.

The study was sponsored by the National Institutes of Health.

View on the News

Major Step in the Right Direction

Although the results are promising, it is important to be cautious in generalizing the success of prenatal surgery for myelomeningoceles to a wider population, Dr. Joe Leigh Simpson and Dr. Michael F. Greene said.

“The study by Adzick et al. is a major step in the right direction, but the still suboptimal rates of poor neonatal outcome and high maternal risk necessitate the use of less invasive approaches if such procedures are to be widely implemented,” they said.

Results might be less successful for patients treated in centers that are not as experienced in the procedure, Dr. Simpson and Dr. Greene noted.

In addition, more research is needed to determine which fetuses are more likely to benefit from the surgery, and whether performing the procedure earlier in gestation would yield even better outcomes, they added.

DR. SIMPSON is at Florida International University in Miami, Fla., and DR. GREENE is at Massachusetts General Hospital in Boston. They made their comments in an accompanying editorial (New Eng. J. Med. 2011 [epub

doi: 10.1056/NEJMe1101228

Prenatal surgery to repair myelomeningoceles significantly reduced the need for shunts at 1 year of age and improved children's motor function at age 30 months, compared with children who had surgery after birth, based on data from a randomized trial of 183 pregnant women.

The results, published online, reflect data from 158 children who were evaluated at 12 months of age and 134 children evaluated at 30 months. Data collection is ongoing.

Surgery to repair the opening in the spine is usually performed after birth, but data from animal studies suggest that prenatal surgery could result in fewer complications, said Dr. N. Scott Adzick of the Children's Hospital of Philadelphia and his colleagues.

In the Management of Myelomeningocele Study (MOMS), 183 volunteer women with singleton pregnancies were randomized to prenatal surgery before the 26th week of pregnancy or surgery for their infants after birth (N. Engl. J. Med. 2011 Feb. 9 [doi:10.1056/NEJMoa 1014379

The children were examined for two primary outcomes. The first outcome, at age 12 months, was patient death or the need for a shunt. The second outcome, at age 30 months, was a composite score of motor function and brain development. The score was based on the Bayley Scales of Infant Development II (BSID-II) Mental Development Index and the difference between each child's actual ability and their expected motor function based on the severity of their spinal defect.

Death or the need for a shunt was significantly less likely in the prenatal surgery group, compared with the postnatal surgery group (68% vs. 98%). The rates of shunt placement were significantly lower for the prenatal surgery group, compared with the postnatal surgery group (40% vs. 82%).

All the fetuses in the study suffered from hindbrain herniation, in which the base of the brain is pulled into the spinal canal.

But at 12 months, 36% of the children in the prenatal surgery group had no evidence of hindbrain herniation, compared with 4% in the postnatal surgery group. Infants in the prenatal surgery group also had lower rates of moderate or severe hindbrain herniation than did the postnatal surgery group (25% vs. 67%).

In addition, infants in the prenatal surgery group scored an average of 21% higher on measures of mental and motor function, compared with infants in the postnatal surgery group, with primary outcome scores of 149 vs. 123, respectively.

Infants who underwent prenatal surgery were born at a mean 34.1 weeks of pregnancy, compared with a mean 37.3 weeks of pregnancy for the postnatal surgery group.

Significantly more infants in the prenatal surgery group had respiratory distress syndrome, compared with the postnatal surgery group (21% vs. 6%).

In terms of secondary outcomes, children in the prenatal surgery group were more likely to be able to walk without crutches or other orthotic devices, compared with the postnatal surgery group (21% vs. 42%).

The mean age of the pregnant women was 29 years. Each fetus had a myelomeningocele located between the T1 and S1 vertebrae, evidence of hindbrain herniation, and a gestational age of 19.0–25.9 weeks.

Exclusion criteria included a body mass index of 35 kg/m

Approximately one-third of the women in the prenatal surgery group showed uterine thinning or an area of dehiscence at the time of delivery. Women undergoing prenatal surgery must understand that they will require a cesarean delivery for the current pregnancy and any future pregnancies, the authors added.

The study was sponsored by the National Institutes of Health.

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Major Step in the Right Direction

Although the results are promising, it is important to be cautious in generalizing the success of prenatal surgery for myelomeningoceles to a wider population, Dr. Joe Leigh Simpson and Dr. Michael F. Greene said.

“The study by Adzick et al. is a major step in the right direction, but the still suboptimal rates of poor neonatal outcome and high maternal risk necessitate the use of less invasive approaches if such procedures are to be widely implemented,” they said.

Results might be less successful for patients treated in centers that are not as experienced in the procedure, Dr. Simpson and Dr. Greene noted.

In addition, more research is needed to determine which fetuses are more likely to benefit from the surgery, and whether performing the procedure earlier in gestation would yield even better outcomes, they added.

DR. SIMPSON is at Florida International University in Miami, Fla., and DR. GREENE is at Massachusetts General Hospital in Boston. They made their comments in an accompanying editorial (New Eng. J. Med. 2011 [epub

doi: 10.1056/NEJMe1101228

Prenatal surgery to repair myelomeningoceles significantly reduced the need for shunts at 1 year of age and improved children's motor function at age 30 months, compared with children who had surgery after birth, based on data from a randomized trial of 183 pregnant women.

The results, published online, reflect data from 158 children who were evaluated at 12 months of age and 134 children evaluated at 30 months. Data collection is ongoing.

Surgery to repair the opening in the spine is usually performed after birth, but data from animal studies suggest that prenatal surgery could result in fewer complications, said Dr. N. Scott Adzick of the Children's Hospital of Philadelphia and his colleagues.

In the Management of Myelomeningocele Study (MOMS), 183 volunteer women with singleton pregnancies were randomized to prenatal surgery before the 26th week of pregnancy or surgery for their infants after birth (N. Engl. J. Med. 2011 Feb. 9 [doi:10.1056/NEJMoa 1014379

The children were examined for two primary outcomes. The first outcome, at age 12 months, was patient death or the need for a shunt. The second outcome, at age 30 months, was a composite score of motor function and brain development. The score was based on the Bayley Scales of Infant Development II (BSID-II) Mental Development Index and the difference between each child's actual ability and their expected motor function based on the severity of their spinal defect.

Death or the need for a shunt was significantly less likely in the prenatal surgery group, compared with the postnatal surgery group (68% vs. 98%). The rates of shunt placement were significantly lower for the prenatal surgery group, compared with the postnatal surgery group (40% vs. 82%).

All the fetuses in the study suffered from hindbrain herniation, in which the base of the brain is pulled into the spinal canal.

But at 12 months, 36% of the children in the prenatal surgery group had no evidence of hindbrain herniation, compared with 4% in the postnatal surgery group. Infants in the prenatal surgery group also had lower rates of moderate or severe hindbrain herniation than did the postnatal surgery group (25% vs. 67%).

In addition, infants in the prenatal surgery group scored an average of 21% higher on measures of mental and motor function, compared with infants in the postnatal surgery group, with primary outcome scores of 149 vs. 123, respectively.

Infants who underwent prenatal surgery were born at a mean 34.1 weeks of pregnancy, compared with a mean 37.3 weeks of pregnancy for the postnatal surgery group.

Significantly more infants in the prenatal surgery group had respiratory distress syndrome, compared with the postnatal surgery group (21% vs. 6%).

In terms of secondary outcomes, children in the prenatal surgery group were more likely to be able to walk without crutches or other orthotic devices, compared with the postnatal surgery group (21% vs. 42%).

The mean age of the pregnant women was 29 years. Each fetus had a myelomeningocele located between the T1 and S1 vertebrae, evidence of hindbrain herniation, and a gestational age of 19.0–25.9 weeks.

Exclusion criteria included a body mass index of 35 kg/m

Approximately one-third of the women in the prenatal surgery group showed uterine thinning or an area of dehiscence at the time of delivery. Women undergoing prenatal surgery must understand that they will require a cesarean delivery for the current pregnancy and any future pregnancies, the authors added.

The study was sponsored by the National Institutes of Health.

View on the News

Major Step in the Right Direction

Although the results are promising, it is important to be cautious in generalizing the success of prenatal surgery for myelomeningoceles to a wider population, Dr. Joe Leigh Simpson and Dr. Michael F. Greene said.

“The study by Adzick et al. is a major step in the right direction, but the still suboptimal rates of poor neonatal outcome and high maternal risk necessitate the use of less invasive approaches if such procedures are to be widely implemented,” they said.

Results might be less successful for patients treated in centers that are not as experienced in the procedure, Dr. Simpson and Dr. Greene noted.

In addition, more research is needed to determine which fetuses are more likely to benefit from the surgery, and whether performing the procedure earlier in gestation would yield even better outcomes, they added.

DR. SIMPSON is at Florida International University in Miami, Fla., and DR. GREENE is at Massachusetts General Hospital in Boston. They made their comments in an accompanying editorial (New Eng. J. Med. 2011 [epub

doi: 10.1056/NEJMe1101228