Mark S. Lesney

FT. LAUDERDALE, FLA. – Appropriate staging of non–small cell lung cancer (NSCLC) is critical to patient treatment and prognosis. Endobronchial ultrasound–guided fine-needle aspiration (EBUS-FNA) has gradually gained acceptance as a diagnostic tool to pathologically stage the mediastinum in patients with NSCLC, according to Dr. Bryan A. Whitson at the annual meeting of the Society of Thoracic Surgeons.

Courtesy of Dr. Rafael Andrade

Because EBUS-FNA is a test to detect cancer, it is critical that it have few false-negative results, i.e., have a high negative predictive value (NPV). However, by virtue of the size and volume of mediastinal lymph node FNA samples, nondiagnostic results occur with some frequency.

Nondiagnostic samples decrease a test’s diagnostic performance, since they cannot help guide a clinical decision, and a portion of these samples may actually be false negatives.

The standard calculation of NPV does not factor in nondiagnostic samples. According to a study by the researchers in the Division of Thoracic and Foregut Surgery at the University of Minnesota, which Dr. Whitson presented, one must take nondiagnostic samples into consideration to determine the true diagnostic performance of EBUS-FNA.

To conservatively calculate NPV, the researchers modified the standard definition (true negatives/[true negatives plus false negatives]), creating an alternative NPV definition (true negatives/[true negatives plus false negatives plus nondiagnostic]). This definition takes into account the possibility that these nondiagnostic samples may be false negatives, which assumes the worst-case scenario.

The thoracic team at the University of Minnesota then compared the results of these two definitions of NPV in a retrospective analysis of their prospective database of patients with NSCLC who had EBUS-FNA between January 2007 and July 2011.

Dr. Bryan Whitson, who is a surgeon at the University of Minnesota, presented the team’s results.

A total of 120 patients with NSCLC who underwent EBUS-FNA were included in the analsyis. EBUS-FNAs were assessed using rapid on-site cytologic evaluation (ROSE) and a false-negative definition consisting of negative FNAs coupled to NSCLC-positive surgical biopsy of the same site. Diagnostic performance was evaluated comparing results of the inclusion or exclusion of nondiagnostic samples in the calculation of NPV.

Seven (5.8%) of the 120 patients had nondiagnostic results. One patient had a false negative. When the seven nondiagnostic procedures were excluded, the NPV was 96.3%; when they were included, the NPV dropped to 76.5%.

Both sensitivity and accuracy also dropped with the inclusion of the nondiagnostic procedures. Sensitivity dropped from 98.8% to 91% and overall accuracy from 98.2% to 92.2% when nondiagnostic procedures were included.

"Our data indicate that a conservative calculation of NPV that includes nondiagnostic samples should be used to assess the real diagnostic accuracy of EBUS-FNA in patients with NSCLC. Otherwise, decisions based on these results could be flawed and patients inappropriately staged. In our experience, and using this assessment, EBUS-FNA shows a true NPV that is less than most clinicians assume," Dr. Whitson said.

Ultimately, the thoracic surgeons at the University of Minnesota believe that "EBUS-FNA should be the primary method to stage the mediastinum in patients with NSCLC, since it enables pathologic staging without the need for an incision, with preservation of tissue planes, and with minimal complications."

However, in view of the limitations of EBUS-FNA, "we perform an immediate surgical biopsy when in doubt of the reliability of an EBUS-FNA result. A thoracic surgeon facile in EBUS can offer most patients minimally invasive mediastinal staging, with selective surgical biopsy in the same anesthetic setting, which can ensure accuracy and streamline patient care," according to Dr. Whitson and his colleagues.

FT. LAUDERDALE, FLA. – Appropriate staging of non–small cell lung cancer (NSCLC) is critical to patient treatment and prognosis. Endobronchial ultrasound–guided fine-needle aspiration (EBUS-FNA) has gradually gained acceptance as a diagnostic tool to pathologically stage the mediastinum in patients with NSCLC, according to Dr. Bryan A. Whitson at the annual meeting of the Society of Thoracic Surgeons.

Courtesy of Dr. Rafael Andrade

Because EBUS-FNA is a test to detect cancer, it is critical that it have few false-negative results, i.e., have a high negative predictive value (NPV). However, by virtue of the size and volume of mediastinal lymph node FNA samples, nondiagnostic results occur with some frequency.

Nondiagnostic samples decrease a test’s diagnostic performance, since they cannot help guide a clinical decision, and a portion of these samples may actually be false negatives.

The standard calculation of NPV does not factor in nondiagnostic samples. According to a study by the researchers in the Division of Thoracic and Foregut Surgery at the University of Minnesota, which Dr. Whitson presented, one must take nondiagnostic samples into consideration to determine the true diagnostic performance of EBUS-FNA.

To conservatively calculate NPV, the researchers modified the standard definition (true negatives/[true negatives plus false negatives]), creating an alternative NPV definition (true negatives/[true negatives plus false negatives plus nondiagnostic]). This definition takes into account the possibility that these nondiagnostic samples may be false negatives, which assumes the worst-case scenario.

The thoracic team at the University of Minnesota then compared the results of these two definitions of NPV in a retrospective analysis of their prospective database of patients with NSCLC who had EBUS-FNA between January 2007 and July 2011.

Dr. Bryan Whitson, who is a surgeon at the University of Minnesota, presented the team’s results.

A total of 120 patients with NSCLC who underwent EBUS-FNA were included in the analsyis. EBUS-FNAs were assessed using rapid on-site cytologic evaluation (ROSE) and a false-negative definition consisting of negative FNAs coupled to NSCLC-positive surgical biopsy of the same site. Diagnostic performance was evaluated comparing results of the inclusion or exclusion of nondiagnostic samples in the calculation of NPV.

Seven (5.8%) of the 120 patients had nondiagnostic results. One patient had a false negative. When the seven nondiagnostic procedures were excluded, the NPV was 96.3%; when they were included, the NPV dropped to 76.5%.

Both sensitivity and accuracy also dropped with the inclusion of the nondiagnostic procedures. Sensitivity dropped from 98.8% to 91% and overall accuracy from 98.2% to 92.2% when nondiagnostic procedures were included.

"Our data indicate that a conservative calculation of NPV that includes nondiagnostic samples should be used to assess the real diagnostic accuracy of EBUS-FNA in patients with NSCLC. Otherwise, decisions based on these results could be flawed and patients inappropriately staged. In our experience, and using this assessment, EBUS-FNA shows a true NPV that is less than most clinicians assume," Dr. Whitson said.

Ultimately, the thoracic surgeons at the University of Minnesota believe that "EBUS-FNA should be the primary method to stage the mediastinum in patients with NSCLC, since it enables pathologic staging without the need for an incision, with preservation of tissue planes, and with minimal complications."

However, in view of the limitations of EBUS-FNA, "we perform an immediate surgical biopsy when in doubt of the reliability of an EBUS-FNA result. A thoracic surgeon facile in EBUS can offer most patients minimally invasive mediastinal staging, with selective surgical biopsy in the same anesthetic setting, which can ensure accuracy and streamline patient care," according to Dr. Whitson and his colleagues.

FT. LAUDERDALE, FLA. – Appropriate staging of non–small cell lung cancer (NSCLC) is critical to patient treatment and prognosis. Endobronchial ultrasound–guided fine-needle aspiration (EBUS-FNA) has gradually gained acceptance as a diagnostic tool to pathologically stage the mediastinum in patients with NSCLC, according to Dr. Bryan A. Whitson at the annual meeting of the Society of Thoracic Surgeons.

Courtesy of Dr. Rafael Andrade

Because EBUS-FNA is a test to detect cancer, it is critical that it have few false-negative results, i.e., have a high negative predictive value (NPV). However, by virtue of the size and volume of mediastinal lymph node FNA samples, nondiagnostic results occur with some frequency.

Nondiagnostic samples decrease a test’s diagnostic performance, since they cannot help guide a clinical decision, and a portion of these samples may actually be false negatives.

The standard calculation of NPV does not factor in nondiagnostic samples. According to a study by the researchers in the Division of Thoracic and Foregut Surgery at the University of Minnesota, which Dr. Whitson presented, one must take nondiagnostic samples into consideration to determine the true diagnostic performance of EBUS-FNA.

To conservatively calculate NPV, the researchers modified the standard definition (true negatives/[true negatives plus false negatives]), creating an alternative NPV definition (true negatives/[true negatives plus false negatives plus nondiagnostic]). This definition takes into account the possibility that these nondiagnostic samples may be false negatives, which assumes the worst-case scenario.

The thoracic team at the University of Minnesota then compared the results of these two definitions of NPV in a retrospective analysis of their prospective database of patients with NSCLC who had EBUS-FNA between January 2007 and July 2011.

Dr. Bryan Whitson, who is a surgeon at the University of Minnesota, presented the team’s results.

A total of 120 patients with NSCLC who underwent EBUS-FNA were included in the analsyis. EBUS-FNAs were assessed using rapid on-site cytologic evaluation (ROSE) and a false-negative definition consisting of negative FNAs coupled to NSCLC-positive surgical biopsy of the same site. Diagnostic performance was evaluated comparing results of the inclusion or exclusion of nondiagnostic samples in the calculation of NPV.

Seven (5.8%) of the 120 patients had nondiagnostic results. One patient had a false negative. When the seven nondiagnostic procedures were excluded, the NPV was 96.3%; when they were included, the NPV dropped to 76.5%.

Both sensitivity and accuracy also dropped with the inclusion of the nondiagnostic procedures. Sensitivity dropped from 98.8% to 91% and overall accuracy from 98.2% to 92.2% when nondiagnostic procedures were included.

"Our data indicate that a conservative calculation of NPV that includes nondiagnostic samples should be used to assess the real diagnostic accuracy of EBUS-FNA in patients with NSCLC. Otherwise, decisions based on these results could be flawed and patients inappropriately staged. In our experience, and using this assessment, EBUS-FNA shows a true NPV that is less than most clinicians assume," Dr. Whitson said.

Ultimately, the thoracic surgeons at the University of Minnesota believe that "EBUS-FNA should be the primary method to stage the mediastinum in patients with NSCLC, since it enables pathologic staging without the need for an incision, with preservation of tissue planes, and with minimal complications."

However, in view of the limitations of EBUS-FNA, "we perform an immediate surgical biopsy when in doubt of the reliability of an EBUS-FNA result. A thoracic surgeon facile in EBUS can offer most patients minimally invasive mediastinal staging, with selective surgical biopsy in the same anesthetic setting, which can ensure accuracy and streamline patient care," according to Dr. Whitson and his colleagues.

FT. LAUDERDALE, FLA. – Appropriate staging of non–small cell lung cancer (NSCLC) is critical to patient treatment and prognosis. Endobronchial ultrasound–guided fine-needle aspiration (EBUS-FNA) has gradually gained acceptance as a diagnostic tool to pathologically stage the mediastinum in patients with NSCLC, according to Dr. Bryan A. Whitson at the annual meeting of the Society of Thoracic Surgeons.

Courtesy of Dr. Rafael Andrade

Because EBUS-FNA is a test to detect cancer, it is critical that it have few false-negative results, i.e., have a high negative predictive value (NPV). However, by virtue of the size and volume of mediastinal lymph node FNA samples, nondiagnostic results occur with some frequency.

Nondiagnostic samples decrease a test’s diagnostic performance, since they cannot help guide a clinical decision, and a portion of these samples may actually be false negatives.

The standard calculation of NPV does not factor in nondiagnostic samples. According to a study by the researchers in the Division of Thoracic and Foregut Surgery at the University of Minnesota, which Dr. Whitson presented, one must take nondiagnostic samples into consideration to determine the true diagnostic performance of EBUS-FNA.

To conservatively calculate NPV, the researchers modified the standard definition (true negatives/[true negatives plus false negatives]), creating an alternative NPV definition (true negatives/[true negatives plus false negatives plus nondiagnostic]). This definition takes into account the possibility that these nondiagnostic samples may be false negatives, which assumes the worst-case scenario.

The thoracic team at the University of Minnesota then compared the results of these two definitions of NPV in a retrospective analysis of their prospective database of patients with NSCLC who had EBUS-FNA between January 2007 and July 2011.

Dr. Bryan Whitson, who is a surgeon at the University of Minnesota, presented the team’s results.

A total of 120 patients with NSCLC who underwent EBUS-FNA were included in the analsyis. EBUS-FNAs were assessed using rapid on-site cytologic evaluation (ROSE) and a false-negative definition consisting of negative FNAs coupled to NSCLC-positive surgical biopsy of the same site. Diagnostic performance was evaluated comparing results of the inclusion or exclusion of nondiagnostic samples in the calculation of NPV.

Seven (5.8%) of the 120 patients had nondiagnostic results. One patient had a false negative. When the seven nondiagnostic procedures were excluded, the NPV was 96.3%; when they were included, the NPV dropped to 76.5%.

Both sensitivity and accuracy also dropped with the inclusion of the nondiagnostic procedures. Sensitivity dropped from 98.8% to 91% and overall accuracy from 98.2% to 92.2% when nondiagnostic procedures were included.

"Our data indicate that a conservative calculation of NPV that includes nondiagnostic samples should be used to assess the real diagnostic accuracy of EBUS-FNA in patients with NSCLC. Otherwise, decisions based on these results could be flawed and patients inappropriately staged. In our experience, and using this assessment, EBUS-FNA shows a true NPV that is less than most clinicians assume," Dr. Whitson said.

Ultimately, the thoracic surgeons at the University of Minnesota believe that "EBUS-FNA should be the primary method to stage the mediastinum in patients with NSCLC, since it enables pathologic staging without the need for an incision, with preservation of tissue planes, and with minimal complications."

However, in view of the limitations of EBUS-FNA, "we perform an immediate surgical biopsy when in doubt of the reliability of an EBUS-FNA result. A thoracic surgeon facile in EBUS can offer most patients minimally invasive mediastinal staging, with selective surgical biopsy in the same anesthetic setting, which can ensure accuracy and streamline patient care," according to Dr. Whitson and his colleagues.

FT. LAUDERDALE, FLA. – Appropriate staging of non–small cell lung cancer (NSCLC) is critical to patient treatment and prognosis. Endobronchial ultrasound–guided fine-needle aspiration (EBUS-FNA) has gradually gained acceptance as a diagnostic tool to pathologically stage the mediastinum in patients with NSCLC, according to Dr. Bryan A. Whitson at the annual meeting of the Society of Thoracic Surgeons.

Courtesy of Dr. Rafael Andrade

Because EBUS-FNA is a test to detect cancer, it is critical that it have few false-negative results, i.e., have a high negative predictive value (NPV). However, by virtue of the size and volume of mediastinal lymph node FNA samples, nondiagnostic results occur with some frequency.

Nondiagnostic samples decrease a test’s diagnostic performance, since they cannot help guide a clinical decision, and a portion of these samples may actually be false negatives.

The standard calculation of NPV does not factor in nondiagnostic samples. According to a study by the researchers in the Division of Thoracic and Foregut Surgery at the University of Minnesota, which Dr. Whitson presented, one must take nondiagnostic samples into consideration to determine the true diagnostic performance of EBUS-FNA.

To conservatively calculate NPV, the researchers modified the standard definition (true negatives/[true negatives plus false negatives]), creating an alternative NPV definition (true negatives/[true negatives plus false negatives plus nondiagnostic]). This definition takes into account the possibility that these nondiagnostic samples may be false negatives, which assumes the worst-case scenario.

The thoracic team at the University of Minnesota then compared the results of these two definitions of NPV in a retrospective analysis of their prospective database of patients with NSCLC who had EBUS-FNA between January 2007 and July 2011.

Dr. Bryan Whitson, who is a surgeon at the University of Minnesota, presented the team’s results.

A total of 120 patients with NSCLC who underwent EBUS-FNA were included in the analsyis. EBUS-FNAs were assessed using rapid on-site cytologic evaluation (ROSE) and a false-negative definition consisting of negative FNAs coupled to NSCLC-positive surgical biopsy of the same site. Diagnostic performance was evaluated comparing results of the inclusion or exclusion of nondiagnostic samples in the calculation of NPV.

Seven (5.8%) of the 120 patients had nondiagnostic results. One patient had a false negative. When the seven nondiagnostic procedures were excluded, the NPV was 96.3%; when they were included, the NPV dropped to 76.5%.

Both sensitivity and accuracy also dropped with the inclusion of the nondiagnostic procedures. Sensitivity dropped from 98.8% to 91% and overall accuracy from 98.2% to 92.2% when nondiagnostic procedures were included.

"Our data indicate that a conservative calculation of NPV that includes nondiagnostic samples should be used to assess the real diagnostic accuracy of EBUS-FNA in patients with NSCLC. Otherwise, decisions based on these results could be flawed and patients inappropriately staged. In our experience, and using this assessment, EBUS-FNA shows a true NPV that is less than most clinicians assume," Dr. Whitson said.

Ultimately, the thoracic surgeons at the University of Minnesota believe that "EBUS-FNA should be the primary method to stage the mediastinum in patients with NSCLC, since it enables pathologic staging without the need for an incision, with preservation of tissue planes, and with minimal complications."

However, in view of the limitations of EBUS-FNA, "we perform an immediate surgical biopsy when in doubt of the reliability of an EBUS-FNA result. A thoracic surgeon facile in EBUS can offer most patients minimally invasive mediastinal staging, with selective surgical biopsy in the same anesthetic setting, which can ensure accuracy and streamline patient care," according to Dr. Whitson and his colleagues.

FT. LAUDERDALE, FLA. – Appropriate staging of non–small cell lung cancer (NSCLC) is critical to patient treatment and prognosis. Endobronchial ultrasound–guided fine-needle aspiration (EBUS-FNA) has gradually gained acceptance as a diagnostic tool to pathologically stage the mediastinum in patients with NSCLC, according to Dr. Bryan A. Whitson at the annual meeting of the Society of Thoracic Surgeons.

Courtesy of Dr. Rafael Andrade

Because EBUS-FNA is a test to detect cancer, it is critical that it have few false-negative results, i.e., have a high negative predictive value (NPV). However, by virtue of the size and volume of mediastinal lymph node FNA samples, nondiagnostic results occur with some frequency.

Nondiagnostic samples decrease a test’s diagnostic performance, since they cannot help guide a clinical decision, and a portion of these samples may actually be false negatives.

The standard calculation of NPV does not factor in nondiagnostic samples. According to a study by the researchers in the Division of Thoracic and Foregut Surgery at the University of Minnesota, which Dr. Whitson presented, one must take nondiagnostic samples into consideration to determine the true diagnostic performance of EBUS-FNA.

To conservatively calculate NPV, the researchers modified the standard definition (true negatives/[true negatives plus false negatives]), creating an alternative NPV definition (true negatives/[true negatives plus false negatives plus nondiagnostic]). This definition takes into account the possibility that these nondiagnostic samples may be false negatives, which assumes the worst-case scenario.

The thoracic team at the University of Minnesota then compared the results of these two definitions of NPV in a retrospective analysis of their prospective database of patients with NSCLC who had EBUS-FNA between January 2007 and July 2011.

Dr. Bryan Whitson, who is a surgeon at the University of Minnesota, presented the team’s results.

A total of 120 patients with NSCLC who underwent EBUS-FNA were included in the analsyis. EBUS-FNAs were assessed using rapid on-site cytologic evaluation (ROSE) and a false-negative definition consisting of negative FNAs coupled to NSCLC-positive surgical biopsy of the same site. Diagnostic performance was evaluated comparing results of the inclusion or exclusion of nondiagnostic samples in the calculation of NPV.

Seven (5.8%) of the 120 patients had nondiagnostic results. One patient had a false negative. When the seven nondiagnostic procedures were excluded, the NPV was 96.3%; when they were included, the NPV dropped to 76.5%.

Both sensitivity and accuracy also dropped with the inclusion of the nondiagnostic procedures. Sensitivity dropped from 98.8% to 91% and overall accuracy from 98.2% to 92.2% when nondiagnostic procedures were included.

"Our data indicate that a conservative calculation of NPV that includes nondiagnostic samples should be used to assess the real diagnostic accuracy of EBUS-FNA in patients with NSCLC. Otherwise, decisions based on these results could be flawed and patients inappropriately staged. In our experience, and using this assessment, EBUS-FNA shows a true NPV that is less than most clinicians assume," Dr. Whitson said.

Ultimately, the thoracic surgeons at the University of Minnesota believe that "EBUS-FNA should be the primary method to stage the mediastinum in patients with NSCLC, since it enables pathologic staging without the need for an incision, with preservation of tissue planes, and with minimal complications."

However, in view of the limitations of EBUS-FNA, "we perform an immediate surgical biopsy when in doubt of the reliability of an EBUS-FNA result. A thoracic surgeon facile in EBUS can offer most patients minimally invasive mediastinal staging, with selective surgical biopsy in the same anesthetic setting, which can ensure accuracy and streamline patient care," according to Dr. Whitson and his colleagues.

Because anticoagulation is a balancing act between the prevention of clots and the risk of major bleeds, tremendous efforts have been made to find the safest, most effective drugs possible. The foundations of anticoagulant therapy – warfarin (taken orally) and heparin (taken intravenously) – are being shaken by an onslaught of the newer oral factor Xa inhibitors and direct thrombin inhibitors.

Two of these inhibitors are currently approved by the Food and Drug Administration, with others poised for approval.

Warfarin, the current standard for outpatient oral anticoagulant therapy, leaves a lot to be desired. The need for International Normalized Ratio (INR) monitoring has made patient compliance a significant problem, as some patients must travel routinely to their doctor’s office or warfarin clinics for blood monitoring (although there has been some movement toward putting the INR-monitoring process into patient hands). Even for compliant patients, reaching and maintaining an appropriate INR can be difficult, and warfarin carries the risk of a major bleed, especially among fragile elderly patients.

But is a move from warfarin to the new drugs premature? Many concerns remain, including potential difficulties with surgery in patients taking these agents (See "New Oral Anticoagulants Troublesome in the Trauma Setting," below).

The two FDA-approved drugs are rivaroxaban (Xarelto, marketed by Janssen Pharmaceuticals), which is a direct factor Xa inhibitor, and dabigatran (Pradaxa, marketed by Boehringer Ingelheim), a direct thrombin inhibitor.

Rivaroxaban (a member of the "xaban" family) was approved for two separate indications: the prevention of deep vein thrombosis in knee or hip replacement surgery (July 2011) and stroke prophylaxis in patients with nonvalvular atrial fibrillation (November 2011). Taken as a once-daily dose, the drug does not require routine blood monitoring – a key advantage over warfarin. According to the ROCKET-AF trial on which the approval was based, rivaroxaban had a major bleeding rate similar to that of warfarin; however, while it caused less bleeding into the brain, it caused more bleeding into the stomach and intestines.

During the approval process for rivaroxaban, FDA panelists questioned whether the drug was properly compared with the highest contemporary standards for warfarin and noted that it did not provide a "robust noninferiority" to dabigatran. These concerns led the panel to suggest that rivaroxaban be used only as a third-line therapy when warfarin and dabigatran are not options. Panelists also wondered what happens when patients stop using the drug. Rivaroxaban is now marketed with a boxed warning that sudden discontinuation increases the risk of stroke.

The FDA approved dabigatran in October 2010 for long-term anticoagulation in patients with atrial fibrillation, and by late August 2011, U.S. physicians had written 250,000 prescriptions for the drug.

But questions about the drug’s safety have been raised recently. In December 2011, the FDA announced that it was looking into reports of serious bleeding events associated with dabigatran, while reaffirming its belief that "the benefit of Pradaxa continues to exceed the potential risks when the drug is used appropriately." The FDA’s concerns were prompted in part by a European Medicines Agency (EMA) safety update in November noting "a worldwide total of 256 spontaneous case reports of serious bleeding resulting in death."

In October, the EMA’s Committee for Medicinal Products for Human Use had recommended that dabigatran be labeled to advise testing for renal function in all patients before starting treatment and, for those taking the drug, renal function assessment at least once a year in patients older than 75 years and patients of any age with a suspected decline in renal function.

A meta-analysis of seven randomized clinical trials published online in the January 2012 Archives of Internal Medicine (Arch. Intern. Med. 2012 Jan. 9 [doi:10.1001/archinternmed.2011.1666]) showed that dabigatran appeared to increase the risk of myocardial infarction and acute coronary syndrome, compared with warfarin, enoxaparin, and placebo. The incidence of these events was 1.19% in those taking dabigatran vs. 0.79% in the controls.

Another new anticoagulant, apixaban, has been approved as Eliquis in the European Union and fast-tracked for approval in the United States. Apixaban outperformed warfarin in the ARISTOTLE trial in preventing stroke, reducing bleeding, and increasing survival, regardless of how well-controlled patients were on warfarin, dabigatran, and rivaroxaban. Results achieved with apixaban were better than those seen in the trials of dabigatran and rivaroxaban against warfarin (N. Engl. J. Med 2011;365:981-92).

Of particular interest is apixaban’s good bleeding profile, compared with those of the other drugs (N. Engl. J. Med. 2011;364:806-17). "We have two trials in a large program showing this safety. In AVERROES, the bleeding risk with apixaban was the same as with low-dose aspirin," Dr. Lars Wallentin said in an interview. Dr. Wallentin is professor and head of cardiology research at Uppsala (Sweden) University and a coinvestigator in the ARISTOTLE trial.

The APPRAISE-2 trial showed that adding apixaban to standard antiplatelet therapy in patients with acute cardiac syndrome resulted in a 1.3% rate of major bleeding, compared with 0.5% with placebo, including five fatal bleeding events vs. none with placebo.

Unlike warfarin, these new anticoagulants have no defined antidotes – a lack that is of particular concern to surgeons. In a review of the new antithrombotic drugs presented at the 2011 VEITH symposium, Dr. Russell H. Samson said of dabigatran: "There is no antidote, so this drug should be used sparingly if surgery is anticipated. Thus, it is probably not a drug that should be used to prevent graft failure." Dr. Samson is a clinical associate professor of vascular surgery at Florida State University in Tallahassee.

A recent editorial in the New England Journal of Medicine sounded another note of caution. "Switching to a newer agent may not be necessary for the patient in whom INR has been well controlled with warfarin for years," Dr. Jessica Mega of Brigham and Women’s Hospital, Boston wrote (N. Engl. J. Med. 2011;365:1052-4). "In addition, although the newer anticoagulants have a more rapid onset and termination of anticoagulation than does warfarin, agents to reverse the effects of the drugs are still under development and are not routinely available."

The enthusiasm for the new anticoagulants may be premature for other reasons as well, such as the cost-effectiveness of these drugs, compared with the much cheaper warfarin, Dr. Mega said.

Elizabeth Mechcatie, Kerri Wachter, and Mitchel L. Zoler contributed to this report.

Because anticoagulation is a balancing act between the prevention of clots and the risk of major bleeds, tremendous efforts have been made to find the safest, most effective drugs possible. The foundations of anticoagulant therapy – warfarin (taken orally) and heparin (taken intravenously) – are being shaken by an onslaught of the newer oral factor Xa inhibitors and direct thrombin inhibitors.

Two of these inhibitors are currently approved by the Food and Drug Administration, with others poised for approval.

Warfarin, the current standard for outpatient oral anticoagulant therapy, leaves a lot to be desired. The need for International Normalized Ratio (INR) monitoring has made patient compliance a significant problem, as some patients must travel routinely to their doctor’s office or warfarin clinics for blood monitoring (although there has been some movement toward putting the INR-monitoring process into patient hands). Even for compliant patients, reaching and maintaining an appropriate INR can be difficult, and warfarin carries the risk of a major bleed, especially among fragile elderly patients.

But is a move from warfarin to the new drugs premature? Many concerns remain, including potential difficulties with surgery in patients taking these agents (See "New Oral Anticoagulants Troublesome in the Trauma Setting," below).

The two FDA-approved drugs are rivaroxaban (Xarelto, marketed by Janssen Pharmaceuticals), which is a direct factor Xa inhibitor, and dabigatran (Pradaxa, marketed by Boehringer Ingelheim), a direct thrombin inhibitor.

Rivaroxaban (a member of the "xaban" family) was approved for two separate indications: the prevention of deep vein thrombosis in knee or hip replacement surgery (July 2011) and stroke prophylaxis in patients with nonvalvular atrial fibrillation (November 2011). Taken as a once-daily dose, the drug does not require routine blood monitoring – a key advantage over warfarin. According to the ROCKET-AF trial on which the approval was based, rivaroxaban had a major bleeding rate similar to that of warfarin; however, while it caused less bleeding into the brain, it caused more bleeding into the stomach and intestines.

During the approval process for rivaroxaban, FDA panelists questioned whether the drug was properly compared with the highest contemporary standards for warfarin and noted that it did not provide a "robust noninferiority" to dabigatran. These concerns led the panel to suggest that rivaroxaban be used only as a third-line therapy when warfarin and dabigatran are not options. Panelists also wondered what happens when patients stop using the drug. Rivaroxaban is now marketed with a boxed warning that sudden discontinuation increases the risk of stroke.

The FDA approved dabigatran in October 2010 for long-term anticoagulation in patients with atrial fibrillation, and by late August 2011, U.S. physicians had written 250,000 prescriptions for the drug.

But questions about the drug’s safety have been raised recently. In December 2011, the FDA announced that it was looking into reports of serious bleeding events associated with dabigatran, while reaffirming its belief that "the benefit of Pradaxa continues to exceed the potential risks when the drug is used appropriately." The FDA’s concerns were prompted in part by a European Medicines Agency (EMA) safety update in November noting "a worldwide total of 256 spontaneous case reports of serious bleeding resulting in death."

In October, the EMA’s Committee for Medicinal Products for Human Use had recommended that dabigatran be labeled to advise testing for renal function in all patients before starting treatment and, for those taking the drug, renal function assessment at least once a year in patients older than 75 years and patients of any age with a suspected decline in renal function.

A meta-analysis of seven randomized clinical trials published online in the January 2012 Archives of Internal Medicine (Arch. Intern. Med. 2012 Jan. 9 [doi:10.1001/archinternmed.2011.1666]) showed that dabigatran appeared to increase the risk of myocardial infarction and acute coronary syndrome, compared with warfarin, enoxaparin, and placebo. The incidence of these events was 1.19% in those taking dabigatran vs. 0.79% in the controls.

Another new anticoagulant, apixaban, has been approved as Eliquis in the European Union and fast-tracked for approval in the United States. Apixaban outperformed warfarin in the ARISTOTLE trial in preventing stroke, reducing bleeding, and increasing survival, regardless of how well-controlled patients were on warfarin, dabigatran, and rivaroxaban. Results achieved with apixaban were better than those seen in the trials of dabigatran and rivaroxaban against warfarin (N. Engl. J. Med 2011;365:981-92).

Of particular interest is apixaban’s good bleeding profile, compared with those of the other drugs (N. Engl. J. Med. 2011;364:806-17). "We have two trials in a large program showing this safety. In AVERROES, the bleeding risk with apixaban was the same as with low-dose aspirin," Dr. Lars Wallentin said in an interview. Dr. Wallentin is professor and head of cardiology research at Uppsala (Sweden) University and a coinvestigator in the ARISTOTLE trial.

The APPRAISE-2 trial showed that adding apixaban to standard antiplatelet therapy in patients with acute cardiac syndrome resulted in a 1.3% rate of major bleeding, compared with 0.5% with placebo, including five fatal bleeding events vs. none with placebo.

Unlike warfarin, these new anticoagulants have no defined antidotes – a lack that is of particular concern to surgeons. In a review of the new antithrombotic drugs presented at the 2011 VEITH symposium, Dr. Russell H. Samson said of dabigatran: "There is no antidote, so this drug should be used sparingly if surgery is anticipated. Thus, it is probably not a drug that should be used to prevent graft failure." Dr. Samson is a clinical associate professor of vascular surgery at Florida State University in Tallahassee.

A recent editorial in the New England Journal of Medicine sounded another note of caution. "Switching to a newer agent may not be necessary for the patient in whom INR has been well controlled with warfarin for years," Dr. Jessica Mega of Brigham and Women’s Hospital, Boston wrote (N. Engl. J. Med. 2011;365:1052-4). "In addition, although the newer anticoagulants have a more rapid onset and termination of anticoagulation than does warfarin, agents to reverse the effects of the drugs are still under development and are not routinely available."

The enthusiasm for the new anticoagulants may be premature for other reasons as well, such as the cost-effectiveness of these drugs, compared with the much cheaper warfarin, Dr. Mega said.

Elizabeth Mechcatie, Kerri Wachter, and Mitchel L. Zoler contributed to this report.

Because anticoagulation is a balancing act between the prevention of clots and the risk of major bleeds, tremendous efforts have been made to find the safest, most effective drugs possible. The foundations of anticoagulant therapy – warfarin (taken orally) and heparin (taken intravenously) – are being shaken by an onslaught of the newer oral factor Xa inhibitors and direct thrombin inhibitors.

Two of these inhibitors are currently approved by the Food and Drug Administration, with others poised for approval.

Warfarin, the current standard for outpatient oral anticoagulant therapy, leaves a lot to be desired. The need for International Normalized Ratio (INR) monitoring has made patient compliance a significant problem, as some patients must travel routinely to their doctor’s office or warfarin clinics for blood monitoring (although there has been some movement toward putting the INR-monitoring process into patient hands). Even for compliant patients, reaching and maintaining an appropriate INR can be difficult, and warfarin carries the risk of a major bleed, especially among fragile elderly patients.

But is a move from warfarin to the new drugs premature? Many concerns remain, including potential difficulties with surgery in patients taking these agents (See "New Oral Anticoagulants Troublesome in the Trauma Setting," below).

The two FDA-approved drugs are rivaroxaban (Xarelto, marketed by Janssen Pharmaceuticals), which is a direct factor Xa inhibitor, and dabigatran (Pradaxa, marketed by Boehringer Ingelheim), a direct thrombin inhibitor.

Rivaroxaban (a member of the "xaban" family) was approved for two separate indications: the prevention of deep vein thrombosis in knee or hip replacement surgery (July 2011) and stroke prophylaxis in patients with nonvalvular atrial fibrillation (November 2011). Taken as a once-daily dose, the drug does not require routine blood monitoring – a key advantage over warfarin. According to the ROCKET-AF trial on which the approval was based, rivaroxaban had a major bleeding rate similar to that of warfarin; however, while it caused less bleeding into the brain, it caused more bleeding into the stomach and intestines.

During the approval process for rivaroxaban, FDA panelists questioned whether the drug was properly compared with the highest contemporary standards for warfarin and noted that it did not provide a "robust noninferiority" to dabigatran. These concerns led the panel to suggest that rivaroxaban be used only as a third-line therapy when warfarin and dabigatran are not options. Panelists also wondered what happens when patients stop using the drug. Rivaroxaban is now marketed with a boxed warning that sudden discontinuation increases the risk of stroke.

The FDA approved dabigatran in October 2010 for long-term anticoagulation in patients with atrial fibrillation, and by late August 2011, U.S. physicians had written 250,000 prescriptions for the drug.

But questions about the drug’s safety have been raised recently. In December 2011, the FDA announced that it was looking into reports of serious bleeding events associated with dabigatran, while reaffirming its belief that "the benefit of Pradaxa continues to exceed the potential risks when the drug is used appropriately." The FDA’s concerns were prompted in part by a European Medicines Agency (EMA) safety update in November noting "a worldwide total of 256 spontaneous case reports of serious bleeding resulting in death."

In October, the EMA’s Committee for Medicinal Products for Human Use had recommended that dabigatran be labeled to advise testing for renal function in all patients before starting treatment and, for those taking the drug, renal function assessment at least once a year in patients older than 75 years and patients of any age with a suspected decline in renal function.

A meta-analysis of seven randomized clinical trials published online in the January 2012 Archives of Internal Medicine (Arch. Intern. Med. 2012 Jan. 9 [doi:10.1001/archinternmed.2011.1666]) showed that dabigatran appeared to increase the risk of myocardial infarction and acute coronary syndrome, compared with warfarin, enoxaparin, and placebo. The incidence of these events was 1.19% in those taking dabigatran vs. 0.79% in the controls.

Another new anticoagulant, apixaban, has been approved as Eliquis in the European Union and fast-tracked for approval in the United States. Apixaban outperformed warfarin in the ARISTOTLE trial in preventing stroke, reducing bleeding, and increasing survival, regardless of how well-controlled patients were on warfarin, dabigatran, and rivaroxaban. Results achieved with apixaban were better than those seen in the trials of dabigatran and rivaroxaban against warfarin (N. Engl. J. Med 2011;365:981-92).

Of particular interest is apixaban’s good bleeding profile, compared with those of the other drugs (N. Engl. J. Med. 2011;364:806-17). "We have two trials in a large program showing this safety. In AVERROES, the bleeding risk with apixaban was the same as with low-dose aspirin," Dr. Lars Wallentin said in an interview. Dr. Wallentin is professor and head of cardiology research at Uppsala (Sweden) University and a coinvestigator in the ARISTOTLE trial.

The APPRAISE-2 trial showed that adding apixaban to standard antiplatelet therapy in patients with acute cardiac syndrome resulted in a 1.3% rate of major bleeding, compared with 0.5% with placebo, including five fatal bleeding events vs. none with placebo.

Unlike warfarin, these new anticoagulants have no defined antidotes – a lack that is of particular concern to surgeons. In a review of the new antithrombotic drugs presented at the 2011 VEITH symposium, Dr. Russell H. Samson said of dabigatran: "There is no antidote, so this drug should be used sparingly if surgery is anticipated. Thus, it is probably not a drug that should be used to prevent graft failure." Dr. Samson is a clinical associate professor of vascular surgery at Florida State University in Tallahassee.

A recent editorial in the New England Journal of Medicine sounded another note of caution. "Switching to a newer agent may not be necessary for the patient in whom INR has been well controlled with warfarin for years," Dr. Jessica Mega of Brigham and Women’s Hospital, Boston wrote (N. Engl. J. Med. 2011;365:1052-4). "In addition, although the newer anticoagulants have a more rapid onset and termination of anticoagulation than does warfarin, agents to reverse the effects of the drugs are still under development and are not routinely available."

The enthusiasm for the new anticoagulants may be premature for other reasons as well, such as the cost-effectiveness of these drugs, compared with the much cheaper warfarin, Dr. Mega said.

Elizabeth Mechcatie, Kerri Wachter, and Mitchel L. Zoler contributed to this report.

Medical device studies have shown persistent underrepresentation of women – a sex gap that could have a profound impact on the health of women who receive such devices.

In an attempt to correct this disparity, the Food and Drug Administration’s Center for Devices and Radiological Health (CDRH) issued draft guidance in December 2011 outlining the center’s expectations regarding sex-specific patient enrollment, data analysis, and reporting.

The goal of the guidance is to improve the quality and consistency of data on the performance of medical devices in both sexes, in particular addressing the underrepresentation of women in such studies. When the document is finalized after a 90-day comment period ending in March, it will represent the FDA’s current thinking on the topic.

In a recent evaluation of all cardiovascular Premarket Approval Applications submitted between 2000 and 2007, researchers reported that even among the pivotal studies that reported sex, an average of only 33.9% women were enrolled (Am. J. Therapeutics 2010;17:2-7).

This problem mirrors an earlier underrepresentation of women in clinical drug studies, which the FDA’s Office of Special Health Issues addressed in 2003.

Not a Matter of Political Correctness

As with drug trials, the lack of representation of women in clinical device trials is not just an abstract problem. There are very real differences in the responses and potential responses of women and men to medical devices, as described in the FDA guidance report.

For example, in recent studies of next-generation ventricular assist devices (VADs), females or covariates associated with sex (body surface area) exhibited a higher rate of stroke than males, at 18% and 6%, respectively, and women also showed a trend toward increased bleeding and infection. This led to an FDA Advisory Committee recommendation that a postapproval study be conducted with adequate collection of data on both sex and body surface area to determine whether differences existed in device performance.

The case of VADs is also instructive with regard to overall sex-related differences in initial device development and design. Original devices were generally too large for many women and the pediatric population. According to the National Heart, Lung, and Blood Institute, "until recently, VADs were too big to fit in many people’s chests, especially women. Only people who had large chests could get one. Now implantable VADs can fit in most adults and even some older children."

Devices for infants and smaller children are in various stages of development, with Berlin Heart’s Excor being the first to receive a Humanitarian Device Exemption from the FDA in December 2011.

Physiologic differences between the sexes also have the potential to affect device performance. In a recent study, post hoc sex-specific analysis demonstrated that cardiac resynchronization therapy defibrillators (CRT-Ds) – as compared to simple implantable cardioverter defibrillators – showed a significantly greater reduction in the composite end point of all-cause mortality or first heart failure in women vs. men (77% vs. 42%, respectively). This study also showed that left bundle branch block, which is a marker of an electrical conduction disorder in the heart associated with a greater benefit in patients receiving CRT, was significantly more common in women than in men (87% vs. 65%) (J. Am. Coll. Cardiol. 2011;57:813-20).

Addressing Enrollment Problems

Much of the current CDRH report addressing medical devices is based on the results of an FDA workshop held in 2008 to address the issue. Participants in that workshop admitted that there were significant barriers to the enrollment of women in clinical studies of medical devices, including:

• Fear of consequences to a fetus if the woman becomes pregnant (especially with regard to radiographic assessments or concomitant drug therapy).

• Lack of understanding of differences in disease etiology and pathophysiology that may lead to underdiagnosis and underreferral of women.

• Avoidance of female patients due to perceived difficulties in recruitment.

• Inclusion/exclusion criteria that may unintentionally exclude women (e.g., upper age limit).

• Family responsibilities that may limit participation of women.

Nevertheless, the FDA guidance makes specific recommendations for achieving representative enrollment of women in clinical trials. With regard to potential sex differences of relevance to a new device, the agency recommends providing background information on sex-specific prevalence of the condition; sex-specific diagnostic and treatment patterns; identification of proportions of women included in past studies for the target indication; and identification of any known, clinically significant sex differences in outcomes related to either safety or effectiveness.

This information should be included in study and submission documents, new or ongoing studies, completed studies in the marketing application stage, and postmarket studies – with specific details for each level of the studies.

Such efforts should be directed not only with regard to women, but also to the underrepresentation of men in areas such as breast cancer and bone-density loss research, where the majority of affected subjects tend to be women, according to the guidance report.

Sex-specific statistical analysis should also be part of the study designs, and there are reporting and language recommendations for sex-specific information in summaries and labeling of devices.

Good Intentions Not Enough?

FDA guidance documents do not establish legally enforceable responsibilities, according to the agency; instead, they describe the current thinking on a topic and should be viewed only as recommendations unless specific statutory or regulatory requirements are cited.

The FDA document provides a number of helpful guidelines to support adequate enrollment of women in clinical trials, according to an editorial comment by Dr. Sanket S. Dhruva and Dr. Rita F. Redberg of the University of California, San Francisco, published online Feb. 29 in JAMA (doi:10.1001/jama.2012.254).

"Following this recommendation so that women are enrolled in proportion to disease prevalence would do the most to ensure sufficient data about the effect of a medical device on women," they said.

"By not limiting its guidance to new studies, the FDA is indicating that it hopes changes will occur more immediately. ... The recommendations in this draft guidance may help ensure safe and effective medical devices in both sexes," they added.

However, despite the FDA’s laudable attempts to expand the participation of women patients in clinical trials of medical devices, according to Dr. Dhruva and Dr. Redberg, there is the inevitable problem of creating "nonbinding" guidelines in an era when the expense of conducting clinical trials is already considered one of the main barriers to developing and deploying new drugs and medical devices.

Nonbinding means nonparticipation, they added, citing as proof the example of the National Institutes of Health. The NIH developed sex bias guidelines in the late 1980s, and first adopted them as nonbinding encouragement for enrollment of women patients in all federally funded research. A few years later, the NIH noted that little progress had been made, and in the early 1990s, inclusion of women became a requirement for NIH funding, and annual progress reports were required. These changes led to a substantial increase in the number of women included in studies.

"The FDA should return device applications that have not enrolled sufficient numbers of women (or justified the reason for insufficient enrollment of women) or performed sex-specific analyses per the guidance document," wrote Dr. Dhruva and Dr. Redberg. Specifically, sex-specific analyses "should be performed for primary effectiveness end points, primary safety end points, and key secondary end points," they said.

In addition, the FDA should require transparency. "The practice of keeping sex-specific analyses ‘confidential’ must end," they said. And postmarketing analyses of outcomes must be performed in women as well as men, with penalties for noncompliance.

They concluded that it was time to ensure that FDA approval of medical devices be "based on data that they are safe and effective in both women and men."

Dr. Dhruva and Dr. Redberg stated that they had no conflicts of interest.

Final Note: A Question of Sexual Identity?

In formulating its guideline, the FDA felt the need to indulge in some elementary sex education – specifically by addressing the confusion regarding sex and gender that occurs in the literature and in medical device parlance. The agency referred to a 2001 consensus report published by the Institute of Medicine titled "Exploring the Biological Contributions to Human Health: Does Sex Matter?"which indicated that the terms have distinct definitions that should be used consistently to describe research results.

Sex refers to differences associated with biological difference, and as such is of greatest interest to the Center for Devices and Radiological Health, the FDA indicated. Gender refers to a person’s self-representation as male or female or how that person is responded to by social institutions based on the individual’s gender presentation. Gender, though rooted in biology, is shaped by environment and experience, the report stated.

The FDA noted that most medical device studies have used gender as a surrogate for sex. However, the agency said that its guidance "is focused on addressing potential differences in study design, conduct, and interpretations that should be considered to ensure sex-specific issues are adequately addressed in clinical studies."

Medical device studies have shown persistent underrepresentation of women – a sex gap that could have a profound impact on the health of women who receive such devices.

In an attempt to correct this disparity, the Food and Drug Administration’s Center for Devices and Radiological Health (CDRH) issued draft guidance in December 2011 outlining the center’s expectations regarding sex-specific patient enrollment, data analysis, and reporting.

The goal of the guidance is to improve the quality and consistency of data on the performance of medical devices in both sexes, in particular addressing the underrepresentation of women in such studies. When the document is finalized after a 90-day comment period ending in March, it will represent the FDA’s current thinking on the topic.

In a recent evaluation of all cardiovascular Premarket Approval Applications submitted between 2000 and 2007, researchers reported that even among the pivotal studies that reported sex, an average of only 33.9% women were enrolled (Am. J. Therapeutics 2010;17:2-7).

This problem mirrors an earlier underrepresentation of women in clinical drug studies, which the FDA’s Office of Special Health Issues addressed in 2003.

Not a Matter of Political Correctness

As with drug trials, the lack of representation of women in clinical device trials is not just an abstract problem. There are very real differences in the responses and potential responses of women and men to medical devices, as described in the FDA guidance report.

For example, in recent studies of next-generation ventricular assist devices (VADs), females or covariates associated with sex (body surface area) exhibited a higher rate of stroke than males, at 18% and 6%, respectively, and women also showed a trend toward increased bleeding and infection. This led to an FDA Advisory Committee recommendation that a postapproval study be conducted with adequate collection of data on both sex and body surface area to determine whether differences existed in device performance.

The case of VADs is also instructive with regard to overall sex-related differences in initial device development and design. Original devices were generally too large for many women and the pediatric population. According to the National Heart, Lung, and Blood Institute, "until recently, VADs were too big to fit in many people’s chests, especially women. Only people who had large chests could get one. Now implantable VADs can fit in most adults and even some older children."

Devices for infants and smaller children are in various stages of development, with Berlin Heart’s Excor being the first to receive a Humanitarian Device Exemption from the FDA in December 2011.

Physiologic differences between the sexes also have the potential to affect device performance. In a recent study, post hoc sex-specific analysis demonstrated that cardiac resynchronization therapy defibrillators (CRT-Ds) – as compared to simple implantable cardioverter defibrillators – showed a significantly greater reduction in the composite end point of all-cause mortality or first heart failure in women vs. men (77% vs. 42%, respectively). This study also showed that left bundle branch block, which is a marker of an electrical conduction disorder in the heart associated with a greater benefit in patients receiving CRT, was significantly more common in women than in men (87% vs. 65%) (J. Am. Coll. Cardiol. 2011;57:813-20).

Addressing Enrollment Problems

Much of the current CDRH report addressing medical devices is based on the results of an FDA workshop held in 2008 to address the issue. Participants in that workshop admitted that there were significant barriers to the enrollment of women in clinical studies of medical devices, including:

• Fear of consequences to a fetus if the woman becomes pregnant (especially with regard to radiographic assessments or concomitant drug therapy).

• Lack of understanding of differences in disease etiology and pathophysiology that may lead to underdiagnosis and underreferral of women.

• Avoidance of female patients due to perceived difficulties in recruitment.

• Inclusion/exclusion criteria that may unintentionally exclude women (e.g., upper age limit).

• Family responsibilities that may limit participation of women.

Nevertheless, the FDA guidance makes specific recommendations for achieving representative enrollment of women in clinical trials. With regard to potential sex differences of relevance to a new device, the agency recommends providing background information on sex-specific prevalence of the condition; sex-specific diagnostic and treatment patterns; identification of proportions of women included in past studies for the target indication; and identification of any known, clinically significant sex differences in outcomes related to either safety or effectiveness.

This information should be included in study and submission documents, new or ongoing studies, completed studies in the marketing application stage, and postmarket studies – with specific details for each level of the studies.

Such efforts should be directed not only with regard to women, but also to the underrepresentation of men in areas such as breast cancer and bone-density loss research, where the majority of affected subjects tend to be women, according to the guidance report.

Sex-specific statistical analysis should also be part of the study designs, and there are reporting and language recommendations for sex-specific information in summaries and labeling of devices.

Good Intentions Not Enough?

FDA guidance documents do not establish legally enforceable responsibilities, according to the agency; instead, they describe the current thinking on a topic and should be viewed only as recommendations unless specific statutory or regulatory requirements are cited.

The FDA document provides a number of helpful guidelines to support adequate enrollment of women in clinical trials, according to an editorial comment by Dr. Sanket S. Dhruva and Dr. Rita F. Redberg of the University of California, San Francisco, published online Feb. 29 in JAMA (doi:10.1001/jama.2012.254).

"Following this recommendation so that women are enrolled in proportion to disease prevalence would do the most to ensure sufficient data about the effect of a medical device on women," they said.

"By not limiting its guidance to new studies, the FDA is indicating that it hopes changes will occur more immediately. ... The recommendations in this draft guidance may help ensure safe and effective medical devices in both sexes," they added.

However, despite the FDA’s laudable attempts to expand the participation of women patients in clinical trials of medical devices, according to Dr. Dhruva and Dr. Redberg, there is the inevitable problem of creating "nonbinding" guidelines in an era when the expense of conducting clinical trials is already considered one of the main barriers to developing and deploying new drugs and medical devices.

Nonbinding means nonparticipation, they added, citing as proof the example of the National Institutes of Health. The NIH developed sex bias guidelines in the late 1980s, and first adopted them as nonbinding encouragement for enrollment of women patients in all federally funded research. A few years later, the NIH noted that little progress had been made, and in the early 1990s, inclusion of women became a requirement for NIH funding, and annual progress reports were required. These changes led to a substantial increase in the number of women included in studies.

"The FDA should return device applications that have not enrolled sufficient numbers of women (or justified the reason for insufficient enrollment of women) or performed sex-specific analyses per the guidance document," wrote Dr. Dhruva and Dr. Redberg. Specifically, sex-specific analyses "should be performed for primary effectiveness end points, primary safety end points, and key secondary end points," they said.

In addition, the FDA should require transparency. "The practice of keeping sex-specific analyses ‘confidential’ must end," they said. And postmarketing analyses of outcomes must be performed in women as well as men, with penalties for noncompliance.

They concluded that it was time to ensure that FDA approval of medical devices be "based on data that they are safe and effective in both women and men."

Dr. Dhruva and Dr. Redberg stated that they had no conflicts of interest.

Final Note: A Question of Sexual Identity?

In formulating its guideline, the FDA felt the need to indulge in some elementary sex education – specifically by addressing the confusion regarding sex and gender that occurs in the literature and in medical device parlance. The agency referred to a 2001 consensus report published by the Institute of Medicine titled "Exploring the Biological Contributions to Human Health: Does Sex Matter?"which indicated that the terms have distinct definitions that should be used consistently to describe research results.

Sex refers to differences associated with biological difference, and as such is of greatest interest to the Center for Devices and Radiological Health, the FDA indicated. Gender refers to a person’s self-representation as male or female or how that person is responded to by social institutions based on the individual’s gender presentation. Gender, though rooted in biology, is shaped by environment and experience, the report stated.

The FDA noted that most medical device studies have used gender as a surrogate for sex. However, the agency said that its guidance "is focused on addressing potential differences in study design, conduct, and interpretations that should be considered to ensure sex-specific issues are adequately addressed in clinical studies."

Medical device studies have shown persistent underrepresentation of women – a sex gap that could have a profound impact on the health of women who receive such devices.

In an attempt to correct this disparity, the Food and Drug Administration’s Center for Devices and Radiological Health (CDRH) issued draft guidance in December 2011 outlining the center’s expectations regarding sex-specific patient enrollment, data analysis, and reporting.

The goal of the guidance is to improve the quality and consistency of data on the performance of medical devices in both sexes, in particular addressing the underrepresentation of women in such studies. When the document is finalized after a 90-day comment period ending in March, it will represent the FDA’s current thinking on the topic.

In a recent evaluation of all cardiovascular Premarket Approval Applications submitted between 2000 and 2007, researchers reported that even among the pivotal studies that reported sex, an average of only 33.9% women were enrolled (Am. J. Therapeutics 2010;17:2-7).

This problem mirrors an earlier underrepresentation of women in clinical drug studies, which the FDA’s Office of Special Health Issues addressed in 2003.

Not a Matter of Political Correctness

As with drug trials, the lack of representation of women in clinical device trials is not just an abstract problem. There are very real differences in the responses and potential responses of women and men to medical devices, as described in the FDA guidance report.

For example, in recent studies of next-generation ventricular assist devices (VADs), females or covariates associated with sex (body surface area) exhibited a higher rate of stroke than males, at 18% and 6%, respectively, and women also showed a trend toward increased bleeding and infection. This led to an FDA Advisory Committee recommendation that a postapproval study be conducted with adequate collection of data on both sex and body surface area to determine whether differences existed in device performance.

The case of VADs is also instructive with regard to overall sex-related differences in initial device development and design. Original devices were generally too large for many women and the pediatric population. According to the National Heart, Lung, and Blood Institute, "until recently, VADs were too big to fit in many people’s chests, especially women. Only people who had large chests could get one. Now implantable VADs can fit in most adults and even some older children."

Devices for infants and smaller children are in various stages of development, with Berlin Heart’s Excor being the first to receive a Humanitarian Device Exemption from the FDA in December 2011.

Physiologic differences between the sexes also have the potential to affect device performance. In a recent study, post hoc sex-specific analysis demonstrated that cardiac resynchronization therapy defibrillators (CRT-Ds) – as compared to simple implantable cardioverter defibrillators – showed a significantly greater reduction in the composite end point of all-cause mortality or first heart failure in women vs. men (77% vs. 42%, respectively). This study also showed that left bundle branch block, which is a marker of an electrical conduction disorder in the heart associated with a greater benefit in patients receiving CRT, was significantly more common in women than in men (87% vs. 65%) (J. Am. Coll. Cardiol. 2011;57:813-20).

Addressing Enrollment Problems

Much of the current CDRH report addressing medical devices is based on the results of an FDA workshop held in 2008 to address the issue. Participants in that workshop admitted that there were significant barriers to the enrollment of women in clinical studies of medical devices, including:

• Fear of consequences to a fetus if the woman becomes pregnant (especially with regard to radiographic assessments or concomitant drug therapy).

• Lack of understanding of differences in disease etiology and pathophysiology that may lead to underdiagnosis and underreferral of women.

• Avoidance of female patients due to perceived difficulties in recruitment.

• Inclusion/exclusion criteria that may unintentionally exclude women (e.g., upper age limit).

• Family responsibilities that may limit participation of women.

Nevertheless, the FDA guidance makes specific recommendations for achieving representative enrollment of women in clinical trials. With regard to potential sex differences of relevance to a new device, the agency recommends providing background information on sex-specific prevalence of the condition; sex-specific diagnostic and treatment patterns; identification of proportions of women included in past studies for the target indication; and identification of any known, clinically significant sex differences in outcomes related to either safety or effectiveness.

This information should be included in study and submission documents, new or ongoing studies, completed studies in the marketing application stage, and postmarket studies – with specific details for each level of the studies.

Such efforts should be directed not only with regard to women, but also to the underrepresentation of men in areas such as breast cancer and bone-density loss research, where the majority of affected subjects tend to be women, according to the guidance report.

Sex-specific statistical analysis should also be part of the study designs, and there are reporting and language recommendations for sex-specific information in summaries and labeling of devices.

Good Intentions Not Enough?

FDA guidance documents do not establish legally enforceable responsibilities, according to the agency; instead, they describe the current thinking on a topic and should be viewed only as recommendations unless specific statutory or regulatory requirements are cited.

The FDA document provides a number of helpful guidelines to support adequate enrollment of women in clinical trials, according to an editorial comment by Dr. Sanket S. Dhruva and Dr. Rita F. Redberg of the University of California, San Francisco, published online Feb. 29 in JAMA (doi:10.1001/jama.2012.254).

"Following this recommendation so that women are enrolled in proportion to disease prevalence would do the most to ensure sufficient data about the effect of a medical device on women," they said.

"By not limiting its guidance to new studies, the FDA is indicating that it hopes changes will occur more immediately. ... The recommendations in this draft guidance may help ensure safe and effective medical devices in both sexes," they added.

However, despite the FDA’s laudable attempts to expand the participation of women patients in clinical trials of medical devices, according to Dr. Dhruva and Dr. Redberg, there is the inevitable problem of creating "nonbinding" guidelines in an era when the expense of conducting clinical trials is already considered one of the main barriers to developing and deploying new drugs and medical devices.

Nonbinding means nonparticipation, they added, citing as proof the example of the National Institutes of Health. The NIH developed sex bias guidelines in the late 1980s, and first adopted them as nonbinding encouragement for enrollment of women patients in all federally funded research. A few years later, the NIH noted that little progress had been made, and in the early 1990s, inclusion of women became a requirement for NIH funding, and annual progress reports were required. These changes led to a substantial increase in the number of women included in studies.

"The FDA should return device applications that have not enrolled sufficient numbers of women (or justified the reason for insufficient enrollment of women) or performed sex-specific analyses per the guidance document," wrote Dr. Dhruva and Dr. Redberg. Specifically, sex-specific analyses "should be performed for primary effectiveness end points, primary safety end points, and key secondary end points," they said.

In addition, the FDA should require transparency. "The practice of keeping sex-specific analyses ‘confidential’ must end," they said. And postmarketing analyses of outcomes must be performed in women as well as men, with penalties for noncompliance.

They concluded that it was time to ensure that FDA approval of medical devices be "based on data that they are safe and effective in both women and men."

Dr. Dhruva and Dr. Redberg stated that they had no conflicts of interest.

Final Note: A Question of Sexual Identity?

In formulating its guideline, the FDA felt the need to indulge in some elementary sex education – specifically by addressing the confusion regarding sex and gender that occurs in the literature and in medical device parlance. The agency referred to a 2001 consensus report published by the Institute of Medicine titled "Exploring the Biological Contributions to Human Health: Does Sex Matter?"which indicated that the terms have distinct definitions that should be used consistently to describe research results.

Sex refers to differences associated with biological difference, and as such is of greatest interest to the Center for Devices and Radiological Health, the FDA indicated. Gender refers to a person’s self-representation as male or female or how that person is responded to by social institutions based on the individual’s gender presentation. Gender, though rooted in biology, is shaped by environment and experience, the report stated.

The FDA noted that most medical device studies have used gender as a surrogate for sex. However, the agency said that its guidance "is focused on addressing potential differences in study design, conduct, and interpretations that should be considered to ensure sex-specific issues are adequately addressed in clinical studies."

FT. LAUDERDALE, FLA. – Pretreatment staging of presumed N0 non–small cell lung cancer (NSCLC) misses unsuspected lymph node metastases that are subsequently discovered during surgical specimen evaluation in 10%-25% of cases. Thus it is critically important that surgical node dissection be done sufficiently completely to capture these misses, providing the appropriate upstaging for treatment decisions.

With the increasing movement to video-assisted thoracic surgery (VATS) approaches to lobectomy and segmentectomy, it is important to evaluate the comparative efficiency of VATS vs. thoracotomy (Open) in capturing this upstaging.

Martin Allred/Elsevier Global Medical News

To this end, an examination of the Society of Thoracic Surgeons (STS) General Thoracic Database was performed to determine the frequency of nodal metastases identified in clinically node-negative tumors by Open and VATS approaches to compare completeness of surgical nodal dissections, according to Dr. Daniel J. Boffa.

A total of 11,531 clinical stage I primary lung cancers resected from 2001 to 2010 were analyzed from the STS General Thoracic Database. These comprised 7,137 Open and 4,394 VATS procedures.

The researchers found significantly greater nodal upstaging in the Open groups (14.3%) as compared with the VATS group (11.6%).

Dr. Boffa stated that this was primarily due to the significantly greater upstaging from N0 to N1 that was seen in the Open (9.8%) versus the VATS group (7.0%). In contrast, upstaging from N0 to N2 was found to be similar in both groups (5.5% Open vs. 5.2% VATS, a non-significant difference).

Dr. Boffa presented this research at the annual meeting of the Society of Thoracic Surgeons.

When a multivariate analysis controlling for T status, laterality, body mass index, age, and sex was performed, N0 to N1 upstaging remained significantly less common with VATS than with Open surgery.

In a separate analysis, pathologic confirmation of clinical N1 also occurred significantly less often in the VATS group (42%) as compared with the Open group (54%), according to Dr. Boffa, who is an assistant professor of surgery at the Yale School of Medicine, New Haven, Conn.

"Mediastinal nodal evaluation by VATS and thoracotomy results in equivalent upstaging. However, lower rates of N1 upstaging and stage confirmation in the VATS group may indicate variability in the completeness of the peribronchial and hilar lymph node evaluation," according to Dr. Boffa.

"Systematic hilar dissection is encouraged, particularly as more surgeons adopt the VATS approach," he concluded, reiterating the importance of appropriate staging in the planning of patient treatment.

Dr. Boffa presented his research as one of the Richard E. Clark database papers during the STS annual meeting.

Dr. Boffa reported that he had no relevant conflicts of interest.

FT. LAUDERDALE, FLA. – Pretreatment staging of presumed N0 non–small cell lung cancer (NSCLC) misses unsuspected lymph node metastases that are subsequently discovered during surgical specimen evaluation in 10%-25% of cases. Thus it is critically important that surgical node dissection be done sufficiently completely to capture these misses, providing the appropriate upstaging for treatment decisions.

With the increasing movement to video-assisted thoracic surgery (VATS) approaches to lobectomy and segmentectomy, it is important to evaluate the comparative efficiency of VATS vs. thoracotomy (Open) in capturing this upstaging.

Martin Allred/Elsevier Global Medical News

To this end, an examination of the Society of Thoracic Surgeons (STS) General Thoracic Database was performed to determine the frequency of nodal metastases identified in clinically node-negative tumors by Open and VATS approaches to compare completeness of surgical nodal dissections, according to Dr. Daniel J. Boffa.

A total of 11,531 clinical stage I primary lung cancers resected from 2001 to 2010 were analyzed from the STS General Thoracic Database. These comprised 7,137 Open and 4,394 VATS procedures.

The researchers found significantly greater nodal upstaging in the Open groups (14.3%) as compared with the VATS group (11.6%).

Dr. Boffa stated that this was primarily due to the significantly greater upstaging from N0 to N1 that was seen in the Open (9.8%) versus the VATS group (7.0%). In contrast, upstaging from N0 to N2 was found to be similar in both groups (5.5% Open vs. 5.2% VATS, a non-significant difference).

Dr. Boffa presented this research at the annual meeting of the Society of Thoracic Surgeons.

When a multivariate analysis controlling for T status, laterality, body mass index, age, and sex was performed, N0 to N1 upstaging remained significantly less common with VATS than with Open surgery.

In a separate analysis, pathologic confirmation of clinical N1 also occurred significantly less often in the VATS group (42%) as compared with the Open group (54%), according to Dr. Boffa, who is an assistant professor of surgery at the Yale School of Medicine, New Haven, Conn.

"Mediastinal nodal evaluation by VATS and thoracotomy results in equivalent upstaging. However, lower rates of N1 upstaging and stage confirmation in the VATS group may indicate variability in the completeness of the peribronchial and hilar lymph node evaluation," according to Dr. Boffa.

"Systematic hilar dissection is encouraged, particularly as more surgeons adopt the VATS approach," he concluded, reiterating the importance of appropriate staging in the planning of patient treatment.

Dr. Boffa presented his research as one of the Richard E. Clark database papers during the STS annual meeting.

Dr. Boffa reported that he had no relevant conflicts of interest.

FT. LAUDERDALE, FLA. – Pretreatment staging of presumed N0 non–small cell lung cancer (NSCLC) misses unsuspected lymph node metastases that are subsequently discovered during surgical specimen evaluation in 10%-25% of cases. Thus it is critically important that surgical node dissection be done sufficiently completely to capture these misses, providing the appropriate upstaging for treatment decisions.

With the increasing movement to video-assisted thoracic surgery (VATS) approaches to lobectomy and segmentectomy, it is important to evaluate the comparative efficiency of VATS vs. thoracotomy (Open) in capturing this upstaging.

Martin Allred/Elsevier Global Medical News

To this end, an examination of the Society of Thoracic Surgeons (STS) General Thoracic Database was performed to determine the frequency of nodal metastases identified in clinically node-negative tumors by Open and VATS approaches to compare completeness of surgical nodal dissections, according to Dr. Daniel J. Boffa.

A total of 11,531 clinical stage I primary lung cancers resected from 2001 to 2010 were analyzed from the STS General Thoracic Database. These comprised 7,137 Open and 4,394 VATS procedures.

The researchers found significantly greater nodal upstaging in the Open groups (14.3%) as compared with the VATS group (11.6%).

Dr. Boffa stated that this was primarily due to the significantly greater upstaging from N0 to N1 that was seen in the Open (9.8%) versus the VATS group (7.0%). In contrast, upstaging from N0 to N2 was found to be similar in both groups (5.5% Open vs. 5.2% VATS, a non-significant difference).

Dr. Boffa presented this research at the annual meeting of the Society of Thoracic Surgeons.

When a multivariate analysis controlling for T status, laterality, body mass index, age, and sex was performed, N0 to N1 upstaging remained significantly less common with VATS than with Open surgery.

In a separate analysis, pathologic confirmation of clinical N1 also occurred significantly less often in the VATS group (42%) as compared with the Open group (54%), according to Dr. Boffa, who is an assistant professor of surgery at the Yale School of Medicine, New Haven, Conn.

"Mediastinal nodal evaluation by VATS and thoracotomy results in equivalent upstaging. However, lower rates of N1 upstaging and stage confirmation in the VATS group may indicate variability in the completeness of the peribronchial and hilar lymph node evaluation," according to Dr. Boffa.

"Systematic hilar dissection is encouraged, particularly as more surgeons adopt the VATS approach," he concluded, reiterating the importance of appropriate staging in the planning of patient treatment.

Dr. Boffa presented his research as one of the Richard E. Clark database papers during the STS annual meeting.

Dr. Boffa reported that he had no relevant conflicts of interest.

FT. LAUDERDALE, FLA. – Pretreatment staging of presumed N0 non–small cell lung cancer (NSCLC) misses unsuspected lymph node metastases that are subsequently discovered during surgical specimen evaluation in 10%-25% of cases. Thus it is critically important that surgical node dissection be done sufficiently completely to capture these misses, providing the appropriate upstaging for treatment decisions.

With the increasing movement to video-assisted thoracic surgery (VATS) approaches to lobectomy and segmentectomy, it is important to evaluate the comparative efficiency of VATS vs. thoracotomy (Open) in capturing this upstaging.

Martin Allred/Elsevier Global Medical News

To this end, an examination of the Society of Thoracic Surgeons (STS) General Thoracic Database was performed to determine the frequency of nodal metastases identified in clinically node-negative tumors by Open and VATS approaches to compare completeness of surgical nodal dissections, according to Dr. Daniel J. Boffa.

A total of 11,531 clinical stage I primary lung cancers resected from 2001 to 2010 were analyzed from the STS General Thoracic Database. These comprised 7,137 Open and 4,394 VATS procedures.

The researchers found significantly greater nodal upstaging in the Open groups (14.3%) as compared with the VATS group (11.6%).

Dr. Boffa stated that this was primarily due to the significantly greater upstaging from N0 to N1 that was seen in the Open (9.8%) versus the VATS group (7.0%). In contrast, upstaging from N0 to N2 was found to be similar in both groups (5.5% Open vs. 5.2% VATS, a non-significant difference).

Dr. Boffa presented this research at the annual meeting of the Society of Thoracic Surgeons.

When a multivariate analysis controlling for T status, laterality, body mass index, age, and sex was performed, N0 to N1 upstaging remained significantly less common with VATS than with Open surgery.

In a separate analysis, pathologic confirmation of clinical N1 also occurred significantly less often in the VATS group (42%) as compared with the Open group (54%), according to Dr. Boffa, who is an assistant professor of surgery at the Yale School of Medicine, New Haven, Conn.

"Mediastinal nodal evaluation by VATS and thoracotomy results in equivalent upstaging. However, lower rates of N1 upstaging and stage confirmation in the VATS group may indicate variability in the completeness of the peribronchial and hilar lymph node evaluation," according to Dr. Boffa.

"Systematic hilar dissection is encouraged, particularly as more surgeons adopt the VATS approach," he concluded, reiterating the importance of appropriate staging in the planning of patient treatment.

Dr. Boffa presented his research as one of the Richard E. Clark database papers during the STS annual meeting.

Dr. Boffa reported that he had no relevant conflicts of interest.

FT. LAUDERDALE, FLA. – Pretreatment staging of presumed N0 non–small cell lung cancer (NSCLC) misses unsuspected lymph node metastases that are subsequently discovered during surgical specimen evaluation in 10%-25% of cases. Thus it is critically important that surgical node dissection be done sufficiently completely to capture these misses, providing the appropriate upstaging for treatment decisions.

With the increasing movement to video-assisted thoracic surgery (VATS) approaches to lobectomy and segmentectomy, it is important to evaluate the comparative efficiency of VATS vs. thoracotomy (Open) in capturing this upstaging.

Martin Allred/Elsevier Global Medical News

To this end, an examination of the Society of Thoracic Surgeons (STS) General Thoracic Database was performed to determine the frequency of nodal metastases identified in clinically node-negative tumors by Open and VATS approaches to compare completeness of surgical nodal dissections, according to Dr. Daniel J. Boffa.

A total of 11,531 clinical stage I primary lung cancers resected from 2001 to 2010 were analyzed from the STS General Thoracic Database. These comprised 7,137 Open and 4,394 VATS procedures.

The researchers found significantly greater nodal upstaging in the Open groups (14.3%) as compared with the VATS group (11.6%).

Dr. Boffa stated that this was primarily due to the significantly greater upstaging from N0 to N1 that was seen in the Open (9.8%) versus the VATS group (7.0%). In contrast, upstaging from N0 to N2 was found to be similar in both groups (5.5% Open vs. 5.2% VATS, a non-significant difference).

Dr. Boffa presented this research at the annual meeting of the Society of Thoracic Surgeons.

When a multivariate analysis controlling for T status, laterality, body mass index, age, and sex was performed, N0 to N1 upstaging remained significantly less common with VATS than with Open surgery.

In a separate analysis, pathologic confirmation of clinical N1 also occurred significantly less often in the VATS group (42%) as compared with the Open group (54%), according to Dr. Boffa, who is an assistant professor of surgery at the Yale School of Medicine, New Haven, Conn.

"Mediastinal nodal evaluation by VATS and thoracotomy results in equivalent upstaging. However, lower rates of N1 upstaging and stage confirmation in the VATS group may indicate variability in the completeness of the peribronchial and hilar lymph node evaluation," according to Dr. Boffa.

"Systematic hilar dissection is encouraged, particularly as more surgeons adopt the VATS approach," he concluded, reiterating the importance of appropriate staging in the planning of patient treatment.

Dr. Boffa presented his research as one of the Richard E. Clark database papers during the STS annual meeting.

Dr. Boffa reported that he had no relevant conflicts of interest.

FT. LAUDERDALE, FLA. – Pretreatment staging of presumed N0 non–small cell lung cancer (NSCLC) misses unsuspected lymph node metastases that are subsequently discovered during surgical specimen evaluation in 10%-25% of cases. Thus it is critically important that surgical node dissection be done sufficiently completely to capture these misses, providing the appropriate upstaging for treatment decisions.

With the increasing movement to video-assisted thoracic surgery (VATS) approaches to lobectomy and segmentectomy, it is important to evaluate the comparative efficiency of VATS vs. thoracotomy (Open) in capturing this upstaging.

Martin Allred/Elsevier Global Medical News

To this end, an examination of the Society of Thoracic Surgeons (STS) General Thoracic Database was performed to determine the frequency of nodal metastases identified in clinically node-negative tumors by Open and VATS approaches to compare completeness of surgical nodal dissections, according to Dr. Daniel J. Boffa.

A total of 11,531 clinical stage I primary lung cancers resected from 2001 to 2010 were analyzed from the STS General Thoracic Database. These comprised 7,137 Open and 4,394 VATS procedures.

The researchers found significantly greater nodal upstaging in the Open groups (14.3%) as compared with the VATS group (11.6%).

Dr. Boffa stated that this was primarily due to the significantly greater upstaging from N0 to N1 that was seen in the Open (9.8%) versus the VATS group (7.0%). In contrast, upstaging from N0 to N2 was found to be similar in both groups (5.5% Open vs. 5.2% VATS, a non-significant difference).

Dr. Boffa presented this research at the annual meeting of the Society of Thoracic Surgeons.

When a multivariate analysis controlling for T status, laterality, body mass index, age, and sex was performed, N0 to N1 upstaging remained significantly less common with VATS than with Open surgery.

In a separate analysis, pathologic confirmation of clinical N1 also occurred significantly less often in the VATS group (42%) as compared with the Open group (54%), according to Dr. Boffa, who is an assistant professor of surgery at the Yale School of Medicine, New Haven, Conn.

"Mediastinal nodal evaluation by VATS and thoracotomy results in equivalent upstaging. However, lower rates of N1 upstaging and stage confirmation in the VATS group may indicate variability in the completeness of the peribronchial and hilar lymph node evaluation," according to Dr. Boffa.

"Systematic hilar dissection is encouraged, particularly as more surgeons adopt the VATS approach," he concluded, reiterating the importance of appropriate staging in the planning of patient treatment.

Dr. Boffa presented his research as one of the Richard E. Clark database papers during the STS annual meeting.

Dr. Boffa reported that he had no relevant conflicts of interest.

Women represent a minority of cardiothoracic surgeons in the United States, with roughly equal numbers being found in academic and private practice, according to a recent survey presented at the annual meeting of the Society for Thoracic Surgeons.

Overall, these women reported a high level of job satisfaction and the vast majority of them were still in practice.

Although there were comparatively few women in senior staff and faculty positions, in part because over 50% of women currently in practice entered the profession since the year 2000, "this exponential increase in the number of women in the field over the past ten years provides optimism for a continued recruitment," according to the report by Dr. Jessica S. Donington, assistant professor of cardiothoracic surgery at New York University, New York, N.Y.,and her colleagues on behalf of The Women in Thoracic Surgery (WTS).

The WTS was established as a professional organization in 1986, with the designated mission of providing mutual support and facilitating the professional advancement of women in cardiothoracic surgery.

With 2011 being the 50th anniversary of the first certification of a woman by the American Board of Thoracic Surgery (ABTS) and the year in which the 200th female was certified by the ABTS, the WTS deemed it important to survey the status of female cardiothoracic surgeons in the United States.

The WTS survey was designed to measure career progression and to provide insights in order to improve recruitment. All ABTS-certified women were surveyed anonymously in December 2010 using tools from surveymonkey.com, according to Dr. Donington.

Contact information was obtained from CTSNet, Google, and institutions of known employment.

Of the 204 living women with ABTS certification, 190 were contacted. Of these, 64% responded to the survey. The questions comprised five areas: demographics, training, practice activities, activities of non-practicing CT surgeons, and career satisfaction.

The researchers grouped the respondents by year of certification: Group 1 (1961-1999) and Group 2 (2000-2010). They used the STS/AATS 2009 practice survey of the entire thoracic surgery workforce in order to make broad-based comparisons.

The mean age of the women respondents was 48 years, with the majority being white (nearly 78%) and urban dwellers (61%).

Half of the women were certified within the past 10 years. Overall, the respondents had been practicing for a mean of 8 years, worked in groups of 2-10 surgeons, and were the only female surgeon in their group. The respondents had a mean of 9.1 years of training with 56% reporting non-Accreditation Council for Graduate Medical Education (ACGME) training time.

There was a significant increase in the duration of training and in the resultant debt over time. Group 1 respondents reported training for 8.5 years vs. 9.5 years in Group 2, with a doubling of graduates with educational debt greater than $100,000 in the later era.

Overall, the distribution of 118 respondents who answered the subspecialty question was 28% adult cardiac; 8.5% congenital cardiac; slightly less than 1% cardiopulmonary transplant; and 13.2% mixed subspecialties.

The 35.6% percent of women who identified themselves as general thoracic surgeons is higher than the 18% reported by the entire thoracic surgery workforce, with the percentage of women who identified themselves as general thoracic surgeons more than doubling in the second cohort of diplomates as compared with the first.

Slightly over 10% of respondents were no longer in CT surgery practice. All of these were certified prior to 2000, and the majority left practice due to retirement, health issues, or career advancement, according to their responses.

There was a large shift from the mixed category, which was cited by nearly 28% of the 51 women certified prior to 2000, compared with 3% of the 67 women certified after 2000.

This could be accounted for primarily by large increases in the adult cardiac (from nearly 20% prior to 2000 compared with 34% after 2000) and the general thoracic (from around 22% to 46%) subspecialty categories, reflecting the increase in subspecialization of our field.

Half of the women who responded had academic appointments, with 52% of these at the assistant professor level and 20% at the professor level. A minority of the women (20%) had protected research time, and 30% had secured research funding.

Overall, 64% of respondents reported that they were always or almost always satisfied with their profession.

The greatest source of dissatisfaction reported by both groups was demands on time, with workplace politics being a key concern expressed by Group 1 respondents, and lack of support a key concern expressed by Group 2.

Eighty percent of those polled stated that, if given the opportunity to choose a profession based on what they knew now, they would pursue cardiothoracic surgery again.

"Women still represent a minority of cardiothoracic surgeons in the United States, and over half are still very junior, having entered the profession since the year 2000.

Although the majority report being satisfied with their careers, and important academic milestones have been reached by some, there remains a scarcity of women in senior leadership positions.

"Since mentors and positive role models are consistently reported as significant factors in specialty decisions by surgical residents, this may still be the largest hurdle to recruiting women into cardiothoracic surgery," concluded Dr. Donington, in her presentation of the report.

Dr. Donington reported that she had no relevant financial disclosures.☐

Women represent a minority of cardiothoracic surgeons in the United States, with roughly equal numbers being found in academic and private practice, according to a recent survey presented at the annual meeting of the Society for Thoracic Surgeons.

Overall, these women reported a high level of job satisfaction and the vast majority of them were still in practice.

Although there were comparatively few women in senior staff and faculty positions, in part because over 50% of women currently in practice entered the profession since the year 2000, "this exponential increase in the number of women in the field over the past ten years provides optimism for a continued recruitment," according to the report by Dr. Jessica S. Donington, assistant professor of cardiothoracic surgery at New York University, New York, N.Y.,and her colleagues on behalf of The Women in Thoracic Surgery (WTS).

The WTS was established as a professional organization in 1986, with the designated mission of providing mutual support and facilitating the professional advancement of women in cardiothoracic surgery.

With 2011 being the 50th anniversary of the first certification of a woman by the American Board of Thoracic Surgery (ABTS) and the year in which the 200th female was certified by the ABTS, the WTS deemed it important to survey the status of female cardiothoracic surgeons in the United States.

The WTS survey was designed to measure career progression and to provide insights in order to improve recruitment. All ABTS-certified women were surveyed anonymously in December 2010 using tools from surveymonkey.com, according to Dr. Donington.

Contact information was obtained from CTSNet, Google, and institutions of known employment.

Of the 204 living women with ABTS certification, 190 were contacted. Of these, 64% responded to the survey. The questions comprised five areas: demographics, training, practice activities, activities of non-practicing CT surgeons, and career satisfaction.

The researchers grouped the respondents by year of certification: Group 1 (1961-1999) and Group 2 (2000-2010). They used the STS/AATS 2009 practice survey of the entire thoracic surgery workforce in order to make broad-based comparisons.

The mean age of the women respondents was 48 years, with the majority being white (nearly 78%) and urban dwellers (61%).

Half of the women were certified within the past 10 years. Overall, the respondents had been practicing for a mean of 8 years, worked in groups of 2-10 surgeons, and were the only female surgeon in their group. The respondents had a mean of 9.1 years of training with 56% reporting non-Accreditation Council for Graduate Medical Education (ACGME) training time.

There was a significant increase in the duration of training and in the resultant debt over time. Group 1 respondents reported training for 8.5 years vs. 9.5 years in Group 2, with a doubling of graduates with educational debt greater than $100,000 in the later era.

Overall, the distribution of 118 respondents who answered the subspecialty question was 28% adult cardiac; 8.5% congenital cardiac; slightly less than 1% cardiopulmonary transplant; and 13.2% mixed subspecialties.

The 35.6% percent of women who identified themselves as general thoracic surgeons is higher than the 18% reported by the entire thoracic surgery workforce, with the percentage of women who identified themselves as general thoracic surgeons more than doubling in the second cohort of diplomates as compared with the first.

Slightly over 10% of respondents were no longer in CT surgery practice. All of these were certified prior to 2000, and the majority left practice due to retirement, health issues, or career advancement, according to their responses.

There was a large shift from the mixed category, which was cited by nearly 28% of the 51 women certified prior to 2000, compared with 3% of the 67 women certified after 2000.

This could be accounted for primarily by large increases in the adult cardiac (from nearly 20% prior to 2000 compared with 34% after 2000) and the general thoracic (from around 22% to 46%) subspecialty categories, reflecting the increase in subspecialization of our field.

Half of the women who responded had academic appointments, with 52% of these at the assistant professor level and 20% at the professor level. A minority of the women (20%) had protected research time, and 30% had secured research funding.

Overall, 64% of respondents reported that they were always or almost always satisfied with their profession.

The greatest source of dissatisfaction reported by both groups was demands on time, with workplace politics being a key concern expressed by Group 1 respondents, and lack of support a key concern expressed by Group 2.

Eighty percent of those polled stated that, if given the opportunity to choose a profession based on what they knew now, they would pursue cardiothoracic surgery again.

"Women still represent a minority of cardiothoracic surgeons in the United States, and over half are still very junior, having entered the profession since the year 2000.

Although the majority report being satisfied with their careers, and important academic milestones have been reached by some, there remains a scarcity of women in senior leadership positions.

"Since mentors and positive role models are consistently reported as significant factors in specialty decisions by surgical residents, this may still be the largest hurdle to recruiting women into cardiothoracic surgery," concluded Dr. Donington, in her presentation of the report.

Dr. Donington reported that she had no relevant financial disclosures.☐

Women represent a minority of cardiothoracic surgeons in the United States, with roughly equal numbers being found in academic and private practice, according to a recent survey presented at the annual meeting of the Society for Thoracic Surgeons.

Overall, these women reported a high level of job satisfaction and the vast majority of them were still in practice.

Although there were comparatively few women in senior staff and faculty positions, in part because over 50% of women currently in practice entered the profession since the year 2000, "this exponential increase in the number of women in the field over the past ten years provides optimism for a continued recruitment," according to the report by Dr. Jessica S. Donington, assistant professor of cardiothoracic surgery at New York University, New York, N.Y.,and her colleagues on behalf of The Women in Thoracic Surgery (WTS).

The WTS was established as a professional organization in 1986, with the designated mission of providing mutual support and facilitating the professional advancement of women in cardiothoracic surgery.

With 2011 being the 50th anniversary of the first certification of a woman by the American Board of Thoracic Surgery (ABTS) and the year in which the 200th female was certified by the ABTS, the WTS deemed it important to survey the status of female cardiothoracic surgeons in the United States.

The WTS survey was designed to measure career progression and to provide insights in order to improve recruitment. All ABTS-certified women were surveyed anonymously in December 2010 using tools from surveymonkey.com, according to Dr. Donington.

Contact information was obtained from CTSNet, Google, and institutions of known employment.

Of the 204 living women with ABTS certification, 190 were contacted. Of these, 64% responded to the survey. The questions comprised five areas: demographics, training, practice activities, activities of non-practicing CT surgeons, and career satisfaction.

The researchers grouped the respondents by year of certification: Group 1 (1961-1999) and Group 2 (2000-2010). They used the STS/AATS 2009 practice survey of the entire thoracic surgery workforce in order to make broad-based comparisons.

The mean age of the women respondents was 48 years, with the majority being white (nearly 78%) and urban dwellers (61%).

Half of the women were certified within the past 10 years. Overall, the respondents had been practicing for a mean of 8 years, worked in groups of 2-10 surgeons, and were the only female surgeon in their group. The respondents had a mean of 9.1 years of training with 56% reporting non-Accreditation Council for Graduate Medical Education (ACGME) training time.

There was a significant increase in the duration of training and in the resultant debt over time. Group 1 respondents reported training for 8.5 years vs. 9.5 years in Group 2, with a doubling of graduates with educational debt greater than $100,000 in the later era.

Overall, the distribution of 118 respondents who answered the subspecialty question was 28% adult cardiac; 8.5% congenital cardiac; slightly less than 1% cardiopulmonary transplant; and 13.2% mixed subspecialties.

The 35.6% percent of women who identified themselves as general thoracic surgeons is higher than the 18% reported by the entire thoracic surgery workforce, with the percentage of women who identified themselves as general thoracic surgeons more than doubling in the second cohort of diplomates as compared with the first.

Slightly over 10% of respondents were no longer in CT surgery practice. All of these were certified prior to 2000, and the majority left practice due to retirement, health issues, or career advancement, according to their responses.

There was a large shift from the mixed category, which was cited by nearly 28% of the 51 women certified prior to 2000, compared with 3% of the 67 women certified after 2000.

This could be accounted for primarily by large increases in the adult cardiac (from nearly 20% prior to 2000 compared with 34% after 2000) and the general thoracic (from around 22% to 46%) subspecialty categories, reflecting the increase in subspecialization of our field.

Half of the women who responded had academic appointments, with 52% of these at the assistant professor level and 20% at the professor level. A minority of the women (20%) had protected research time, and 30% had secured research funding.

Overall, 64% of respondents reported that they were always or almost always satisfied with their profession.

The greatest source of dissatisfaction reported by both groups was demands on time, with workplace politics being a key concern expressed by Group 1 respondents, and lack of support a key concern expressed by Group 2.

Eighty percent of those polled stated that, if given the opportunity to choose a profession based on what they knew now, they would pursue cardiothoracic surgery again.

"Women still represent a minority of cardiothoracic surgeons in the United States, and over half are still very junior, having entered the profession since the year 2000.

Although the majority report being satisfied with their careers, and important academic milestones have been reached by some, there remains a scarcity of women in senior leadership positions.

"Since mentors and positive role models are consistently reported as significant factors in specialty decisions by surgical residents, this may still be the largest hurdle to recruiting women into cardiothoracic surgery," concluded Dr. Donington, in her presentation of the report.

Dr. Donington reported that she had no relevant financial disclosures.☐

Women represent a minority of cardiothoracic surgeons in the United States, with roughly equal numbers being found in academic and private practice, according to a recent survey presented at the annual meeting of the Society for Thoracic Surgeons.

Overall, these women reported a high level of job satisfaction and the vast majority of them were still in practice.

Although there were comparatively few women in senior staff and faculty positions, in part because over 50% of women currently in practice entered the profession since the year 2000, "this exponential increase in the number of women in the field over the past ten years provides optimism for a continued recruitment," according to the report by Dr. Jessica S. Donington, assistant professor of cardiothoracic surgery at New York University, New York, N.Y.,and her colleagues on behalf of The Women in Thoracic Surgery (WTS).

The WTS was established as a professional organization in 1986, with the designated mission of providing mutual support and facilitating the professional advancement of women in cardiothoracic surgery.

With 2011 being the 50th anniversary of the first certification of a woman by the American Board of Thoracic Surgery (ABTS) and the year in which the 200th female was certified by the ABTS, the WTS deemed it important to survey the status of female cardiothoracic surgeons in the United States.

The WTS survey was designed to measure career progression and to provide insights in order to improve recruitment. All ABTS-certified women were surveyed anonymously in December 2010 using tools from surveymonkey.com, according to Dr. Donington.

Contact information was obtained from CTSNet, Google, and institutions of known employment.

Of the 204 living women with ABTS certification, 190 were contacted. Of these, 64% responded to the survey. The questions comprised five areas: demographics, training, practice activities, activities of non-practicing CT surgeons, and career satisfaction.

The researchers grouped the respondents by year of certification: Group 1 (1961-1999) and Group 2 (2000-2010). They used the STS/AATS 2009 practice survey of the entire thoracic surgery workforce in order to make broad-based comparisons.

The mean age of the women respondents was 48 years, with the majority being white (nearly 78%) and urban dwellers (61%).

Half of the women were certified within the past 10 years. Overall, the respondents had been practicing for a mean of 8 years, worked in groups of 2-10 surgeons, and were the only female surgeon in their group. The respondents had a mean of 9.1 years of training with 56% reporting non-Accreditation Council for Graduate Medical Education (ACGME) training time.

There was a significant increase in the duration of training and in the resultant debt over time. Group 1 respondents reported training for 8.5 years vs. 9.5 years in Group 2, with a doubling of graduates with educational debt greater than $100,000 in the later era.

Overall, the distribution of 118 respondents who answered the subspecialty question was 28% adult cardiac; 8.5% congenital cardiac; slightly less than 1% cardiopulmonary transplant; and 13.2% mixed subspecialties.

The 35.6% percent of women who identified themselves as general thoracic surgeons is higher than the 18% reported by the entire thoracic surgery workforce, with the percentage of women who identified themselves as general thoracic surgeons more than doubling in the second cohort of diplomates as compared with the first.

Slightly over 10% of respondents were no longer in CT surgery practice. All of these were certified prior to 2000, and the majority left practice due to retirement, health issues, or career advancement, according to their responses.

There was a large shift from the mixed category, which was cited by nearly 28% of the 51 women certified prior to 2000, compared with 3% of the 67 women certified after 2000.

This could be accounted for primarily by large increases in the adult cardiac (from nearly 20% prior to 2000 compared with 34% after 2000) and the general thoracic (from around 22% to 46%) subspecialty categories, reflecting the increase in subspecialization of our field.

Half of the women who responded had academic appointments, with 52% of these at the assistant professor level and 20% at the professor level. A minority of the women (20%) had protected research time, and 30% had secured research funding.

Overall, 64% of respondents reported that they were always or almost always satisfied with their profession.

The greatest source of dissatisfaction reported by both groups was demands on time, with workplace politics being a key concern expressed by Group 1 respondents, and lack of support a key concern expressed by Group 2.

Eighty percent of those polled stated that, if given the opportunity to choose a profession based on what they knew now, they would pursue cardiothoracic surgery again.

"Women still represent a minority of cardiothoracic surgeons in the United States, and over half are still very junior, having entered the profession since the year 2000.

Although the majority report being satisfied with their careers, and important academic milestones have been reached by some, there remains a scarcity of women in senior leadership positions.

"Since mentors and positive role models are consistently reported as significant factors in specialty decisions by surgical residents, this may still be the largest hurdle to recruiting women into cardiothoracic surgery," concluded Dr. Donington, in her presentation of the report.

Dr. Donington reported that she had no relevant financial disclosures.☐

Women represent a minority of cardiothoracic surgeons in the United States, with roughly equal numbers being found in academic and private practice, according to a recent survey presented at the annual meeting of the Society for Thoracic Surgeons.

Overall, these women reported a high level of job satisfaction and the vast majority of them were still in practice.

Although there were comparatively few women in senior staff and faculty positions, in part because over 50% of women currently in practice entered the profession since the year 2000, "this exponential increase in the number of women in the field over the past ten years provides optimism for a continued recruitment," according to the report by Dr. Jessica S. Donington, assistant professor of cardiothoracic surgery at New York University, New York, N.Y.,and her colleagues on behalf of The Women in Thoracic Surgery (WTS).

The WTS was established as a professional organization in 1986, with the designated mission of providing mutual support and facilitating the professional advancement of women in cardiothoracic surgery.

With 2011 being the 50th anniversary of the first certification of a woman by the American Board of Thoracic Surgery (ABTS) and the year in which the 200th female was certified by the ABTS, the WTS deemed it important to survey the status of female cardiothoracic surgeons in the United States.

The WTS survey was designed to measure career progression and to provide insights in order to improve recruitment. All ABTS-certified women were surveyed anonymously in December 2010 using tools from surveymonkey.com, according to Dr. Donington.

Contact information was obtained from CTSNet, Google, and institutions of known employment.

Of the 204 living women with ABTS certification, 190 were contacted. Of these, 64% responded to the survey. The questions comprised five areas: demographics, training, practice activities, activities of non-practicing CT surgeons, and career satisfaction.

The researchers grouped the respondents by year of certification: Group 1 (1961-1999) and Group 2 (2000-2010). They used the STS/AATS 2009 practice survey of the entire thoracic surgery workforce in order to make broad-based comparisons.

The mean age of the women respondents was 48 years, with the majority being white (nearly 78%) and urban dwellers (61%).

Half of the women were certified within the past 10 years. Overall, the respondents had been practicing for a mean of 8 years, worked in groups of 2-10 surgeons, and were the only female surgeon in their group. The respondents had a mean of 9.1 years of training with 56% reporting non-Accreditation Council for Graduate Medical Education (ACGME) training time.

There was a significant increase in the duration of training and in the resultant debt over time. Group 1 respondents reported training for 8.5 years vs. 9.5 years in Group 2, with a doubling of graduates with educational debt greater than $100,000 in the later era.

Overall, the distribution of 118 respondents who answered the subspecialty question was 28% adult cardiac; 8.5% congenital cardiac; slightly less than 1% cardiopulmonary transplant; and 13.2% mixed subspecialties.

The 35.6% percent of women who identified themselves as general thoracic surgeons is higher than the 18% reported by the entire thoracic surgery workforce, with the percentage of women who identified themselves as general thoracic surgeons more than doubling in the second cohort of diplomates as compared with the first.

Slightly over 10% of respondents were no longer in CT surgery practice. All of these were certified prior to 2000, and the majority left practice due to retirement, health issues, or career advancement, according to their responses.

There was a large shift from the mixed category, which was cited by nearly 28% of the 51 women certified prior to 2000, compared with 3% of the 67 women certified after 2000.

This could be accounted for primarily by large increases in the adult cardiac (from nearly 20% prior to 2000 compared with 34% after 2000) and the general thoracic (from around 22% to 46%) subspecialty categories, reflecting the increase in subspecialization of our field.

Half of the women who responded had academic appointments, with 52% of these at the assistant professor level and 20% at the professor level. A minority of the women (20%) had protected research time, and 30% had secured research funding.

Overall, 64% of respondents reported that they were always or almost always satisfied with their profession.

The greatest source of dissatisfaction reported by both groups was demands on time, with workplace politics being a key concern expressed by Group 1 respondents, and lack of support a key concern expressed by Group 2.

Eighty percent of those polled stated that, if given the opportunity to choose a profession based on what they knew now, they would pursue cardiothoracic surgery again.

"Women still represent a minority of cardiothoracic surgeons in the United States, and over half are still very junior, having entered the profession since the year 2000.

Although the majority report being satisfied with their careers, and important academic milestones have been reached by some, there remains a scarcity of women in senior leadership positions.

"Since mentors and positive role models are consistently reported as significant factors in specialty decisions by surgical residents, this may still be the largest hurdle to recruiting women into cardiothoracic surgery," concluded Dr. Donington, in her presentation of the report.

Dr. Donington reported that she had no relevant financial disclosures.☐

Women represent a minority of cardiothoracic surgeons in the United States, with roughly equal numbers being found in academic and private practice, according to a recent survey presented at the annual meeting of the Society for Thoracic Surgeons.

Overall, these women reported a high level of job satisfaction and the vast majority of them were still in practice.

Although there were comparatively few women in senior staff and faculty positions, in part because over 50% of women currently in practice entered the profession since the year 2000, "this exponential increase in the number of women in the field over the past ten years provides optimism for a continued recruitment," according to the report by Dr. Jessica S. Donington, assistant professor of cardiothoracic surgery at New York University, New York, N.Y.,and her colleagues on behalf of The Women in Thoracic Surgery (WTS).

The WTS was established as a professional organization in 1986, with the designated mission of providing mutual support and facilitating the professional advancement of women in cardiothoracic surgery.

With 2011 being the 50th anniversary of the first certification of a woman by the American Board of Thoracic Surgery (ABTS) and the year in which the 200th female was certified by the ABTS, the WTS deemed it important to survey the status of female cardiothoracic surgeons in the United States.

The WTS survey was designed to measure career progression and to provide insights in order to improve recruitment. All ABTS-certified women were surveyed anonymously in December 2010 using tools from surveymonkey.com, according to Dr. Donington.

Contact information was obtained from CTSNet, Google, and institutions of known employment.

Of the 204 living women with ABTS certification, 190 were contacted. Of these, 64% responded to the survey. The questions comprised five areas: demographics, training, practice activities, activities of non-practicing CT surgeons, and career satisfaction.

The researchers grouped the respondents by year of certification: Group 1 (1961-1999) and Group 2 (2000-2010). They used the STS/AATS 2009 practice survey of the entire thoracic surgery workforce in order to make broad-based comparisons.

The mean age of the women respondents was 48 years, with the majority being white (nearly 78%) and urban dwellers (61%).

Half of the women were certified within the past 10 years. Overall, the respondents had been practicing for a mean of 8 years, worked in groups of 2-10 surgeons, and were the only female surgeon in their group. The respondents had a mean of 9.1 years of training with 56% reporting non-Accreditation Council for Graduate Medical Education (ACGME) training time.

There was a significant increase in the duration of training and in the resultant debt over time. Group 1 respondents reported training for 8.5 years vs. 9.5 years in Group 2, with a doubling of graduates with educational debt greater than $100,000 in the later era.

Overall, the distribution of 118 respondents who answered the subspecialty question was 28% adult cardiac; 8.5% congenital cardiac; slightly less than 1% cardiopulmonary transplant; and 13.2% mixed subspecialties.

The 35.6% percent of women who identified themselves as general thoracic surgeons is higher than the 18% reported by the entire thoracic surgery workforce, with the percentage of women who identified themselves as general thoracic surgeons more than doubling in the second cohort of diplomates as compared with the first.

Slightly over 10% of respondents were no longer in CT surgery practice. All of these were certified prior to 2000, and the majority left practice due to retirement, health issues, or career advancement, according to their responses.

There was a large shift from the mixed category, which was cited by nearly 28% of the 51 women certified prior to 2000, compared with 3% of the 67 women certified after 2000.

This could be accounted for primarily by large increases in the adult cardiac (from nearly 20% prior to 2000 compared with 34% after 2000) and the general thoracic (from around 22% to 46%) subspecialty categories, reflecting the increase in subspecialization of our field.

Half of the women who responded had academic appointments, with 52% of these at the assistant professor level and 20% at the professor level. A minority of the women (20%) had protected research time, and 30% had secured research funding.

Overall, 64% of respondents reported that they were always or almost always satisfied with their profession.

The greatest source of dissatisfaction reported by both groups was demands on time, with workplace politics being a key concern expressed by Group 1 respondents, and lack of support a key concern expressed by Group 2.

Eighty percent of those polled stated that, if given the opportunity to choose a profession based on what they knew now, they would pursue cardiothoracic surgery again.

"Women still represent a minority of cardiothoracic surgeons in the United States, and over half are still very junior, having entered the profession since the year 2000.

Although the majority report being satisfied with their careers, and important academic milestones have been reached by some, there remains a scarcity of women in senior leadership positions.

"Since mentors and positive role models are consistently reported as significant factors in specialty decisions by surgical residents, this may still be the largest hurdle to recruiting women into cardiothoracic surgery," concluded Dr. Donington, in her presentation of the report.

Dr. Donington reported that she had no relevant financial disclosures.☐

Because anticoagulation is a balancing act between the prevention of clots and the risk of major bleeds, tremendous efforts have been made to find the safest, most effective drugs possible. The foundations of anticoagulant therapy – warfarin (taken orally) and heparin (taken intravenously) – are being shaken by an onslaught of the newer oral factor Xa inhibitors and a direct thrombin inhibitor.

Two of these inhibitors are currently approved by the Food and Drug Administration, with others poised for approval.

Warfarin, the current standard for outpatient oral anticoagulant therapy, leaves a lot to be desired. The need for International Normalized Ratio (INR) monitoring has made patient compliance a significant problem, as some patients must travel routinely to their doctor’s office or warfarin clinics for blood monitoring (although there has been some movement toward putting the INR-monitoring process into patient hands). Even for compliant patients, reaching and maintaining an appropriate INR can be difficult, and warfarin carries the risk of a major bleed, especially among fragile elderly patients.

But is a move from warfarin to the new drugs premature? Many concerns remain, including potential difficulties with surgery in patients taking these agents.

The two FDA-approved drugs are rivaroxaban (Xarelto, marketed by Janssen Pharmaceuticals), which is a direct factor Xa inhibitor, and dabigatran (Pradaxa, marketed by Boehringer Ingelheim), a direct thrombin inhibitor.*

Rivaroxaban (a member of the "xaban" family) was approved for two separate indications: the prevention of deep vein thrombosis in knee or hip replacement surgery (July 2011) and stroke prophylaxis in patients with nonvalvular atrial fibrillation (November 2011). Taken as a once-daily dose, the drug does not require routine blood monitoring – a key advantage over warfarin. According to the ROCKET-AF trial on which the approval was based, rivaroxaban had a major bleeding rate similar to that of warfarin; however, while it caused less bleeding into the brain, it caused more bleeding into the stomach and intestines.

During the approval process for rivaroxaban, FDA panelists questioned whether the drug was properly compared with the highest contemporary standards for warfarin and noted that it did not provide a "robust noninferiority" to dabigatran. These concerns led the panel to suggest that rivaroxaban be used only as a third-line therapy when warfarin and dabigatran are not options. Panelists also wondered what happens when patients stop using the drug. Rivaroxaban is now marketed with a boxed warning that sudden discontinuation increases the risk of stroke.

The FDA approved dabigatran in October 2010 for long-term anticoagulation in patients with atrial fibrillation, and by late August 2011, U.S. physicians had written 250,000 prescriptions for the drug.

But questions about the drug’s safety have been raised recently. In December 2011, the FDA announced that it was looking into reports of serious bleeding events associated with dabigatran, while reaffirming its belief that "the benefit of Pradaxa continues to exceed the potential risks when the drug is used appropriately."

The FDA’s concerns were prompted in part by a European Medicines Agency (EMA) safety update in November noting "a worldwide total of 256 spontaneous case reports of serious bleeding resulting in death."

In October, the EMA’s Committee for Medicinal Products for Human Use had recommended that dabigatran be labeled to advise testing for renal function in all patients before starting treatment and, for those taking the drug, renal function assessment at least once a year in patients older than 75 years and in patients of any age with a suspected decline in renal function.

A meta-analysis of seven randomized clinical trials published online in the January 2012 Archives of Internal Medicine (Arch. Intern. Med. 2012 Jan. 9 [doi:10.1001/archinternmed.2011.1666]) showed that dabigatran appeared to increase the risk of myocardial infarction and acute coronary syndrome, compared with warfarin, enoxaparin, and placebo. The incidence of these events was 1.19% in those taking dabigatran vs. 0.79% in the controls.

Another new anticoagulant, apixaban, has been approved as Eliquis in the European Union and fast-tracked for approval in the United States. Apixaban outperformed warfarin in the ARISTOTLE trial in preventing stroke, reducing bleeding, and increasing survival, regardless of how well controlled patients were on warfarin, dabigatran, and rivaroxaban. Results achieved with apixaban were better than those seen in the trials of dabigatran and rivaroxaban against warfarin (N. Engl. J. Med 2011;365:981-92).

Of particular interest is apixaban’s good bleeding profile, compared with those of the other drugs (N. Engl. J. Med. 2011;364:806-17). "We have two trials in a large program showing this safety. In AVERROES, the bleeding risk with apixaban was the same as with low-dose aspirin," Dr. Lars Wallentin said in an interview. Dr. Wallentin is professor and head of cardiology research at Uppsala (Sweden) University and a coinvestigator in the ARISTOTLE trial.

The APPRAISE-2 trial showed that adding apixaban to standard antiplatelet therapy in patients with acute cardiac syndrome resulted in a 1.3% rate of major bleeding, compared with 0.5% with placebo, including five fatal bleeding events vs. none with placebo.

Unlike warfarin, these new anticoagulants have no defined antidotes – a lack that is of particular concern to surgeons. In a review of the new antithrombotic drugs presented at the 2011 VEITH symposium, Dr. Russell H. Samson said of dabigatran: "There is no antidote, so this drug should be used sparingly if surgery is anticipated. Thus, it is probably not a drug that should be used to prevent graft failure." Dr. Samson is a clinical associate professor of vascular surgery at Florida State University in Tallahassee.

A recent editorial in the New England Journal of Medicine sounded another note of caution. "Switching to a newer agent may not be necessary for the individual patient in whom INR has been well controlled with warfarin for years," Dr. Jessica Mega of Brigham and Women’s Hospital, Boston wrote (N. Engl. J. Med. 2011;365:1052-4). "In addition, although the newer anticoagulants have a more rapid onset and termination of anticoagulation than does warfarin, agents to reverse the effects of the drugs are still under development and are not routinely available."

The enthusiasm for the new anticoagulants may be premature for other reasons as well, such as the cost-effectiveness of these drugs, compared with the much cheaper warfarin, Dr. Mega said.

Elizabeth Mechcatie, Kerri Wachter, and Mitchel L. Zoler contributed to this report.

*3/6/2012 Correction: An earlier version of this story misclassified dabigatran. It is a direct thrombin inhibitor.

Because anticoagulation is a balancing act between the prevention of clots and the risk of major bleeds, tremendous efforts have been made to find the safest, most effective drugs possible. The foundations of anticoagulant therapy – warfarin (taken orally) and heparin (taken intravenously) – are being shaken by an onslaught of the newer oral factor Xa inhibitors and a direct thrombin inhibitor.

Two of these inhibitors are currently approved by the Food and Drug Administration, with others poised for approval.

Warfarin, the current standard for outpatient oral anticoagulant therapy, leaves a lot to be desired. The need for International Normalized Ratio (INR) monitoring has made patient compliance a significant problem, as some patients must travel routinely to their doctor’s office or warfarin clinics for blood monitoring (although there has been some movement toward putting the INR-monitoring process into patient hands). Even for compliant patients, reaching and maintaining an appropriate INR can be difficult, and warfarin carries the risk of a major bleed, especially among fragile elderly patients.

But is a move from warfarin to the new drugs premature? Many concerns remain, including potential difficulties with surgery in patients taking these agents.

The two FDA-approved drugs are rivaroxaban (Xarelto, marketed by Janssen Pharmaceuticals), which is a direct factor Xa inhibitor, and dabigatran (Pradaxa, marketed by Boehringer Ingelheim), a direct thrombin inhibitor.*

Rivaroxaban (a member of the "xaban" family) was approved for two separate indications: the prevention of deep vein thrombosis in knee or hip replacement surgery (July 2011) and stroke prophylaxis in patients with nonvalvular atrial fibrillation (November 2011). Taken as a once-daily dose, the drug does not require routine blood monitoring – a key advantage over warfarin. According to the ROCKET-AF trial on which the approval was based, rivaroxaban had a major bleeding rate similar to that of warfarin; however, while it caused less bleeding into the brain, it caused more bleeding into the stomach and intestines.

During the approval process for rivaroxaban, FDA panelists questioned whether the drug was properly compared with the highest contemporary standards for warfarin and noted that it did not provide a "robust noninferiority" to dabigatran. These concerns led the panel to suggest that rivaroxaban be used only as a third-line therapy when warfarin and dabigatran are not options. Panelists also wondered what happens when patients stop using the drug. Rivaroxaban is now marketed with a boxed warning that sudden discontinuation increases the risk of stroke.

The FDA approved dabigatran in October 2010 for long-term anticoagulation in patients with atrial fibrillation, and by late August 2011, U.S. physicians had written 250,000 prescriptions for the drug.

But questions about the drug’s safety have been raised recently. In December 2011, the FDA announced that it was looking into reports of serious bleeding events associated with dabigatran, while reaffirming its belief that "the benefit of Pradaxa continues to exceed the potential risks when the drug is used appropriately."

The FDA’s concerns were prompted in part by a European Medicines Agency (EMA) safety update in November noting "a worldwide total of 256 spontaneous case reports of serious bleeding resulting in death."

In October, the EMA’s Committee for Medicinal Products for Human Use had recommended that dabigatran be labeled to advise testing for renal function in all patients before starting treatment and, for those taking the drug, renal function assessment at least once a year in patients older than 75 years and in patients of any age with a suspected decline in renal function.

A meta-analysis of seven randomized clinical trials published online in the January 2012 Archives of Internal Medicine (Arch. Intern. Med. 2012 Jan. 9 [doi:10.1001/archinternmed.2011.1666]) showed that dabigatran appeared to increase the risk of myocardial infarction and acute coronary syndrome, compared with warfarin, enoxaparin, and placebo. The incidence of these events was 1.19% in those taking dabigatran vs. 0.79% in the controls.

Another new anticoagulant, apixaban, has been approved as Eliquis in the European Union and fast-tracked for approval in the United States. Apixaban outperformed warfarin in the ARISTOTLE trial in preventing stroke, reducing bleeding, and increasing survival, regardless of how well controlled patients were on warfarin, dabigatran, and rivaroxaban. Results achieved with apixaban were better than those seen in the trials of dabigatran and rivaroxaban against warfarin (N. Engl. J. Med 2011;365:981-92).

Of particular interest is apixaban’s good bleeding profile, compared with those of the other drugs (N. Engl. J. Med. 2011;364:806-17). "We have two trials in a large program showing this safety. In AVERROES, the bleeding risk with apixaban was the same as with low-dose aspirin," Dr. Lars Wallentin said in an interview. Dr. Wallentin is professor and head of cardiology research at Uppsala (Sweden) University and a coinvestigator in the ARISTOTLE trial.

The APPRAISE-2 trial showed that adding apixaban to standard antiplatelet therapy in patients with acute cardiac syndrome resulted in a 1.3% rate of major bleeding, compared with 0.5% with placebo, including five fatal bleeding events vs. none with placebo.

Unlike warfarin, these new anticoagulants have no defined antidotes – a lack that is of particular concern to surgeons. In a review of the new antithrombotic drugs presented at the 2011 VEITH symposium, Dr. Russell H. Samson said of dabigatran: "There is no antidote, so this drug should be used sparingly if surgery is anticipated. Thus, it is probably not a drug that should be used to prevent graft failure." Dr. Samson is a clinical associate professor of vascular surgery at Florida State University in Tallahassee.

A recent editorial in the New England Journal of Medicine sounded another note of caution. "Switching to a newer agent may not be necessary for the individual patient in whom INR has been well controlled with warfarin for years," Dr. Jessica Mega of Brigham and Women’s Hospital, Boston wrote (N. Engl. J. Med. 2011;365:1052-4). "In addition, although the newer anticoagulants have a more rapid onset and termination of anticoagulation than does warfarin, agents to reverse the effects of the drugs are still under development and are not routinely available."

The enthusiasm for the new anticoagulants may be premature for other reasons as well, such as the cost-effectiveness of these drugs, compared with the much cheaper warfarin, Dr. Mega said.

Elizabeth Mechcatie, Kerri Wachter, and Mitchel L. Zoler contributed to this report.

*3/6/2012 Correction: An earlier version of this story misclassified dabigatran. It is a direct thrombin inhibitor.

Because anticoagulation is a balancing act between the prevention of clots and the risk of major bleeds, tremendous efforts have been made to find the safest, most effective drugs possible. The foundations of anticoagulant therapy – warfarin (taken orally) and heparin (taken intravenously) – are being shaken by an onslaught of the newer oral factor Xa inhibitors and a direct thrombin inhibitor.

Two of these inhibitors are currently approved by the Food and Drug Administration, with others poised for approval.

Warfarin, the current standard for outpatient oral anticoagulant therapy, leaves a lot to be desired. The need for International Normalized Ratio (INR) monitoring has made patient compliance a significant problem, as some patients must travel routinely to their doctor’s office or warfarin clinics for blood monitoring (although there has been some movement toward putting the INR-monitoring process into patient hands). Even for compliant patients, reaching and maintaining an appropriate INR can be difficult, and warfarin carries the risk of a major bleed, especially among fragile elderly patients.

But is a move from warfarin to the new drugs premature? Many concerns remain, including potential difficulties with surgery in patients taking these agents.

The two FDA-approved drugs are rivaroxaban (Xarelto, marketed by Janssen Pharmaceuticals), which is a direct factor Xa inhibitor, and dabigatran (Pradaxa, marketed by Boehringer Ingelheim), a direct thrombin inhibitor.*

Rivaroxaban (a member of the "xaban" family) was approved for two separate indications: the prevention of deep vein thrombosis in knee or hip replacement surgery (July 2011) and stroke prophylaxis in patients with nonvalvular atrial fibrillation (November 2011). Taken as a once-daily dose, the drug does not require routine blood monitoring – a key advantage over warfarin. According to the ROCKET-AF trial on which the approval was based, rivaroxaban had a major bleeding rate similar to that of warfarin; however, while it caused less bleeding into the brain, it caused more bleeding into the stomach and intestines.

During the approval process for rivaroxaban, FDA panelists questioned whether the drug was properly compared with the highest contemporary standards for warfarin and noted that it did not provide a "robust noninferiority" to dabigatran. These concerns led the panel to suggest that rivaroxaban be used only as a third-line therapy when warfarin and dabigatran are not options. Panelists also wondered what happens when patients stop using the drug. Rivaroxaban is now marketed with a boxed warning that sudden discontinuation increases the risk of stroke.

The FDA approved dabigatran in October 2010 for long-term anticoagulation in patients with atrial fibrillation, and by late August 2011, U.S. physicians had written 250,000 prescriptions for the drug.

But questions about the drug’s safety have been raised recently. In December 2011, the FDA announced that it was looking into reports of serious bleeding events associated with dabigatran, while reaffirming its belief that "the benefit of Pradaxa continues to exceed the potential risks when the drug is used appropriately."

The FDA’s concerns were prompted in part by a European Medicines Agency (EMA) safety update in November noting "a worldwide total of 256 spontaneous case reports of serious bleeding resulting in death."

In October, the EMA’s Committee for Medicinal Products for Human Use had recommended that dabigatran be labeled to advise testing for renal function in all patients before starting treatment and, for those taking the drug, renal function assessment at least once a year in patients older than 75 years and in patients of any age with a suspected decline in renal function.

A meta-analysis of seven randomized clinical trials published online in the January 2012 Archives of Internal Medicine (Arch. Intern. Med. 2012 Jan. 9 [doi:10.1001/archinternmed.2011.1666]) showed that dabigatran appeared to increase the risk of myocardial infarction and acute coronary syndrome, compared with warfarin, enoxaparin, and placebo. The incidence of these events was 1.19% in those taking dabigatran vs. 0.79% in the controls.

Another new anticoagulant, apixaban, has been approved as Eliquis in the European Union and fast-tracked for approval in the United States. Apixaban outperformed warfarin in the ARISTOTLE trial in preventing stroke, reducing bleeding, and increasing survival, regardless of how well controlled patients were on warfarin, dabigatran, and rivaroxaban. Results achieved with apixaban were better than those seen in the trials of dabigatran and rivaroxaban against warfarin (N. Engl. J. Med 2011;365:981-92).

Of particular interest is apixaban’s good bleeding profile, compared with those of the other drugs (N. Engl. J. Med. 2011;364:806-17). "We have two trials in a large program showing this safety. In AVERROES, the bleeding risk with apixaban was the same as with low-dose aspirin," Dr. Lars Wallentin said in an interview. Dr. Wallentin is professor and head of cardiology research at Uppsala (Sweden) University and a coinvestigator in the ARISTOTLE trial.

The APPRAISE-2 trial showed that adding apixaban to standard antiplatelet therapy in patients with acute cardiac syndrome resulted in a 1.3% rate of major bleeding, compared with 0.5% with placebo, including five fatal bleeding events vs. none with placebo.

Unlike warfarin, these new anticoagulants have no defined antidotes – a lack that is of particular concern to surgeons. In a review of the new antithrombotic drugs presented at the 2011 VEITH symposium, Dr. Russell H. Samson said of dabigatran: "There is no antidote, so this drug should be used sparingly if surgery is anticipated. Thus, it is probably not a drug that should be used to prevent graft failure." Dr. Samson is a clinical associate professor of vascular surgery at Florida State University in Tallahassee.

A recent editorial in the New England Journal of Medicine sounded another note of caution. "Switching to a newer agent may not be necessary for the individual patient in whom INR has been well controlled with warfarin for years," Dr. Jessica Mega of Brigham and Women’s Hospital, Boston wrote (N. Engl. J. Med. 2011;365:1052-4). "In addition, although the newer anticoagulants have a more rapid onset and termination of anticoagulation than does warfarin, agents to reverse the effects of the drugs are still under development and are not routinely available."

The enthusiasm for the new anticoagulants may be premature for other reasons as well, such as the cost-effectiveness of these drugs, compared with the much cheaper warfarin, Dr. Mega said.

Elizabeth Mechcatie, Kerri Wachter, and Mitchel L. Zoler contributed to this report.

*3/6/2012 Correction: An earlier version of this story misclassified dabigatran. It is a direct thrombin inhibitor.

FT. LAUDERDALE, FLA. – More than a decade ago, the Department of Health and Human Services issued the "Final Rule on Organ Procurement and Transplantation Network Amendments," which was intended to ensure that "organs will be [allocated] based on medical criteria, not accidents of geography." Despite the introduction of this final rule, disparities in waiting list outcomes are known to be significantly influenced by where the transplantation candidate lives, and lower priority candidates are receiving organs at the expense of the more severely ill.

Although all candidates are ranked based on an objective priority score known as the Lung Allocation Score (LAS), lung allocation remains a locally based system. Organs are first allocated based on geography regardless of LAS score. Therefore, organs are initially offered only to the subset of matched lung transplant candidates (based on blood group and size) within the donor’s local Donor Service Area (DSA).

As a result, if an available organ is first accepted for a candidate within the local DSA, it is never offered to potentially more-severely ill candidates at the broader regional or national level – even if the regional or national candidate has a much higher priority score. There is evidence that this is a frequent occurrence, according to research presented by Dr. Mark J. Russo at the annual meeting of the Society of Thoracic Surgeons.

Dr. Russo and his colleagues analyzed data provided by the United Network for Organ Sharing to determine the frequency with which donor lungs were allocated to local candidates when blood group– and size-matched candidates with a higher LAS existed in the same region.

Their study cohort included all locally allocated organs for double lung transplantation in the United States in the year 2009. The researchers then identified all cases in which ABO blood group– and height-matched (within 10 cm) double-lung candidates in the same region had a higher LAS than did the local candidates who actually received the lung. They also calculated the number of these events in which the LAS difference was greater than 10 and greater than 25. The number of these bypassed regional candidates who then died on the waiting list was also determined.

Among the 580 locally allocated double-lung transplants analyzed, there was a mean of 6.0 blood group – and height-matched double-lung events per transplant (3,454 total, impacting 1,193 different candidates) in the same region where candidates had a higher LAS than did the local candidate who received the organ. A total of 24% (828) of the events involved skipping over a regional candidate with an LAS greater than 10 points higher than the local recipient, with 7.2% (250) of events involving a regional candidate with an LAS greater than 25 points higher than the local recipient. Overall, 185 of the bypassed regional candidates died on the waiting list.

Dr. Russo said that although the issue of transportation is important, generally the adverse impact of an additional hour or two of ischemic time due to transportation is not clinically significant, and should not be a major factor in the decision as to local vs. regional candidates. In addition, the regional candidate is often not far from the donor, he added.

"Ideally, a suitable donor organ would be available for every lung transplant candidate who could benefit from transplantation. Unfortunately, there remains a critical scarcity of donor organs available for transplantation. Therefore, efficient allocation of organs is necessary to ensure maximum benefit from the available organs," according to Dr. Russo, a cardiothoracic surgeon at the University of Chicago Medical Center.

"Locally-based allocation results in a high number of events in which a lung is allocated to a lower-priority candidate when an appropriately matched, higher-priority candidate exists in the same region. As a result, low-priority candidates, defined by an LAS less than 50, account for nearly 90% of lung transplant recipients, while candidates with higher LAS scores, defined by an LAS greater than 75, continue to die at extremely high rates while awaiting transplantation," Dr. Russo stated.

Dr. Russo said further that because this study considered only double-lung candidates, did not consider the possibility of national matching, and did not allow for blood groups to be crossed, it likely significantly underestimates the frequency of these events and lives lost.

"These findings suggest that further study of organ sharing over broader geographies should be pursued to determine if it would improve [waiting] list outcomes, including higher rates of organ allocation to higher-priority candidates, improved survival on the waiting list, and greater net benefit from the organs available for transplantation," he concluded.

Dr. Russo reported that he had no financial disclosures.

FT. LAUDERDALE, FLA. – More than a decade ago, the Department of Health and Human Services issued the "Final Rule on Organ Procurement and Transplantation Network Amendments," which was intended to ensure that "organs will be [allocated] based on medical criteria, not accidents of geography." Despite the introduction of this final rule, disparities in waiting list outcomes are known to be significantly influenced by where the transplantation candidate lives, and lower priority candidates are receiving organs at the expense of the more severely ill.

Although all candidates are ranked based on an objective priority score known as the Lung Allocation Score (LAS), lung allocation remains a locally based system. Organs are first allocated based on geography regardless of LAS score. Therefore, organs are initially offered only to the subset of matched lung transplant candidates (based on blood group and size) within the donor’s local Donor Service Area (DSA).

As a result, if an available organ is first accepted for a candidate within the local DSA, it is never offered to potentially more-severely ill candidates at the broader regional or national level – even if the regional or national candidate has a much higher priority score. There is evidence that this is a frequent occurrence, according to research presented by Dr. Mark J. Russo at the annual meeting of the Society of Thoracic Surgeons.

Dr. Russo and his colleagues analyzed data provided by the United Network for Organ Sharing to determine the frequency with which donor lungs were allocated to local candidates when blood group– and size-matched candidates with a higher LAS existed in the same region.

Their study cohort included all locally allocated organs for double lung transplantation in the United States in the year 2009. The researchers then identified all cases in which ABO blood group– and height-matched (within 10 cm) double-lung candidates in the same region had a higher LAS than did the local candidates who actually received the lung. They also calculated the number of these events in which the LAS difference was greater than 10 and greater than 25. The number of these bypassed regional candidates who then died on the waiting list was also determined.

Among the 580 locally allocated double-lung transplants analyzed, there was a mean of 6.0 blood group – and height-matched double-lung events per transplant (3,454 total, impacting 1,193 different candidates) in the same region where candidates had a higher LAS than did the local candidate who received the organ. A total of 24% (828) of the events involved skipping over a regional candidate with an LAS greater than 10 points higher than the local recipient, with 7.2% (250) of events involving a regional candidate with an LAS greater than 25 points higher than the local recipient. Overall, 185 of the bypassed regional candidates died on the waiting list.

Dr. Russo said that although the issue of transportation is important, generally the adverse impact of an additional hour or two of ischemic time due to transportation is not clinically significant, and should not be a major factor in the decision as to local vs. regional candidates. In addition, the regional candidate is often not far from the donor, he added.

"Ideally, a suitable donor organ would be available for every lung transplant candidate who could benefit from transplantation. Unfortunately, there remains a critical scarcity of donor organs available for transplantation. Therefore, efficient allocation of organs is necessary to ensure maximum benefit from the available organs," according to Dr. Russo, a cardiothoracic surgeon at the University of Chicago Medical Center.

"Locally-based allocation results in a high number of events in which a lung is allocated to a lower-priority candidate when an appropriately matched, higher-priority candidate exists in the same region. As a result, low-priority candidates, defined by an LAS less than 50, account for nearly 90% of lung transplant recipients, while candidates with higher LAS scores, defined by an LAS greater than 75, continue to die at extremely high rates while awaiting transplantation," Dr. Russo stated.

Dr. Russo said further that because this study considered only double-lung candidates, did not consider the possibility of national matching, and did not allow for blood groups to be crossed, it likely significantly underestimates the frequency of these events and lives lost.

"These findings suggest that further study of organ sharing over broader geographies should be pursued to determine if it would improve [waiting] list outcomes, including higher rates of organ allocation to higher-priority candidates, improved survival on the waiting list, and greater net benefit from the organs available for transplantation," he concluded.

Dr. Russo reported that he had no financial disclosures.

FT. LAUDERDALE, FLA. – More than a decade ago, the Department of Health and Human Services issued the "Final Rule on Organ Procurement and Transplantation Network Amendments," which was intended to ensure that "organs will be [allocated] based on medical criteria, not accidents of geography." Despite the introduction of this final rule, disparities in waiting list outcomes are known to be significantly influenced by where the transplantation candidate lives, and lower priority candidates are receiving organs at the expense of the more severely ill.

Although all candidates are ranked based on an objective priority score known as the Lung Allocation Score (LAS), lung allocation remains a locally based system. Organs are first allocated based on geography regardless of LAS score. Therefore, organs are initially offered only to the subset of matched lung transplant candidates (based on blood group and size) within the donor’s local Donor Service Area (DSA).

As a result, if an available organ is first accepted for a candidate within the local DSA, it is never offered to potentially more-severely ill candidates at the broader regional or national level – even if the regional or national candidate has a much higher priority score. There is evidence that this is a frequent occurrence, according to research presented by Dr. Mark J. Russo at the annual meeting of the Society of Thoracic Surgeons.

Dr. Russo and his colleagues analyzed data provided by the United Network for Organ Sharing to determine the frequency with which donor lungs were allocated to local candidates when blood group– and size-matched candidates with a higher LAS existed in the same region.

Their study cohort included all locally allocated organs for double lung transplantation in the United States in the year 2009. The researchers then identified all cases in which ABO blood group– and height-matched (within 10 cm) double-lung candidates in the same region had a higher LAS than did the local candidates who actually received the lung. They also calculated the number of these events in which the LAS difference was greater than 10 and greater than 25. The number of these bypassed regional candidates who then died on the waiting list was also determined.

Among the 580 locally allocated double-lung transplants analyzed, there was a mean of 6.0 blood group – and height-matched double-lung events per transplant (3,454 total, impacting 1,193 different candidates) in the same region where candidates had a higher LAS than did the local candidate who received the organ. A total of 24% (828) of the events involved skipping over a regional candidate with an LAS greater than 10 points higher than the local recipient, with 7.2% (250) of events involving a regional candidate with an LAS greater than 25 points higher than the local recipient. Overall, 185 of the bypassed regional candidates died on the waiting list.

Dr. Russo said that although the issue of transportation is important, generally the adverse impact of an additional hour or two of ischemic time due to transportation is not clinically significant, and should not be a major factor in the decision as to local vs. regional candidates. In addition, the regional candidate is often not far from the donor, he added.

"Ideally, a suitable donor organ would be available for every lung transplant candidate who could benefit from transplantation. Unfortunately, there remains a critical scarcity of donor organs available for transplantation. Therefore, efficient allocation of organs is necessary to ensure maximum benefit from the available organs," according to Dr. Russo, a cardiothoracic surgeon at the University of Chicago Medical Center.

"Locally-based allocation results in a high number of events in which a lung is allocated to a lower-priority candidate when an appropriately matched, higher-priority candidate exists in the same region. As a result, low-priority candidates, defined by an LAS less than 50, account for nearly 90% of lung transplant recipients, while candidates with higher LAS scores, defined by an LAS greater than 75, continue to die at extremely high rates while awaiting transplantation," Dr. Russo stated.

Dr. Russo said further that because this study considered only double-lung candidates, did not consider the possibility of national matching, and did not allow for blood groups to be crossed, it likely significantly underestimates the frequency of these events and lives lost.

"These findings suggest that further study of organ sharing over broader geographies should be pursued to determine if it would improve [waiting] list outcomes, including higher rates of organ allocation to higher-priority candidates, improved survival on the waiting list, and greater net benefit from the organs available for transplantation," he concluded.

Dr. Russo reported that he had no financial disclosures.