HT Staff

Ibrutinib (Imbruvica)
Photo courtesy of
Janssen Biotech, Inc.

The US Food and Drug Administration (FDA) has approved the Bruton’s tyrosine kinase inhibitor ibrutinib (Imbruvica®) for the treatment of marginal zone lymphoma (MZL).

The drug is now approved to treat patients with relapsed/refractory MZL who require systemic therapy and have received at least 1 prior anti-CD20-based therapy.

Ibrutinib has accelerated approval for this indication, based on the overall response rate the drug produced in a phase 2 trial.

Continued approval of ibrutinib as a treatment for MZL may be contingent upon verification and description of clinical benefit in a confirmatory trial.

The FDA’s approval of ibrutinib for MZL makes it the first treatment approved specifically for patients with this disease. It also marks the seventh FDA approval and fifth disease indication for ibrutinib since the drug was first approved in 2013.

Ibrutinib is also FDA-approved to treat chronic lymphocytic leukemia/small lymphocytic lymphoma, patients with mantle cell lymphoma who have received at least 1 prior therapy, and patients with Waldenström’s macroglobulinemia. The approval for mantle cell lymphoma is an accelerated approval.

Ibrutinib is jointly developed and commercialized by Pharmacyclics LLC, an AbbVie company, and Janssen Biotech, Inc.

Phase 2 trial

The FDA’s approval of ibrutinib for MZL is based on data from the phase 2, single-arm PCYC-1121 study, in which researchers evaluated the drug in MZL patients who required systemic therapy and had received at least 1 prior anti-CD20-based therapy.

Results from this study were presented at the 2016 ASH Annual Meeting (abstract 1213).

The efficacy analysis included 63 patients with 3 subtypes of MZL: mucosa-associated lymphoid tissue (n=32), nodal (n=17), and splenic (n=14).

The overall response rate was 46%, with a partial response rate of 42.9% and a complete response rate of 3.2%. Responses were observed across all 3 MZL subtypes.

The median time to response was 4.5 months (range, 2.3-16.4 months). And the median duration of response was not reached (range, 16.7 months to not reached).

Overall, the safety data from this study was consistent with the known safety profile of ibrutinib in B-cell malignancies.

The most common adverse events of all grades (occurring in >20% of patients) were thrombocytopenia (49%), fatigue (44%), anemia (43%), diarrhea (43%), bruising (41%), musculoskeletal pain (40%), hemorrhage (30%), rash (29%), nausea (25%), peripheral edema (24%), arthralgia (24%), neutropenia (22%), cough (22%), dyspnea (21%), and upper respiratory tract infection (21%).

The most common (>10%) grade 3 or 4 events were decreases in hemoglobin and neutrophils (13% each) and pneumonia (10%).

The risks associated with ibrutinib as listed in the Warnings and Precautions section of the prescribing information are hemorrhage, infections, cytopenias, atrial fibrillation, hypertension, secondary primary malignancies, tumor lysis syndrome, and embryo fetal toxicities.

Ibrutinib (Imbruvica)
Photo courtesy of
Janssen Biotech, Inc.

The US Food and Drug Administration (FDA) has approved the Bruton’s tyrosine kinase inhibitor ibrutinib (Imbruvica®) for the treatment of marginal zone lymphoma (MZL).

The drug is now approved to treat patients with relapsed/refractory MZL who require systemic therapy and have received at least 1 prior anti-CD20-based therapy.

Ibrutinib has accelerated approval for this indication, based on the overall response rate the drug produced in a phase 2 trial.

Continued approval of ibrutinib as a treatment for MZL may be contingent upon verification and description of clinical benefit in a confirmatory trial.

The FDA’s approval of ibrutinib for MZL makes it the first treatment approved specifically for patients with this disease. It also marks the seventh FDA approval and fifth disease indication for ibrutinib since the drug was first approved in 2013.

Ibrutinib is also FDA-approved to treat chronic lymphocytic leukemia/small lymphocytic lymphoma, patients with mantle cell lymphoma who have received at least 1 prior therapy, and patients with Waldenström’s macroglobulinemia. The approval for mantle cell lymphoma is an accelerated approval.

Ibrutinib is jointly developed and commercialized by Pharmacyclics LLC, an AbbVie company, and Janssen Biotech, Inc.

Phase 2 trial

The FDA’s approval of ibrutinib for MZL is based on data from the phase 2, single-arm PCYC-1121 study, in which researchers evaluated the drug in MZL patients who required systemic therapy and had received at least 1 prior anti-CD20-based therapy.

Results from this study were presented at the 2016 ASH Annual Meeting (abstract 1213).

The efficacy analysis included 63 patients with 3 subtypes of MZL: mucosa-associated lymphoid tissue (n=32), nodal (n=17), and splenic (n=14).

The overall response rate was 46%, with a partial response rate of 42.9% and a complete response rate of 3.2%. Responses were observed across all 3 MZL subtypes.

The median time to response was 4.5 months (range, 2.3-16.4 months). And the median duration of response was not reached (range, 16.7 months to not reached).

Overall, the safety data from this study was consistent with the known safety profile of ibrutinib in B-cell malignancies.

The most common adverse events of all grades (occurring in >20% of patients) were thrombocytopenia (49%), fatigue (44%), anemia (43%), diarrhea (43%), bruising (41%), musculoskeletal pain (40%), hemorrhage (30%), rash (29%), nausea (25%), peripheral edema (24%), arthralgia (24%), neutropenia (22%), cough (22%), dyspnea (21%), and upper respiratory tract infection (21%).

The most common (>10%) grade 3 or 4 events were decreases in hemoglobin and neutrophils (13% each) and pneumonia (10%).

The risks associated with ibrutinib as listed in the Warnings and Precautions section of the prescribing information are hemorrhage, infections, cytopenias, atrial fibrillation, hypertension, secondary primary malignancies, tumor lysis syndrome, and embryo fetal toxicities.

Ibrutinib (Imbruvica)
Photo courtesy of
Janssen Biotech, Inc.

The US Food and Drug Administration (FDA) has approved the Bruton’s tyrosine kinase inhibitor ibrutinib (Imbruvica®) for the treatment of marginal zone lymphoma (MZL).

The drug is now approved to treat patients with relapsed/refractory MZL who require systemic therapy and have received at least 1 prior anti-CD20-based therapy.

Ibrutinib has accelerated approval for this indication, based on the overall response rate the drug produced in a phase 2 trial.

Continued approval of ibrutinib as a treatment for MZL may be contingent upon verification and description of clinical benefit in a confirmatory trial.

The FDA’s approval of ibrutinib for MZL makes it the first treatment approved specifically for patients with this disease. It also marks the seventh FDA approval and fifth disease indication for ibrutinib since the drug was first approved in 2013.

Ibrutinib is also FDA-approved to treat chronic lymphocytic leukemia/small lymphocytic lymphoma, patients with mantle cell lymphoma who have received at least 1 prior therapy, and patients with Waldenström’s macroglobulinemia. The approval for mantle cell lymphoma is an accelerated approval.

Ibrutinib is jointly developed and commercialized by Pharmacyclics LLC, an AbbVie company, and Janssen Biotech, Inc.

Phase 2 trial

The FDA’s approval of ibrutinib for MZL is based on data from the phase 2, single-arm PCYC-1121 study, in which researchers evaluated the drug in MZL patients who required systemic therapy and had received at least 1 prior anti-CD20-based therapy.

Results from this study were presented at the 2016 ASH Annual Meeting (abstract 1213).

The efficacy analysis included 63 patients with 3 subtypes of MZL: mucosa-associated lymphoid tissue (n=32), nodal (n=17), and splenic (n=14).

The overall response rate was 46%, with a partial response rate of 42.9% and a complete response rate of 3.2%. Responses were observed across all 3 MZL subtypes.

The median time to response was 4.5 months (range, 2.3-16.4 months). And the median duration of response was not reached (range, 16.7 months to not reached).

Overall, the safety data from this study was consistent with the known safety profile of ibrutinib in B-cell malignancies.

The most common adverse events of all grades (occurring in >20% of patients) were thrombocytopenia (49%), fatigue (44%), anemia (43%), diarrhea (43%), bruising (41%), musculoskeletal pain (40%), hemorrhage (30%), rash (29%), nausea (25%), peripheral edema (24%), arthralgia (24%), neutropenia (22%), cough (22%), dyspnea (21%), and upper respiratory tract infection (21%).

The most common (>10%) grade 3 or 4 events were decreases in hemoglobin and neutrophils (13% each) and pneumonia (10%).

The risks associated with ibrutinib as listed in the Warnings and Precautions section of the prescribing information are hemorrhage, infections, cytopenias, atrial fibrillation, hypertension, secondary primary malignancies, tumor lysis syndrome, and embryo fetal toxicities.

Worker preparing drug
capsules for a clinical trial
Photo by Esther Dyson

Financial ties between principal investigators (PIs) and drug companies are independently associated with positive clinical trial results, according to new research.

The study showed a significant association between positive trial outcomes and PIs having financial ties to the manufacturer of the study drug, even after accounting for the source of research funding.

Researchers reported these findings in The BMJ.

Salomeh Keyhani, MD, of the University of California, San Francisco, and her colleagues conducted this research, analyzing a random sample of 195 drug trials published in 2013.

The team found financial ties between PIs and manufacturers of the study drug for 67.7% of the studies (n=132). In all, 58% of the PIs had financial ties to the manufacturers (231/397).

Types of financial ties included:

• Advisor/consultancy payments (39%)
• Speakers’ fees (20%)
• Unspecified financial ties (20%)
• Honoraria (13%)
• Employee relationships (13%)
• Travel fees (13%)
• Stock ownership (10%)
• Having a patent related to the study drug (5%).

PIs reported financial ties to the drug manufacturer in 76% (103/136) of studies with positive results and 49% (29/59) of studies with negative results (P<0.001).

In a multivariate analysis adjusted for the study’s funding source, a financial tie was significantly associated with a positive trial outcome. The odds ratio was 3.57 (P=0.001).

In a multivariate analysis adjusted for a range of other study-related factors as well, a financial tie remained significantly associated with a positive trial outcome. The odds ratio was 3.37 (P=0.006). 

Dr Keyhani and her colleagues stressed that this analysis was observational and cannot be used to draw conclusions about causation.

However, they said, given the importance of industry and academic collaboration in advancing the development of new treatments, “more thought needs to be given to the roles that investigators, policy makers, and journal editors can play in ensuring the credibility of the evidence base.”

Authors of a related editorial said more research is needed to determine how industry funding and financial ties could influence trial results.

The authors—Andreas Lundh, PhD, of the University of Southern Denmark, and Lisa Bero, PhD, of the University of Sydney in Australia—urged trial investigators to share their data and participate in industry-funded trials only if data are made publicly available.

The authors also suggested journals could help by rejecting research by investigators who are unwilling to share their data and by penalizing investigators who fail to disclose financial ties. The role of sponsors, or companies with which investigators have ties, in the research must also be transparent.

In the meantime, trials with industry funding or investigators with financial ties “should be interpreted with caution until all relevant information is fully disclosed and easily accessible,” the authors concluded.

Worker preparing drug
capsules for a clinical trial
Photo by Esther Dyson

Financial ties between principal investigators (PIs) and drug companies are independently associated with positive clinical trial results, according to new research.

The study showed a significant association between positive trial outcomes and PIs having financial ties to the manufacturer of the study drug, even after accounting for the source of research funding.

Researchers reported these findings in The BMJ.

Salomeh Keyhani, MD, of the University of California, San Francisco, and her colleagues conducted this research, analyzing a random sample of 195 drug trials published in 2013.

The team found financial ties between PIs and manufacturers of the study drug for 67.7% of the studies (n=132). In all, 58% of the PIs had financial ties to the manufacturers (231/397).

Types of financial ties included:

• Advisor/consultancy payments (39%)
• Speakers’ fees (20%)
• Unspecified financial ties (20%)
• Honoraria (13%)
• Employee relationships (13%)
• Travel fees (13%)
• Stock ownership (10%)
• Having a patent related to the study drug (5%).

PIs reported financial ties to the drug manufacturer in 76% (103/136) of studies with positive results and 49% (29/59) of studies with negative results (P<0.001).

In a multivariate analysis adjusted for the study’s funding source, a financial tie was significantly associated with a positive trial outcome. The odds ratio was 3.57 (P=0.001).

In a multivariate analysis adjusted for a range of other study-related factors as well, a financial tie remained significantly associated with a positive trial outcome. The odds ratio was 3.37 (P=0.006). 

Dr Keyhani and her colleagues stressed that this analysis was observational and cannot be used to draw conclusions about causation.

However, they said, given the importance of industry and academic collaboration in advancing the development of new treatments, “more thought needs to be given to the roles that investigators, policy makers, and journal editors can play in ensuring the credibility of the evidence base.”

Authors of a related editorial said more research is needed to determine how industry funding and financial ties could influence trial results.

The authors—Andreas Lundh, PhD, of the University of Southern Denmark, and Lisa Bero, PhD, of the University of Sydney in Australia—urged trial investigators to share their data and participate in industry-funded trials only if data are made publicly available.

The authors also suggested journals could help by rejecting research by investigators who are unwilling to share their data and by penalizing investigators who fail to disclose financial ties. The role of sponsors, or companies with which investigators have ties, in the research must also be transparent.

In the meantime, trials with industry funding or investigators with financial ties “should be interpreted with caution until all relevant information is fully disclosed and easily accessible,” the authors concluded.

Worker preparing drug
capsules for a clinical trial
Photo by Esther Dyson

Financial ties between principal investigators (PIs) and drug companies are independently associated with positive clinical trial results, according to new research.

The study showed a significant association between positive trial outcomes and PIs having financial ties to the manufacturer of the study drug, even after accounting for the source of research funding.

Researchers reported these findings in The BMJ.

Salomeh Keyhani, MD, of the University of California, San Francisco, and her colleagues conducted this research, analyzing a random sample of 195 drug trials published in 2013.

The team found financial ties between PIs and manufacturers of the study drug for 67.7% of the studies (n=132). In all, 58% of the PIs had financial ties to the manufacturers (231/397).

Types of financial ties included:

• Advisor/consultancy payments (39%)
• Speakers’ fees (20%)
• Unspecified financial ties (20%)
• Honoraria (13%)
• Employee relationships (13%)
• Travel fees (13%)
• Stock ownership (10%)
• Having a patent related to the study drug (5%).

PIs reported financial ties to the drug manufacturer in 76% (103/136) of studies with positive results and 49% (29/59) of studies with negative results (P<0.001).

In a multivariate analysis adjusted for the study’s funding source, a financial tie was significantly associated with a positive trial outcome. The odds ratio was 3.57 (P=0.001).

In a multivariate analysis adjusted for a range of other study-related factors as well, a financial tie remained significantly associated with a positive trial outcome. The odds ratio was 3.37 (P=0.006). 

Dr Keyhani and her colleagues stressed that this analysis was observational and cannot be used to draw conclusions about causation.

However, they said, given the importance of industry and academic collaboration in advancing the development of new treatments, “more thought needs to be given to the roles that investigators, policy makers, and journal editors can play in ensuring the credibility of the evidence base.”

Authors of a related editorial said more research is needed to determine how industry funding and financial ties could influence trial results.

The authors—Andreas Lundh, PhD, of the University of Southern Denmark, and Lisa Bero, PhD, of the University of Sydney in Australia—urged trial investigators to share their data and participate in industry-funded trials only if data are made publicly available.

The authors also suggested journals could help by rejecting research by investigators who are unwilling to share their data and by penalizing investigators who fail to disclose financial ties. The role of sponsors, or companies with which investigators have ties, in the research must also be transparent.

In the meantime, trials with industry funding or investigators with financial ties “should be interpreted with caution until all relevant information is fully disclosed and easily accessible,” the authors concluded.

Researcher examines
tumor in a test tube
Photo by Rhoda Baer

The US Department of Health and Human Services (HHS) and 15 other federal agencies have issued a final rule to update regulations intended to safeguard individuals who participate in research.

Most provisions in the new rule will go into effect in 2018.

The HHS says the new rule strengthens protections for people who volunteer to participate in research, while ensuring that the oversight system does not add inappropriate administrative burdens.

The current regulations, which have been in place since 1991, are often referred to as the “Common Rule.”

In September 2015, HHS and the other Common Rule agencies published a proposed new rule regarding research subjects—a notice of proposed rulemaking (NPRM)—which drew more than 2100 comments.

In response to concerns raised during the review process, the final rule contains a number of significant changes from the NPRM.

Research covered

The final rule does not cover clinical trials that are not federally funded.

The Common Rule has historically applied only to research conducted or supported by a Common Rule department or agency. And, although the NPRM proposed changing this policy, the final rule remains in line with the Common Rule.

Consent

The final rule requires consent forms to provide potential research subjects with a better understanding of a project’s scope so they can make a more fully informed decision about whether to participate.

Consent forms should include a concise explanation—at the beginning of the document—of the information that would be most important to individuals contemplating participation in a particular study, including the purpose of the research, the risks and benefits, and appropriate alternative treatments that might be beneficial to the prospective subject. 

The rule also requires that consent forms for certain federally funded clinical trials be posted on a public website.

Institutional review boards

The final rule requires, in many cases, use of a single institutional review board (IRB) for multi-institutional research studies.

However, the final rule has been modified from the NPRM to add substantial increased flexibility in now allowing broad groups of studies (instead of just specific studies) to be removed from this requirement.

Privacy

The final rule does not include the standardized privacy safeguards for identifiable private information and identifiable biospecimens that were proposed in the NPRM.

In most respects, the final rule retains the current approach to privacy standards.

For studies on stored identifiable data or identifiable biospecimens, researchers will have the option of relying on broad consent obtained for future research as an alternative to seeking IRB approval to waive the consent requirement.

As under the current rule, researchers will not have to obtain consent for studies on non-identified stored data or biospecimens.

Exemptions

The final rule establishes new exempt categories of research based on the level of risk they pose to participants.

For example, to reduce unnecessary regulatory burden and allow IRBs to focus their attention on higher-risk studies, there is a new exemption for secondary research involving identifiable private information if the research is regulated by and participants are protected under the HIPAA rules.

Review

The final rule removes the requirement to conduct continuing review of ongoing research studies in certain instances where such review does little to protect subjects.

For more details, see the final rule.

Researcher examines
tumor in a test tube
Photo by Rhoda Baer

The US Department of Health and Human Services (HHS) and 15 other federal agencies have issued a final rule to update regulations intended to safeguard individuals who participate in research.

Most provisions in the new rule will go into effect in 2018.

The HHS says the new rule strengthens protections for people who volunteer to participate in research, while ensuring that the oversight system does not add inappropriate administrative burdens.

The current regulations, which have been in place since 1991, are often referred to as the “Common Rule.”

In September 2015, HHS and the other Common Rule agencies published a proposed new rule regarding research subjects—a notice of proposed rulemaking (NPRM)—which drew more than 2100 comments.

In response to concerns raised during the review process, the final rule contains a number of significant changes from the NPRM.

Research covered

The final rule does not cover clinical trials that are not federally funded.

The Common Rule has historically applied only to research conducted or supported by a Common Rule department or agency. And, although the NPRM proposed changing this policy, the final rule remains in line with the Common Rule.

Consent

The final rule requires consent forms to provide potential research subjects with a better understanding of a project’s scope so they can make a more fully informed decision about whether to participate.

Consent forms should include a concise explanation—at the beginning of the document—of the information that would be most important to individuals contemplating participation in a particular study, including the purpose of the research, the risks and benefits, and appropriate alternative treatments that might be beneficial to the prospective subject. 

The rule also requires that consent forms for certain federally funded clinical trials be posted on a public website.

Institutional review boards

The final rule requires, in many cases, use of a single institutional review board (IRB) for multi-institutional research studies.

However, the final rule has been modified from the NPRM to add substantial increased flexibility in now allowing broad groups of studies (instead of just specific studies) to be removed from this requirement.

Privacy

The final rule does not include the standardized privacy safeguards for identifiable private information and identifiable biospecimens that were proposed in the NPRM.

In most respects, the final rule retains the current approach to privacy standards.

For studies on stored identifiable data or identifiable biospecimens, researchers will have the option of relying on broad consent obtained for future research as an alternative to seeking IRB approval to waive the consent requirement.

As under the current rule, researchers will not have to obtain consent for studies on non-identified stored data or biospecimens.

Exemptions

The final rule establishes new exempt categories of research based on the level of risk they pose to participants.

For example, to reduce unnecessary regulatory burden and allow IRBs to focus their attention on higher-risk studies, there is a new exemption for secondary research involving identifiable private information if the research is regulated by and participants are protected under the HIPAA rules.

Review

The final rule removes the requirement to conduct continuing review of ongoing research studies in certain instances where such review does little to protect subjects.

For more details, see the final rule.

Researcher examines
tumor in a test tube
Photo by Rhoda Baer

The US Department of Health and Human Services (HHS) and 15 other federal agencies have issued a final rule to update regulations intended to safeguard individuals who participate in research.

Most provisions in the new rule will go into effect in 2018.

The HHS says the new rule strengthens protections for people who volunteer to participate in research, while ensuring that the oversight system does not add inappropriate administrative burdens.

The current regulations, which have been in place since 1991, are often referred to as the “Common Rule.”

In September 2015, HHS and the other Common Rule agencies published a proposed new rule regarding research subjects—a notice of proposed rulemaking (NPRM)—which drew more than 2100 comments.

In response to concerns raised during the review process, the final rule contains a number of significant changes from the NPRM.

Research covered

The final rule does not cover clinical trials that are not federally funded.

The Common Rule has historically applied only to research conducted or supported by a Common Rule department or agency. And, although the NPRM proposed changing this policy, the final rule remains in line with the Common Rule.

Consent

The final rule requires consent forms to provide potential research subjects with a better understanding of a project’s scope so they can make a more fully informed decision about whether to participate.

Consent forms should include a concise explanation—at the beginning of the document—of the information that would be most important to individuals contemplating participation in a particular study, including the purpose of the research, the risks and benefits, and appropriate alternative treatments that might be beneficial to the prospective subject. 

The rule also requires that consent forms for certain federally funded clinical trials be posted on a public website.

Institutional review boards

The final rule requires, in many cases, use of a single institutional review board (IRB) for multi-institutional research studies.

However, the final rule has been modified from the NPRM to add substantial increased flexibility in now allowing broad groups of studies (instead of just specific studies) to be removed from this requirement.

Privacy

The final rule does not include the standardized privacy safeguards for identifiable private information and identifiable biospecimens that were proposed in the NPRM.

In most respects, the final rule retains the current approach to privacy standards.

For studies on stored identifiable data or identifiable biospecimens, researchers will have the option of relying on broad consent obtained for future research as an alternative to seeking IRB approval to waive the consent requirement.

As under the current rule, researchers will not have to obtain consent for studies on non-identified stored data or biospecimens.

Exemptions

The final rule establishes new exempt categories of research based on the level of risk they pose to participants.

For example, to reduce unnecessary regulatory burden and allow IRBs to focus their attention on higher-risk studies, there is a new exemption for secondary research involving identifiable private information if the research is regulated by and participants are protected under the HIPAA rules.

Review

The final rule removes the requirement to conduct continuing review of ongoing research studies in certain instances where such review does little to protect subjects.

For more details, see the final rule.

Colony of iPSCs
Photo from Salk Institute

Researchers have created an induced pluripotent stem cell (iPSC) library intended to aid the study of sickle cell disease (SCD).

The library consists of iPSCs generated from blood samples taken from ethnically diverse SCD patients from around the world.

The researchers say these iPSCs can be used to create disease models, which may allow scientists to better understand how SCD occurs and develop and test new treatments for the disease.

As a complement to the library, the researchers also designed CRISPR/Cas gene editing tools to correct the sickle hemoglobin mutation.

The team described this work in Stem Cell Reports.

“Sickle cell disease affects millions of people worldwide and is an emerging global health burden,” said study author George Murphy, PhD, of the Center for Regenerative Medicine at Boston University School of Medicine in Massachusetts.

“iPSCs have the potential to revolutionize the way we study human development, model life-threatening diseases, and, eventually, treat patients.”

The researchers’ library includes SCD-specific iPSCs from patients of different ethnicities with different β-globin gene haplotypes and fetal hemoglobin levels.

The researchers generated 54 iPSC lines from blood samples collected from individuals of African American, Brazilian, and Saudi Arabian descent. Both genders were represented, as well as a range of ages (3 to 53 years of age).

Most of the cell lines in the library, along with accompanying genetic and hematologic data, are freely available via the WiCell website.

“In addition to the library, we’ve designed and are using gene editing tools to correct the sickle hemoglobin mutation using the stem cell lines,” said Gustavo Mostoslavsky, MD, PhD, also of the Center for Regenerative Medicine at Boston University School of Medicine.

“When coupled with corrected sickle cell disease-specific iPSCs, these tools could one day provide a functional cure for the disorder.”

Colony of iPSCs
Photo from Salk Institute

Researchers have created an induced pluripotent stem cell (iPSC) library intended to aid the study of sickle cell disease (SCD).

The library consists of iPSCs generated from blood samples taken from ethnically diverse SCD patients from around the world.

The researchers say these iPSCs can be used to create disease models, which may allow scientists to better understand how SCD occurs and develop and test new treatments for the disease.

As a complement to the library, the researchers also designed CRISPR/Cas gene editing tools to correct the sickle hemoglobin mutation.

The team described this work in Stem Cell Reports.

“Sickle cell disease affects millions of people worldwide and is an emerging global health burden,” said study author George Murphy, PhD, of the Center for Regenerative Medicine at Boston University School of Medicine in Massachusetts.

“iPSCs have the potential to revolutionize the way we study human development, model life-threatening diseases, and, eventually, treat patients.”

The researchers’ library includes SCD-specific iPSCs from patients of different ethnicities with different β-globin gene haplotypes and fetal hemoglobin levels.

The researchers generated 54 iPSC lines from blood samples collected from individuals of African American, Brazilian, and Saudi Arabian descent. Both genders were represented, as well as a range of ages (3 to 53 years of age).

Most of the cell lines in the library, along with accompanying genetic and hematologic data, are freely available via the WiCell website.

“In addition to the library, we’ve designed and are using gene editing tools to correct the sickle hemoglobin mutation using the stem cell lines,” said Gustavo Mostoslavsky, MD, PhD, also of the Center for Regenerative Medicine at Boston University School of Medicine.

“When coupled with corrected sickle cell disease-specific iPSCs, these tools could one day provide a functional cure for the disorder.”

Colony of iPSCs
Photo from Salk Institute

Researchers have created an induced pluripotent stem cell (iPSC) library intended to aid the study of sickle cell disease (SCD).

The library consists of iPSCs generated from blood samples taken from ethnically diverse SCD patients from around the world.

The researchers say these iPSCs can be used to create disease models, which may allow scientists to better understand how SCD occurs and develop and test new treatments for the disease.

As a complement to the library, the researchers also designed CRISPR/Cas gene editing tools to correct the sickle hemoglobin mutation.

The team described this work in Stem Cell Reports.

“Sickle cell disease affects millions of people worldwide and is an emerging global health burden,” said study author George Murphy, PhD, of the Center for Regenerative Medicine at Boston University School of Medicine in Massachusetts.

“iPSCs have the potential to revolutionize the way we study human development, model life-threatening diseases, and, eventually, treat patients.”

The researchers’ library includes SCD-specific iPSCs from patients of different ethnicities with different β-globin gene haplotypes and fetal hemoglobin levels.

The researchers generated 54 iPSC lines from blood samples collected from individuals of African American, Brazilian, and Saudi Arabian descent. Both genders were represented, as well as a range of ages (3 to 53 years of age).

Most of the cell lines in the library, along with accompanying genetic and hematologic data, are freely available via the WiCell website.

“In addition to the library, we’ve designed and are using gene editing tools to correct the sickle hemoglobin mutation using the stem cell lines,” said Gustavo Mostoslavsky, MD, PhD, also of the Center for Regenerative Medicine at Boston University School of Medicine.

“When coupled with corrected sickle cell disease-specific iPSCs, these tools could one day provide a functional cure for the disorder.”

Firefighters in front of a
burning building in Quebec
Photo by Sylvain Pedneault

New research suggests that prolonged exposure to work-related stress may increase a man’s risk of several cancers.

The study showed a significant association between work-related stress lasting 15 years or more and non-Hodgkin lymphoma (NHL) as well as lung, colon, rectal, and stomach cancers.

Men who had worked as firefighters, engineers, mechanics, and repair workers were most likely to report work-related stress.

Marie-Élise Parent, PhD, of Institut national de la recherche scientifique (INRS) in Laval, Quebec, Canada, and her colleagues conducted this research and published

the results in Preventive Medicine.

The researchers studied 3103 men with 11 different types of cancer who were diagnosed from 1979 to 1985. The team compared these men to 512 control subjects from the general population.

Both cases and controls were interviewed and asked to describe each job they had during their lifetime, including the occurrence of stress related to a job and the reason for that stress.

The researchers then calculated odds ratios (OR) for the association between perceived workplace stress and its duration, and each cancer site. The analyses were adjusted for lifestyle and occupational factors.

The team found that having at least one stressful job in a lifetime was associated with increased odds of 5 cancers:

• Lung—OR=1.33
• Colon—OR=1.51
• Bladder—OR=1.37
• Rectal—OR=1.52
• Stomach—OR=1.53.

When the researchers looked at the duration of stress, they found no significant association between any of the cancers and work-related stress lasting less than 15 years.

However, there were significant associations for several cancers and work-related stress lasting 15 to 30 years or more than 30 years. These included:

• NHL—15-30 years, OR=1.47; >30 years, OR=1.69 (P=0.02)
• Lung cancer—15-30 years, OR=1.47; >30 years, OR=1.51 (P=0.01)
• Colon cancer—15-30 years, OR=1.32; >30 years, OR=1.64 (P<0.01)
• Rectal cancer—15-30 years, OR=1.84; >30 years, OR=1.48 (P=0.01)
• Stomach cancer—15-30 years, OR=2.15; >30 years, OR=1.48 (P=0.01).

The occupations with the highest prevalence of work-related stress were firefighter (40% of firefighting jobs reported as stressful), industrial and aerospace engineer (31%), and motor vehicle and rail transport mechanic/repair worker (28%).

For the same individual, stress varied depending on the job held.

The study also showed that perceived stress was not limited to high work load and time constraints. Customer service, sales commissions, responsibilities, having an anxious temperament, job insecurity, financial problems, challenging or dangerous work conditions, employee supervision, interpersonal conflict, and a difficult commute were all sources of stress listed by study participants.
 
The researchers said one of the biggest flaws in previous studies of this kind is that none of them assessed work-related stress over a full working lifetime. The team said this made it impossible to determine how the duration of exposure to work-related stress affects cancer development.

This study, on the other hand, shows the importance of measuring stress at different points in an individual’s working life, the researchers said. They added that their results raise the question of whether chronic psychological stress should be viewed as a public health issue.

However, the team also pointed out that these results are unsubstantiated because they are based on a summary assessment of work-related stress for a given job. There is a need for epidemiological studies based on reliable stress measurements, repeated over time, and that take all sources of stress into account.

Firefighters in front of a
burning building in Quebec
Photo by Sylvain Pedneault

New research suggests that prolonged exposure to work-related stress may increase a man’s risk of several cancers.

The study showed a significant association between work-related stress lasting 15 years or more and non-Hodgkin lymphoma (NHL) as well as lung, colon, rectal, and stomach cancers.

Men who had worked as firefighters, engineers, mechanics, and repair workers were most likely to report work-related stress.

Marie-Élise Parent, PhD, of Institut national de la recherche scientifique (INRS) in Laval, Quebec, Canada, and her colleagues conducted this research and published

the results in Preventive Medicine.

The researchers studied 3103 men with 11 different types of cancer who were diagnosed from 1979 to 1985. The team compared these men to 512 control subjects from the general population.

Both cases and controls were interviewed and asked to describe each job they had during their lifetime, including the occurrence of stress related to a job and the reason for that stress.

The researchers then calculated odds ratios (OR) for the association between perceived workplace stress and its duration, and each cancer site. The analyses were adjusted for lifestyle and occupational factors.

The team found that having at least one stressful job in a lifetime was associated with increased odds of 5 cancers:

• Lung—OR=1.33
• Colon—OR=1.51
• Bladder—OR=1.37
• Rectal—OR=1.52
• Stomach—OR=1.53.

When the researchers looked at the duration of stress, they found no significant association between any of the cancers and work-related stress lasting less than 15 years.

However, there were significant associations for several cancers and work-related stress lasting 15 to 30 years or more than 30 years. These included:

• NHL—15-30 years, OR=1.47; >30 years, OR=1.69 (P=0.02)
• Lung cancer—15-30 years, OR=1.47; >30 years, OR=1.51 (P=0.01)
• Colon cancer—15-30 years, OR=1.32; >30 years, OR=1.64 (P<0.01)
• Rectal cancer—15-30 years, OR=1.84; >30 years, OR=1.48 (P=0.01)
• Stomach cancer—15-30 years, OR=2.15; >30 years, OR=1.48 (P=0.01).

The occupations with the highest prevalence of work-related stress were firefighter (40% of firefighting jobs reported as stressful), industrial and aerospace engineer (31%), and motor vehicle and rail transport mechanic/repair worker (28%).

For the same individual, stress varied depending on the job held.

The study also showed that perceived stress was not limited to high work load and time constraints. Customer service, sales commissions, responsibilities, having an anxious temperament, job insecurity, financial problems, challenging or dangerous work conditions, employee supervision, interpersonal conflict, and a difficult commute were all sources of stress listed by study participants.
 
The researchers said one of the biggest flaws in previous studies of this kind is that none of them assessed work-related stress over a full working lifetime. The team said this made it impossible to determine how the duration of exposure to work-related stress affects cancer development.

This study, on the other hand, shows the importance of measuring stress at different points in an individual’s working life, the researchers said. They added that their results raise the question of whether chronic psychological stress should be viewed as a public health issue.

However, the team also pointed out that these results are unsubstantiated because they are based on a summary assessment of work-related stress for a given job. There is a need for epidemiological studies based on reliable stress measurements, repeated over time, and that take all sources of stress into account.

Firefighters in front of a
burning building in Quebec
Photo by Sylvain Pedneault

New research suggests that prolonged exposure to work-related stress may increase a man’s risk of several cancers.

The study showed a significant association between work-related stress lasting 15 years or more and non-Hodgkin lymphoma (NHL) as well as lung, colon, rectal, and stomach cancers.

Men who had worked as firefighters, engineers, mechanics, and repair workers were most likely to report work-related stress.

Marie-Élise Parent, PhD, of Institut national de la recherche scientifique (INRS) in Laval, Quebec, Canada, and her colleagues conducted this research and published

the results in Preventive Medicine.

The researchers studied 3103 men with 11 different types of cancer who were diagnosed from 1979 to 1985. The team compared these men to 512 control subjects from the general population.

Both cases and controls were interviewed and asked to describe each job they had during their lifetime, including the occurrence of stress related to a job and the reason for that stress.

The researchers then calculated odds ratios (OR) for the association between perceived workplace stress and its duration, and each cancer site. The analyses were adjusted for lifestyle and occupational factors.

The team found that having at least one stressful job in a lifetime was associated with increased odds of 5 cancers:

• Lung—OR=1.33
• Colon—OR=1.51
• Bladder—OR=1.37
• Rectal—OR=1.52
• Stomach—OR=1.53.

When the researchers looked at the duration of stress, they found no significant association between any of the cancers and work-related stress lasting less than 15 years.

However, there were significant associations for several cancers and work-related stress lasting 15 to 30 years or more than 30 years. These included:

• NHL—15-30 years, OR=1.47; >30 years, OR=1.69 (P=0.02)
• Lung cancer—15-30 years, OR=1.47; >30 years, OR=1.51 (P=0.01)
• Colon cancer—15-30 years, OR=1.32; >30 years, OR=1.64 (P<0.01)
• Rectal cancer—15-30 years, OR=1.84; >30 years, OR=1.48 (P=0.01)
• Stomach cancer—15-30 years, OR=2.15; >30 years, OR=1.48 (P=0.01).

The occupations with the highest prevalence of work-related stress were firefighter (40% of firefighting jobs reported as stressful), industrial and aerospace engineer (31%), and motor vehicle and rail transport mechanic/repair worker (28%).

For the same individual, stress varied depending on the job held.

The study also showed that perceived stress was not limited to high work load and time constraints. Customer service, sales commissions, responsibilities, having an anxious temperament, job insecurity, financial problems, challenging or dangerous work conditions, employee supervision, interpersonal conflict, and a difficult commute were all sources of stress listed by study participants.
 
The researchers said one of the biggest flaws in previous studies of this kind is that none of them assessed work-related stress over a full working lifetime. The team said this made it impossible to determine how the duration of exposure to work-related stress affects cancer development.

This study, on the other hand, shows the importance of measuring stress at different points in an individual’s working life, the researchers said. They added that their results raise the question of whether chronic psychological stress should be viewed as a public health issue.

However, the team also pointed out that these results are unsubstantiated because they are based on a summary assessment of work-related stress for a given job. There is a need for epidemiological studies based on reliable stress measurements, repeated over time, and that take all sources of stress into account.

Drug production
Photo courtesy of the FDA

An investigation by Kaiser Health News (KHN) suggests some pharmaceutical companies are using the Orphan Drug Act to create monopolies and charge high prices for drugs that are already approved for mass market use in the US.

The US Food and Drug Administration (FDA) grants orphan designation to drugs and biologics intended to treat, diagnose, or prevent conditions that affect fewer than 200,000 people in the US.

The designation provides incentives for sponsors to develop products for rare diseases. This includes a 50% tax break on research and development, a fee waiver, access to federal grants, and 7 years of market exclusivity if the product is approved.

However, the KHN investigation showed that some companies have been applying for—and obtaining—orphan designation for drugs already used to treat large populations.

The report states that more than 70 drugs that currently have orphan status were first approved by the FDA for mass market use.

In fact, 7 of the 10 best-selling drugs of 2015 were also orphan drugs. Included on this list are Rituxan (rituximab), Neulasta (pegfilgrastim), and Revlimid (lenalidomide).

The report also states that more than 80 drugs with orphan designation have been approved to treat more than one rare disease. For example, Gleevec (imatinib) has 9 orphan designations.

The KHN investigation revealed that, overall, about a third of orphan designations granted since the Orphan Drug Act was passed in 1983 have been either for repurposed mass market drugs or drugs that received multiple orphan designations. (Roughly 450 orphan drugs have been brought to market since 1983, according to the report.)

For each orphan designation, a drug’s developer qualifies for “a fresh batch of incentives,” the report notes.

The exclusivity incentive means the FDA won’t approve another version of an orphan drug to treat the rare disease(s) in question for 7 years, even if the company’s patent on the brand-name drug has expired.

For example, generic versions of imatinib are being used to treat chronic myeloid leukemia in the US because the patent for Gleevec has expired. However, because of an orphan designation, Novartis still has exclusivity for Gleevec (and will until 2020) as a treatment for patients with newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia who are also on chemotherapy.

The KHN report notes that exclusivity can be “a potent pricing tool” due to a lack of competition. And this means orphan drugs may “come with astronomical price tags.”

For instance, there are 33 orphan drugs that cost at least $28,000 for a 30-day supply and 4 orphan drugs that cost more than $70,000 per month.

According to the KHN report, the FDA is planning to investigate this issue.

Gayatri Rao, MD, director of the FDA’s Office of Orphan Products Development, has asked for a review of all orphan designations granted in 2010 and 2015. She said the review will not extend further because the FDA does not have the resources to review all orphan drugs.

Drug production
Photo courtesy of the FDA

An investigation by Kaiser Health News (KHN) suggests some pharmaceutical companies are using the Orphan Drug Act to create monopolies and charge high prices for drugs that are already approved for mass market use in the US.

The US Food and Drug Administration (FDA) grants orphan designation to drugs and biologics intended to treat, diagnose, or prevent conditions that affect fewer than 200,000 people in the US.

The designation provides incentives for sponsors to develop products for rare diseases. This includes a 50% tax break on research and development, a fee waiver, access to federal grants, and 7 years of market exclusivity if the product is approved.

However, the KHN investigation showed that some companies have been applying for—and obtaining—orphan designation for drugs already used to treat large populations.

The report states that more than 70 drugs that currently have orphan status were first approved by the FDA for mass market use.

In fact, 7 of the 10 best-selling drugs of 2015 were also orphan drugs. Included on this list are Rituxan (rituximab), Neulasta (pegfilgrastim), and Revlimid (lenalidomide).

The report also states that more than 80 drugs with orphan designation have been approved to treat more than one rare disease. For example, Gleevec (imatinib) has 9 orphan designations.

The KHN investigation revealed that, overall, about a third of orphan designations granted since the Orphan Drug Act was passed in 1983 have been either for repurposed mass market drugs or drugs that received multiple orphan designations. (Roughly 450 orphan drugs have been brought to market since 1983, according to the report.)

For each orphan designation, a drug’s developer qualifies for “a fresh batch of incentives,” the report notes.

The exclusivity incentive means the FDA won’t approve another version of an orphan drug to treat the rare disease(s) in question for 7 years, even if the company’s patent on the brand-name drug has expired.

For example, generic versions of imatinib are being used to treat chronic myeloid leukemia in the US because the patent for Gleevec has expired. However, because of an orphan designation, Novartis still has exclusivity for Gleevec (and will until 2020) as a treatment for patients with newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia who are also on chemotherapy.

The KHN report notes that exclusivity can be “a potent pricing tool” due to a lack of competition. And this means orphan drugs may “come with astronomical price tags.”

For instance, there are 33 orphan drugs that cost at least $28,000 for a 30-day supply and 4 orphan drugs that cost more than $70,000 per month.

According to the KHN report, the FDA is planning to investigate this issue.

Gayatri Rao, MD, director of the FDA’s Office of Orphan Products Development, has asked for a review of all orphan designations granted in 2010 and 2015. She said the review will not extend further because the FDA does not have the resources to review all orphan drugs.

Drug production
Photo courtesy of the FDA

An investigation by Kaiser Health News (KHN) suggests some pharmaceutical companies are using the Orphan Drug Act to create monopolies and charge high prices for drugs that are already approved for mass market use in the US.

The US Food and Drug Administration (FDA) grants orphan designation to drugs and biologics intended to treat, diagnose, or prevent conditions that affect fewer than 200,000 people in the US.

The designation provides incentives for sponsors to develop products for rare diseases. This includes a 50% tax break on research and development, a fee waiver, access to federal grants, and 7 years of market exclusivity if the product is approved.

However, the KHN investigation showed that some companies have been applying for—and obtaining—orphan designation for drugs already used to treat large populations.

The report states that more than 70 drugs that currently have orphan status were first approved by the FDA for mass market use.

In fact, 7 of the 10 best-selling drugs of 2015 were also orphan drugs. Included on this list are Rituxan (rituximab), Neulasta (pegfilgrastim), and Revlimid (lenalidomide).

The report also states that more than 80 drugs with orphan designation have been approved to treat more than one rare disease. For example, Gleevec (imatinib) has 9 orphan designations.

The KHN investigation revealed that, overall, about a third of orphan designations granted since the Orphan Drug Act was passed in 1983 have been either for repurposed mass market drugs or drugs that received multiple orphan designations. (Roughly 450 orphan drugs have been brought to market since 1983, according to the report.)

For each orphan designation, a drug’s developer qualifies for “a fresh batch of incentives,” the report notes.

The exclusivity incentive means the FDA won’t approve another version of an orphan drug to treat the rare disease(s) in question for 7 years, even if the company’s patent on the brand-name drug has expired.

For example, generic versions of imatinib are being used to treat chronic myeloid leukemia in the US because the patent for Gleevec has expired. However, because of an orphan designation, Novartis still has exclusivity for Gleevec (and will until 2020) as a treatment for patients with newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia who are also on chemotherapy.

The KHN report notes that exclusivity can be “a potent pricing tool” due to a lack of competition. And this means orphan drugs may “come with astronomical price tags.”

For instance, there are 33 orphan drugs that cost at least $28,000 for a 30-day supply and 4 orphan drugs that cost more than $70,000 per month.

According to the KHN report, the FDA is planning to investigate this issue.

Gayatri Rao, MD, director of the FDA’s Office of Orphan Products Development, has asked for a review of all orphan designations granted in 2010 and 2015. She said the review will not extend further because the FDA does not have the resources to review all orphan drugs.

Vials of drugs
Photo by Bill Branson

The US Food and Drug Administration (FDA) has released 3 new draft guidance documents for industry.

One document provides an overview of scientific considerations when attempting to demonstrate that a biosimilar product is interchangeable with a reference product.

The other 2 guidance documents are intended to clarify the FDA’s position regarding communications about medical products.

The first draft guidance, “Considerations in Demonstrating Interchangeability With a Reference Product,” is intended to assist applicants in demonstrating that a proposed therapeutic protein product (eg, monoclonal antibodies) is interchangeable with a reference product under section 351(k) of the Public Health Service Act.

An interchangeable biological product is biosimilar to the reference product and can be expected to produce the same clinical result as the reference product in any given patient. 

For a biological product that is administered more than once, the risk in terms of safety or diminished efficacy of alternating or switching between the biological product and the reference product must not be greater than the risk of using the reference product without such alternating/switching.

The approval pathway for biosimilar and interchangeable products was established by the Biologics Price Competition and Innovation Act of 2009, which was enacted as part of the Affordable Care Act in March 2010.

The FDA’s draft guidance on biosimilars contains information on:

• Factors impacting the type and amount of data and information needed to support a demonstration of interchangeability
• The data and information needed to support a demonstration of interchangeability
• Considerations for the design and analysis of a switching study or studies to support a demonstration of interchangeability
• Recommendations regarding the use of US-licensed reference products in a switching study or studies
• Considerations for developing presentations (eg, container closure systems) for proposed interchangeable products.

In addition to soliciting comments on this draft guidance, the FDA is inviting comments on questions posed in the notice of availability about interchangeability in general, the regulation of interchangeable products over their life cycle, and questions about considerations regarding post-approval manufacturing changes. 

The FDA also released a Center for Drug Evaluation and Research “From Our Perspective,” by Leah Christl, describing aspects of this draft guidance.

For more information on how to submit comments on the draft guidance and questions posed in the notice of availability, see the Federal Register notice.

Medical communications

The FDA also released 2 draft guidance documents that, the agency says, will each help provide clarity for medical product companies, as well as other interested parties, on the FDA’s current thinking and recommendations for a few different types of communications about medical products.

The first draft guidance, “Drug and Device Manufacturer Communications with Payors, Formulary Committees, and Similar Entities,” explains the FDA’s current thinking and recommendations on firms’ communication of healthcare economic information about approved drugs under section 502(a) of the Federal Food, Drug, and Cosmetic Act, which was recently amended by the 21st Century Cures Act. 

The guidance also answers common questions and provides the FDA’s recommendations regarding firms’ communications to payors about investigational drugs and devices that are not yet approved or cleared for any use.

The second draft guidance, “Medical Product Communications That Are Consistent With the FDA-Required Labeling,” explains the FDA’s current thinking about firms’ medical product communications that include data and information that are not contained in their products’ FDA-required labeling, but that concern the approved or cleared uses of their products.

The FDA has opened a public comment period for each draft guidance.

The agency is also asking for stakeholder input on another, distinct topic—communications about unapproved uses of approved or cleared medical products.

The FDA held a Part 15 hearing in November 2016 to hear from a broad range of stakeholders regarding this topic. The agency has now reopened the comment period for the docket opened in connection with that public hearing for an additional 90 days (until April 10, 2017) to allow interested parties an opportunity to review the 2 draft guidances before submitting comments to any of the relevant dockets.

The FDA also added a document to the docket for the public hearing titled, “Memorandum: Public Health Interests and First Amendment Considerations Related to Manufacturer Communications Regarding Unapproved Uses of Approved or Cleared Medical Products.”

This document provides additional background on the issues the FDA is considering as part of its review of the agency’s rules and policies relating to firm communications regarding unapproved uses of approved or cleared medical products, including a discussion of First Amendment considerations.

The FDA is requesting input on the memorandum as it relates to the questions set forth in the initial notice of public hearing.

Vials of drugs
Photo by Bill Branson

The US Food and Drug Administration (FDA) has released 3 new draft guidance documents for industry.

One document provides an overview of scientific considerations when attempting to demonstrate that a biosimilar product is interchangeable with a reference product.

The other 2 guidance documents are intended to clarify the FDA’s position regarding communications about medical products.

The first draft guidance, “Considerations in Demonstrating Interchangeability With a Reference Product,” is intended to assist applicants in demonstrating that a proposed therapeutic protein product (eg, monoclonal antibodies) is interchangeable with a reference product under section 351(k) of the Public Health Service Act.

An interchangeable biological product is biosimilar to the reference product and can be expected to produce the same clinical result as the reference product in any given patient. 

For a biological product that is administered more than once, the risk in terms of safety or diminished efficacy of alternating or switching between the biological product and the reference product must not be greater than the risk of using the reference product without such alternating/switching.

The approval pathway for biosimilar and interchangeable products was established by the Biologics Price Competition and Innovation Act of 2009, which was enacted as part of the Affordable Care Act in March 2010.

The FDA’s draft guidance on biosimilars contains information on:

• Factors impacting the type and amount of data and information needed to support a demonstration of interchangeability
• The data and information needed to support a demonstration of interchangeability
• Considerations for the design and analysis of a switching study or studies to support a demonstration of interchangeability
• Recommendations regarding the use of US-licensed reference products in a switching study or studies
• Considerations for developing presentations (eg, container closure systems) for proposed interchangeable products.

In addition to soliciting comments on this draft guidance, the FDA is inviting comments on questions posed in the notice of availability about interchangeability in general, the regulation of interchangeable products over their life cycle, and questions about considerations regarding post-approval manufacturing changes. 

The FDA also released a Center for Drug Evaluation and Research “From Our Perspective,” by Leah Christl, describing aspects of this draft guidance.

For more information on how to submit comments on the draft guidance and questions posed in the notice of availability, see the Federal Register notice.

Medical communications

The FDA also released 2 draft guidance documents that, the agency says, will each help provide clarity for medical product companies, as well as other interested parties, on the FDA’s current thinking and recommendations for a few different types of communications about medical products.

The first draft guidance, “Drug and Device Manufacturer Communications with Payors, Formulary Committees, and Similar Entities,” explains the FDA’s current thinking and recommendations on firms’ communication of healthcare economic information about approved drugs under section 502(a) of the Federal Food, Drug, and Cosmetic Act, which was recently amended by the 21st Century Cures Act. 

The guidance also answers common questions and provides the FDA’s recommendations regarding firms’ communications to payors about investigational drugs and devices that are not yet approved or cleared for any use.

The second draft guidance, “Medical Product Communications That Are Consistent With the FDA-Required Labeling,” explains the FDA’s current thinking about firms’ medical product communications that include data and information that are not contained in their products’ FDA-required labeling, but that concern the approved or cleared uses of their products.

The FDA has opened a public comment period for each draft guidance.

The agency is also asking for stakeholder input on another, distinct topic—communications about unapproved uses of approved or cleared medical products.

The FDA held a Part 15 hearing in November 2016 to hear from a broad range of stakeholders regarding this topic. The agency has now reopened the comment period for the docket opened in connection with that public hearing for an additional 90 days (until April 10, 2017) to allow interested parties an opportunity to review the 2 draft guidances before submitting comments to any of the relevant dockets.

The FDA also added a document to the docket for the public hearing titled, “Memorandum: Public Health Interests and First Amendment Considerations Related to Manufacturer Communications Regarding Unapproved Uses of Approved or Cleared Medical Products.”

This document provides additional background on the issues the FDA is considering as part of its review of the agency’s rules and policies relating to firm communications regarding unapproved uses of approved or cleared medical products, including a discussion of First Amendment considerations.

The FDA is requesting input on the memorandum as it relates to the questions set forth in the initial notice of public hearing.

Vials of drugs
Photo by Bill Branson

The US Food and Drug Administration (FDA) has released 3 new draft guidance documents for industry.

One document provides an overview of scientific considerations when attempting to demonstrate that a biosimilar product is interchangeable with a reference product.

The other 2 guidance documents are intended to clarify the FDA’s position regarding communications about medical products.

The first draft guidance, “Considerations in Demonstrating Interchangeability With a Reference Product,” is intended to assist applicants in demonstrating that a proposed therapeutic protein product (eg, monoclonal antibodies) is interchangeable with a reference product under section 351(k) of the Public Health Service Act.

An interchangeable biological product is biosimilar to the reference product and can be expected to produce the same clinical result as the reference product in any given patient. 

For a biological product that is administered more than once, the risk in terms of safety or diminished efficacy of alternating or switching between the biological product and the reference product must not be greater than the risk of using the reference product without such alternating/switching.

The approval pathway for biosimilar and interchangeable products was established by the Biologics Price Competition and Innovation Act of 2009, which was enacted as part of the Affordable Care Act in March 2010.

The FDA’s draft guidance on biosimilars contains information on:

• Factors impacting the type and amount of data and information needed to support a demonstration of interchangeability
• The data and information needed to support a demonstration of interchangeability
• Considerations for the design and analysis of a switching study or studies to support a demonstration of interchangeability
• Recommendations regarding the use of US-licensed reference products in a switching study or studies
• Considerations for developing presentations (eg, container closure systems) for proposed interchangeable products.

In addition to soliciting comments on this draft guidance, the FDA is inviting comments on questions posed in the notice of availability about interchangeability in general, the regulation of interchangeable products over their life cycle, and questions about considerations regarding post-approval manufacturing changes. 

The FDA also released a Center for Drug Evaluation and Research “From Our Perspective,” by Leah Christl, describing aspects of this draft guidance.

For more information on how to submit comments on the draft guidance and questions posed in the notice of availability, see the Federal Register notice.

Medical communications

The FDA also released 2 draft guidance documents that, the agency says, will each help provide clarity for medical product companies, as well as other interested parties, on the FDA’s current thinking and recommendations for a few different types of communications about medical products.

The first draft guidance, “Drug and Device Manufacturer Communications with Payors, Formulary Committees, and Similar Entities,” explains the FDA’s current thinking and recommendations on firms’ communication of healthcare economic information about approved drugs under section 502(a) of the Federal Food, Drug, and Cosmetic Act, which was recently amended by the 21st Century Cures Act. 

The guidance also answers common questions and provides the FDA’s recommendations regarding firms’ communications to payors about investigational drugs and devices that are not yet approved or cleared for any use.

The second draft guidance, “Medical Product Communications That Are Consistent With the FDA-Required Labeling,” explains the FDA’s current thinking about firms’ medical product communications that include data and information that are not contained in their products’ FDA-required labeling, but that concern the approved or cleared uses of their products.

The FDA has opened a public comment period for each draft guidance.

The agency is also asking for stakeholder input on another, distinct topic—communications about unapproved uses of approved or cleared medical products.

The FDA held a Part 15 hearing in November 2016 to hear from a broad range of stakeholders regarding this topic. The agency has now reopened the comment period for the docket opened in connection with that public hearing for an additional 90 days (until April 10, 2017) to allow interested parties an opportunity to review the 2 draft guidances before submitting comments to any of the relevant dockets.

The FDA also added a document to the docket for the public hearing titled, “Memorandum: Public Health Interests and First Amendment Considerations Related to Manufacturer Communications Regarding Unapproved Uses of Approved or Cleared Medical Products.”

This document provides additional background on the issues the FDA is considering as part of its review of the agency’s rules and policies relating to firm communications regarding unapproved uses of approved or cleared medical products, including a discussion of First Amendment considerations.

The FDA is requesting input on the memorandum as it relates to the questions set forth in the initial notice of public hearing.

Saccharomyces cerevisiae
as it buds before dividing
Image by Carolyn Larabell

L-asparaginase derived from baker’s yeast has shown early promise for treating acute lymphoblastic leukemia (ALL), according to researchers. 

The team isolated L-asparaginase from Saccharomyces cerevisiae and found the enzyme could kill ALL cells in vitro, while largely sparing healthy control cells.

Gisele Monteiro de Souza, PhD, of the University of São Paulo in São Paulo, Brazil, and her colleagues detailed these findings in Scientific Reports.

“In this study, we characterized the enzyme L-asparaginase from S cerevisiae,” Dr Souza said. “The results show this protein can efficiently annihilate leukemia cells with low cytotoxicity to healthy cells.”

She and her colleagues conducted this study in search of alternatives to L-asparaginase extracted from bacteria (Escherichia coli and Erwinia chrysanthemi).

“Our goal in this project wasn’t to produce the enzyme, but rather to find a new source of the biodrug in microorganisms for use in patients who develop resistance to the bacterial enzyme,” said study author Marcos Antonio de Oliveira, of São Paulo State University in São Vicente, Brazil.

To this end, the researchers isolated fungi from several different Brazilian environments as well as marine and land environments in Antarctica. According to Oliveira, these organisms often secrete asparaginase into the extracellular medium in response to a shortage of nitrogen.

“This lowers the cost of purifying the molecule for drug production, an important factor from an industrial standpoint,” he said.

The group also used bioinformatics tools to mine information on the genomes of several microorganisms from international databases.

In this way, they identified a gene responsible for producing an enzyme that closely resembles the enzymes found in E coli and E chrysanthemi, but with a number of advantages, in the genome of S cerevisiae.

The gene of interest from L-asparaginase was cloned, and the researchers used genetic engineering to make E coli express large amounts of the enzyme originally found in yeast.

“We were able to obtain the recombinant protein,” said study author Iris Munhoz Costa, of the University of São Paulo.

“We then performed studies to characterize its secondary structure and identify important regions called catalytic sites. Finally, we evaluated its efficacy in vitro.”

The enzyme was tested in 3 different cell lines: ALL cells incapable of producing asparagine at normal levels (MOLT4), another ALL cell line capable of producing asparagine at normal levels (REH), and non-malignant control cells (HUVECs).

These 3 cell lines were subdivided into 2 groups. One was treated with L-asparaginase derived from E coli enzyme, and the other was treated with L-asparaginase from yeast.

“The bacterial enzyme killed about 90% of the MOLT4 human leukemia cells and displayed low toxicity to the healthy HUVEC cells, killing only 10%,” Dr Souza said.

“The yeast enzyme killed between 70% and 80% of the MOLT4 cells and displayed less than 10% toxicity for HUVEC cells. Neither was significantly effective against REH cells.”

In her view, the results are encouraging, in contrast with those of studies performed with the same enzyme in the 1970s. At that time, the tests involved a version of the protein extracted directly from yeast and containing many impurities.

The group’s next step is to perform new in vitro trials with different cell types to evaluate the immune response and toxicity. If the results are positive, the first tests in animals may be next.

The researchers are also studying possible modifications that could be made to the molecule’s structure to increase antitumor activity and extend the enzyme’s half-life.

Saccharomyces cerevisiae
as it buds before dividing
Image by Carolyn Larabell

L-asparaginase derived from baker’s yeast has shown early promise for treating acute lymphoblastic leukemia (ALL), according to researchers. 

The team isolated L-asparaginase from Saccharomyces cerevisiae and found the enzyme could kill ALL cells in vitro, while largely sparing healthy control cells.

Gisele Monteiro de Souza, PhD, of the University of São Paulo in São Paulo, Brazil, and her colleagues detailed these findings in Scientific Reports.

“In this study, we characterized the enzyme L-asparaginase from S cerevisiae,” Dr Souza said. “The results show this protein can efficiently annihilate leukemia cells with low cytotoxicity to healthy cells.”

She and her colleagues conducted this study in search of alternatives to L-asparaginase extracted from bacteria (Escherichia coli and Erwinia chrysanthemi).

“Our goal in this project wasn’t to produce the enzyme, but rather to find a new source of the biodrug in microorganisms for use in patients who develop resistance to the bacterial enzyme,” said study author Marcos Antonio de Oliveira, of São Paulo State University in São Vicente, Brazil.

To this end, the researchers isolated fungi from several different Brazilian environments as well as marine and land environments in Antarctica. According to Oliveira, these organisms often secrete asparaginase into the extracellular medium in response to a shortage of nitrogen.

“This lowers the cost of purifying the molecule for drug production, an important factor from an industrial standpoint,” he said.

The group also used bioinformatics tools to mine information on the genomes of several microorganisms from international databases.

In this way, they identified a gene responsible for producing an enzyme that closely resembles the enzymes found in E coli and E chrysanthemi, but with a number of advantages, in the genome of S cerevisiae.

The gene of interest from L-asparaginase was cloned, and the researchers used genetic engineering to make E coli express large amounts of the enzyme originally found in yeast.

“We were able to obtain the recombinant protein,” said study author Iris Munhoz Costa, of the University of São Paulo.

“We then performed studies to characterize its secondary structure and identify important regions called catalytic sites. Finally, we evaluated its efficacy in vitro.”

The enzyme was tested in 3 different cell lines: ALL cells incapable of producing asparagine at normal levels (MOLT4), another ALL cell line capable of producing asparagine at normal levels (REH), and non-malignant control cells (HUVECs).

These 3 cell lines were subdivided into 2 groups. One was treated with L-asparaginase derived from E coli enzyme, and the other was treated with L-asparaginase from yeast.

“The bacterial enzyme killed about 90% of the MOLT4 human leukemia cells and displayed low toxicity to the healthy HUVEC cells, killing only 10%,” Dr Souza said.

“The yeast enzyme killed between 70% and 80% of the MOLT4 cells and displayed less than 10% toxicity for HUVEC cells. Neither was significantly effective against REH cells.”

In her view, the results are encouraging, in contrast with those of studies performed with the same enzyme in the 1970s. At that time, the tests involved a version of the protein extracted directly from yeast and containing many impurities.

The group’s next step is to perform new in vitro trials with different cell types to evaluate the immune response and toxicity. If the results are positive, the first tests in animals may be next.

The researchers are also studying possible modifications that could be made to the molecule’s structure to increase antitumor activity and extend the enzyme’s half-life.

Saccharomyces cerevisiae
as it buds before dividing
Image by Carolyn Larabell

L-asparaginase derived from baker’s yeast has shown early promise for treating acute lymphoblastic leukemia (ALL), according to researchers. 

The team isolated L-asparaginase from Saccharomyces cerevisiae and found the enzyme could kill ALL cells in vitro, while largely sparing healthy control cells.

Gisele Monteiro de Souza, PhD, of the University of São Paulo in São Paulo, Brazil, and her colleagues detailed these findings in Scientific Reports.

“In this study, we characterized the enzyme L-asparaginase from S cerevisiae,” Dr Souza said. “The results show this protein can efficiently annihilate leukemia cells with low cytotoxicity to healthy cells.”

She and her colleagues conducted this study in search of alternatives to L-asparaginase extracted from bacteria (Escherichia coli and Erwinia chrysanthemi).

“Our goal in this project wasn’t to produce the enzyme, but rather to find a new source of the biodrug in microorganisms for use in patients who develop resistance to the bacterial enzyme,” said study author Marcos Antonio de Oliveira, of São Paulo State University in São Vicente, Brazil.

To this end, the researchers isolated fungi from several different Brazilian environments as well as marine and land environments in Antarctica. According to Oliveira, these organisms often secrete asparaginase into the extracellular medium in response to a shortage of nitrogen.

“This lowers the cost of purifying the molecule for drug production, an important factor from an industrial standpoint,” he said.

The group also used bioinformatics tools to mine information on the genomes of several microorganisms from international databases.

In this way, they identified a gene responsible for producing an enzyme that closely resembles the enzymes found in E coli and E chrysanthemi, but with a number of advantages, in the genome of S cerevisiae.

The gene of interest from L-asparaginase was cloned, and the researchers used genetic engineering to make E coli express large amounts of the enzyme originally found in yeast.

“We were able to obtain the recombinant protein,” said study author Iris Munhoz Costa, of the University of São Paulo.

“We then performed studies to characterize its secondary structure and identify important regions called catalytic sites. Finally, we evaluated its efficacy in vitro.”

The enzyme was tested in 3 different cell lines: ALL cells incapable of producing asparagine at normal levels (MOLT4), another ALL cell line capable of producing asparagine at normal levels (REH), and non-malignant control cells (HUVECs).

These 3 cell lines were subdivided into 2 groups. One was treated with L-asparaginase derived from E coli enzyme, and the other was treated with L-asparaginase from yeast.

“The bacterial enzyme killed about 90% of the MOLT4 human leukemia cells and displayed low toxicity to the healthy HUVEC cells, killing only 10%,” Dr Souza said.

“The yeast enzyme killed between 70% and 80% of the MOLT4 cells and displayed less than 10% toxicity for HUVEC cells. Neither was significantly effective against REH cells.”

In her view, the results are encouraging, in contrast with those of studies performed with the same enzyme in the 1970s. At that time, the tests involved a version of the protein extracted directly from yeast and containing many impurities.

The group’s next step is to perform new in vitro trials with different cell types to evaluate the immune response and toxicity. If the results are positive, the first tests in animals may be next.

The researchers are also studying possible modifications that could be made to the molecule’s structure to increase antitumor activity and extend the enzyme’s half-life.

Blood donor
Photo by Marja Helander

The Irish Blood Transfusion Service (IBTS) has lifted the lifetime ban on blood donations from men who have sex with men (MSM).

However, prospective MSM blood donors are still subject to deferral.

Now, MSMs are allowed to donate blood in Ireland if it has been more than 12 months since their last sexual contact with a man and if they meet the other blood donor selection criteria.

The IBTS has also introduced new regulations relating to individuals with a history of specific, notifiable sexually transmitted infections (STIs).

These individuals are now allowed to donate blood 5 years after they have completed treatment for their STIs.

“In June of last year, I accepted the recommendations of the IBTS to change their blood donation deferral policies for men who have sex with men, as well as for donors who have had a sexually transmitted infection,” said Ireland’s Health Minister, Simon Harris.

“I would like to take this opportunity to thank the IBTS for their work over the past 6 months, which, today, sees these recommendations brought to fruition within the timescale agreed. [T]he IBTS will continue to keep all deferral policies under active review in the light of scientific evidence, emerging infections, and international experience.”

MSM deferral

The change in deferral policy relating to MSMs follows a 2-year review of the issues by the IBTS.

The agency hosted an international symposium on the topic in April 2016. Experts from 7 countries who had either lifted, or were in the process of lifting, their lifetime ban on MSM blood donors presented their respective stances, research, and the rationale behind their decisions.

The IBTS said its change to a 1-year deferral period for MSMs is supported by the most current scientific evidence available and brings Ireland into line with similar policies in the UK, Canada, and the US.

STI-related deferral

The IBTS said the 1-year deferral policy for MSMs will protect against the risk of HIV transmission. However, there is concern that it may not be sufficient to deal with an emerging infection. 

Therefore, the board of the IBTS decided that individuals who have had a notifiable STI, such as chlamydia or genital herpes, should be deferred from donating blood for 5 years after completing treatment for that STI.  

Individuals who have had syphilis, gonorrhea, lymphogranuloma venereum, or granuloma inguinale are (and have been) permanently banned from donating blood.

Individuals who have taken medication to prevent HIV infection are also deferred from donating blood for 5 years after they take the medication.

Safety of the blood supply

“The IBTS provides a safe, reliable, and robust blood service to the Irish health system and has the necessary program and procedures in place to protect both donors and recipients of blood and blood products,” Harris said.

All prospective blood donors in Ireland undergo nucleic acid testing for a number of diseases, including HIV, hepatitis B, and hepatitis C. This is the most sensitive method of testing available.

The risk of transmitted infection of blood is at its highest when individuals donate blood during the 5- to 15-day period following exposure to a virus.

There is no biological measure to detect infectivity during this period and, as a consequence, the IBTS temporarily or permanently defers, on average, 1 in 10 people from giving blood.

Blood donor
Photo by Marja Helander

The Irish Blood Transfusion Service (IBTS) has lifted the lifetime ban on blood donations from men who have sex with men (MSM).

However, prospective MSM blood donors are still subject to deferral.

Now, MSMs are allowed to donate blood in Ireland if it has been more than 12 months since their last sexual contact with a man and if they meet the other blood donor selection criteria.

The IBTS has also introduced new regulations relating to individuals with a history of specific, notifiable sexually transmitted infections (STIs).

These individuals are now allowed to donate blood 5 years after they have completed treatment for their STIs.

“In June of last year, I accepted the recommendations of the IBTS to change their blood donation deferral policies for men who have sex with men, as well as for donors who have had a sexually transmitted infection,” said Ireland’s Health Minister, Simon Harris.

“I would like to take this opportunity to thank the IBTS for their work over the past 6 months, which, today, sees these recommendations brought to fruition within the timescale agreed. [T]he IBTS will continue to keep all deferral policies under active review in the light of scientific evidence, emerging infections, and international experience.”

MSM deferral

The change in deferral policy relating to MSMs follows a 2-year review of the issues by the IBTS.

The agency hosted an international symposium on the topic in April 2016. Experts from 7 countries who had either lifted, or were in the process of lifting, their lifetime ban on MSM blood donors presented their respective stances, research, and the rationale behind their decisions.

The IBTS said its change to a 1-year deferral period for MSMs is supported by the most current scientific evidence available and brings Ireland into line with similar policies in the UK, Canada, and the US.

STI-related deferral

The IBTS said the 1-year deferral policy for MSMs will protect against the risk of HIV transmission. However, there is concern that it may not be sufficient to deal with an emerging infection. 

Therefore, the board of the IBTS decided that individuals who have had a notifiable STI, such as chlamydia or genital herpes, should be deferred from donating blood for 5 years after completing treatment for that STI.  

Individuals who have had syphilis, gonorrhea, lymphogranuloma venereum, or granuloma inguinale are (and have been) permanently banned from donating blood.

Individuals who have taken medication to prevent HIV infection are also deferred from donating blood for 5 years after they take the medication.

Safety of the blood supply

“The IBTS provides a safe, reliable, and robust blood service to the Irish health system and has the necessary program and procedures in place to protect both donors and recipients of blood and blood products,” Harris said.

All prospective blood donors in Ireland undergo nucleic acid testing for a number of diseases, including HIV, hepatitis B, and hepatitis C. This is the most sensitive method of testing available.

The risk of transmitted infection of blood is at its highest when individuals donate blood during the 5- to 15-day period following exposure to a virus.

There is no biological measure to detect infectivity during this period and, as a consequence, the IBTS temporarily or permanently defers, on average, 1 in 10 people from giving blood.

Blood donor
Photo by Marja Helander

The Irish Blood Transfusion Service (IBTS) has lifted the lifetime ban on blood donations from men who have sex with men (MSM).

However, prospective MSM blood donors are still subject to deferral.

Now, MSMs are allowed to donate blood in Ireland if it has been more than 12 months since their last sexual contact with a man and if they meet the other blood donor selection criteria.

The IBTS has also introduced new regulations relating to individuals with a history of specific, notifiable sexually transmitted infections (STIs).

These individuals are now allowed to donate blood 5 years after they have completed treatment for their STIs.

“In June of last year, I accepted the recommendations of the IBTS to change their blood donation deferral policies for men who have sex with men, as well as for donors who have had a sexually transmitted infection,” said Ireland’s Health Minister, Simon Harris.

“I would like to take this opportunity to thank the IBTS for their work over the past 6 months, which, today, sees these recommendations brought to fruition within the timescale agreed. [T]he IBTS will continue to keep all deferral policies under active review in the light of scientific evidence, emerging infections, and international experience.”

MSM deferral

The change in deferral policy relating to MSMs follows a 2-year review of the issues by the IBTS.

The agency hosted an international symposium on the topic in April 2016. Experts from 7 countries who had either lifted, or were in the process of lifting, their lifetime ban on MSM blood donors presented their respective stances, research, and the rationale behind their decisions.

The IBTS said its change to a 1-year deferral period for MSMs is supported by the most current scientific evidence available and brings Ireland into line with similar policies in the UK, Canada, and the US.

STI-related deferral

The IBTS said the 1-year deferral policy for MSMs will protect against the risk of HIV transmission. However, there is concern that it may not be sufficient to deal with an emerging infection. 

Therefore, the board of the IBTS decided that individuals who have had a notifiable STI, such as chlamydia or genital herpes, should be deferred from donating blood for 5 years after completing treatment for that STI.  

Individuals who have had syphilis, gonorrhea, lymphogranuloma venereum, or granuloma inguinale are (and have been) permanently banned from donating blood.

Individuals who have taken medication to prevent HIV infection are also deferred from donating blood for 5 years after they take the medication.

Safety of the blood supply

“The IBTS provides a safe, reliable, and robust blood service to the Irish health system and has the necessary program and procedures in place to protect both donors and recipients of blood and blood products,” Harris said.

All prospective blood donors in Ireland undergo nucleic acid testing for a number of diseases, including HIV, hepatitis B, and hepatitis C. This is the most sensitive method of testing available.

The risk of transmitted infection of blood is at its highest when individuals donate blood during the 5- to 15-day period following exposure to a virus.

There is no biological measure to detect infectivity during this period and, as a consequence, the IBTS temporarily or permanently defers, on average, 1 in 10 people from giving blood.

Umbilical cord clamping
Photo by Meutia Chaerani
and Indradi Soemardjan

Delaying umbilical cord clamping by a few minutes can reduce the risk of anemia several months after birth, according to research published in JAMA Pediatrics.

A randomized clinical trial showed that delaying cord clamping by 3 minutes or more after birth—rather than clamping within 1 minute of birth—reduced the prevalence of anemia, iron deficiency, and iron deficiency anemia in infants at 8 months and 12 months of age.

Ola Andersson, MD, PhD, of Uppsala University in Uppsala, Sweden, and his colleagues conducted this research in Nepal, a country with a high prevalence of anemia.

The study included 540 infants—281 boys and 259 girls—with a mean gestational age of 39.2 weeks. Half of the subjects were randomized to delayed cord clamping (3 minutes or more after birth) or early cord clamping (within 1 minute of birth).

At 8 months of age, 78.5% of infants from the delayed clamping group and 69.6% from the early clamping group returned for blood sampling.

Results showed that infants in the delayed clamping group had higher levels of hemoglobin than infants in the early clamping group—10.4 g/dL and 10.2 g/dL, respectively (P=0.008).

Infants in the delayed clamping group also had a lower incidence of:

• Anemia (hemoglobin level <11.0 g/dL)—73.0% and 82.2%, respectively (P=0.01)
• Iron deficiency—22.2% and 38.1%, respectively (P<0.001)
• Iron deficiency anemia—19.3% and 33.3%, respectively (P<0.001).

The relative risk (RR) of anemia was 0.89, the RR of iron deficiency was 0.58, and the RR of iron deficiency anemia was 0.58.

Results were similar when the infants reached 12 months of age, although all the between-group differences were not statistically significant.

Again, infants in the delayed clamping group had higher levels of hemoglobin than infants in the early clamping group—10.3 g/dL and 10.1 g/dL, respectively (P=0.02).

And infants in the delayed clamping group had a lower incidence of:

• Anemia—77.8% and 85.9%, respectively (P=0.02)
• Iron deficiency—35.6% and 43%, respectively (P=0.09)
• Iron deficiency anemia—30.4% and 37.8%, respectively (P=0.08).

The RR of anemia was 0.91, the RR of iron deficiency was 0.83, and the RR of iron deficiency anemia was 0.80.

The researchers said this study shows that delayed cord clamping was an effective intervention to reduce anemia in a high-risk population, with minimal cost and without apparent adverse effects.

The team believes that, if this intervention were implemented on a global scale, this could translate to 5 million fewer infants with anemia at 8 months of age.

Umbilical cord clamping
Photo by Meutia Chaerani
and Indradi Soemardjan

Delaying umbilical cord clamping by a few minutes can reduce the risk of anemia several months after birth, according to research published in JAMA Pediatrics.

A randomized clinical trial showed that delaying cord clamping by 3 minutes or more after birth—rather than clamping within 1 minute of birth—reduced the prevalence of anemia, iron deficiency, and iron deficiency anemia in infants at 8 months and 12 months of age.

Ola Andersson, MD, PhD, of Uppsala University in Uppsala, Sweden, and his colleagues conducted this research in Nepal, a country with a high prevalence of anemia.

The study included 540 infants—281 boys and 259 girls—with a mean gestational age of 39.2 weeks. Half of the subjects were randomized to delayed cord clamping (3 minutes or more after birth) or early cord clamping (within 1 minute of birth).

At 8 months of age, 78.5% of infants from the delayed clamping group and 69.6% from the early clamping group returned for blood sampling.

Results showed that infants in the delayed clamping group had higher levels of hemoglobin than infants in the early clamping group—10.4 g/dL and 10.2 g/dL, respectively (P=0.008).

Infants in the delayed clamping group also had a lower incidence of:

• Anemia (hemoglobin level <11.0 g/dL)—73.0% and 82.2%, respectively (P=0.01)
• Iron deficiency—22.2% and 38.1%, respectively (P<0.001)
• Iron deficiency anemia—19.3% and 33.3%, respectively (P<0.001).

The relative risk (RR) of anemia was 0.89, the RR of iron deficiency was 0.58, and the RR of iron deficiency anemia was 0.58.

Results were similar when the infants reached 12 months of age, although all the between-group differences were not statistically significant.

Again, infants in the delayed clamping group had higher levels of hemoglobin than infants in the early clamping group—10.3 g/dL and 10.1 g/dL, respectively (P=0.02).

And infants in the delayed clamping group had a lower incidence of:

• Anemia—77.8% and 85.9%, respectively (P=0.02)
• Iron deficiency—35.6% and 43%, respectively (P=0.09)
• Iron deficiency anemia—30.4% and 37.8%, respectively (P=0.08).

The RR of anemia was 0.91, the RR of iron deficiency was 0.83, and the RR of iron deficiency anemia was 0.80.

The researchers said this study shows that delayed cord clamping was an effective intervention to reduce anemia in a high-risk population, with minimal cost and without apparent adverse effects.

The team believes that, if this intervention were implemented on a global scale, this could translate to 5 million fewer infants with anemia at 8 months of age.

Umbilical cord clamping
Photo by Meutia Chaerani
and Indradi Soemardjan

Delaying umbilical cord clamping by a few minutes can reduce the risk of anemia several months after birth, according to research published in JAMA Pediatrics.

A randomized clinical trial showed that delaying cord clamping by 3 minutes or more after birth—rather than clamping within 1 minute of birth—reduced the prevalence of anemia, iron deficiency, and iron deficiency anemia in infants at 8 months and 12 months of age.

Ola Andersson, MD, PhD, of Uppsala University in Uppsala, Sweden, and his colleagues conducted this research in Nepal, a country with a high prevalence of anemia.

The study included 540 infants—281 boys and 259 girls—with a mean gestational age of 39.2 weeks. Half of the subjects were randomized to delayed cord clamping (3 minutes or more after birth) or early cord clamping (within 1 minute of birth).

At 8 months of age, 78.5% of infants from the delayed clamping group and 69.6% from the early clamping group returned for blood sampling.

Results showed that infants in the delayed clamping group had higher levels of hemoglobin than infants in the early clamping group—10.4 g/dL and 10.2 g/dL, respectively (P=0.008).

Infants in the delayed clamping group also had a lower incidence of:

• Anemia (hemoglobin level <11.0 g/dL)—73.0% and 82.2%, respectively (P=0.01)
• Iron deficiency—22.2% and 38.1%, respectively (P<0.001)
• Iron deficiency anemia—19.3% and 33.3%, respectively (P<0.001).

The relative risk (RR) of anemia was 0.89, the RR of iron deficiency was 0.58, and the RR of iron deficiency anemia was 0.58.

Results were similar when the infants reached 12 months of age, although all the between-group differences were not statistically significant.

Again, infants in the delayed clamping group had higher levels of hemoglobin than infants in the early clamping group—10.3 g/dL and 10.1 g/dL, respectively (P=0.02).

And infants in the delayed clamping group had a lower incidence of:

• Anemia—77.8% and 85.9%, respectively (P=0.02)
• Iron deficiency—35.6% and 43%, respectively (P=0.09)
• Iron deficiency anemia—30.4% and 37.8%, respectively (P=0.08).

The RR of anemia was 0.91, the RR of iron deficiency was 0.83, and the RR of iron deficiency anemia was 0.80.

The researchers said this study shows that delayed cord clamping was an effective intervention to reduce anemia in a high-risk population, with minimal cost and without apparent adverse effects.

The team believes that, if this intervention were implemented on a global scale, this could translate to 5 million fewer infants with anemia at 8 months of age.