Related Issues

Photo courtesy of the CDC

The US Food and Drug Administration (FDA) has launched a new search tool designed to improve access to data in the FDA’s Adverse Event Reporting System (FAERS).

FAERS includes data on adverse events (AEs) associated with drug and biologic products.

The new FAERs public dashboard allows users to search for and organize data by criteria such as drug/biological product, age of the patient, type of AE, year the AE occurred, or within a specific time frame.

The FDA intends for this tool to increase transparency by making it easier for people to see reports the agency receives.

The FDA hopes this, in turn, will spur the submission of more detailed and complete reports from consumers, healthcare professionals, and others.

The FDA uses FAERS for surveillance, such as looking for new safety concerns that might be related to a marketed product, evaluating a manufacturer’s compliance with reporting regulations, and responding to outside requests for information.

The reports in FAERS are evaluated by clinical reviewers in the FDA’s Center for Drug Evaluation and Research and Center for Biologics Evaluation and Research to monitor the safety of products after they are marketed. If a potential safety concern is identified in FAERS, further evaluation is performed.

“Our focus on safety extends beyond approval,” said Janet Woodcock, MD, director of the FDA’s Center for Drug Evaluation and Research.

“In fact, our staff spends a lot of time looking at FAERS reports received regarding approved drug and biologic products, and these reports can be very valuable components of our safety assessments. By giving people a better understanding of these data, and the associated limitations, we hope the new interface will encourage people to submit more complete reports.”

The FDA encourages healthcare professionals and consumers to report AEs or quality problems related to drugs and biologics to the FDA’s MedWatch Adverse Event Reporting Program.

In addition to the FAERS database for drugs and biologics, the FDA has AE reporting programs and databases for foods, dietary supplements, and cosmetics (CFSAN Adverse Event Reporting System [CAERS]), medical devices (Manufacturer and User Facility Device Experience [MAUDE]), and vaccines (Vaccine Adverse Event Reporting System [VAERS], which the FDA co-manages with the Centers for Disease Control and Prevention).

Photo courtesy of the CDC

The US Food and Drug Administration (FDA) has launched a new search tool designed to improve access to data in the FDA’s Adverse Event Reporting System (FAERS).

FAERS includes data on adverse events (AEs) associated with drug and biologic products.

The new FAERs public dashboard allows users to search for and organize data by criteria such as drug/biological product, age of the patient, type of AE, year the AE occurred, or within a specific time frame.

The FDA intends for this tool to increase transparency by making it easier for people to see reports the agency receives.

The FDA hopes this, in turn, will spur the submission of more detailed and complete reports from consumers, healthcare professionals, and others.

The FDA uses FAERS for surveillance, such as looking for new safety concerns that might be related to a marketed product, evaluating a manufacturer’s compliance with reporting regulations, and responding to outside requests for information.

The reports in FAERS are evaluated by clinical reviewers in the FDA’s Center for Drug Evaluation and Research and Center for Biologics Evaluation and Research to monitor the safety of products after they are marketed. If a potential safety concern is identified in FAERS, further evaluation is performed.

“Our focus on safety extends beyond approval,” said Janet Woodcock, MD, director of the FDA’s Center for Drug Evaluation and Research.

“In fact, our staff spends a lot of time looking at FAERS reports received regarding approved drug and biologic products, and these reports can be very valuable components of our safety assessments. By giving people a better understanding of these data, and the associated limitations, we hope the new interface will encourage people to submit more complete reports.”

The FDA encourages healthcare professionals and consumers to report AEs or quality problems related to drugs and biologics to the FDA’s MedWatch Adverse Event Reporting Program.

In addition to the FAERS database for drugs and biologics, the FDA has AE reporting programs and databases for foods, dietary supplements, and cosmetics (CFSAN Adverse Event Reporting System [CAERS]), medical devices (Manufacturer and User Facility Device Experience [MAUDE]), and vaccines (Vaccine Adverse Event Reporting System [VAERS], which the FDA co-manages with the Centers for Disease Control and Prevention).

Photo courtesy of the CDC

The US Food and Drug Administration (FDA) has launched a new search tool designed to improve access to data in the FDA’s Adverse Event Reporting System (FAERS).

FAERS includes data on adverse events (AEs) associated with drug and biologic products.

The new FAERs public dashboard allows users to search for and organize data by criteria such as drug/biological product, age of the patient, type of AE, year the AE occurred, or within a specific time frame.

The FDA intends for this tool to increase transparency by making it easier for people to see reports the agency receives.

The FDA hopes this, in turn, will spur the submission of more detailed and complete reports from consumers, healthcare professionals, and others.

The FDA uses FAERS for surveillance, such as looking for new safety concerns that might be related to a marketed product, evaluating a manufacturer’s compliance with reporting regulations, and responding to outside requests for information.

The reports in FAERS are evaluated by clinical reviewers in the FDA’s Center for Drug Evaluation and Research and Center for Biologics Evaluation and Research to monitor the safety of products after they are marketed. If a potential safety concern is identified in FAERS, further evaluation is performed.

“Our focus on safety extends beyond approval,” said Janet Woodcock, MD, director of the FDA’s Center for Drug Evaluation and Research.

“In fact, our staff spends a lot of time looking at FAERS reports received regarding approved drug and biologic products, and these reports can be very valuable components of our safety assessments. By giving people a better understanding of these data, and the associated limitations, we hope the new interface will encourage people to submit more complete reports.”

The FDA encourages healthcare professionals and consumers to report AEs or quality problems related to drugs and biologics to the FDA’s MedWatch Adverse Event Reporting Program.

In addition to the FAERS database for drugs and biologics, the FDA has AE reporting programs and databases for foods, dietary supplements, and cosmetics (CFSAN Adverse Event Reporting System [CAERS]), medical devices (Manufacturer and User Facility Device Experience [MAUDE]), and vaccines (Vaccine Adverse Event Reporting System [VAERS], which the FDA co-manages with the Centers for Disease Control and Prevention).

of Medical Research

Carbohydrates on the surface of malaria parasites play a critical role in the parasites’ ability to infect mosquito and human hosts, according to research published in Nature Communications.

Researchers found that Plasmodium falciparum “tags” its proteins with carbohydrates in order to stabilize and transport them.

And this process is crucial to completing the parasite’s life cycle.

“Malaria parasites have a complex life cycle that involves constant shape-shifting to evade detection and infect humans and, subsequently, mosquitoes,” said study author Justin Boddey, PhD, of The Walter and Eliza Hall Institute of Medical Research in Parkville, Victoria, Australia.

“We found that the parasite’s ability to ‘tag’ key proteins with carbohydrates is important for 2 stages of the malaria life cycle. It is critical for the earliest stages of human infection, when the parasite migrates through the body and invades in the liver, and later, when it is transmitted back to the mosquito from an infected human, enabling the parasite to be spread between people.”

“Interfering with the parasite’s ability to attach these carbohydrates to its proteins hinders liver infection and transmission to the mosquito and weakens the parasite to the point that it cannot survive in the host.”

Dr Boddey and his colleagues said this research suggests steps that may improve the efficacy of the malaria vaccine RTS,S/AS01 (Mosquirix).

“The protein used in the RTS,S vaccine mimics one of the proteins we’ve been studying on the surface of the malaria parasite that is readily recognized by the immune system,” said study author Ethan D. Goddard-Borger, PhD, of The Walter and Eliza Hall Institute of Medical Research.

“It was hoped that the vaccine would generate a good antibody response that protected against the parasite. However, it has, unfortunately, not been as effective at evoking protective immunity as hoped.”

“With this study, we’ve shown that the parasite protein is tagged with carbohydrates, making it slightly different to the vaccine, so the antibodies produced may not be optimal for recognizing target parasites.”

Dr Goddard-Borger said there were many documented cases where attaching carbohydrates to a protein improved its efficacy as a vaccine.

“It may be that a version of RTS,S with added carbohydrates will perform better than the current vaccine,” he said. “Now that we know how important these carbohydrates are to the parasite, we can be confident that the malaria parasite cannot ‘escape’ vaccination pressure by doing away with its carbohydrates.”

of Medical Research

Carbohydrates on the surface of malaria parasites play a critical role in the parasites’ ability to infect mosquito and human hosts, according to research published in Nature Communications.

Researchers found that Plasmodium falciparum “tags” its proteins with carbohydrates in order to stabilize and transport them.

And this process is crucial to completing the parasite’s life cycle.

“Malaria parasites have a complex life cycle that involves constant shape-shifting to evade detection and infect humans and, subsequently, mosquitoes,” said study author Justin Boddey, PhD, of The Walter and Eliza Hall Institute of Medical Research in Parkville, Victoria, Australia.

“We found that the parasite’s ability to ‘tag’ key proteins with carbohydrates is important for 2 stages of the malaria life cycle. It is critical for the earliest stages of human infection, when the parasite migrates through the body and invades in the liver, and later, when it is transmitted back to the mosquito from an infected human, enabling the parasite to be spread between people.”

“Interfering with the parasite’s ability to attach these carbohydrates to its proteins hinders liver infection and transmission to the mosquito and weakens the parasite to the point that it cannot survive in the host.”

Dr Boddey and his colleagues said this research suggests steps that may improve the efficacy of the malaria vaccine RTS,S/AS01 (Mosquirix).

“The protein used in the RTS,S vaccine mimics one of the proteins we’ve been studying on the surface of the malaria parasite that is readily recognized by the immune system,” said study author Ethan D. Goddard-Borger, PhD, of The Walter and Eliza Hall Institute of Medical Research.

“It was hoped that the vaccine would generate a good antibody response that protected against the parasite. However, it has, unfortunately, not been as effective at evoking protective immunity as hoped.”

“With this study, we’ve shown that the parasite protein is tagged with carbohydrates, making it slightly different to the vaccine, so the antibodies produced may not be optimal for recognizing target parasites.”

Dr Goddard-Borger said there were many documented cases where attaching carbohydrates to a protein improved its efficacy as a vaccine.

“It may be that a version of RTS,S with added carbohydrates will perform better than the current vaccine,” he said. “Now that we know how important these carbohydrates are to the parasite, we can be confident that the malaria parasite cannot ‘escape’ vaccination pressure by doing away with its carbohydrates.”

of Medical Research

Carbohydrates on the surface of malaria parasites play a critical role in the parasites’ ability to infect mosquito and human hosts, according to research published in Nature Communications.

Researchers found that Plasmodium falciparum “tags” its proteins with carbohydrates in order to stabilize and transport them.

And this process is crucial to completing the parasite’s life cycle.

“Malaria parasites have a complex life cycle that involves constant shape-shifting to evade detection and infect humans and, subsequently, mosquitoes,” said study author Justin Boddey, PhD, of The Walter and Eliza Hall Institute of Medical Research in Parkville, Victoria, Australia.

“We found that the parasite’s ability to ‘tag’ key proteins with carbohydrates is important for 2 stages of the malaria life cycle. It is critical for the earliest stages of human infection, when the parasite migrates through the body and invades in the liver, and later, when it is transmitted back to the mosquito from an infected human, enabling the parasite to be spread between people.”

“Interfering with the parasite’s ability to attach these carbohydrates to its proteins hinders liver infection and transmission to the mosquito and weakens the parasite to the point that it cannot survive in the host.”

Dr Boddey and his colleagues said this research suggests steps that may improve the efficacy of the malaria vaccine RTS,S/AS01 (Mosquirix).

“The protein used in the RTS,S vaccine mimics one of the proteins we’ve been studying on the surface of the malaria parasite that is readily recognized by the immune system,” said study author Ethan D. Goddard-Borger, PhD, of The Walter and Eliza Hall Institute of Medical Research.

“It was hoped that the vaccine would generate a good antibody response that protected against the parasite. However, it has, unfortunately, not been as effective at evoking protective immunity as hoped.”

“With this study, we’ve shown that the parasite protein is tagged with carbohydrates, making it slightly different to the vaccine, so the antibodies produced may not be optimal for recognizing target parasites.”

Dr Goddard-Borger said there were many documented cases where attaching carbohydrates to a protein improved its efficacy as a vaccine.

“It may be that a version of RTS,S with added carbohydrates will perform better than the current vaccine,” he said. “Now that we know how important these carbohydrates are to the parasite, we can be confident that the malaria parasite cannot ‘escape’ vaccination pressure by doing away with its carbohydrates.”

Research Hospital

Life-long hematopoiesis relies on hundreds more blood progenitors than previously reported, according to preclinical research published in Nature Cell Biology.

Previous studies linked life-long mammalian blood production to just a handful of precursor cells that emerge during prenatal development.

In the current study, researchers found that, in mice, roughly 600 to 700 developmental precursors contribute to life-long hematopoiesis.

The number of precursor cells in humans is likely at least 10 times greater, according to researchers.

“All previous studies had reported that very few precursor cells are involved in establishing the blood system,” said study author Shannon McKinney-Freeman, PhD, of St. Jude Children’s Research Hospital in Memphis, Tennessee.

“But data in this study show that, actually, hundreds of cells are involved and that the developing blood system is more complex and may be shaped, in part, by regulatory bottlenecks that occur late in development and serve to restrict the number of blood-forming stem cells.”

For this study, Miguel Ganuza, PhD, a fellow in Dr McKinney-Freeman’s lab, adapted a system used to study the cellular makeup of solid tumors. The multi-colored labeling system is activated by genes expressed during specific windows of development.

Dr Ganuza used the system to label and track the fate of precursor cells from various developmental stages in mice.

“We wanted to understand what was happening with different progenitor cells at different stages of development when we knew important decisions on the fate of cells occurred,” Dr Ganuza said.

David Finkelstein, PhD, of the St. Jude Department of Computational Biology, then used mathematical modeling to work backward from peripheral blood in adult mice to track the contribution of precursor cells from the early, middle, and late stages of prenatal development.

The results showed that far more precursor cells than expected contribute to life-long hematopoiesis in adult mice.

The researchers found about 719 Flk1⁺ mesodermal precursors emerged at embryonic days 7 to 8.5, 633 VE-cadherin⁺ endothelial precursors emerged at embryonic days 8.5 to 11.5, and 545 Vav1⁺ nascent hematopoietic stem and progenitor cells emerged at embryonic days 11.5 to 14.5.

The team also said specification of hemogenic endothelial cells begins at embryonic day 8.5 and ends by embryonic day 10.5. After that, it cannot be reactivated.

Finally, the researchers found that intra-aortic hematopoietic clusters are polyclonal in origin.

The team said these findings raised questions about the role of the fetal liver in hematopoiesis.

“For decades, the fetal liver was thought to be where the number of blood stem cells expanded dramatically,” Dr McKinney-Freeman said.

“The results in this study raise questions about that model and even suggest the presence of developmental bottlenecks in the fetal liver or at later stages of development that restrict the blood stem cell population. This is when science is most interesting, when you see things you didn’t expect.”

While unexpected, the newly revealed size and complexity of the emerging blood system make sense developmentally, Dr McKinney-Freeman said.

“Producing hundreds of progenitor cells during different developmental stages means the organism has greater flexibility to adapt to issues and problems that might emerge as development progresses,” she noted.

The findings also have clinical implications, according to Dr McKinney-Freeman.

“Understanding how the blood system emerges, including the number and complexity of the progenitor cells involved, will help us unravel the origins of disease and identify cells that might be susceptible to disease-causing mutations,” she concluded.

Research Hospital

Life-long hematopoiesis relies on hundreds more blood progenitors than previously reported, according to preclinical research published in Nature Cell Biology.

Previous studies linked life-long mammalian blood production to just a handful of precursor cells that emerge during prenatal development.

In the current study, researchers found that, in mice, roughly 600 to 700 developmental precursors contribute to life-long hematopoiesis.

The number of precursor cells in humans is likely at least 10 times greater, according to researchers.

“All previous studies had reported that very few precursor cells are involved in establishing the blood system,” said study author Shannon McKinney-Freeman, PhD, of St. Jude Children’s Research Hospital in Memphis, Tennessee.

“But data in this study show that, actually, hundreds of cells are involved and that the developing blood system is more complex and may be shaped, in part, by regulatory bottlenecks that occur late in development and serve to restrict the number of blood-forming stem cells.”

For this study, Miguel Ganuza, PhD, a fellow in Dr McKinney-Freeman’s lab, adapted a system used to study the cellular makeup of solid tumors. The multi-colored labeling system is activated by genes expressed during specific windows of development.

Dr Ganuza used the system to label and track the fate of precursor cells from various developmental stages in mice.

“We wanted to understand what was happening with different progenitor cells at different stages of development when we knew important decisions on the fate of cells occurred,” Dr Ganuza said.

David Finkelstein, PhD, of the St. Jude Department of Computational Biology, then used mathematical modeling to work backward from peripheral blood in adult mice to track the contribution of precursor cells from the early, middle, and late stages of prenatal development.

The results showed that far more precursor cells than expected contribute to life-long hematopoiesis in adult mice.

The researchers found about 719 Flk1⁺ mesodermal precursors emerged at embryonic days 7 to 8.5, 633 VE-cadherin⁺ endothelial precursors emerged at embryonic days 8.5 to 11.5, and 545 Vav1⁺ nascent hematopoietic stem and progenitor cells emerged at embryonic days 11.5 to 14.5.

The team also said specification of hemogenic endothelial cells begins at embryonic day 8.5 and ends by embryonic day 10.5. After that, it cannot be reactivated.

Finally, the researchers found that intra-aortic hematopoietic clusters are polyclonal in origin.

The team said these findings raised questions about the role of the fetal liver in hematopoiesis.

“For decades, the fetal liver was thought to be where the number of blood stem cells expanded dramatically,” Dr McKinney-Freeman said.

“The results in this study raise questions about that model and even suggest the presence of developmental bottlenecks in the fetal liver or at later stages of development that restrict the blood stem cell population. This is when science is most interesting, when you see things you didn’t expect.”

While unexpected, the newly revealed size and complexity of the emerging blood system make sense developmentally, Dr McKinney-Freeman said.

“Producing hundreds of progenitor cells during different developmental stages means the organism has greater flexibility to adapt to issues and problems that might emerge as development progresses,” she noted.

The findings also have clinical implications, according to Dr McKinney-Freeman.

“Understanding how the blood system emerges, including the number and complexity of the progenitor cells involved, will help us unravel the origins of disease and identify cells that might be susceptible to disease-causing mutations,” she concluded.

Research Hospital

Life-long hematopoiesis relies on hundreds more blood progenitors than previously reported, according to preclinical research published in Nature Cell Biology.

Previous studies linked life-long mammalian blood production to just a handful of precursor cells that emerge during prenatal development.

In the current study, researchers found that, in mice, roughly 600 to 700 developmental precursors contribute to life-long hematopoiesis.

The number of precursor cells in humans is likely at least 10 times greater, according to researchers.

“All previous studies had reported that very few precursor cells are involved in establishing the blood system,” said study author Shannon McKinney-Freeman, PhD, of St. Jude Children’s Research Hospital in Memphis, Tennessee.

“But data in this study show that, actually, hundreds of cells are involved and that the developing blood system is more complex and may be shaped, in part, by regulatory bottlenecks that occur late in development and serve to restrict the number of blood-forming stem cells.”

For this study, Miguel Ganuza, PhD, a fellow in Dr McKinney-Freeman’s lab, adapted a system used to study the cellular makeup of solid tumors. The multi-colored labeling system is activated by genes expressed during specific windows of development.

Dr Ganuza used the system to label and track the fate of precursor cells from various developmental stages in mice.

“We wanted to understand what was happening with different progenitor cells at different stages of development when we knew important decisions on the fate of cells occurred,” Dr Ganuza said.

David Finkelstein, PhD, of the St. Jude Department of Computational Biology, then used mathematical modeling to work backward from peripheral blood in adult mice to track the contribution of precursor cells from the early, middle, and late stages of prenatal development.

The results showed that far more precursor cells than expected contribute to life-long hematopoiesis in adult mice.

The researchers found about 719 Flk1⁺ mesodermal precursors emerged at embryonic days 7 to 8.5, 633 VE-cadherin⁺ endothelial precursors emerged at embryonic days 8.5 to 11.5, and 545 Vav1⁺ nascent hematopoietic stem and progenitor cells emerged at embryonic days 11.5 to 14.5.

The team also said specification of hemogenic endothelial cells begins at embryonic day 8.5 and ends by embryonic day 10.5. After that, it cannot be reactivated.

Finally, the researchers found that intra-aortic hematopoietic clusters are polyclonal in origin.

The team said these findings raised questions about the role of the fetal liver in hematopoiesis.

“For decades, the fetal liver was thought to be where the number of blood stem cells expanded dramatically,” Dr McKinney-Freeman said.

“The results in this study raise questions about that model and even suggest the presence of developmental bottlenecks in the fetal liver or at later stages of development that restrict the blood stem cell population. This is when science is most interesting, when you see things you didn’t expect.”

While unexpected, the newly revealed size and complexity of the emerging blood system make sense developmentally, Dr McKinney-Freeman said.

“Producing hundreds of progenitor cells during different developmental stages means the organism has greater flexibility to adapt to issues and problems that might emerge as development progresses,” she noted.

The findings also have clinical implications, according to Dr McKinney-Freeman.

“Understanding how the blood system emerges, including the number and complexity of the progenitor cells involved, will help us unravel the origins of disease and identify cells that might be susceptible to disease-causing mutations,” she concluded.

Photo by Rhoda Baer

Deaths from cancer are on the decline in the US, but new cases of cancer are on the rise, according to the 7th annual American Association for Cancer Research (AACR) Cancer Progress Report.

The data suggest the cancer death rate declined by 35% from 1991 to 2014 for children and by 25% for adults, a reduction that translates to 2.1 million cancer deaths avoided.

However, 600,920 people in the US are projected to die from cancer in 2017.

And the number of new cancer cases is predicted to rise from 1.7 million in 2017 to 2.3 million in 2030.

The report also estimates there will be 62,130 new cases of leukemia in 2017 and 24,500 leukemia deaths this year.

This includes:

• 5970 cases of acute lymphocytic leukemia and 1440 deaths
• 20,110 cases of chronic lymphocytic leukemia and 4660 deaths
• 21,380 cases of acute myeloid leukemia (AML) and 10,590 deaths
• 8950 cases of chronic myeloid leukemia and 1080 deaths.

The estimate for lymphomas is 80,500 new cases and 21,210 deaths.

This includes:

• 8260 cases of Hodgkin lymphoma (HL) and 1070 deaths
• 72,240 cases of non-Hodgkin lymphoma and 20,140 deaths.

The estimate for myeloma is 30,280 new cases and 12,590 deaths.

The report says the estimated new cases of cancer are based on cancer incidence rates from 49 states and the District of Columbia from 1995 through 2013, as reported by the North American Association of Central Cancer Registries. This represents about 98% of the US population.

The estimated deaths are based on US mortality data from 1997 through 2013, taken from the National Center for Health Statistics of the Centers for Disease Control and Prevention.

Drug approvals

The AACR report notes that, between August 1, 2016, and July 31, 2017, the US Food and Drug Administration (FDA) approved new uses for 15 anticancer agents, 9 of which had no previous FDA approval.

Five of the agents are immunotherapies, which the report dubs “revolutionary treatments that are increasing survival and improving quality of life for patients.”

Among the recently approved therapies are 3 used for hematology indications:

• Ibrutinib (Imbruvica), approved to treat patients with relapsed/refractory marginal zone lymphoma who require systemic therapy and have received at least 1 prior anti-CD20-based therapy
• Midostaurin (Rydapt), approved as monotherapy for adults with advanced systemic mastocytosis and for use in combination with standard cytarabine and daunorubicin induction, followed by cytarabine consolidation, in adults with newly diagnosed AML who are FLT3 mutation-positive, as detected by an FDA-approved test.
• Pembrolizumab (Keytruda), approved to treat adult and pediatric patients with refractory classical HL or those with classical HL who have relapsed after 3 or more prior lines of therapy.

Disparities and costs

The AACR report points out that advances against cancer have not benefited everyone equally, and cancer health disparities are some of the most pressing challenges.

Among the disparities listed is the fact that adolescents and young adults (ages 15 to 39) with AML have a 5-year relative survival rate that is 22% lower than that of children (ages 1 to 14) with AML.

And Hispanic children are 24% more likely to develop leukemia than non-Hispanic children.

Another concern mentioned in the report is the cost of cancer care. The direct medical costs of cancer care in 2014 were estimated to be nearly $87.6 billion. This number does not include the indirect costs of lost productivity due to cancer-related morbidity and mortality.

With this in mind, the AACR is calling for a $2 billion increase in funding for the National Institutes of Health in fiscal year 2018, for a total funding level of $36.2 billion.

The AACR also recommends an $80 million increase in the FDA budget, bringing it to $2.8 billion for fiscal year 2018.

Photo by Rhoda Baer

Deaths from cancer are on the decline in the US, but new cases of cancer are on the rise, according to the 7th annual American Association for Cancer Research (AACR) Cancer Progress Report.

The data suggest the cancer death rate declined by 35% from 1991 to 2014 for children and by 25% for adults, a reduction that translates to 2.1 million cancer deaths avoided.

However, 600,920 people in the US are projected to die from cancer in 2017.

And the number of new cancer cases is predicted to rise from 1.7 million in 2017 to 2.3 million in 2030.

The report also estimates there will be 62,130 new cases of leukemia in 2017 and 24,500 leukemia deaths this year.

This includes:

• 5970 cases of acute lymphocytic leukemia and 1440 deaths
• 20,110 cases of chronic lymphocytic leukemia and 4660 deaths
• 21,380 cases of acute myeloid leukemia (AML) and 10,590 deaths
• 8950 cases of chronic myeloid leukemia and 1080 deaths.

The estimate for lymphomas is 80,500 new cases and 21,210 deaths.

This includes:

• 8260 cases of Hodgkin lymphoma (HL) and 1070 deaths
• 72,240 cases of non-Hodgkin lymphoma and 20,140 deaths.

The estimate for myeloma is 30,280 new cases and 12,590 deaths.

The report says the estimated new cases of cancer are based on cancer incidence rates from 49 states and the District of Columbia from 1995 through 2013, as reported by the North American Association of Central Cancer Registries. This represents about 98% of the US population.

The estimated deaths are based on US mortality data from 1997 through 2013, taken from the National Center for Health Statistics of the Centers for Disease Control and Prevention.

Drug approvals

The AACR report notes that, between August 1, 2016, and July 31, 2017, the US Food and Drug Administration (FDA) approved new uses for 15 anticancer agents, 9 of which had no previous FDA approval.

Five of the agents are immunotherapies, which the report dubs “revolutionary treatments that are increasing survival and improving quality of life for patients.”

Among the recently approved therapies are 3 used for hematology indications:

• Ibrutinib (Imbruvica), approved to treat patients with relapsed/refractory marginal zone lymphoma who require systemic therapy and have received at least 1 prior anti-CD20-based therapy
• Midostaurin (Rydapt), approved as monotherapy for adults with advanced systemic mastocytosis and for use in combination with standard cytarabine and daunorubicin induction, followed by cytarabine consolidation, in adults with newly diagnosed AML who are FLT3 mutation-positive, as detected by an FDA-approved test.
• Pembrolizumab (Keytruda), approved to treat adult and pediatric patients with refractory classical HL or those with classical HL who have relapsed after 3 or more prior lines of therapy.

Disparities and costs

The AACR report points out that advances against cancer have not benefited everyone equally, and cancer health disparities are some of the most pressing challenges.

Among the disparities listed is the fact that adolescents and young adults (ages 15 to 39) with AML have a 5-year relative survival rate that is 22% lower than that of children (ages 1 to 14) with AML.

And Hispanic children are 24% more likely to develop leukemia than non-Hispanic children.

Another concern mentioned in the report is the cost of cancer care. The direct medical costs of cancer care in 2014 were estimated to be nearly $87.6 billion. This number does not include the indirect costs of lost productivity due to cancer-related morbidity and mortality.

With this in mind, the AACR is calling for a $2 billion increase in funding for the National Institutes of Health in fiscal year 2018, for a total funding level of $36.2 billion.

The AACR also recommends an $80 million increase in the FDA budget, bringing it to $2.8 billion for fiscal year 2018.

Photo by Rhoda Baer

Deaths from cancer are on the decline in the US, but new cases of cancer are on the rise, according to the 7th annual American Association for Cancer Research (AACR) Cancer Progress Report.

The data suggest the cancer death rate declined by 35% from 1991 to 2014 for children and by 25% for adults, a reduction that translates to 2.1 million cancer deaths avoided.

However, 600,920 people in the US are projected to die from cancer in 2017.

And the number of new cancer cases is predicted to rise from 1.7 million in 2017 to 2.3 million in 2030.

The report also estimates there will be 62,130 new cases of leukemia in 2017 and 24,500 leukemia deaths this year.

This includes:

• 5970 cases of acute lymphocytic leukemia and 1440 deaths
• 20,110 cases of chronic lymphocytic leukemia and 4660 deaths
• 21,380 cases of acute myeloid leukemia (AML) and 10,590 deaths
• 8950 cases of chronic myeloid leukemia and 1080 deaths.

The estimate for lymphomas is 80,500 new cases and 21,210 deaths.

This includes:

• 8260 cases of Hodgkin lymphoma (HL) and 1070 deaths
• 72,240 cases of non-Hodgkin lymphoma and 20,140 deaths.

The estimate for myeloma is 30,280 new cases and 12,590 deaths.

The report says the estimated new cases of cancer are based on cancer incidence rates from 49 states and the District of Columbia from 1995 through 2013, as reported by the North American Association of Central Cancer Registries. This represents about 98% of the US population.

The estimated deaths are based on US mortality data from 1997 through 2013, taken from the National Center for Health Statistics of the Centers for Disease Control and Prevention.

Drug approvals

The AACR report notes that, between August 1, 2016, and July 31, 2017, the US Food and Drug Administration (FDA) approved new uses for 15 anticancer agents, 9 of which had no previous FDA approval.

Five of the agents are immunotherapies, which the report dubs “revolutionary treatments that are increasing survival and improving quality of life for patients.”

Among the recently approved therapies are 3 used for hematology indications:

• Ibrutinib (Imbruvica), approved to treat patients with relapsed/refractory marginal zone lymphoma who require systemic therapy and have received at least 1 prior anti-CD20-based therapy
• Midostaurin (Rydapt), approved as monotherapy for adults with advanced systemic mastocytosis and for use in combination with standard cytarabine and daunorubicin induction, followed by cytarabine consolidation, in adults with newly diagnosed AML who are FLT3 mutation-positive, as detected by an FDA-approved test.
• Pembrolizumab (Keytruda), approved to treat adult and pediatric patients with refractory classical HL or those with classical HL who have relapsed after 3 or more prior lines of therapy.

Disparities and costs

The AACR report points out that advances against cancer have not benefited everyone equally, and cancer health disparities are some of the most pressing challenges.

Among the disparities listed is the fact that adolescents and young adults (ages 15 to 39) with AML have a 5-year relative survival rate that is 22% lower than that of children (ages 1 to 14) with AML.

And Hispanic children are 24% more likely to develop leukemia than non-Hispanic children.

Another concern mentioned in the report is the cost of cancer care. The direct medical costs of cancer care in 2014 were estimated to be nearly $87.6 billion. This number does not include the indirect costs of lost productivity due to cancer-related morbidity and mortality.

With this in mind, the AACR is calling for a $2 billion increase in funding for the National Institutes of Health in fiscal year 2018, for a total funding level of $36.2 billion.

The AACR also recommends an $80 million increase in the FDA budget, bringing it to $2.8 billion for fiscal year 2018.

Photo courtesy of the CDC

New research has provided an updated estimate of the spending needed to bring a cancer drug to the US market.

In analyzing data from 10 companies bringing a cancer drug to market, researchers found that sales revenue from these drugs was roughly 7 times higher than the research and development (R&D) costs.

The total sales revenue for the drugs—during a median follow-up of 4 years—was $67.0 billion, and the total R&D spending was $9.1 billion (including 7% opportunity costs).

Researchers reported these figures in JAMA Internal Medicine.

“[T]he price of cancer drugs is currently rising higher and higher each year,” said study author Vinay Prasad, MD, of Oregon Health and Science University in Portland.

“The cost of 1 drug for 1 year of treatment is now routinely in excess of $100,000 . . . . One of the often-cited reasons why cancer drugs cost so much—one of the justifications for the high price—is that the outlay by the biopharmaceutical industry to bring these drugs to market is sizable, and there have been a wide range of estimates for what that R&D outlay is.”

“The most-cited estimate is one that comes out of the Tufts Medical Group¹ that puts the cost to bring a cancer drug to market, when adjusted for 2017 dollars, at $2.7 billion. Another estimate is from the group Public Citizen.² And that is a much lower estimate, finding the cost to bring a drug to market of $320 million.”

“Both of these estimates have limitations in the methods for how they estimated the cost to bring a drug to market. Notably, the Tufts group is rather non-transparent. Because of confidentiality agreements, we don’t know what drugs and what companies they’re looking at, and we can’t independently verify their analysis.”

“The Public Citizen group, in contrast, is comparing expenditures over a period of time against the number of drugs in a different period of time to make an estimate of the cost to bring a drug to market, but this isn’t exactly the cost of bringing those particular drugs to market.”

These issues prompted Dr Prasad and Sham Mailankody, MBBS, of the Memorial Sloan Kettering Cancer Center in New York, to conduct the current study.

Analysis

The researchers analyzed US Securities and Exchange Commission filings for 10 drug companies that received approval from the US Food and Drug Administration for a cancer drug from 2006 through 2015.

Prior to this, none of the companies had any drugs approved for use in the US. However, the companies had a median of 3.5 (range, 2-11) drugs in development during the study period.

The researchers said the fact that these companies had no prior drug approvals eliminated biases that may be present when analyzing larger drug companies, such as redundancies in R&D development and tax incentives for listing different endeavors as R&D spending.

In addition, the fact that the 10 companies were developing other drugs during the study period means this study takes into account the cost of failure in bringing a drug to market.

Results

For the 10 companies and drugs analyzed, the median duration of drug development was 7.3 years (range, 5.8 to 15.2 years).

The median cost of drug development (in 2017 US dollars) was $648.0 million (range, $157.3 to $1950.8 million). For a 7% per annum cost of capital (or opportunity costs), the median cost was $757.4 million (range, $203.6 to $2601.7 million).

The median time from approval to analysis in December 2016 (or until the company sold or licensed the compound to another company) was 4.0 years (range, 0.8 years to 8.8 years).

The total revenue from sales of the 10 drugs during this time was $67.0 billion.

The total R&D spending was $7.2 billion, or $9.1 billion when including 7% opportunity costs.

The following table includes data broken down by drug.

*Received accelerated approval. (The other 5 drugs received regular approval.)

**Did not receive orphan designation. (Nine of the 10 drugs received orphan designation.)

“So I think what we’re showing is . . .  a transparent analysis of cancer drugs and companies, looking at the cost to bring a drug to market,” Dr Mailankody said. “And our estimate of $648 million is substantially lower than the often-cited number of $2.7 billion.”

“We’re also showing that, for these 10 drugs, revenue since approval is quite a bit higher than the R&D spending, almost 7-fold higher, and some of these companies have already had revenue of 10-fold or higher, compared to the R&D expenses.”

The researchers acknowledged that this study is limited by a small data set and the fact that the findings cannot be extrapolated to other types of drugs.

1. DiMasi JA et al. Innovation in the pharmaceutical industry: new estimates of R&D costs. J Health Econ. 2016;47:20-33.

2. Young B et al. Rx R&D Myths: The Case Against the Drug Industry’s R&D “Scare Card.” Washington, DC: Public Citizen’s Congress Watch; 2001. https://www.citizen.org/sites/default/files/rdmyths.pdf.

Photo courtesy of the CDC

New research has provided an updated estimate of the spending needed to bring a cancer drug to the US market.

In analyzing data from 10 companies bringing a cancer drug to market, researchers found that sales revenue from these drugs was roughly 7 times higher than the research and development (R&D) costs.

The total sales revenue for the drugs—during a median follow-up of 4 years—was $67.0 billion, and the total R&D spending was $9.1 billion (including 7% opportunity costs).

Researchers reported these figures in JAMA Internal Medicine.

“[T]he price of cancer drugs is currently rising higher and higher each year,” said study author Vinay Prasad, MD, of Oregon Health and Science University in Portland.

“The cost of 1 drug for 1 year of treatment is now routinely in excess of $100,000 . . . . One of the often-cited reasons why cancer drugs cost so much—one of the justifications for the high price—is that the outlay by the biopharmaceutical industry to bring these drugs to market is sizable, and there have been a wide range of estimates for what that R&D outlay is.”

“The most-cited estimate is one that comes out of the Tufts Medical Group¹ that puts the cost to bring a cancer drug to market, when adjusted for 2017 dollars, at $2.7 billion. Another estimate is from the group Public Citizen.² And that is a much lower estimate, finding the cost to bring a drug to market of $320 million.”

“Both of these estimates have limitations in the methods for how they estimated the cost to bring a drug to market. Notably, the Tufts group is rather non-transparent. Because of confidentiality agreements, we don’t know what drugs and what companies they’re looking at, and we can’t independently verify their analysis.”

“The Public Citizen group, in contrast, is comparing expenditures over a period of time against the number of drugs in a different period of time to make an estimate of the cost to bring a drug to market, but this isn’t exactly the cost of bringing those particular drugs to market.”

These issues prompted Dr Prasad and Sham Mailankody, MBBS, of the Memorial Sloan Kettering Cancer Center in New York, to conduct the current study.

Analysis

The researchers analyzed US Securities and Exchange Commission filings for 10 drug companies that received approval from the US Food and Drug Administration for a cancer drug from 2006 through 2015.

Prior to this, none of the companies had any drugs approved for use in the US. However, the companies had a median of 3.5 (range, 2-11) drugs in development during the study period.

The researchers said the fact that these companies had no prior drug approvals eliminated biases that may be present when analyzing larger drug companies, such as redundancies in R&D development and tax incentives for listing different endeavors as R&D spending.

In addition, the fact that the 10 companies were developing other drugs during the study period means this study takes into account the cost of failure in bringing a drug to market.

Results

For the 10 companies and drugs analyzed, the median duration of drug development was 7.3 years (range, 5.8 to 15.2 years).

The median cost of drug development (in 2017 US dollars) was $648.0 million (range, $157.3 to $1950.8 million). For a 7% per annum cost of capital (or opportunity costs), the median cost was $757.4 million (range, $203.6 to $2601.7 million).

The median time from approval to analysis in December 2016 (or until the company sold or licensed the compound to another company) was 4.0 years (range, 0.8 years to 8.8 years).

The total revenue from sales of the 10 drugs during this time was $67.0 billion.

The total R&D spending was $7.2 billion, or $9.1 billion when including 7% opportunity costs.

The following table includes data broken down by drug.

*Received accelerated approval. (The other 5 drugs received regular approval.)

**Did not receive orphan designation. (Nine of the 10 drugs received orphan designation.)

“So I think what we’re showing is . . .  a transparent analysis of cancer drugs and companies, looking at the cost to bring a drug to market,” Dr Mailankody said. “And our estimate of $648 million is substantially lower than the often-cited number of $2.7 billion.”

“We’re also showing that, for these 10 drugs, revenue since approval is quite a bit higher than the R&D spending, almost 7-fold higher, and some of these companies have already had revenue of 10-fold or higher, compared to the R&D expenses.”

The researchers acknowledged that this study is limited by a small data set and the fact that the findings cannot be extrapolated to other types of drugs.

1. DiMasi JA et al. Innovation in the pharmaceutical industry: new estimates of R&D costs. J Health Econ. 2016;47:20-33.

2. Young B et al. Rx R&D Myths: The Case Against the Drug Industry’s R&D “Scare Card.” Washington, DC: Public Citizen’s Congress Watch; 2001. https://www.citizen.org/sites/default/files/rdmyths.pdf.

Photo courtesy of the CDC

New research has provided an updated estimate of the spending needed to bring a cancer drug to the US market.

In analyzing data from 10 companies bringing a cancer drug to market, researchers found that sales revenue from these drugs was roughly 7 times higher than the research and development (R&D) costs.

The total sales revenue for the drugs—during a median follow-up of 4 years—was $67.0 billion, and the total R&D spending was $9.1 billion (including 7% opportunity costs).

Researchers reported these figures in JAMA Internal Medicine.

“[T]he price of cancer drugs is currently rising higher and higher each year,” said study author Vinay Prasad, MD, of Oregon Health and Science University in Portland.

“The cost of 1 drug for 1 year of treatment is now routinely in excess of $100,000 . . . . One of the often-cited reasons why cancer drugs cost so much—one of the justifications for the high price—is that the outlay by the biopharmaceutical industry to bring these drugs to market is sizable, and there have been a wide range of estimates for what that R&D outlay is.”

“The most-cited estimate is one that comes out of the Tufts Medical Group¹ that puts the cost to bring a cancer drug to market, when adjusted for 2017 dollars, at $2.7 billion. Another estimate is from the group Public Citizen.² And that is a much lower estimate, finding the cost to bring a drug to market of $320 million.”

“Both of these estimates have limitations in the methods for how they estimated the cost to bring a drug to market. Notably, the Tufts group is rather non-transparent. Because of confidentiality agreements, we don’t know what drugs and what companies they’re looking at, and we can’t independently verify their analysis.”

“The Public Citizen group, in contrast, is comparing expenditures over a period of time against the number of drugs in a different period of time to make an estimate of the cost to bring a drug to market, but this isn’t exactly the cost of bringing those particular drugs to market.”

These issues prompted Dr Prasad and Sham Mailankody, MBBS, of the Memorial Sloan Kettering Cancer Center in New York, to conduct the current study.

Analysis

The researchers analyzed US Securities and Exchange Commission filings for 10 drug companies that received approval from the US Food and Drug Administration for a cancer drug from 2006 through 2015.

Prior to this, none of the companies had any drugs approved for use in the US. However, the companies had a median of 3.5 (range, 2-11) drugs in development during the study period.

The researchers said the fact that these companies had no prior drug approvals eliminated biases that may be present when analyzing larger drug companies, such as redundancies in R&D development and tax incentives for listing different endeavors as R&D spending.

In addition, the fact that the 10 companies were developing other drugs during the study period means this study takes into account the cost of failure in bringing a drug to market.

Results

For the 10 companies and drugs analyzed, the median duration of drug development was 7.3 years (range, 5.8 to 15.2 years).

The median cost of drug development (in 2017 US dollars) was $648.0 million (range, $157.3 to $1950.8 million). For a 7% per annum cost of capital (or opportunity costs), the median cost was $757.4 million (range, $203.6 to $2601.7 million).

The median time from approval to analysis in December 2016 (or until the company sold or licensed the compound to another company) was 4.0 years (range, 0.8 years to 8.8 years).

The total revenue from sales of the 10 drugs during this time was $67.0 billion.

The total R&D spending was $7.2 billion, or $9.1 billion when including 7% opportunity costs.

The following table includes data broken down by drug.

*Received accelerated approval. (The other 5 drugs received regular approval.)

**Did not receive orphan designation. (Nine of the 10 drugs received orphan designation.)

“So I think what we’re showing is . . .  a transparent analysis of cancer drugs and companies, looking at the cost to bring a drug to market,” Dr Mailankody said. “And our estimate of $648 million is substantially lower than the often-cited number of $2.7 billion.”

“We’re also showing that, for these 10 drugs, revenue since approval is quite a bit higher than the R&D spending, almost 7-fold higher, and some of these companies have already had revenue of 10-fold or higher, compared to the R&D expenses.”

The researchers acknowledged that this study is limited by a small data set and the fact that the findings cannot be extrapolated to other types of drugs.

1. DiMasi JA et al. Innovation in the pharmaceutical industry: new estimates of R&D costs. J Health Econ. 2016;47:20-33.

2. Young B et al. Rx R&D Myths: The Case Against the Drug Industry’s R&D “Scare Card.” Washington, DC: Public Citizen’s Congress Watch; 2001. https://www.citizen.org/sites/default/files/rdmyths.pdf.

Paula Burch-Celentano

A new drug is effective against non-severe cases of malaria, according to results from a phase 2 trial published in The Lancet Infectious Diseases.

The drug, AQ-13, was able to clear patients of the malaria parasite Plasmodium falciparum within a week, matching the effectiveness of combination treatment with artemether and lumefantrine.

“The clinical trial results are extraordinarily encouraging,” said study author Donald Krogstad, MD, of Tulane University in New Orleans, Louisiana.

“Compared to the current first-line recommendation for treatment of malaria, the new drug comes out very well.”

For this study, Dr Krogstad and his colleagues recruited 66 adult men in Mali with uncomplicated malaria. Half of the subjects were randomized to receive AQ-13, and the other half received combination treatment with artemether and lumefantrine.

The researchers found that asexual parasites were cleared by day 7 in both treatment groups.

In a per-protocol analysis, the cure rate was 100% (28/28) in the AQ-13 group and 93.9% (28/31) in the combination group (P=0.50, difference −6.1%, 95% CI −14.7 to 2.4).

In the intention-to-treat analysis, the cure rate was 84.8% (28/33) in the AQ-13 group and 93.9% in the combination group (P=0.43, difference 9.1%, 95% CI −5.6 to 23.8).

Grade 1 or lower adverse events (AEs) occurred in 239 patients in the AQ-13 group and 214 in the combination group. There were no grade 2-4 AEs.

The most common AEs (in the AQ-13 and combination groups, respectively) were fever (97% and 88%), weakness (82% and 85%), myalgias and arthralgias (82% and 76%), headache (97% and 94%), and anorexia (73% and 61%).

Two subjects in AQ-13 group left the study, and 3 were lost to follow-up. Two subjects in the combination group had late treatment failures with recurrence of their original infections.

The researchers hope to expand testing of AQ-13 to more participants, including women and children.

Dr Krogstad said the same biotechnology that helped the researchers develop AQ-13 has also revealed similar drugs that hold promise against drug-resistant parasites.

“The potential long-term implications are bigger than one drug,” Dr Krogstad said. “The conceptual step here is that if you understand the resistance well enough, you may actually be able to develop others as well. We synthesized over 200 analogues and, of those, 66 worked against the resistant parasites.”

Paula Burch-Celentano

A new drug is effective against non-severe cases of malaria, according to results from a phase 2 trial published in The Lancet Infectious Diseases.

The drug, AQ-13, was able to clear patients of the malaria parasite Plasmodium falciparum within a week, matching the effectiveness of combination treatment with artemether and lumefantrine.

“The clinical trial results are extraordinarily encouraging,” said study author Donald Krogstad, MD, of Tulane University in New Orleans, Louisiana.

“Compared to the current first-line recommendation for treatment of malaria, the new drug comes out very well.”

For this study, Dr Krogstad and his colleagues recruited 66 adult men in Mali with uncomplicated malaria. Half of the subjects were randomized to receive AQ-13, and the other half received combination treatment with artemether and lumefantrine.

The researchers found that asexual parasites were cleared by day 7 in both treatment groups.

In a per-protocol analysis, the cure rate was 100% (28/28) in the AQ-13 group and 93.9% (28/31) in the combination group (P=0.50, difference −6.1%, 95% CI −14.7 to 2.4).

In the intention-to-treat analysis, the cure rate was 84.8% (28/33) in the AQ-13 group and 93.9% in the combination group (P=0.43, difference 9.1%, 95% CI −5.6 to 23.8).

Grade 1 or lower adverse events (AEs) occurred in 239 patients in the AQ-13 group and 214 in the combination group. There were no grade 2-4 AEs.

The most common AEs (in the AQ-13 and combination groups, respectively) were fever (97% and 88%), weakness (82% and 85%), myalgias and arthralgias (82% and 76%), headache (97% and 94%), and anorexia (73% and 61%).

Two subjects in AQ-13 group left the study, and 3 were lost to follow-up. Two subjects in the combination group had late treatment failures with recurrence of their original infections.

The researchers hope to expand testing of AQ-13 to more participants, including women and children.

Dr Krogstad said the same biotechnology that helped the researchers develop AQ-13 has also revealed similar drugs that hold promise against drug-resistant parasites.

“The potential long-term implications are bigger than one drug,” Dr Krogstad said. “The conceptual step here is that if you understand the resistance well enough, you may actually be able to develop others as well. We synthesized over 200 analogues and, of those, 66 worked against the resistant parasites.”

Paula Burch-Celentano

A new drug is effective against non-severe cases of malaria, according to results from a phase 2 trial published in The Lancet Infectious Diseases.

The drug, AQ-13, was able to clear patients of the malaria parasite Plasmodium falciparum within a week, matching the effectiveness of combination treatment with artemether and lumefantrine.

“The clinical trial results are extraordinarily encouraging,” said study author Donald Krogstad, MD, of Tulane University in New Orleans, Louisiana.

“Compared to the current first-line recommendation for treatment of malaria, the new drug comes out very well.”

For this study, Dr Krogstad and his colleagues recruited 66 adult men in Mali with uncomplicated malaria. Half of the subjects were randomized to receive AQ-13, and the other half received combination treatment with artemether and lumefantrine.

The researchers found that asexual parasites were cleared by day 7 in both treatment groups.

In a per-protocol analysis, the cure rate was 100% (28/28) in the AQ-13 group and 93.9% (28/31) in the combination group (P=0.50, difference −6.1%, 95% CI −14.7 to 2.4).

In the intention-to-treat analysis, the cure rate was 84.8% (28/33) in the AQ-13 group and 93.9% in the combination group (P=0.43, difference 9.1%, 95% CI −5.6 to 23.8).

Grade 1 or lower adverse events (AEs) occurred in 239 patients in the AQ-13 group and 214 in the combination group. There were no grade 2-4 AEs.

The most common AEs (in the AQ-13 and combination groups, respectively) were fever (97% and 88%), weakness (82% and 85%), myalgias and arthralgias (82% and 76%), headache (97% and 94%), and anorexia (73% and 61%).

Two subjects in AQ-13 group left the study, and 3 were lost to follow-up. Two subjects in the combination group had late treatment failures with recurrence of their original infections.

The researchers hope to expand testing of AQ-13 to more participants, including women and children.

Dr Krogstad said the same biotechnology that helped the researchers develop AQ-13 has also revealed similar drugs that hold promise against drug-resistant parasites.

“The potential long-term implications are bigger than one drug,” Dr Krogstad said. “The conceptual step here is that if you understand the resistance well enough, you may actually be able to develop others as well. We synthesized over 200 analogues and, of those, 66 worked against the resistant parasites.”

Photo by Daniel Sone

A new study has revealed a lack of registration and publication of clinical trials, as well as discrepancies in the reporting of primary outcomes.

However, this study is limited in that it only included 113 clinical trials approved in Finland.

An-Wen Chan, MD, DPhil, of the University of Toronto in Ontario, Canada, and his colleagues reported findings from the study in JAMA.

The results were also presented at the Eighth International Congress on Peer Review and Scientific Publication.

The researchers examined adherence to trial registration and its association with subsequent publication and reporting of primary outcomes.

The team looked at 113 clinical trial protocols approved in 2007 by the research ethics committee for the region of Helsinki and Uusimaa, Finland.

Sixty-one percent of the trials were prospectively registered, which was defined as registration within 1 month of the trial start date to allow for incomplete start dates and processing delays in the registry.

Fifty-seven percent of the trials were published, and 80% had a defined primary outcome.

Prospective registration was significantly associated with subsequent publication, with 68% of registered trials and 39% of unregistered trials getting published (adjusted odds ratio=4.53 [95% CI, 1.12-18.34]).

In addition, registered trials were significantly more likely than unregistered trials to be published with the same primary outcomes as defined in the protocol—64% and 25%, respectively (adjusted odds ratio=5.79 [95% CI, 1.42-23.65]).

The researchers assessed discrepancies in primary outcomes between the protocol and the registry/publication. These were defined as:

• A new primary outcome being reported that was not specified as primary in the protocol
• A protocol-defined primary outcome being omitted or downgraded (reported as secondary or unspecified) in the registry or publication.

The researchers found discrepancies between the registry and the protocol in 23% of the prospectively registered trials. There were discrepancies between the publication and the protocol for 16% of published trials.

Discrepancies between the protocol and publication were more common in unregistered trials than registered trials—55% and 6%, respectively (P<0.001).

Based on these results, the researchers concluded that prospective registration should be mandatory for all clinical trials.

Photo by Daniel Sone

A new study has revealed a lack of registration and publication of clinical trials, as well as discrepancies in the reporting of primary outcomes.

However, this study is limited in that it only included 113 clinical trials approved in Finland.

An-Wen Chan, MD, DPhil, of the University of Toronto in Ontario, Canada, and his colleagues reported findings from the study in JAMA.

The results were also presented at the Eighth International Congress on Peer Review and Scientific Publication.

The researchers examined adherence to trial registration and its association with subsequent publication and reporting of primary outcomes.

The team looked at 113 clinical trial protocols approved in 2007 by the research ethics committee for the region of Helsinki and Uusimaa, Finland.

Sixty-one percent of the trials were prospectively registered, which was defined as registration within 1 month of the trial start date to allow for incomplete start dates and processing delays in the registry.

Fifty-seven percent of the trials were published, and 80% had a defined primary outcome.

Prospective registration was significantly associated with subsequent publication, with 68% of registered trials and 39% of unregistered trials getting published (adjusted odds ratio=4.53 [95% CI, 1.12-18.34]).

In addition, registered trials were significantly more likely than unregistered trials to be published with the same primary outcomes as defined in the protocol—64% and 25%, respectively (adjusted odds ratio=5.79 [95% CI, 1.42-23.65]).

The researchers assessed discrepancies in primary outcomes between the protocol and the registry/publication. These were defined as:

• A new primary outcome being reported that was not specified as primary in the protocol
• A protocol-defined primary outcome being omitted or downgraded (reported as secondary or unspecified) in the registry or publication.

The researchers found discrepancies between the registry and the protocol in 23% of the prospectively registered trials. There were discrepancies between the publication and the protocol for 16% of published trials.

Discrepancies between the protocol and publication were more common in unregistered trials than registered trials—55% and 6%, respectively (P<0.001).

Based on these results, the researchers concluded that prospective registration should be mandatory for all clinical trials.

Photo by Daniel Sone

A new study has revealed a lack of registration and publication of clinical trials, as well as discrepancies in the reporting of primary outcomes.

However, this study is limited in that it only included 113 clinical trials approved in Finland.

An-Wen Chan, MD, DPhil, of the University of Toronto in Ontario, Canada, and his colleagues reported findings from the study in JAMA.

The results were also presented at the Eighth International Congress on Peer Review and Scientific Publication.

The researchers examined adherence to trial registration and its association with subsequent publication and reporting of primary outcomes.

The team looked at 113 clinical trial protocols approved in 2007 by the research ethics committee for the region of Helsinki and Uusimaa, Finland.

Sixty-one percent of the trials were prospectively registered, which was defined as registration within 1 month of the trial start date to allow for incomplete start dates and processing delays in the registry.

Fifty-seven percent of the trials were published, and 80% had a defined primary outcome.

Prospective registration was significantly associated with subsequent publication, with 68% of registered trials and 39% of unregistered trials getting published (adjusted odds ratio=4.53 [95% CI, 1.12-18.34]).

In addition, registered trials were significantly more likely than unregistered trials to be published with the same primary outcomes as defined in the protocol—64% and 25%, respectively (adjusted odds ratio=5.79 [95% CI, 1.42-23.65]).

The researchers assessed discrepancies in primary outcomes between the protocol and the registry/publication. These were defined as:

• A new primary outcome being reported that was not specified as primary in the protocol
• A protocol-defined primary outcome being omitted or downgraded (reported as secondary or unspecified) in the registry or publication.

The researchers found discrepancies between the registry and the protocol in 23% of the prospectively registered trials. There were discrepancies between the publication and the protocol for 16% of published trials.

Discrepancies between the protocol and publication were more common in unregistered trials than registered trials—55% and 6%, respectively (P<0.001).

Based on these results, the researchers concluded that prospective registration should be mandatory for all clinical trials.

Photo by Esther Dyson

MADRID—Results of a nationwide study suggest many cancer patients in Ireland don’t understand key aspects of clinical trial methodology.

Most of the patients surveyed, which included individuals who had participated in a clinical trial, did not understand the concepts of randomization or equipoise.

“Over half of previous medical trial participants and 73% of those who had never been on a cancer clinical trial did not understand that, in a randomized trial, the treatment given was decided by chance,” said study investigator Catherine Kelly, MB BCh, of Mater Misericordiae University Hospital in Dublin, Ireland.

“We also found that most patients did not understand clinical equipoise—the fact that no one knows which treatment is best. Surprisingly, this was more marked in previous clinical trial participants, 60% of whom believed that their doctor would know which study arm was best.”

Dr Kelly and her colleagues presented these findings at the ESMO 2017 Congress (abstract 1465P_PR).

The researchers surveyed 1090 adult cancer patients treated at 1 of 14 participating oncology centers across Ireland.

The patients’ median age was 60 (range, 50-69), 64.4% were female, and 66% were diagnosed between 2014 and 2016. The most common cancer types were breast (31.4%), colorectal (15.6%), hematologic (12.6%), genitourinary (11.6%), and lung (6.8%).

The patients filled out anonymized questionnaires in which they were asked to evaluate statements about clinical trials. The patients had to determine whether a statement is true or false, or they could indicate that they didn’t know an answer.

A majority of the patients (82.3%) said they understood what a medical or cancer clinical trial is. And 27.8% of patients said they had previously participated in a cancer trial.

However, many patients didn’t know when clinical trials may be an option. Twenty-two percent of patients said it is true that “clinical trials are only used when standard treatments have not worked,” and 26.6% said they didn’t know if this statement is true or false.

Roughly a third (33.5%) of patients said it is true that, in a randomized trial, treatment is decided by chance, but 41.4% of patients said this is false, and 25% said they didn’t know.

More than half of patients (56.5%) said their doctor would know which treatment was superior in a clinical trial, and 23.2% of patients said they didn’t know if their doctor would know.

About 61% of all patients said their doctor would make sure they received the superior treatment in a clinical trial. An even greater percentage—63.6%—of patients who had previously participated in a clinical trial said the same.

“To provide informed consent when participating in a trial, patients need to understand these key concepts, and doctors explaining them well is essential to alleviating any fears that might prevent patients from participating,” Dr Kelly said.

“Doctors have a responsibility to properly inform their patients in this regard because they are the ones patients trust the most. As we analyze the data further, we will be able to offer physicians a more detailed picture of the questions patients need answered and the factors that influence their decision-making according to age group, cancer type, educational background, and other demographics.”

Funding for this research was provided to Cancer Trials Ireland by Amgen, Abbvie, Bayor, and Inveva.

Photo by Esther Dyson

MADRID—Results of a nationwide study suggest many cancer patients in Ireland don’t understand key aspects of clinical trial methodology.

Most of the patients surveyed, which included individuals who had participated in a clinical trial, did not understand the concepts of randomization or equipoise.

“Over half of previous medical trial participants and 73% of those who had never been on a cancer clinical trial did not understand that, in a randomized trial, the treatment given was decided by chance,” said study investigator Catherine Kelly, MB BCh, of Mater Misericordiae University Hospital in Dublin, Ireland.

“We also found that most patients did not understand clinical equipoise—the fact that no one knows which treatment is best. Surprisingly, this was more marked in previous clinical trial participants, 60% of whom believed that their doctor would know which study arm was best.”

Dr Kelly and her colleagues presented these findings at the ESMO 2017 Congress (abstract 1465P_PR).

The researchers surveyed 1090 adult cancer patients treated at 1 of 14 participating oncology centers across Ireland.

The patients’ median age was 60 (range, 50-69), 64.4% were female, and 66% were diagnosed between 2014 and 2016. The most common cancer types were breast (31.4%), colorectal (15.6%), hematologic (12.6%), genitourinary (11.6%), and lung (6.8%).

The patients filled out anonymized questionnaires in which they were asked to evaluate statements about clinical trials. The patients had to determine whether a statement is true or false, or they could indicate that they didn’t know an answer.

A majority of the patients (82.3%) said they understood what a medical or cancer clinical trial is. And 27.8% of patients said they had previously participated in a cancer trial.

However, many patients didn’t know when clinical trials may be an option. Twenty-two percent of patients said it is true that “clinical trials are only used when standard treatments have not worked,” and 26.6% said they didn’t know if this statement is true or false.

Roughly a third (33.5%) of patients said it is true that, in a randomized trial, treatment is decided by chance, but 41.4% of patients said this is false, and 25% said they didn’t know.

More than half of patients (56.5%) said their doctor would know which treatment was superior in a clinical trial, and 23.2% of patients said they didn’t know if their doctor would know.

About 61% of all patients said their doctor would make sure they received the superior treatment in a clinical trial. An even greater percentage—63.6%—of patients who had previously participated in a clinical trial said the same.

“To provide informed consent when participating in a trial, patients need to understand these key concepts, and doctors explaining them well is essential to alleviating any fears that might prevent patients from participating,” Dr Kelly said.

“Doctors have a responsibility to properly inform their patients in this regard because they are the ones patients trust the most. As we analyze the data further, we will be able to offer physicians a more detailed picture of the questions patients need answered and the factors that influence their decision-making according to age group, cancer type, educational background, and other demographics.”

Funding for this research was provided to Cancer Trials Ireland by Amgen, Abbvie, Bayor, and Inveva.

Photo by Esther Dyson

MADRID—Results of a nationwide study suggest many cancer patients in Ireland don’t understand key aspects of clinical trial methodology.

Most of the patients surveyed, which included individuals who had participated in a clinical trial, did not understand the concepts of randomization or equipoise.

“Over half of previous medical trial participants and 73% of those who had never been on a cancer clinical trial did not understand that, in a randomized trial, the treatment given was decided by chance,” said study investigator Catherine Kelly, MB BCh, of Mater Misericordiae University Hospital in Dublin, Ireland.

“We also found that most patients did not understand clinical equipoise—the fact that no one knows which treatment is best. Surprisingly, this was more marked in previous clinical trial participants, 60% of whom believed that their doctor would know which study arm was best.”

Dr Kelly and her colleagues presented these findings at the ESMO 2017 Congress (abstract 1465P_PR).

The researchers surveyed 1090 adult cancer patients treated at 1 of 14 participating oncology centers across Ireland.

The patients’ median age was 60 (range, 50-69), 64.4% were female, and 66% were diagnosed between 2014 and 2016. The most common cancer types were breast (31.4%), colorectal (15.6%), hematologic (12.6%), genitourinary (11.6%), and lung (6.8%).

The patients filled out anonymized questionnaires in which they were asked to evaluate statements about clinical trials. The patients had to determine whether a statement is true or false, or they could indicate that they didn’t know an answer.

A majority of the patients (82.3%) said they understood what a medical or cancer clinical trial is. And 27.8% of patients said they had previously participated in a cancer trial.

However, many patients didn’t know when clinical trials may be an option. Twenty-two percent of patients said it is true that “clinical trials are only used when standard treatments have not worked,” and 26.6% said they didn’t know if this statement is true or false.

Roughly a third (33.5%) of patients said it is true that, in a randomized trial, treatment is decided by chance, but 41.4% of patients said this is false, and 25% said they didn’t know.

More than half of patients (56.5%) said their doctor would know which treatment was superior in a clinical trial, and 23.2% of patients said they didn’t know if their doctor would know.

About 61% of all patients said their doctor would make sure they received the superior treatment in a clinical trial. An even greater percentage—63.6%—of patients who had previously participated in a clinical trial said the same.

“To provide informed consent when participating in a trial, patients need to understand these key concepts, and doctors explaining them well is essential to alleviating any fears that might prevent patients from participating,” Dr Kelly said.

“Doctors have a responsibility to properly inform their patients in this regard because they are the ones patients trust the most. As we analyze the data further, we will be able to offer physicians a more detailed picture of the questions patients need answered and the factors that influence their decision-making according to age group, cancer type, educational background, and other demographics.”

Funding for this research was provided to Cancer Trials Ireland by Amgen, Abbvie, Bayor, and Inveva.

Photo by Whaldener Endo

Molecular analysis has confirmed zoonotic transmission of malaria in southern Brazil, according to an article published in The Lancet Global Health.

Researchers identified 28 humans infected with Plasmodium simium, a malaria parasite usually only found in monkeys.

The researchers said screening of local monkeys and mosquitoes will be required to evaluate the extent of the emerging zoonotic threat to public health.

Malaria was thought to have been eliminated from southern Brazil over 50 years ago. However, between 2006 and 2014, 43 cases of malaria were reported in the Atlantic Forest area in southern Brazil. An additional 49 cases were reported from 2015 through 2016.

This prompted researchers to investigate the possibility of zoonotic transmission. The team looked at the 49 cases reported in 2015 and 2016, and they were able to sequence DNA samples from 28 of the 49 patients.

In all 28 cases, the parasite was confirmed to be P simium—not the human parasite Plasmodium vivax, as previously thought.

P simium is transmitted via the Anopheles mosquito and is known to infect some species of howler and capuchin monkeys in the Atlantic Forest region.

All 28 humans infected with P simium had entered the forest or visited the surrounding area. The patients’ main symptom was fever, none of them were admitted to the hospital, and all made full recoveries following treatment.

“There is no evidence that zoonotic malaria can be transmitted from human to human via mosquitoes,” said study author Patrícia Brasil, MD, of Instituto Nacional de Infectologia Evandro Chagas in Rio de Janeiro, Brazil.

“In addition, there is no current threat to people in the city of Rio de Janeiro or in other non-forest areas of the Rio de Janeiro state where transmission of the disease does not exist. However, its unique mode of transmission via monkeys and the fact that it occurs in areas of high forest coverage mean that zoonotic malaria poses a unique problem for malaria control efforts and may complicate the drive towards eventual elimination of the disease. Although [this type of malaria is] benign and treatable, visitors should follow measures to avoid insect bites when going into the forest.”

Dr Brasil and her colleagues noted that samples from previous malaria cases reported in the Atlantic Forest area have not yet been tested. Therefore, it is not possible to establish whether P simium has only recently acquired the ability to infect human beings or if zoonotic malaria has previously infected humans in this region.

“In the 1960s, there was a probable case of zoonotic malaria described in a forest guard in the Atlantic Forest of São Paulo, but, until now, there has been no molecular evidence of the parasite being present in humans,” said study author Cláudio Tadeu Daniel-Ribeiro, MD, of Instituto Oswaldo Cruz in Rio de Janeiro, Brazil.

“This is the first demonstration of P simium naturally infecting human beings in forest locations in a region considered to have eliminated transmission of malaria at least 50 years ago.”

Photo by Whaldener Endo

Molecular analysis has confirmed zoonotic transmission of malaria in southern Brazil, according to an article published in The Lancet Global Health.

Researchers identified 28 humans infected with Plasmodium simium, a malaria parasite usually only found in monkeys.

The researchers said screening of local monkeys and mosquitoes will be required to evaluate the extent of the emerging zoonotic threat to public health.

Malaria was thought to have been eliminated from southern Brazil over 50 years ago. However, between 2006 and 2014, 43 cases of malaria were reported in the Atlantic Forest area in southern Brazil. An additional 49 cases were reported from 2015 through 2016.

This prompted researchers to investigate the possibility of zoonotic transmission. The team looked at the 49 cases reported in 2015 and 2016, and they were able to sequence DNA samples from 28 of the 49 patients.

In all 28 cases, the parasite was confirmed to be P simium—not the human parasite Plasmodium vivax, as previously thought.

P simium is transmitted via the Anopheles mosquito and is known to infect some species of howler and capuchin monkeys in the Atlantic Forest region.

All 28 humans infected with P simium had entered the forest or visited the surrounding area. The patients’ main symptom was fever, none of them were admitted to the hospital, and all made full recoveries following treatment.

“There is no evidence that zoonotic malaria can be transmitted from human to human via mosquitoes,” said study author Patrícia Brasil, MD, of Instituto Nacional de Infectologia Evandro Chagas in Rio de Janeiro, Brazil.

“In addition, there is no current threat to people in the city of Rio de Janeiro or in other non-forest areas of the Rio de Janeiro state where transmission of the disease does not exist. However, its unique mode of transmission via monkeys and the fact that it occurs in areas of high forest coverage mean that zoonotic malaria poses a unique problem for malaria control efforts and may complicate the drive towards eventual elimination of the disease. Although [this type of malaria is] benign and treatable, visitors should follow measures to avoid insect bites when going into the forest.”

Dr Brasil and her colleagues noted that samples from previous malaria cases reported in the Atlantic Forest area have not yet been tested. Therefore, it is not possible to establish whether P simium has only recently acquired the ability to infect human beings or if zoonotic malaria has previously infected humans in this region.

“In the 1960s, there was a probable case of zoonotic malaria described in a forest guard in the Atlantic Forest of São Paulo, but, until now, there has been no molecular evidence of the parasite being present in humans,” said study author Cláudio Tadeu Daniel-Ribeiro, MD, of Instituto Oswaldo Cruz in Rio de Janeiro, Brazil.

“This is the first demonstration of P simium naturally infecting human beings in forest locations in a region considered to have eliminated transmission of malaria at least 50 years ago.”

Photo by Whaldener Endo

Molecular analysis has confirmed zoonotic transmission of malaria in southern Brazil, according to an article published in The Lancet Global Health.

Researchers identified 28 humans infected with Plasmodium simium, a malaria parasite usually only found in monkeys.

The researchers said screening of local monkeys and mosquitoes will be required to evaluate the extent of the emerging zoonotic threat to public health.

Malaria was thought to have been eliminated from southern Brazil over 50 years ago. However, between 2006 and 2014, 43 cases of malaria were reported in the Atlantic Forest area in southern Brazil. An additional 49 cases were reported from 2015 through 2016.

This prompted researchers to investigate the possibility of zoonotic transmission. The team looked at the 49 cases reported in 2015 and 2016, and they were able to sequence DNA samples from 28 of the 49 patients.

In all 28 cases, the parasite was confirmed to be P simium—not the human parasite Plasmodium vivax, as previously thought.

P simium is transmitted via the Anopheles mosquito and is known to infect some species of howler and capuchin monkeys in the Atlantic Forest region.

All 28 humans infected with P simium had entered the forest or visited the surrounding area. The patients’ main symptom was fever, none of them were admitted to the hospital, and all made full recoveries following treatment.

“There is no evidence that zoonotic malaria can be transmitted from human to human via mosquitoes,” said study author Patrícia Brasil, MD, of Instituto Nacional de Infectologia Evandro Chagas in Rio de Janeiro, Brazil.

“In addition, there is no current threat to people in the city of Rio de Janeiro or in other non-forest areas of the Rio de Janeiro state where transmission of the disease does not exist. However, its unique mode of transmission via monkeys and the fact that it occurs in areas of high forest coverage mean that zoonotic malaria poses a unique problem for malaria control efforts and may complicate the drive towards eventual elimination of the disease. Although [this type of malaria is] benign and treatable, visitors should follow measures to avoid insect bites when going into the forest.”

Dr Brasil and her colleagues noted that samples from previous malaria cases reported in the Atlantic Forest area have not yet been tested. Therefore, it is not possible to establish whether P simium has only recently acquired the ability to infect human beings or if zoonotic malaria has previously infected humans in this region.

“In the 1960s, there was a probable case of zoonotic malaria described in a forest guard in the Atlantic Forest of São Paulo, but, until now, there has been no molecular evidence of the parasite being present in humans,” said study author Cláudio Tadeu Daniel-Ribeiro, MD, of Instituto Oswaldo Cruz in Rio de Janeiro, Brazil.

“This is the first demonstration of P simium naturally infecting human beings in forest locations in a region considered to have eliminated transmission of malaria at least 50 years ago.”

Images courtesy of Jonathan B. Grimm

Chemists have reported the creation of new fluorescent dyes that can be used in cells, tissues, and animals.

The scientists found that swapping out specific chemical building blocks in fluorescent molecules called rhodamines can generate dyes of nearly every color.

Such an expanded palette of dyes could help researchers better illuminate the inner workings of cells, said Luke Lavis, PhD, of the Howard Hughes Medical Institute’s Janelia Research Campus in Ashburn, Virginia.

Dr Lavis and his colleagues used their new dyes to light up cell nuclei, label living brain tissue from fruit fly larvae, and highlight visual cortex neurons in mice that had tiny glass windows fitted into their skulls.

The team detailed their work in Nature Methods.

Dr Lavis noted that scientists used to concoct different dyes mostly by trial and error.

“Now, we’ve figured out the rules, and we can make almost any color,” he said.

Dr Lavis’s team focused their research on rhodamines because they’re especially bright and cell-permeable.

Chemists had been working with rhodamines for more than 100 years but created only a few dozen colors. Most were similar shades ranging from green to orange.

That’s because, until recently, making new rhodamines wasn’t easy. Scientists still used techniques from the earliest days of chemistry, boiling chemical ingredients in sulfuric acid. This forces the molecules to link together in a condensation reaction.

Mixing in different building blocks could yield new and unusual dyes, but ingredients had to be tough enough to survive the boiling acid bath. This didn’t leave a lot of options.

In 2011, Dr Lavis’s team developed a new way to tinker with rhodamines’ structure, under milder conditions. Using a reaction sparked by the metal palladium, the scientists could skip the acid step and construct dyes with more complicated building blocks than had been used before.

Four years later, the team revealed the Janelia Fluor dyes. The secret behind these dyes is a tiny, square-shaped appendage called an azetidine ring.

The scientists found that incorporating 4-membered azetidine rings into classic fluorophore structures elicited “substantial increases in brightness and photostability.” In fact, the Janelia Fluor dyes are up to 50 times brighter than other dyes.

Now, Dr Lavis’s group has figured out how to fine-tune their fluorescent dyes by tweaking rhodamines’ structure even further. The team showed that incorporating 3-substituted azetidine groups allowed them to tune spectral and chemical properties with “unprecedented precision.”

The dyes can be synthesized in a single step with inexpensive ingredients. The low cost has allowed Dr Lavis and his colleagues to share their work, shipping thousands of vials to hundreds of labs around the world.

Images courtesy of Jonathan B. Grimm

Chemists have reported the creation of new fluorescent dyes that can be used in cells, tissues, and animals.

The scientists found that swapping out specific chemical building blocks in fluorescent molecules called rhodamines can generate dyes of nearly every color.

Such an expanded palette of dyes could help researchers better illuminate the inner workings of cells, said Luke Lavis, PhD, of the Howard Hughes Medical Institute’s Janelia Research Campus in Ashburn, Virginia.

Dr Lavis and his colleagues used their new dyes to light up cell nuclei, label living brain tissue from fruit fly larvae, and highlight visual cortex neurons in mice that had tiny glass windows fitted into their skulls.

The team detailed their work in Nature Methods.

Dr Lavis noted that scientists used to concoct different dyes mostly by trial and error.

“Now, we’ve figured out the rules, and we can make almost any color,” he said.

Dr Lavis’s team focused their research on rhodamines because they’re especially bright and cell-permeable.

Chemists had been working with rhodamines for more than 100 years but created only a few dozen colors. Most were similar shades ranging from green to orange.

That’s because, until recently, making new rhodamines wasn’t easy. Scientists still used techniques from the earliest days of chemistry, boiling chemical ingredients in sulfuric acid. This forces the molecules to link together in a condensation reaction.

Mixing in different building blocks could yield new and unusual dyes, but ingredients had to be tough enough to survive the boiling acid bath. This didn’t leave a lot of options.

In 2011, Dr Lavis’s team developed a new way to tinker with rhodamines’ structure, under milder conditions. Using a reaction sparked by the metal palladium, the scientists could skip the acid step and construct dyes with more complicated building blocks than had been used before.

Four years later, the team revealed the Janelia Fluor dyes. The secret behind these dyes is a tiny, square-shaped appendage called an azetidine ring.

The scientists found that incorporating 4-membered azetidine rings into classic fluorophore structures elicited “substantial increases in brightness and photostability.” In fact, the Janelia Fluor dyes are up to 50 times brighter than other dyes.

Now, Dr Lavis’s group has figured out how to fine-tune their fluorescent dyes by tweaking rhodamines’ structure even further. The team showed that incorporating 3-substituted azetidine groups allowed them to tune spectral and chemical properties with “unprecedented precision.”

The dyes can be synthesized in a single step with inexpensive ingredients. The low cost has allowed Dr Lavis and his colleagues to share their work, shipping thousands of vials to hundreds of labs around the world.

Images courtesy of Jonathan B. Grimm

Chemists have reported the creation of new fluorescent dyes that can be used in cells, tissues, and animals.

The scientists found that swapping out specific chemical building blocks in fluorescent molecules called rhodamines can generate dyes of nearly every color.

Such an expanded palette of dyes could help researchers better illuminate the inner workings of cells, said Luke Lavis, PhD, of the Howard Hughes Medical Institute’s Janelia Research Campus in Ashburn, Virginia.

Dr Lavis and his colleagues used their new dyes to light up cell nuclei, label living brain tissue from fruit fly larvae, and highlight visual cortex neurons in mice that had tiny glass windows fitted into their skulls.

The team detailed their work in Nature Methods.

Dr Lavis noted that scientists used to concoct different dyes mostly by trial and error.

“Now, we’ve figured out the rules, and we can make almost any color,” he said.

Dr Lavis’s team focused their research on rhodamines because they’re especially bright and cell-permeable.

Chemists had been working with rhodamines for more than 100 years but created only a few dozen colors. Most were similar shades ranging from green to orange.

That’s because, until recently, making new rhodamines wasn’t easy. Scientists still used techniques from the earliest days of chemistry, boiling chemical ingredients in sulfuric acid. This forces the molecules to link together in a condensation reaction.

Mixing in different building blocks could yield new and unusual dyes, but ingredients had to be tough enough to survive the boiling acid bath. This didn’t leave a lot of options.

In 2011, Dr Lavis’s team developed a new way to tinker with rhodamines’ structure, under milder conditions. Using a reaction sparked by the metal palladium, the scientists could skip the acid step and construct dyes with more complicated building blocks than had been used before.

Four years later, the team revealed the Janelia Fluor dyes. The secret behind these dyes is a tiny, square-shaped appendage called an azetidine ring.

The scientists found that incorporating 4-membered azetidine rings into classic fluorophore structures elicited “substantial increases in brightness and photostability.” In fact, the Janelia Fluor dyes are up to 50 times brighter than other dyes.

Now, Dr Lavis’s group has figured out how to fine-tune their fluorescent dyes by tweaking rhodamines’ structure even further. The team showed that incorporating 3-substituted azetidine groups allowed them to tune spectral and chemical properties with “unprecedented precision.”

The dyes can be synthesized in a single step with inexpensive ingredients. The low cost has allowed Dr Lavis and his colleagues to share their work, shipping thousands of vials to hundreds of labs around the world.