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The Food and Drug Administration is planning a pilot study of a new HIV risk questionnaire, as part of a comprehensive and ongoing evaluation of its blood donation policies for men who have sex with men (MSM).

At a meeting of the FDA’s Blood Products Advisory Committee, the agency shared the content of the 5-item questionnaire and reviewed the proposed study design with committee members, who were asked to comment – but not vote – on the best path forward for MSM donation policies.

The FDA is “committed to ongoing evaluation of the MSM deferral policy” and remains open to adjusting the policy based on the best available scientific evidence, said Barbee Whitaker, PhD, a lead scientist in the agency’s Office of Emerging and Transfusion Transmitted Disease

After recruiting 2,000 men who have had sex with men at least once during the past 3 months, the study will aim to identify individuals who have very recently become HIV infected, in order to assess the discriminant function of the set of behavioral questions that are proposed in the questionnaire.

The crux of the problem currently, noted Dr. Whitaker, is identifying those individuals who are very recently infected with HIV. Nucleic acid testing has tightened the window of undetectability considerably, but the current 12-month deferral window after men have had sexual contact with other men is designed to ensure safety of the blood supply.

Social justice concerns have been raised about the blanket deferral, said Dr. Whitaker; the behavioral questions in the pilot study will ask about the number of different sexual partners men have had within the past 1, 3, and 12 months and ask about the type of sexual contact (oral sex, or anal penetrative or receptive intercourse). The questionnaire also asks about sex with a partner known to be HIV positive, condom use, and use of pre-exposure prophylaxis (PrEP).

The FDA will ask for proposals to conduct the study with an eye to having sites in such cities as Washington, Atlanta, and Miami, which have high incidences of HIV, to improve chances of early detection.

The behavioral questionnaire is not seen as an immediate replacement for the 12-month deferral policy, the FDA made clear in its briefing documents and in discussion with the committee. Instead, its utility will be in the information gleaned from the pilot study and a follow-on that may include several hundred thousand individuals. These data should provide “population-based evidence upon which to base regulatory decisions to ensure blood safety,” she said.

 

 

Donation policies outside the United States

Whether a change in blood donation deferral policies for MSM would be a shortened window or a move toward a behavioral questionnaire is currently not known. Globally, a variety of practices are used for blood screening, said Mindy Goldman, MD, medical director of Canadian Blood Services, who reviewed international perspectives on blood donation for MSM.

“There’s no general consensus on donation deferrals internationally,” she said. Factors influencing policy can include epidemiology, risk analysis, modeling, and history of response to threats in the past.

However, “there’s basically a couple of main approaches” to handling deferrals for MSM, Dr. Goldman said. One is time-based deferral – the strategy used in the United States, as well as Canada, the United Kingdom, Japan, and Australia.

Japan and the U.K. have recently moved to 3-month deferral periods, a figure arrived at by doubling the window period for nucleic acid testing for HIV, roughly, Dr. Goldman said. Early data from the U.K. experience has not shown an increase in HIV rates among donors, or an increase in NAT-only positive donors, she said. An application to move from a 12-month to a 3-month deferral period is pending in Canada.

A strong advantage of time-based deferral as a risk management strategy, Dr. Goldman said, is standardization. “For us, standardization is close to godliness.”

However, she added, “another major limitation is that you’re still deferring all sexually active MSM, including those who are in a stable monogamous relationship from donating. From a justice perspective for the lowest risk population of MSM – they are still being deferred using this type of approach.”

Some nations, such as Spain and Italy, use individual risk assessment via physician-led interviews. These approaches are often not standardized. “There’s no national uniform questionnaire, so there’s less standardization, and more variability between blood centers,” Dr. Goldman said. “So you wind up trying to compare apples with oranges.”

This means the results are harder to evaluate on a national level. However, there appears to be higher residual risk, with HIV rates among first-time donors approaching those of the general population, Dr. Goldman said.

Another strategy, used in France, is a test-retest model, where blood from first-time MSM that initially tests negative for HIV is held until the individual returns for re-testing or an additional donation, with a second negative test. This approach increases operational complexity and cost, noted Dr. Goldman, and because of the short shelf life of platelets, it’s not practical for this blood component.

In general questioning and discussion after this and other background presentations, the committee could agree on one point: this isn’t an easy question.

“I’m increasingly struck by how difficult this problem is,” said committee member Roger Lewis, MD, PhD, professor at the University of California, Los Angeles, and chair of the department of emergency medicine at Harbor-UCLA Medical Center. Regarding just the problem of completing the pilot study, Dr. Lewis commented, “It sounds like it’s going to be impossible to get the data that directly answers the questions.”

Peter Marx, MD, PhD, who directs the FDA’s Center for Biologics Evaluation and Research (CBER), which oversees blood products safety, joined the discussion to acknowledge the difficulty, but underscore the social importance of a careful examination of the current MSM donation policy.

“We understand the issues here…. With all due respect to our European colleagues, there’s not enough data. That’s the point of this study; we also know that the U.S. has a very different epidemiology of HIV than the U.K. and a lot of other places,” Dr. Marx said. “The pilot study is a way to get some data where we might be able to get away from a time-based deferral. The LGBT community finds any time-based deferral discriminatory.”

 

 

Pathogen reduction technology

The committee heard a proposal for a completely different strategy during its afternoon session: pathogen reduction technology (PRT) holds promise to achieve virtual elimination of HIV and other pathogens from donated blood products.

The FDA is reviewing a variance request from the nonprofit blood donation organization Bloodworks Northwest organization to use PRT for apheresis platelet donations from MSM who would otherwise be deferred because of sexual activity within the 12-month deferral window.

James AuBuchon, MD, president of Bloodworks Northwest, explained that his organization takes in about 225,000 donations annually. The variance sought would use the FDA-approved INTERCEPT device to achieve pathogen reduction for donations that meet all requirements except the MSM deferral, and that would still undergo all relevant transfusion transmitted infection testing.

The INTERCEPT device uses amotosalen, which intercalates with DNA and RNA, inactivating it after exposure to ultraviolet A light. Amotosalen is then removed from the blood product before administration. The pathogen reduction activity doesn’t interfere with platelets or plasma, and is active against a wide range of viruses, bacteria, and fungal pathogens, explained Dr. AuBuchon, who is also a professor of hematology at the University of Washington, Seattle.

Dr. AuBuchon walked the committee through procedures designed to flag donors for PRT platelet apheresis, and to ensure these donations receive the intended PRT treatment. Platelets were chosen for this variance request, he explained, because demand outstrips supply. “We are all spending additional time and resources in recruiting a new framework and demographic, and it is exceedingly difficult to keep enough donors coming through the door,” he said. “Our platelet utilization climbs continually – it’s up 15% in the last 4 years.”

Committee members circled around the idea that all risk can’t be eliminated, even with the highly effective PRT technology. But the risk is exceedingly low, said committee chair Richard Kaufman, MD, medical director of the adult transfusion service at Brigham and Women’s Hospital, Boston. “It’s not possible to get rid of the window. We can kind of hammer down the risk by shrinking down the window by using incredibly sensitive tests. But that risk continues to exist. Pathogen reduction can take care of that residual risk…. So what’s left is really quite a low risk,” Dr. Kaufman said.

Susan Stramer, PhD, vice president of scientific affairs for the American Red Cross, concurred, noting that pathogen reduction techniques are already in use for many other blood products, particularly within the plasma industry.

Wrapping up, Dr. Kaufman asked individual committee members to summarize their position on the variance request, though the FDA had not placed a voting question before the committee. Consensus in the room was that this real-world examination of PRT could point to a path to expanding the donor pool while maintaining patient safety – a concern all agreed was paramount.

The FDA usually follows the recommendations of its committees.

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The Food and Drug Administration is planning a pilot study of a new HIV risk questionnaire, as part of a comprehensive and ongoing evaluation of its blood donation policies for men who have sex with men (MSM).

At a meeting of the FDA’s Blood Products Advisory Committee, the agency shared the content of the 5-item questionnaire and reviewed the proposed study design with committee members, who were asked to comment – but not vote – on the best path forward for MSM donation policies.

The FDA is “committed to ongoing evaluation of the MSM deferral policy” and remains open to adjusting the policy based on the best available scientific evidence, said Barbee Whitaker, PhD, a lead scientist in the agency’s Office of Emerging and Transfusion Transmitted Disease

After recruiting 2,000 men who have had sex with men at least once during the past 3 months, the study will aim to identify individuals who have very recently become HIV infected, in order to assess the discriminant function of the set of behavioral questions that are proposed in the questionnaire.

The crux of the problem currently, noted Dr. Whitaker, is identifying those individuals who are very recently infected with HIV. Nucleic acid testing has tightened the window of undetectability considerably, but the current 12-month deferral window after men have had sexual contact with other men is designed to ensure safety of the blood supply.

Social justice concerns have been raised about the blanket deferral, said Dr. Whitaker; the behavioral questions in the pilot study will ask about the number of different sexual partners men have had within the past 1, 3, and 12 months and ask about the type of sexual contact (oral sex, or anal penetrative or receptive intercourse). The questionnaire also asks about sex with a partner known to be HIV positive, condom use, and use of pre-exposure prophylaxis (PrEP).

The FDA will ask for proposals to conduct the study with an eye to having sites in such cities as Washington, Atlanta, and Miami, which have high incidences of HIV, to improve chances of early detection.

The behavioral questionnaire is not seen as an immediate replacement for the 12-month deferral policy, the FDA made clear in its briefing documents and in discussion with the committee. Instead, its utility will be in the information gleaned from the pilot study and a follow-on that may include several hundred thousand individuals. These data should provide “population-based evidence upon which to base regulatory decisions to ensure blood safety,” she said.

 

 

Donation policies outside the United States

Whether a change in blood donation deferral policies for MSM would be a shortened window or a move toward a behavioral questionnaire is currently not known. Globally, a variety of practices are used for blood screening, said Mindy Goldman, MD, medical director of Canadian Blood Services, who reviewed international perspectives on blood donation for MSM.

“There’s no general consensus on donation deferrals internationally,” she said. Factors influencing policy can include epidemiology, risk analysis, modeling, and history of response to threats in the past.

However, “there’s basically a couple of main approaches” to handling deferrals for MSM, Dr. Goldman said. One is time-based deferral – the strategy used in the United States, as well as Canada, the United Kingdom, Japan, and Australia.

Japan and the U.K. have recently moved to 3-month deferral periods, a figure arrived at by doubling the window period for nucleic acid testing for HIV, roughly, Dr. Goldman said. Early data from the U.K. experience has not shown an increase in HIV rates among donors, or an increase in NAT-only positive donors, she said. An application to move from a 12-month to a 3-month deferral period is pending in Canada.

A strong advantage of time-based deferral as a risk management strategy, Dr. Goldman said, is standardization. “For us, standardization is close to godliness.”

However, she added, “another major limitation is that you’re still deferring all sexually active MSM, including those who are in a stable monogamous relationship from donating. From a justice perspective for the lowest risk population of MSM – they are still being deferred using this type of approach.”

Some nations, such as Spain and Italy, use individual risk assessment via physician-led interviews. These approaches are often not standardized. “There’s no national uniform questionnaire, so there’s less standardization, and more variability between blood centers,” Dr. Goldman said. “So you wind up trying to compare apples with oranges.”

This means the results are harder to evaluate on a national level. However, there appears to be higher residual risk, with HIV rates among first-time donors approaching those of the general population, Dr. Goldman said.

Another strategy, used in France, is a test-retest model, where blood from first-time MSM that initially tests negative for HIV is held until the individual returns for re-testing or an additional donation, with a second negative test. This approach increases operational complexity and cost, noted Dr. Goldman, and because of the short shelf life of platelets, it’s not practical for this blood component.

In general questioning and discussion after this and other background presentations, the committee could agree on one point: this isn’t an easy question.

“I’m increasingly struck by how difficult this problem is,” said committee member Roger Lewis, MD, PhD, professor at the University of California, Los Angeles, and chair of the department of emergency medicine at Harbor-UCLA Medical Center. Regarding just the problem of completing the pilot study, Dr. Lewis commented, “It sounds like it’s going to be impossible to get the data that directly answers the questions.”

Peter Marx, MD, PhD, who directs the FDA’s Center for Biologics Evaluation and Research (CBER), which oversees blood products safety, joined the discussion to acknowledge the difficulty, but underscore the social importance of a careful examination of the current MSM donation policy.

“We understand the issues here…. With all due respect to our European colleagues, there’s not enough data. That’s the point of this study; we also know that the U.S. has a very different epidemiology of HIV than the U.K. and a lot of other places,” Dr. Marx said. “The pilot study is a way to get some data where we might be able to get away from a time-based deferral. The LGBT community finds any time-based deferral discriminatory.”

 

 

Pathogen reduction technology

The committee heard a proposal for a completely different strategy during its afternoon session: pathogen reduction technology (PRT) holds promise to achieve virtual elimination of HIV and other pathogens from donated blood products.

The FDA is reviewing a variance request from the nonprofit blood donation organization Bloodworks Northwest organization to use PRT for apheresis platelet donations from MSM who would otherwise be deferred because of sexual activity within the 12-month deferral window.

James AuBuchon, MD, president of Bloodworks Northwest, explained that his organization takes in about 225,000 donations annually. The variance sought would use the FDA-approved INTERCEPT device to achieve pathogen reduction for donations that meet all requirements except the MSM deferral, and that would still undergo all relevant transfusion transmitted infection testing.

The INTERCEPT device uses amotosalen, which intercalates with DNA and RNA, inactivating it after exposure to ultraviolet A light. Amotosalen is then removed from the blood product before administration. The pathogen reduction activity doesn’t interfere with platelets or plasma, and is active against a wide range of viruses, bacteria, and fungal pathogens, explained Dr. AuBuchon, who is also a professor of hematology at the University of Washington, Seattle.

Dr. AuBuchon walked the committee through procedures designed to flag donors for PRT platelet apheresis, and to ensure these donations receive the intended PRT treatment. Platelets were chosen for this variance request, he explained, because demand outstrips supply. “We are all spending additional time and resources in recruiting a new framework and demographic, and it is exceedingly difficult to keep enough donors coming through the door,” he said. “Our platelet utilization climbs continually – it’s up 15% in the last 4 years.”

Committee members circled around the idea that all risk can’t be eliminated, even with the highly effective PRT technology. But the risk is exceedingly low, said committee chair Richard Kaufman, MD, medical director of the adult transfusion service at Brigham and Women’s Hospital, Boston. “It’s not possible to get rid of the window. We can kind of hammer down the risk by shrinking down the window by using incredibly sensitive tests. But that risk continues to exist. Pathogen reduction can take care of that residual risk…. So what’s left is really quite a low risk,” Dr. Kaufman said.

Susan Stramer, PhD, vice president of scientific affairs for the American Red Cross, concurred, noting that pathogen reduction techniques are already in use for many other blood products, particularly within the plasma industry.

Wrapping up, Dr. Kaufman asked individual committee members to summarize their position on the variance request, though the FDA had not placed a voting question before the committee. Consensus in the room was that this real-world examination of PRT could point to a path to expanding the donor pool while maintaining patient safety – a concern all agreed was paramount.

The FDA usually follows the recommendations of its committees.

The Food and Drug Administration is planning a pilot study of a new HIV risk questionnaire, as part of a comprehensive and ongoing evaluation of its blood donation policies for men who have sex with men (MSM).

At a meeting of the FDA’s Blood Products Advisory Committee, the agency shared the content of the 5-item questionnaire and reviewed the proposed study design with committee members, who were asked to comment – but not vote – on the best path forward for MSM donation policies.

The FDA is “committed to ongoing evaluation of the MSM deferral policy” and remains open to adjusting the policy based on the best available scientific evidence, said Barbee Whitaker, PhD, a lead scientist in the agency’s Office of Emerging and Transfusion Transmitted Disease

After recruiting 2,000 men who have had sex with men at least once during the past 3 months, the study will aim to identify individuals who have very recently become HIV infected, in order to assess the discriminant function of the set of behavioral questions that are proposed in the questionnaire.

The crux of the problem currently, noted Dr. Whitaker, is identifying those individuals who are very recently infected with HIV. Nucleic acid testing has tightened the window of undetectability considerably, but the current 12-month deferral window after men have had sexual contact with other men is designed to ensure safety of the blood supply.

Social justice concerns have been raised about the blanket deferral, said Dr. Whitaker; the behavioral questions in the pilot study will ask about the number of different sexual partners men have had within the past 1, 3, and 12 months and ask about the type of sexual contact (oral sex, or anal penetrative or receptive intercourse). The questionnaire also asks about sex with a partner known to be HIV positive, condom use, and use of pre-exposure prophylaxis (PrEP).

The FDA will ask for proposals to conduct the study with an eye to having sites in such cities as Washington, Atlanta, and Miami, which have high incidences of HIV, to improve chances of early detection.

The behavioral questionnaire is not seen as an immediate replacement for the 12-month deferral policy, the FDA made clear in its briefing documents and in discussion with the committee. Instead, its utility will be in the information gleaned from the pilot study and a follow-on that may include several hundred thousand individuals. These data should provide “population-based evidence upon which to base regulatory decisions to ensure blood safety,” she said.

 

 

Donation policies outside the United States

Whether a change in blood donation deferral policies for MSM would be a shortened window or a move toward a behavioral questionnaire is currently not known. Globally, a variety of practices are used for blood screening, said Mindy Goldman, MD, medical director of Canadian Blood Services, who reviewed international perspectives on blood donation for MSM.

“There’s no general consensus on donation deferrals internationally,” she said. Factors influencing policy can include epidemiology, risk analysis, modeling, and history of response to threats in the past.

However, “there’s basically a couple of main approaches” to handling deferrals for MSM, Dr. Goldman said. One is time-based deferral – the strategy used in the United States, as well as Canada, the United Kingdom, Japan, and Australia.

Japan and the U.K. have recently moved to 3-month deferral periods, a figure arrived at by doubling the window period for nucleic acid testing for HIV, roughly, Dr. Goldman said. Early data from the U.K. experience has not shown an increase in HIV rates among donors, or an increase in NAT-only positive donors, she said. An application to move from a 12-month to a 3-month deferral period is pending in Canada.

A strong advantage of time-based deferral as a risk management strategy, Dr. Goldman said, is standardization. “For us, standardization is close to godliness.”

However, she added, “another major limitation is that you’re still deferring all sexually active MSM, including those who are in a stable monogamous relationship from donating. From a justice perspective for the lowest risk population of MSM – they are still being deferred using this type of approach.”

Some nations, such as Spain and Italy, use individual risk assessment via physician-led interviews. These approaches are often not standardized. “There’s no national uniform questionnaire, so there’s less standardization, and more variability between blood centers,” Dr. Goldman said. “So you wind up trying to compare apples with oranges.”

This means the results are harder to evaluate on a national level. However, there appears to be higher residual risk, with HIV rates among first-time donors approaching those of the general population, Dr. Goldman said.

Another strategy, used in France, is a test-retest model, where blood from first-time MSM that initially tests negative for HIV is held until the individual returns for re-testing or an additional donation, with a second negative test. This approach increases operational complexity and cost, noted Dr. Goldman, and because of the short shelf life of platelets, it’s not practical for this blood component.

In general questioning and discussion after this and other background presentations, the committee could agree on one point: this isn’t an easy question.

“I’m increasingly struck by how difficult this problem is,” said committee member Roger Lewis, MD, PhD, professor at the University of California, Los Angeles, and chair of the department of emergency medicine at Harbor-UCLA Medical Center. Regarding just the problem of completing the pilot study, Dr. Lewis commented, “It sounds like it’s going to be impossible to get the data that directly answers the questions.”

Peter Marx, MD, PhD, who directs the FDA’s Center for Biologics Evaluation and Research (CBER), which oversees blood products safety, joined the discussion to acknowledge the difficulty, but underscore the social importance of a careful examination of the current MSM donation policy.

“We understand the issues here…. With all due respect to our European colleagues, there’s not enough data. That’s the point of this study; we also know that the U.S. has a very different epidemiology of HIV than the U.K. and a lot of other places,” Dr. Marx said. “The pilot study is a way to get some data where we might be able to get away from a time-based deferral. The LGBT community finds any time-based deferral discriminatory.”

 

 

Pathogen reduction technology

The committee heard a proposal for a completely different strategy during its afternoon session: pathogen reduction technology (PRT) holds promise to achieve virtual elimination of HIV and other pathogens from donated blood products.

The FDA is reviewing a variance request from the nonprofit blood donation organization Bloodworks Northwest organization to use PRT for apheresis platelet donations from MSM who would otherwise be deferred because of sexual activity within the 12-month deferral window.

James AuBuchon, MD, president of Bloodworks Northwest, explained that his organization takes in about 225,000 donations annually. The variance sought would use the FDA-approved INTERCEPT device to achieve pathogen reduction for donations that meet all requirements except the MSM deferral, and that would still undergo all relevant transfusion transmitted infection testing.

The INTERCEPT device uses amotosalen, which intercalates with DNA and RNA, inactivating it after exposure to ultraviolet A light. Amotosalen is then removed from the blood product before administration. The pathogen reduction activity doesn’t interfere with platelets or plasma, and is active against a wide range of viruses, bacteria, and fungal pathogens, explained Dr. AuBuchon, who is also a professor of hematology at the University of Washington, Seattle.

Dr. AuBuchon walked the committee through procedures designed to flag donors for PRT platelet apheresis, and to ensure these donations receive the intended PRT treatment. Platelets were chosen for this variance request, he explained, because demand outstrips supply. “We are all spending additional time and resources in recruiting a new framework and demographic, and it is exceedingly difficult to keep enough donors coming through the door,” he said. “Our platelet utilization climbs continually – it’s up 15% in the last 4 years.”

Committee members circled around the idea that all risk can’t be eliminated, even with the highly effective PRT technology. But the risk is exceedingly low, said committee chair Richard Kaufman, MD, medical director of the adult transfusion service at Brigham and Women’s Hospital, Boston. “It’s not possible to get rid of the window. We can kind of hammer down the risk by shrinking down the window by using incredibly sensitive tests. But that risk continues to exist. Pathogen reduction can take care of that residual risk…. So what’s left is really quite a low risk,” Dr. Kaufman said.

Susan Stramer, PhD, vice president of scientific affairs for the American Red Cross, concurred, noting that pathogen reduction techniques are already in use for many other blood products, particularly within the plasma industry.

Wrapping up, Dr. Kaufman asked individual committee members to summarize their position on the variance request, though the FDA had not placed a voting question before the committee. Consensus in the room was that this real-world examination of PRT could point to a path to expanding the donor pool while maintaining patient safety – a concern all agreed was paramount.

The FDA usually follows the recommendations of its committees.

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