Pregnancy exposure registries confirmed useful in assessing product safety

BELLEVUE, WASH. – Registries that collect data on pregnant women’s exposures to medical products and outcomes are contributing to product safety in this population, as intended, suggests an exploratory review conducted by the Food and Drug Administration.

But they do have some shortcomings.

"Currently, pregnancy registries are the most common type of postapproval study in pregnant women that are either required or requested by FDA from pharmaceutical companies," first author Dr. Leyla Sahin, an FDA medical officer on the Pediatric and Maternal Health Staff of the Maternal Health Team, in Harvard, Mass., explained at the annual meeting of the Teratology Society.

"However, recently, the Agency has had a concern that pregnancy registries often fail to provide useful information, and usually this is due to low enrollment. ... Companies will come back to the agency a few years later and say, ‘We have been unable to recruit enough patients into our study, so please release us from our postmarketing requirement,’" she added. So, FDA sought to discover "what characteristics determine a successful registry so that we could then provide guidance to industry."

Dr. Sahin and her colleagues studied 38 pregnancy registries listed on the FDA’s Pregnancy Registry website that tracked 59 medical products–drugs, biologics, or vaccines.

Findings showed that for 12% of the products, registry results led to changes in the labeling for that product, as in the cases of the Bupropion Pregnancy Registry and the Pregnancy Registry for Varicella Zoster Virus–Containing Vaccines.

Similarly, for 12% of products, registry results had informed practice guidelines, as in the cases of the Pregnancy Registry for Gardasil and the Antiretroviral Pregnancy Registry.

Of the seven products that had registry data added to their approved labeling, 86% also had their results published in a peer-reviewed journal. Of the 59 products overall, 37% had interim or final registry results published in a peer-reviewed journal.

But the registries did struggle with enrollment. Overall, 17% had been closed for feasibility reasons, meaning they had not been able to enroll sufficient patients. And of the 22 products that had a target enrollment stated in the pregnancy registry protocol, just 14% had achieved that enrollment.

Additionally, for the 21 products having registries that provided information about loss to follow-up and that had at least moderate enrollment, the median rate of loss to follow-up of enrolled women was 23.4%.

"What we took away from this review is that basically, pregnancy registries have contributed safety data to labeling and to clinical guidelines, and have been published in the medical literature. However, there is room for improvement in terms of doing a better job with recruitment and enrollment into these studies," commented Dr. Sahin.

"Unfortunately, we are not able to draw conclusions from this review on the characteristics that result in a successful registry because of limitations" such as the lack of inclusion of disease-based registries, the review’s exploratory nature (as opposed to a comprehensive one), and no assessment of factors such as registries’ data quality, resources used, and expertise.

"Pregnancy registries by themselves may not be sufficient to collect data that inform product labeling, so we need to explore complementary study methods to do this," Dr. Sahin maintained. To address that and related issues, the agency held a public meeting in May.

"The key messages that we obtained from experts and stakeholders at the meeting are that pregnancy registries continue to have an important role in data collection, but that improvements are needed in the methodology and conduct," she reported. Participants suggested, for example, using a combination of approaches that include complementary study designs to overcome the limitations of individual study designs; developing personal connections with both patients and health care providers, using "champions" enthusiastic about registries to boost recruitment and enrollment; and harnessing electronic medical records to improve data collection.

"The next steps now for the agency are to review the transcripts from the public meeting, and then to develop future policies in terms of what to request as postmarketing requirements from companies. And then developing policy, and integrating what we got from the public meeting into revising the pregnancy registry guidance for industry," Dr. Sahin said. Plans additionally include "working on developing further communication and outreach, looking at the FDA Pregnancy Registry web page, and how that can be specifically designed to meet the needs of all stakeholders, and then also continuing to explore opportunities for collaboration through public-private partnership."

In an interview, session cochair Marlissa Campbell, Ph.D., said, "In general, I think FDA’s purpose in reviewing the registries in order to help manufacturers improve the process to obtain useful data is good, and potentially very important. I had not known that attaining enrollment goals for these registries was proving to be so difficult."

The feedback from the public meeting may go a long way toward improving data collection in these registries, she agreed. "Getting input from clinicians, as well as manufacturers and other registry programs should help the agency formulate next steps." Dr. Campbell is staff toxicologist with the Office of Environmental Health Hazard Assessment (OEHHA), California Environmental Protection Agency, Sacramento.

Dr. Sahin disclosed no relevant conflicts of interest.

Do you tell your pregnant patients about pregnancy exposure registries and suggest that they sign up? Take our Quick Poll on the ObGyn News homepage.

BELLEVUE, WASH. – Registries that collect data on pregnant women’s exposures to medical products and outcomes are contributing to product safety in this population, as intended, suggests an exploratory review conducted by the Food and Drug Administration.

But they do have some shortcomings.

"Currently, pregnancy registries are the most common type of postapproval study in pregnant women that are either required or requested by FDA from pharmaceutical companies," first author Dr. Leyla Sahin, an FDA medical officer on the Pediatric and Maternal Health Staff of the Maternal Health Team, in Harvard, Mass., explained at the annual meeting of the Teratology Society.

"However, recently, the Agency has had a concern that pregnancy registries often fail to provide useful information, and usually this is due to low enrollment. ... Companies will come back to the agency a few years later and say, ‘We have been unable to recruit enough patients into our study, so please release us from our postmarketing requirement,’" she added. So, FDA sought to discover "what characteristics determine a successful registry so that we could then provide guidance to industry."

Dr. Sahin and her colleagues studied 38 pregnancy registries listed on the FDA’s Pregnancy Registry website that tracked 59 medical products–drugs, biologics, or vaccines.

Findings showed that for 12% of the products, registry results led to changes in the labeling for that product, as in the cases of the Bupropion Pregnancy Registry and the Pregnancy Registry for Varicella Zoster Virus–Containing Vaccines.

Similarly, for 12% of products, registry results had informed practice guidelines, as in the cases of the Pregnancy Registry for Gardasil and the Antiretroviral Pregnancy Registry.

Of the seven products that had registry data added to their approved labeling, 86% also had their results published in a peer-reviewed journal. Of the 59 products overall, 37% had interim or final registry results published in a peer-reviewed journal.

But the registries did struggle with enrollment. Overall, 17% had been closed for feasibility reasons, meaning they had not been able to enroll sufficient patients. And of the 22 products that had a target enrollment stated in the pregnancy registry protocol, just 14% had achieved that enrollment.

Additionally, for the 21 products having registries that provided information about loss to follow-up and that had at least moderate enrollment, the median rate of loss to follow-up of enrolled women was 23.4%.

"What we took away from this review is that basically, pregnancy registries have contributed safety data to labeling and to clinical guidelines, and have been published in the medical literature. However, there is room for improvement in terms of doing a better job with recruitment and enrollment into these studies," commented Dr. Sahin.

"Unfortunately, we are not able to draw conclusions from this review on the characteristics that result in a successful registry because of limitations" such as the lack of inclusion of disease-based registries, the review’s exploratory nature (as opposed to a comprehensive one), and no assessment of factors such as registries’ data quality, resources used, and expertise.

"Pregnancy registries by themselves may not be sufficient to collect data that inform product labeling, so we need to explore complementary study methods to do this," Dr. Sahin maintained. To address that and related issues, the agency held a public meeting in May.

"The key messages that we obtained from experts and stakeholders at the meeting are that pregnancy registries continue to have an important role in data collection, but that improvements are needed in the methodology and conduct," she reported. Participants suggested, for example, using a combination of approaches that include complementary study designs to overcome the limitations of individual study designs; developing personal connections with both patients and health care providers, using "champions" enthusiastic about registries to boost recruitment and enrollment; and harnessing electronic medical records to improve data collection.

"The next steps now for the agency are to review the transcripts from the public meeting, and then to develop future policies in terms of what to request as postmarketing requirements from companies. And then developing policy, and integrating what we got from the public meeting into revising the pregnancy registry guidance for industry," Dr. Sahin said. Plans additionally include "working on developing further communication and outreach, looking at the FDA Pregnancy Registry web page, and how that can be specifically designed to meet the needs of all stakeholders, and then also continuing to explore opportunities for collaboration through public-private partnership."

In an interview, session cochair Marlissa Campbell, Ph.D., said, "In general, I think FDA’s purpose in reviewing the registries in order to help manufacturers improve the process to obtain useful data is good, and potentially very important. I had not known that attaining enrollment goals for these registries was proving to be so difficult."

The feedback from the public meeting may go a long way toward improving data collection in these registries, she agreed. "Getting input from clinicians, as well as manufacturers and other registry programs should help the agency formulate next steps." Dr. Campbell is staff toxicologist with the Office of Environmental Health Hazard Assessment (OEHHA), California Environmental Protection Agency, Sacramento.

Dr. Sahin disclosed no relevant conflicts of interest.

Do you tell your pregnant patients about pregnancy exposure registries and suggest that they sign up? Take our Quick Poll on the ObGyn News homepage.

BELLEVUE, WASH. – Registries that collect data on pregnant women’s exposures to medical products and outcomes are contributing to product safety in this population, as intended, suggests an exploratory review conducted by the Food and Drug Administration.

But they do have some shortcomings.

"Currently, pregnancy registries are the most common type of postapproval study in pregnant women that are either required or requested by FDA from pharmaceutical companies," first author Dr. Leyla Sahin, an FDA medical officer on the Pediatric and Maternal Health Staff of the Maternal Health Team, in Harvard, Mass., explained at the annual meeting of the Teratology Society.

"However, recently, the Agency has had a concern that pregnancy registries often fail to provide useful information, and usually this is due to low enrollment. ... Companies will come back to the agency a few years later and say, ‘We have been unable to recruit enough patients into our study, so please release us from our postmarketing requirement,’" she added. So, FDA sought to discover "what characteristics determine a successful registry so that we could then provide guidance to industry."

Dr. Sahin and her colleagues studied 38 pregnancy registries listed on the FDA’s Pregnancy Registry website that tracked 59 medical products–drugs, biologics, or vaccines.

Findings showed that for 12% of the products, registry results led to changes in the labeling for that product, as in the cases of the Bupropion Pregnancy Registry and the Pregnancy Registry for Varicella Zoster Virus–Containing Vaccines.

Similarly, for 12% of products, registry results had informed practice guidelines, as in the cases of the Pregnancy Registry for Gardasil and the Antiretroviral Pregnancy Registry.

Of the seven products that had registry data added to their approved labeling, 86% also had their results published in a peer-reviewed journal. Of the 59 products overall, 37% had interim or final registry results published in a peer-reviewed journal.

But the registries did struggle with enrollment. Overall, 17% had been closed for feasibility reasons, meaning they had not been able to enroll sufficient patients. And of the 22 products that had a target enrollment stated in the pregnancy registry protocol, just 14% had achieved that enrollment.

Additionally, for the 21 products having registries that provided information about loss to follow-up and that had at least moderate enrollment, the median rate of loss to follow-up of enrolled women was 23.4%.

"What we took away from this review is that basically, pregnancy registries have contributed safety data to labeling and to clinical guidelines, and have been published in the medical literature. However, there is room for improvement in terms of doing a better job with recruitment and enrollment into these studies," commented Dr. Sahin.

"Unfortunately, we are not able to draw conclusions from this review on the characteristics that result in a successful registry because of limitations" such as the lack of inclusion of disease-based registries, the review’s exploratory nature (as opposed to a comprehensive one), and no assessment of factors such as registries’ data quality, resources used, and expertise.

"Pregnancy registries by themselves may not be sufficient to collect data that inform product labeling, so we need to explore complementary study methods to do this," Dr. Sahin maintained. To address that and related issues, the agency held a public meeting in May.

"The key messages that we obtained from experts and stakeholders at the meeting are that pregnancy registries continue to have an important role in data collection, but that improvements are needed in the methodology and conduct," she reported. Participants suggested, for example, using a combination of approaches that include complementary study designs to overcome the limitations of individual study designs; developing personal connections with both patients and health care providers, using "champions" enthusiastic about registries to boost recruitment and enrollment; and harnessing electronic medical records to improve data collection.

"The next steps now for the agency are to review the transcripts from the public meeting, and then to develop future policies in terms of what to request as postmarketing requirements from companies. And then developing policy, and integrating what we got from the public meeting into revising the pregnancy registry guidance for industry," Dr. Sahin said. Plans additionally include "working on developing further communication and outreach, looking at the FDA Pregnancy Registry web page, and how that can be specifically designed to meet the needs of all stakeholders, and then also continuing to explore opportunities for collaboration through public-private partnership."

In an interview, session cochair Marlissa Campbell, Ph.D., said, "In general, I think FDA’s purpose in reviewing the registries in order to help manufacturers improve the process to obtain useful data is good, and potentially very important. I had not known that attaining enrollment goals for these registries was proving to be so difficult."

The feedback from the public meeting may go a long way toward improving data collection in these registries, she agreed. "Getting input from clinicians, as well as manufacturers and other registry programs should help the agency formulate next steps." Dr. Campbell is staff toxicologist with the Office of Environmental Health Hazard Assessment (OEHHA), California Environmental Protection Agency, Sacramento.

Dr. Sahin disclosed no relevant conflicts of interest.

Do you tell your pregnant patients about pregnancy exposure registries and suggest that they sign up? Take our Quick Poll on the ObGyn News homepage.