Your patient’s medication label lacks human safety information: What now?

Nearly 9 in 10 U.S. women take a medication at some point in their pregnancy, with approximately 50% of women taking at least one prescription medication.¹ These medications may be prescribed without the benefit of knowledge gained through clinical trials. Knowledge is gained after market, often after multiple years, and potentially following widespread use. The situation is similar for vaccines, as was recently seen with the SARS-CoV2 pandemic. Early in the pandemic, evidence emerged that pregnancy increased the risk for severe illness from COVID-19, yet pregnant people and their providers were forced to make a difficult decision of risk/benefit with little data to guide them.

The FDA product label provides a summary and narrative of animal and human safety studies relating to pregnancy. But what if that label contains little to no information, or reports studies with conflicting results? Perhaps the product is new on the market or is infrequently used during pregnancy. Regardless, health care providers and pregnant patients still need to make decisions about medication use. The following list outlines information that can be found, and strategies to support providers and patients in making informed choices for a treatment plan.


Taking stock of the available information:

• If possible, connect with the specialist who prescribed the patient’s medication in question. They may have already assembled information regarding use of that medication in pregnancy.
• The sponsor may have published useful information from the phase 3 trials, including the outcomes of enrolled patients who inadvertently became pregnant.
• Review the animal data in the product label. Regulators require the careful selection of animal models, and this data can present a source of adjunct information regarding the medication’s effects on pregnancy, reproduction, and development. Negative results can be as revealing as positive results.
• Pharmacologic data in the label can also be informative. Although most labels have pharmacologic data based on trials in healthy nonpregnant individuals, understanding pregnancy physiology and the patient’s preexisting or pregnancy-specific condition(s) can provide insights.² Close patient monitoring and follow-up are of key importance.
• Consider viable alternatives that may address the patient’s needs. There may be effective alternatives that have been better studied and shown to have low reproductive toxicity.
• Consider the risks to the patient as well as the developing fetus if the preexisting or pregnancy-specific condition is uncontrolled.
• Consult a teratogen specialist who can provide information to both patients and health care providers on the reproductive hazards or safety of many exposures, even those with limited data regarding use in pregnancy. For example, MotherToBaby provides a network of teratogen specialists.

Understanding perceptions of risk, decision-making, and strategies to support informed choices:

• Perceptions of risk: Each person perceives risk and benefit differently. The few studies that have attempted to investigate perception of teratogenic risk have found that many pregnant people overestimate the magnitude of teratogenic risk associated with a particular exposure.³ Alternatively, a medication’s benefit in controlling the maternal condition is often not considered sufficiently. Health care providers may have their own distorted perceptions of risk, even in the presence of evidence.
• Decision-making: Most teratogen data inherently involve uncertainty; it is rare to have completely nonconflicting data with which to make a decision. This makes decisions about whether or not to utilize a particular medication or other agent in pregnancy very difficult. For example, a patient would prefer to be told a black and white answer such as vaccines are either 100% safe or 100% harmful. However, no medical treatment is held to that standard of certainty. Even though it may be more comfortable to avoid an action and “just let things happen,” the lack of a decision is still a decision. The decision to not take medication may have risks inherent in not treating a condition and may result in adverse outcomes in the developing fetus. Lastly, presenting teratogen information often involves challenges in portraying and interpreting numerical risk. For example, when considering data presented in fraction format, patients and some health care providers may focus on the numerator or count of adverse events, while ignoring the magnitude of the denominator.
• Strategies: Health literacy “best practice” strategies are useful whether there is a lot of data or very little. These include the of use plain language and messages delivered in a clear and respectful voice, the use of visual aids, and the use effective teaching methods such as asking open-ended questions to assess understanding. Other strategies include using caution in framing information: for example, discussing a 1% increase in risk for a baby to have a medication-associated birth defect should also be presented as a 99% chance the medication will not cause a birth defect. Numeracy challenges can also be addressed by using natural numbers rather than fractions or percentages: for example, if there were 100 women in this room, one would have a baby with a birth defect after taking this medication in pregnancy, but 99 of these women would not.

In today’s medical world, shared decision-making is the preferred approach to choices. Communicating and appropriately utilizing information to make choices about medication safety in pregnancy are vital undertakings. An important provider responsibility is helping patients understand that science is built on evidence that amasses and changes over time and that it represents rich shades of gray rather than “black and white” options.

Contributing to evidence: A pregnancy exposure registry is a study that collects health information from women who take prescription medicines or vaccines when they are pregnant. Information is also collected on the neonate. This information is compared with women who have not taken medicine during pregnancy. Enrolling in a pregnancy exposure registry can help improve safety information for medication used during pregnancy and can be used to update drug labeling. Please consult the Food and Drug Administration listing below to learn if there is an ongoing registry for the patient’s medication in question. If there is and the patient is eligible, provide her with the information. If she is interested and willing, help her enroll. It’s a great step toward building the scientific evidence on medication safety in pregnancy.

For further information about health literacy, consult:

https://www.cdc.gov/pregnancy/meds/treatingfortwo/index.html

https://www.cdc.gov/ncbddd/birthdefects/index.html

https://mothertobaby.org

The MotherToBaby web page has hundreds of fact sheets written in a way that patients can understand, and available in English and Spanish. MotherToBaby coordinates research studies on specific agents. The toll-free number is 866-626-6847.

For a listing of pregnancy registries, consult:

https://www.fda.gov/science-research/womens-health-research/pregnancy-registries

Dr. Hardy is executive director, head of pharmacoepidemiology, Biohaven Pharmaceuticals. She serves as a member of Council for the Society for Birth Defects Research and Prevention (BDRP), represents the BDRP on the Coalition to Advance Maternal Therapeutics, and is a member of the North American Board for Amandla Development, South Africa. Dr. Conover is the director of Nebraska MotherToBaby. She is assistant professor at the Munroe Meyer Institute, University of Nebraska Medical Center.

References

1. Mitchell AA et al. Am J Obstet Gynecol. 2011;205(1):51:e1-e8.

2. Feghali M et al. Semin Perinatol 2015;39:512-9.

3. Conover EA, Polifka JE. Am J Med Genet Part C Semin Med Genet 2011;157:227-33.

Nearly 9 in 10 U.S. women take a medication at some point in their pregnancy, with approximately 50% of women taking at least one prescription medication.¹ These medications may be prescribed without the benefit of knowledge gained through clinical trials. Knowledge is gained after market, often after multiple years, and potentially following widespread use. The situation is similar for vaccines, as was recently seen with the SARS-CoV2 pandemic. Early in the pandemic, evidence emerged that pregnancy increased the risk for severe illness from COVID-19, yet pregnant people and their providers were forced to make a difficult decision of risk/benefit with little data to guide them.

The FDA product label provides a summary and narrative of animal and human safety studies relating to pregnancy. But what if that label contains little to no information, or reports studies with conflicting results? Perhaps the product is new on the market or is infrequently used during pregnancy. Regardless, health care providers and pregnant patients still need to make decisions about medication use. The following list outlines information that can be found, and strategies to support providers and patients in making informed choices for a treatment plan.


Taking stock of the available information:

• If possible, connect with the specialist who prescribed the patient’s medication in question. They may have already assembled information regarding use of that medication in pregnancy.
• The sponsor may have published useful information from the phase 3 trials, including the outcomes of enrolled patients who inadvertently became pregnant.
• Review the animal data in the product label. Regulators require the careful selection of animal models, and this data can present a source of adjunct information regarding the medication’s effects on pregnancy, reproduction, and development. Negative results can be as revealing as positive results.
• Pharmacologic data in the label can also be informative. Although most labels have pharmacologic data based on trials in healthy nonpregnant individuals, understanding pregnancy physiology and the patient’s preexisting or pregnancy-specific condition(s) can provide insights.² Close patient monitoring and follow-up are of key importance.
• Consider viable alternatives that may address the patient’s needs. There may be effective alternatives that have been better studied and shown to have low reproductive toxicity.
• Consider the risks to the patient as well as the developing fetus if the preexisting or pregnancy-specific condition is uncontrolled.
• Consult a teratogen specialist who can provide information to both patients and health care providers on the reproductive hazards or safety of many exposures, even those with limited data regarding use in pregnancy. For example, MotherToBaby provides a network of teratogen specialists.

Understanding perceptions of risk, decision-making, and strategies to support informed choices:

• Perceptions of risk: Each person perceives risk and benefit differently. The few studies that have attempted to investigate perception of teratogenic risk have found that many pregnant people overestimate the magnitude of teratogenic risk associated with a particular exposure.³ Alternatively, a medication’s benefit in controlling the maternal condition is often not considered sufficiently. Health care providers may have their own distorted perceptions of risk, even in the presence of evidence.
• Decision-making: Most teratogen data inherently involve uncertainty; it is rare to have completely nonconflicting data with which to make a decision. This makes decisions about whether or not to utilize a particular medication or other agent in pregnancy very difficult. For example, a patient would prefer to be told a black and white answer such as vaccines are either 100% safe or 100% harmful. However, no medical treatment is held to that standard of certainty. Even though it may be more comfortable to avoid an action and “just let things happen,” the lack of a decision is still a decision. The decision to not take medication may have risks inherent in not treating a condition and may result in adverse outcomes in the developing fetus. Lastly, presenting teratogen information often involves challenges in portraying and interpreting numerical risk. For example, when considering data presented in fraction format, patients and some health care providers may focus on the numerator or count of adverse events, while ignoring the magnitude of the denominator.
• Strategies: Health literacy “best practice” strategies are useful whether there is a lot of data or very little. These include the of use plain language and messages delivered in a clear and respectful voice, the use of visual aids, and the use effective teaching methods such as asking open-ended questions to assess understanding. Other strategies include using caution in framing information: for example, discussing a 1% increase in risk for a baby to have a medication-associated birth defect should also be presented as a 99% chance the medication will not cause a birth defect. Numeracy challenges can also be addressed by using natural numbers rather than fractions or percentages: for example, if there were 100 women in this room, one would have a baby with a birth defect after taking this medication in pregnancy, but 99 of these women would not.

In today’s medical world, shared decision-making is the preferred approach to choices. Communicating and appropriately utilizing information to make choices about medication safety in pregnancy are vital undertakings. An important provider responsibility is helping patients understand that science is built on evidence that amasses and changes over time and that it represents rich shades of gray rather than “black and white” options.

Contributing to evidence: A pregnancy exposure registry is a study that collects health information from women who take prescription medicines or vaccines when they are pregnant. Information is also collected on the neonate. This information is compared with women who have not taken medicine during pregnancy. Enrolling in a pregnancy exposure registry can help improve safety information for medication used during pregnancy and can be used to update drug labeling. Please consult the Food and Drug Administration listing below to learn if there is an ongoing registry for the patient’s medication in question. If there is and the patient is eligible, provide her with the information. If she is interested and willing, help her enroll. It’s a great step toward building the scientific evidence on medication safety in pregnancy.

For further information about health literacy, consult:

https://www.cdc.gov/pregnancy/meds/treatingfortwo/index.html

https://www.cdc.gov/ncbddd/birthdefects/index.html

https://mothertobaby.org

The MotherToBaby web page has hundreds of fact sheets written in a way that patients can understand, and available in English and Spanish. MotherToBaby coordinates research studies on specific agents. The toll-free number is 866-626-6847.

For a listing of pregnancy registries, consult:

https://www.fda.gov/science-research/womens-health-research/pregnancy-registries

Dr. Hardy is executive director, head of pharmacoepidemiology, Biohaven Pharmaceuticals. She serves as a member of Council for the Society for Birth Defects Research and Prevention (BDRP), represents the BDRP on the Coalition to Advance Maternal Therapeutics, and is a member of the North American Board for Amandla Development, South Africa. Dr. Conover is the director of Nebraska MotherToBaby. She is assistant professor at the Munroe Meyer Institute, University of Nebraska Medical Center.

References

1. Mitchell AA et al. Am J Obstet Gynecol. 2011;205(1):51:e1-e8.

2. Feghali M et al. Semin Perinatol 2015;39:512-9.

3. Conover EA, Polifka JE. Am J Med Genet Part C Semin Med Genet 2011;157:227-33.

Nearly 9 in 10 U.S. women take a medication at some point in their pregnancy, with approximately 50% of women taking at least one prescription medication.¹ These medications may be prescribed without the benefit of knowledge gained through clinical trials. Knowledge is gained after market, often after multiple years, and potentially following widespread use. The situation is similar for vaccines, as was recently seen with the SARS-CoV2 pandemic. Early in the pandemic, evidence emerged that pregnancy increased the risk for severe illness from COVID-19, yet pregnant people and their providers were forced to make a difficult decision of risk/benefit with little data to guide them.

The FDA product label provides a summary and narrative of animal and human safety studies relating to pregnancy. But what if that label contains little to no information, or reports studies with conflicting results? Perhaps the product is new on the market or is infrequently used during pregnancy. Regardless, health care providers and pregnant patients still need to make decisions about medication use. The following list outlines information that can be found, and strategies to support providers and patients in making informed choices for a treatment plan.


Taking stock of the available information:

• If possible, connect with the specialist who prescribed the patient’s medication in question. They may have already assembled information regarding use of that medication in pregnancy.
• The sponsor may have published useful information from the phase 3 trials, including the outcomes of enrolled patients who inadvertently became pregnant.
• Review the animal data in the product label. Regulators require the careful selection of animal models, and this data can present a source of adjunct information regarding the medication’s effects on pregnancy, reproduction, and development. Negative results can be as revealing as positive results.
• Pharmacologic data in the label can also be informative. Although most labels have pharmacologic data based on trials in healthy nonpregnant individuals, understanding pregnancy physiology and the patient’s preexisting or pregnancy-specific condition(s) can provide insights.² Close patient monitoring and follow-up are of key importance.
• Consider viable alternatives that may address the patient’s needs. There may be effective alternatives that have been better studied and shown to have low reproductive toxicity.
• Consider the risks to the patient as well as the developing fetus if the preexisting or pregnancy-specific condition is uncontrolled.
• Consult a teratogen specialist who can provide information to both patients and health care providers on the reproductive hazards or safety of many exposures, even those with limited data regarding use in pregnancy. For example, MotherToBaby provides a network of teratogen specialists.

Understanding perceptions of risk, decision-making, and strategies to support informed choices:

• Perceptions of risk: Each person perceives risk and benefit differently. The few studies that have attempted to investigate perception of teratogenic risk have found that many pregnant people overestimate the magnitude of teratogenic risk associated with a particular exposure.³ Alternatively, a medication’s benefit in controlling the maternal condition is often not considered sufficiently. Health care providers may have their own distorted perceptions of risk, even in the presence of evidence.
• Decision-making: Most teratogen data inherently involve uncertainty; it is rare to have completely nonconflicting data with which to make a decision. This makes decisions about whether or not to utilize a particular medication or other agent in pregnancy very difficult. For example, a patient would prefer to be told a black and white answer such as vaccines are either 100% safe or 100% harmful. However, no medical treatment is held to that standard of certainty. Even though it may be more comfortable to avoid an action and “just let things happen,” the lack of a decision is still a decision. The decision to not take medication may have risks inherent in not treating a condition and may result in adverse outcomes in the developing fetus. Lastly, presenting teratogen information often involves challenges in portraying and interpreting numerical risk. For example, when considering data presented in fraction format, patients and some health care providers may focus on the numerator or count of adverse events, while ignoring the magnitude of the denominator.
• Strategies: Health literacy “best practice” strategies are useful whether there is a lot of data or very little. These include the of use plain language and messages delivered in a clear and respectful voice, the use of visual aids, and the use effective teaching methods such as asking open-ended questions to assess understanding. Other strategies include using caution in framing information: for example, discussing a 1% increase in risk for a baby to have a medication-associated birth defect should also be presented as a 99% chance the medication will not cause a birth defect. Numeracy challenges can also be addressed by using natural numbers rather than fractions or percentages: for example, if there were 100 women in this room, one would have a baby with a birth defect after taking this medication in pregnancy, but 99 of these women would not.

In today’s medical world, shared decision-making is the preferred approach to choices. Communicating and appropriately utilizing information to make choices about medication safety in pregnancy are vital undertakings. An important provider responsibility is helping patients understand that science is built on evidence that amasses and changes over time and that it represents rich shades of gray rather than “black and white” options.

Contributing to evidence: A pregnancy exposure registry is a study that collects health information from women who take prescription medicines or vaccines when they are pregnant. Information is also collected on the neonate. This information is compared with women who have not taken medicine during pregnancy. Enrolling in a pregnancy exposure registry can help improve safety information for medication used during pregnancy and can be used to update drug labeling. Please consult the Food and Drug Administration listing below to learn if there is an ongoing registry for the patient’s medication in question. If there is and the patient is eligible, provide her with the information. If she is interested and willing, help her enroll. It’s a great step toward building the scientific evidence on medication safety in pregnancy.

For further information about health literacy, consult:

https://www.cdc.gov/pregnancy/meds/treatingfortwo/index.html

https://www.cdc.gov/ncbddd/birthdefects/index.html

https://mothertobaby.org

The MotherToBaby web page has hundreds of fact sheets written in a way that patients can understand, and available in English and Spanish. MotherToBaby coordinates research studies on specific agents. The toll-free number is 866-626-6847.

For a listing of pregnancy registries, consult:

https://www.fda.gov/science-research/womens-health-research/pregnancy-registries

Dr. Hardy is executive director, head of pharmacoepidemiology, Biohaven Pharmaceuticals. She serves as a member of Council for the Society for Birth Defects Research and Prevention (BDRP), represents the BDRP on the Coalition to Advance Maternal Therapeutics, and is a member of the North American Board for Amandla Development, South Africa. Dr. Conover is the director of Nebraska MotherToBaby. She is assistant professor at the Munroe Meyer Institute, University of Nebraska Medical Center.

References

1. Mitchell AA et al. Am J Obstet Gynecol. 2011;205(1):51:e1-e8.

2. Feghali M et al. Semin Perinatol 2015;39:512-9.

3. Conover EA, Polifka JE. Am J Med Genet Part C Semin Med Genet 2011;157:227-33.