List of Recommendations from the Task Force on Research Specific to Pregnant Women and Lactating Women (PRGLAC)

This information comes from the PRGLAC Report to the HHS Secretary and Congress, September 2018 (PDF 7 MB).

The Task Force submits the following recommendations to the Secretary of HHS regarding research and the development of safe and effective therapies specific to pregnant women and lactating women based on information gleaned during four meetings and a public comment period. The Task Force developed these recommendations in open, public sessions and voted on each recommendation at the May 2018 meeting.

The central theme of all recommendations is the need to alter cultural assumptions that have significantly limited scientific knowledge of therapeutic safety, effectiveness, and dosing for pregnant and lactating women. It is critical to facilitate and augment research on therapies for these populations.

Include and integrate pregnant women and lactating women in the clinical research agenda
- Remove pregnant women as an example of a vulnerable population in the Common Rule
- The Food and Drug Administration (FDA) should harmonize with the Common Rule and remove pregnant women as a vulnerable population
- The Department of Health and Human Services (HHS) should develop guidance to facilitate the conduct of research in pregnant women and lactating women
Increase the quantity, quality, and timeliness of research on safety and efficacy of therapeutic products used by pregnant women and lactating women
- Provide additional resources and funding for research to obtain clinically meaningful and relevant data for specific and co-existing conditions in pregnant women and lactating women, including but not limited to:
  - Develop preclinical models
  - Expand basic science research to inform drug development
  - Develop new tools and methods to assay therapeutic products, such as those that utilize small volumes and are sensitive to detect minute quantities in human milk
  - Develop new tools to assess pharmacodynamic response in pregnant women, lactating women, and children
  - Fund clinically relevant research and studies to inform therapeutic product use in pregnant women and lactating women
  - Design trials to capture long-term maternal, obstetric, and child outcomes
- Utilize longer award periods by government funders (beyond the typical 5-year award), when needed, for study design and data collection
Expand the workforce of clinicians and research investigators with expertise in obstetric and lactation pharmacology and therapeutics
- Develop and support training and career development opportunities in obstetric and lactation pharmacology and therapeutics for both clinical and basic science
- Develop mentors in obstetric and lactation pharmacology and therapeutics for both clinical and basic science
- Increase the knowledge and engagement of health care providers regarding obstetric and lactation pharmacology and therapeutics
Remove regulatory barriers to research in pregnant women
- Modify subpart B of the Common Rule
  - Change 46.204(e) in subpart B to maternal consent alone
    - Given the recognized autonomy of a pregnant woman, the evolution of family structure, that for a child only one parental signature is required for research to benefit the child and to align with parental consent for pediatrics
  - Add in the option of “Minor increase over minimal risk” from subpart D to 36.046
Create a public awareness campaign to engage the public and health care providers in research on pregnant women and lactating women
- Highlight the importance of research on therapeutic products in pregnant women and lactating women, including the impact of not taking the medication during pregnancy and lactation as well as the impact of not breastfeeding on mother and child
- Engage stakeholders such as Department of Health and Human Services (HHS), professional societies, industry, advocacy groups, and public and global partners
Develop and implement evidence-based communication strategies with health care providers on information relevant to research on pregnant women and lactating women
- Increase the knowledge of health care providers regarding obstetric and lactation therapeutics and research needs
- Increase the engagement of health care providers to disseminate information from research findings to their patients
- Increase the engagement of health care providers to discuss participation in clinical trials, research, and registries
- Develop appropriate strategies for sharing and interpreting research findings and risk
Reduce liability to facilitate an evidence base for new therapeutic products that may be used by women who are, or may become, pregnant and by lactating women
- Implement a liability-mitigation strategy for conducting research and evaluating new therapeutic products in pregnant women and lactating women
  - Using the Vaccine Injury Compensation Program (VICP) as a model, however include mitigation whether or not the therapeutic product achieves marketing approval
- If liability mitigation is insufficient, consider implementing a targeted incentive program and/or strengthening FDA authority to require clinically relevant data (such as pharmacologic and clinical data) on pregnant women and lactating women to inform dosing and safety
Develop separate programs to study therapeutic products used off-patent in pregnant women and lactating women using the NIH BPCA as a model
- Provide specific funding
- Develop separate prioritization processes for therapies and/or conditions in pregnant women and lactating women
Develop programs to drive discovery and development of therapeutics and new therapeutic products for conditions specific to pregnant women and lactating women
- Create separate prioritization processes for pregnant women and lactating women
  - Unmet need examples in lactation: low milk supply, mastitis
  - Unmet need examples in pregnancy: preterm labor, hyperemesis
- Consider a Biomedical Advanced Research and Development Authority (BARDA)-like model and the NIH vaccine model that takes clinical development up to phase II
Implement a proactive approach to protocol development and study design to include pregnant women and lactating women in clinical research
- Investigators/sponsors must specifically justify exclusion in study design
- Ensure studies are designed to capture the time dependency of physiologic changes in pregnancy and lactation
- Develop a systematic plan on how data for pregnant women and lactating women will be obtained in a timely fashion to include pharmacokinetics/pharmacodynamics and safety
- Develop guidance for institutional review boards and investigators about the inclusion of pregnant women and lactating women in research
- Develop a systematic plan for if a woman becomes pregnant in a study to include whether product should continue, if un-blinding is necessary, how to capture opportunistic information on pharmacology, clinical data, and pregnancy outcome information
Leverage established and support new infrastructures/collaborations to perform research in pregnant women and lactating women
- Provide financial support and incentives to established and develop new multicenter infrastructures that capitalize on standard of care procedures (opportunistic studies), innovative designs, and methodologies.
- Broaden focus of ongoing research networks to include research on therapeutic products in pregnant women and lactating women
- Encourage networks/collaborations to engage in public-private partnerships to facilitate research
Utilize and improve existing resources for data to inform the evidence and provide a foundation for research on pregnant women and lactating women
- Design health record systems to link mother and infant records
- Leverage large studies and databases including health systems, health plans, surveillance systems, electronic medical records, registries
- Use novel data resources
- Use innovative methods of data analytics
- Require common data elements to facilitate collaboration and use
Optimize registries for pregnancy and lactation
- Create a user-friendly website for registry listing
- Develop registry standards and common data elements that facilitate input of pertinent data with easy, transparent access to obtain information in real time
  - Include maternal, obstetric, and child outcomes, along with birth defects
- Facilitate access to data and transparency of information in registries
  - Use the ART registry as a model
- Develop disease/condition-focused registries
  - Move toward a single registry for all therapeutic products with input from stakeholders
The Department of Health and Human Services Secretary should consider exercising the authority provided in law to extend the PRGLAC Task Force when its charter expires in March 2019 (Extended March 13, 2019 – March 13, 2021)
Establish an Advisory Committee to monitor and report on implementation of recommendations, updating regulations, and guidance, as applicable, regarding the inclusion of pregnant women and lactating women in clinical research (Deferred)