Advancing Clinical Research with Pregnant and Lactating Populations Overcoming Real and Perceived Liability Risks (2024) / Chapter Skim
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6 Recommendations
6 Recommendations
Pages 179-206
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From page 179... ...
The first entails strategies that directly mitigate liability; the second is through minimizing potential harm to research participants and thereby reducing the grounds for liability; and the third aims to allay the concerns that dis courage researchers and sponsors from including pregnant and lactating women in clinical research which, as elaborated in Chapter 5, are factors that are weighed alongside the potential for liability These three strategies are interconnected, as mitigating liability and reducing potential harm will also improve and address perceptions of liability. The committee's nine recommendations attend to the interests and concerns of the multiple stakeholders and decision makers involved along the medical product development pathway.
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From page 180... ...
As exem plified throughout this report, the avoidance of clinical research with pregnant and lactating women has resulted in insufficient evidence on the safety, efficacy, and dosage of the medical products being used by pregnant and lactating women. FDA guidance on how to appropriately PREPUBLICATION COPY -- Uncorrected Proofs A02260_Advancing_Clinical_Research_CH06.indd 180 3/20/24 2:08 PM
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From page 181... ...
In regard to the timing of studies that include pregnant and lactating women, FDA may consider whether certain condi tions, such as the development of a treatment or vaccine in response to a pandemic, merits inclusion of pregnant and lactating women earlier in the product development pathway. However, the committee emphasizes that the approval of a medical product for the general population is not to be contingent on the completion of clinical studies in pregnant and lactating women.
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From page 182... ...
Revitalization Act in 1993, Congress affirmed that federally sponsored research needed to improve its inclu sion of women and racially and ethnically minority populations, who had long been historically excluded and disproportionately underrepresented in clinical research. Congress renewed its commitment to the inclusion of more diverse populations in clinical research through the require ment for medical products sponsors to develop diversity action plans, enacted in the Food and Drug Omnibus Reform Act (FDORA)
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From page 183... ...
studies can help sponsors, in coordina tion with FDA, to identify and minimize potential safety risks before preg nant or lactating women are exposed to medical products. It is essential that DART studies be conducted as early as can feasibly be done to gener ate preclinical data capable of guiding decisions regarding clinical studies with pregnant and lactating women.
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From page 184... ...
If the preclinical data presented in the diversity action plans raises safety con cerns for conducting human trials in pregnant and lactating women, a justification for not conducting clinical studies must be submitted along with the diversity action plan outlining the evidence for concerns. When FDA reviewers agree there are safety concerns regarding clinical testing in pregnant and lactating women, trials are not to be com pleted and the safety information must be included in the drug labeling.
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From page 185... ...
The Office for Human Research Protections (OHRP) has not issued guidance on pregnant and lactating women as research subjects, includ ing guidance for IRBs on interpreting Subpart B nor on the applicability of Subpart D to these populations.
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From page 186... ...
OHRP should pro vide guidance documents that help clinical researchers, insti tutional review boards (IRBs) , and data and safety monitoring boards ensure that pregnant and lactating women who partici pate in clinical research are adequately protected without creat ing undue burdens for their participation.
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From page 187... ...
The commit tee concludes that this coupling of incentives and accountability would likewise spur research in clinical studies on the dosage, efficacy, and safety of drugs, biologics, and vaccines, as well as the efficacy and safety of devices for pregnant and lactating women. However, the committee acknowledges that while it believes an approach that incorporates an incentive and requirement would be ben eficial for driving clinical research in pregnant and lactating women, there are fundamental ethical and regulatory differences between pregnant populations, lactating populations, and pediatric populations that should be acknowledged before applying that approach.
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From page 188... ...
The committee is not recommending that a separate regulatory cat egory be created for pregnant and lactating women, since that would make the use of most licensed drugs "off-label" for pregnant and lactat ing women and markedly restrict access for those patients. However, it is important to note that sponsors lack the additional incentive of an expanded indication in conducting clinical studies in pregnant and lac tating women that exists with pediatric studies under the PREA and the BCPA.
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From page 189... ...
Despite certain limitations and key differences between pediatric and pregnant and lactating populations, the BPCA and the PREA do serve as useful models for the type of legislation that would provide FDA with the necessary authority to impose requirements for additional study with pregnant and lactating women while also providing incentives needed to stimulate additional research with pregnant and lactating women. The data generated through clinical studies conducted under the BPCA and the PREA have promoted the health of children who now have access to medical products supported by high-quality evidence.
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From page 190... ...
Under the BPCA, the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) has developed a process for prioritizing medical products to be studied with public funding (FDA, n.d.)
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From page 191... ...
The U.S. Congress should pass legisla tion modeled on the Best Pharmaceuticals for Children Act to encourage and incentivize additional studies to provide more information in labeling on the safety and efficacy of approved medical products for pregnant and lactating women.
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From page 192... ...
c. Grant the secretary of HHS the authority to make a written request to the patent holder of medical products subject to patent or exclusivity protections to conduct clinical studies involving pregnant and lactating women concerning one or more of the on-patent medical products identified in part (a)
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From page 193... ...
In considering the potential for unintended consequences for requir ing sponsors to conduct clinical studies in pregnant and lactating women, the committee recognizes that there are two scenarios in which it may be appropriate to defer or waive such a requirement. First, if a medi cal product is ready for approval in the general adult population and the sponsor demonstrates that studies in pregnant and lactating women are being conducted or will be conducted with due diligence and at the earliest possible times, it may be appropriate for FDA to grant a deferral to the sponsor.
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From page 194... ...
to identify and characterize risks to pregnant and lactating women and their offspring" as a justification for requiring postmarket ing studies and postmarketing clinical trials.
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From page 195... ...
The NIH Common Fund presents an opportunity to systematically engage the many institutes and centers within NIH to address a high priority challenge, such as the paucity of clinical research including preg nant and lactating women (NIH, 2023c)
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From page 196... ...
b. The Eunice Kennedy Shriver National Institute of Child Health and Human Development should expand and sus tain its network of institutions with expertise in conducting clinical research with pregnant and lactating women, with considerations for the equitable access of potential research participants.
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From page 197... ...
. Because acquiring clinical trial insurance imposes an additional cost to the study, it would be appropriate for NIH to cover the cost of clinical trial insurance for NIH-funded research involving pregnant and lactating women, which is within its authority (Henry et al., 2015)
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From page 198... ...
Real-world data collected through observational studies are important for detecting rare adverse events and understanding the long-term safety profile of medical products, but the current system of real-world data capture and analysis needs substantial improvement before it can play a major role in increasing knowledge about the effects of medical products in pregnant and lactating women. FDA has developed draft guidance for industry on postapproval pregnancy safety studies, which provides considerations on the design, use, and analysis of pregnancy exposure registries and complementary databases (FDA, 2019)
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From page 199... ...
For exam ple, the repository could have prepopulated submission categories with information requested in FDA's "Guidance for Industry on Establishing Pregnancy Exposure Registries," and dropdown menu selections, where relevant. Additionally, nonproprietary information in the status report for each registry that would be useful to be made public in the repository includes: • Number of pregnant women enrolled to date, • Number of pregnancies with unknown outcomes, • Number of pregnancies with outcome pending, • Number of pregnancies lost to follow-up, and • Number and type of adverse events reported.
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From page 200... ...
. The linkage of parental and offspring electronic health records is vital to understanding fetal and infant outcomes related to exposure to medical products in utero.
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From page 201... ...
b. Release guidelines on the content and format of data to be submitted to the central repository from existing pregnancy and lactation exposure registries, which should include, at a minimum, the following: number of pregnant and lactating women enrolled to date, number of pregnant and lactating women with unknown outcomes, number of pregnant and lactating women with pending outcomes, number of preg nant and lactating women lost to follow-up, and number and types of adverse events reported in pregnant and lactat ing women.
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From page 202... ...
Constitution protected the right to an abortion, research participants may be exposed to new legal liability depending on state laws and local enforcement. Charges of civil or criminal liability could be brought against research participants that experience a spontane ous abortion or seek an elective abortion.
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From page 203... ...
In Women and health research: Ethical and legal issues of in cluding women in clinical studies: Workshop and commissioned papers, vol.
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From page 204... ...
2020. The pathway for ward: Insights on factors that facilitate research with pregnant women.
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From page 205... ...
. PRGLAC Task Force (Task Force on Research Specific to Pregnant Women and Lactating Women)
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From page 206... ...
In Clinical Research Involving Pregnant Women, edited by F Baylis and A
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