Challenges in Designing Clinical Trials to Test New Drugs in the Pregnant Woman and Fetus

Turner, Mark A.; Kenny, Louise C.; Alfirević, Z̄arko

doi:10.1016/j.clp.2019.02.015

Cited by 6 publications

(6 citation statements)

References 62 publications

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“…Future clinical studies could evaluate the real‐life efficacy of this simulated regimen. Data sharing enables data from previous clinical trials to be used in both physiologically‐based pharmacokinetic and population pharmacokinetic modeling 36 . However, most studies do not make their primary data sets available.…”

Section: Study Design Data Management Ethical and Regulatory Considmentioning

confidence: 99%

“…Data sharing enables data from previous clinical trials to be used in both physiologically-based pharmacokinetic and population pharmacokinetic modeling. 36 However, most studies do not make their primary data sets available. Increasing awareness of the need to make data findable, accessible, interoperable, and reusable (FAIR) has not yet translated to improved access to data in studies relating to anti-infective exposure in pregnancy.…”

Section: Study Design Data Management Ethical and Regulatory Considerationsmentioning

confidence: 99%

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Anti‐Infective Dosing in Special Populations: Pregnancy

Hazenberg

Navaratnam

Busuulwa

et al. 2021

Clin Pharma and Therapeutics

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Section: Study Design Data Management Ethical and Regulatory Considmentioning

confidence: 99%

Section: Study Design Data Management Ethical and Regulatory Considerationsmentioning

confidence: 99%

Anti‐Infective Dosing in Special Populations: Pregnancy

Hazenberg

Navaratnam

Busuulwa

et al. 2021

Clin Pharma and Therapeutics

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“…However, it took decades of observational human population studies to support and propose a clinical trial to confirm the therapeutic benefit of folic acid supplementation [ 87 ], and there are likely many more nutrient or environmental factors that influence NTDs and other developmental disorders. Overall, there is a need for new preclinical models that capture the underlying biological processes of human development [ 88 ]. In addition to the screening for teratogenic effects of pharmacologic compounds, advancements in models of human development are needed that can provide a discovery platform for identifying potential drugs or drug-like compounds that can potentially mitigate developmental disorders.…”

Section: Specific Preclinical Model Limitations In Different Researchmentioning

confidence: 99%

Engineered tissues and strategies to overcome challenges in drug development

Khalil

Jaenisch

Mooney

2020

Advanced Drug Delivery Reviews

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Current preclinical studies in drug development utilize high-throughput in vitro screens to identify lead drug candidates, followed by both in vitro and in vivo models to predict lead candidates' pharmacokinetic and pharmacodynamic properties. The goal of these studies is to reduce the number of lead drug candidates down to the most likely to succeed in later human clinical trials. However, only 1 in 10 drug candidates that emerge from preclinical studies will succeed and become an approved therapeutic. Lack of efficacy or undetected toxicity represents roughly 75% of the causes for these failures, despite these parameters being the primary exclusion criteria in preclinical studies. Recently, advances in both biology and engineering have created new tools for constructing new preclinical models. These models can complement those used in current preclinical studies by helping to create more realistic representations of human tissues in vitro and in vivo . In this review, we describe current preclinical models to identify their value and limitations and then discuss select areas of research where improvements in preclinical models are particularly needed to advance drug development. Following this, we discuss design considerations for constructing preclinical models and then highlight recent advances in these efforts. Taken together, we aim to review the advances as of 2020 surrounding the prospect of biological and engineering tools for adding enhanced biological relevance to preclinical studies to aid in the challenges of failed drug candidates and the burden this poses on the drug development enterprise and thus healthcare.

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“…A key point of contention for application of the Common Rule requirements revolves around the definitions of minimal risk and direct benefit. 28 Per 45 CFR §46.102.i, minimal risk is defined as "the probability and magnitude of harm or discomfort anticipated in the research are not greater in and of themselves than those ordinarily encountered in daily life or during the performance of routine physical or psychological examinations or tests." 12 Applying this standard to the fetus is problematic.…”

Section: Table Code Of Federal Regulations Requirements For Inclusiomentioning

confidence: 99%

Research in Pregnant Subjects: Increasingly Important, but Challenging

Biggio

2020

TOJ

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Background: The number of pregnant women with medical comorbidities continues to increase. A large proportion of pregnant women are exposed to medications during pregnancy, but only a fraction of the medications used have been investigated during pregnancy with regard to benefits, risks, and doses. Methods: This article includes a review of potential deterrents and barriers to pregnant women enrolling in clinical research studies and the federal regulations governing enrollment of pregnant women in research. Results: Research in pregnant women has been hampered by concerns for liability, the complex physiology of pregnancy with changes related to stage of pregnancy, and federal regulations that deemed pregnant women a vulnerable population. While recent revisions to federal regulations have removed pregnant women from the classification of vulnerable population, regulations regarding consent requirements still limit women's ability to decide on participation in clinical trials. The Department of Health and Human Services established the Task Force on Research Specific to Pregnant Women and Lactating Women to help identify and reduce these barriers. Conclusion: While recognition of the need for more scientific knowledge on the effects of medications and other interventions in pregnancy is widespread, a number of barriers that hinder enrollment of pregnant women in clinical trials remain.

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Challenges in Designing Clinical Trials to Test New Drugs in the Pregnant Woman and Fetus

Cited by 6 publications

References 62 publications

Anti‐Infective Dosing in Special Populations: Pregnancy

Anti‐Infective Dosing in Special Populations: Pregnancy

Engineered tissues and strategies to overcome challenges in drug development

Research in Pregnant Subjects: Increasingly Important, but Challenging

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