Challenges in Conducting Therapeutic Trials in Pregnancy: Emphasizing Recent Lessons Learned

Bank, Tracy Caroline; Stika, Catherine S.; Venkataramanan, Raman; Field, Christine; Costantine, Maged M.

doi:10.1002/jcph.2226

Cited by 4 publications

(2 citation statements)

References 69 publications

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“…First was the uncertainty characterising pharmacological decision-making in pregnancy, given often unclear and potentially misaligned risks and benefits of medications for mother and child. Traditionally centred on medication use [ 20 , 21 ], discussions about the risk–benefit balance for determining suitable antenatal doses were perceived as arduous by HCP participants. Among other factors, this complexity arose from most HCPs’ limited knowledge of pharmacokinetics and the poor availability and accessibility of supportive evidence.…”

Section: Discussionmentioning

confidence: 99%

Perceived barriers and facilitators for model-informed dosing in pregnancy: a qualitative study across healthcare practitioners and pregnant women

Koldeweij,

Kleuskens,

Litjens

et al. 2024

BMC Med

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Background Most women use medication during pregnancy. Pregnancy-induced changes in physiology may require antenatal dose alterations. Yet, evidence-based doses in pregnancy are missing. Given historically limited data, pharmacokinetic models may inform pregnancy-adjusted doses. However, implementing model-informed doses in clinical practice requires support from relevant stakeholders. Purpose To explore the perceived barriers and facilitators for model-informed antenatal doses among healthcare practitioners (HCPs) and pregnant women. Methods Online focus groups and interviews were held among healthcare practitioners (HCPs) and pregnant women from eight countries across Europe, Africa and Asia. Purposive sampling was used to identify pregnant women plus HCPs across various specialties prescribing or providing advice on medication to pregnant women. Perceived barriers and facilitators for implementing model-informed doses in pregnancy were identified and categorised using a hybrid thematic analysis. Results Fifty HCPs and 11 pregnant women participated in 12 focus groups and 16 interviews between January 2022 and March 2023. HCPs worked in the Netherlands (n = 32), the UK (n = 7), South Africa (n = 5), Uganda (n = 4), Kenya, Cameroon, India and Vietnam (n = 1 each). All pregnant women resided in the Netherlands. Barriers and facilitators identified by HCPs spanned 14 categories across four domains whereas pregnant women described barriers and facilitators spanning nine categories within the same domains. Most participants found current antenatal dosing information inadequate and regarded model-informed doses in pregnancy as a valuable and for some, much-needed addition to antenatal care. Although willingness-to-follow model-informed antenatal doses was high across both groups, several barriers for implementation were identified. HCPs underlined the need for transparent model validation and endorsement of the methodology by recognised institutions. Foetal safety was deemed a critical knowledge gap by both groups. HCPs’ information needs and preferred features for model-informed doses in pregnancy varied. Several pregnant women expressed a desire to access information and partake in decisions on antenatal dosing. Conclusions Given the perceived limitations of current pharmacotherapy for pregnant women and foetuses, model-informed dosing in pregnancy was seen as a promising means to enhance antenatal care by pregnant women and healthcare practitioners.

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Section: Discussionmentioning

confidence: 99%

Perceived barriers and facilitators for model-informed dosing in pregnancy: a qualitative study across healthcare practitioners and pregnant women

Koldeweij,

Kleuskens,

Litjens

et al. 2024

BMC Med

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“…However, while over 80% of pregnant women use medications (5), specifically researched antenatal doses are lacking for most drugs (4,6). Despite efforts to increase enrollment of pregnant women in clinical research (7,8), ethical concerns about potential fetal harm and the lack of obligation for pharmaceutical companies to investigate antenatal dosing before market access contribute to a paucity of data to support evidence-based antenatal doses (9,10). Information on the pharmacokinetics, safety and efficacy of drugs in pregnancy remains scarce (6,(11)(12)(13)(14).…”

Section: Introductionmentioning

confidence: 99%

A user-driven framework for dose selection in pregnancy: proof-of-concept for sertraline

Koldeweij,

Dibbets,

Franklin

et al. 2024

Preprint

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Despite growing knowledge of pregnancy-induced changes in physiology that may alter maternal and fetal pharmacokinetics, and therefore drug efficacy and safety, evidence-based antenatal doses are lacking for most drugs. Pharmacokinetic models and expanding clinical data in pregnancy may support antenatal doses. In this article, we introduce a comprehensive and user-driven Framework for Dose Selection in Pregnancy (FDSP), developed and validated to support the clinical implementation of best-evidence and in some cases, model-informed doses for pregnant women and/or fetuses. After initial development and validation by experts, the framework prototype was piloted to formulate an antenatal dosing strategy for sertraline in depression and anxiety disorders. Next, the framework was validated and assessed for usability by a multidisciplinary working committee of end-users comprising healthcare practitioners, experts from other disciplines including pharmacometrics, reproductive toxicology and medical ethics, alongside pregnant women and a partner. The resulting framework encompasses the following: rationale for drug selection, a comprehensive analysis of pharmacokinetic and dose-related efficacy and safety data, and implementation aspects including feasibility and desirability of the recommended antenatal dose based on a structured maternal and fetal benefit-risk assessment. An antenatal dose recommendation for sertraline, as a proof-of-concept, was formulated using this approach and endorsed for clinical use by the working committee. The FDSP, as demonstrated by the example of sertraline, is fit for supporting the development of best-evidence acceptable and clinically feasible antenatal doses.

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New approach methods on the bench side to accelerate clinical trials during pregnancy

Menon,

Richardson,

Kammala

2024

Expert Opinion on Drug Metabolism & Toxicology

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Challenges in Conducting Therapeutic Trials in Pregnancy: Emphasizing Recent Lessons Learned

Cited by 4 publications

References 69 publications

Perceived barriers and facilitators for model-informed dosing in pregnancy: a qualitative study across healthcare practitioners and pregnant women

Perceived barriers and facilitators for model-informed dosing in pregnancy: a qualitative study across healthcare practitioners and pregnant women

A user-driven framework for dose selection in pregnancy: proof-of-concept for sertraline

New approach methods on the bench side to accelerate clinical trials during pregnancy

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