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. 2025 Jun;48(6):643-654.
doi: 10.1007/s40264-025-01521-0. Epub 2025 Feb 5.

Delphi Method Consensus on Statistical Analysis and Reporting Recommendations for Single-Arm Pregnancy Medication Safety Studies Investigating Pregnancy, Birth and Neonatal Health Outcomes: A Contribution from IMI-ConcePTION

Jonathan L Richardson  1 , Alan Moore  2 , Michael Stellfeld  3 , Yvonne Geissbühler  2 , Ursula Winterfeld  4 , Guillaume Favre  4 , Christina Chambers  5 , Evelin Beck  6 , Marlies Onken  6 , Katarina Dathe  6 , Michael Ceulemans  7   8 , Orna Diav-Citrin  9 , Svetlana Shechtman  9 , Alison M Oliver  10 , Kenneth K Hodson  10 , Dee-Dee Shiller  11 , Amalia Alexe  2 , Eugène P van Puijenbroek  12   13 , David J Lewis  2   14 , Laura M Yates  15   16
Affiliations

Delphi Method Consensus on Statistical Analysis and Reporting Recommendations for Single-Arm Pregnancy Medication Safety Studies Investigating Pregnancy, Birth and Neonatal Health Outcomes: A Contribution from IMI-ConcePTION

Jonathan L Richardson et al. Drug Saf. 2025 Jun.

Abstract

Background and objective: Standardised procedures for performing and reporting safety monitoring studies investigating medications use in pregnancy may help improve data quality and the speed of data generation. The objective of this study was to provide recommendations on the statistical analysis and reporting of single-arm pregnancy medication safety studies using primary source datasets.

Methods: A Delphi consensus-setting protocol was used to acquire agreement on recommendations from experts with extensive knowledge and experience in conducting studies investigating medication safety in pregnancy. A series of recommendations, along with their scientific justifications and examples of how to calculate and describe exposure and outcome incidences, were critiqued and improved through a series of online Delphi review rounds. Agreement to inclusion scoring was assessed using a five-point Likert scale. Recommendations with a median Likert-scale score of at least 4, where ≥ 80% of the expert panel scored the recommendation at level 4 or higher, was used as the threshold for inclusion.

Results: The Delphi consensus methodology produced a set of 30 recommendations spread over five themes. These included descriptions of (1) study sample, (2) medication exposure, (3) maternal outcomes, (4) pregnancy and birth outcomes, and (5) fetal and neonatal outcomes. Of the 30 recommendations, 19 were strongly advised while 11 were included for consideration where their implementation may be beneficial for supplementing data communication.

Conclusion: Use of the finalised set of recommendations should be encouraged to help standardise published evidence around medication use in pregnancy.

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Conflict of interest statement

Declarations. Funding: The ConcePTION project is jointly funded by the Innovative Medicines Initiative (call 13, topic 9, grant agreement number 821520) and through benefit in kind contributions from European Federation of Pharmaceutical Industries (EFPIA) companies. The contribution of EFPIA partners to this manuscript has involved the provision of personnel time and expertise only. No academic/clinical partners have received financial incentives from EFPIA partners during the performance of this task. All of the recommendations provided required consensual agreement. The research leading to the results communicated in this manuscript was conducted as part of the ConcePTION consortium. This paper only reflects the personal views of the stated authors. The research activities of Michael Ceulemans are supported by a Senior Postdoctoral Fellowship fundamental research of the Research Foundation Flanders (FWO, 1246425N). Conflict of interest: JLR, MC, AO, UW, GF, KKH declare no conflicts of interest; no other financial relationships with any organisations that might have an interest in the submitted work in the previous 3 years; no previous or ongoing relationships or activities that could appear to have influenced the submitted work. AM and DJL were Novartis associates whist working on this manuscript and other aspects of the ConcePTION project, and both hold shares in Novartis Pharma AG. DJL also owns shares in Alcon, Novartis, Sandoz, and GlaxoSmithKline, and is an Honorary Senior Lecturer (Clinical), School of Life and Medical Sciences, University of Hertfordshire. AA is a current Novartis associate and holds shares in Novartis Pharma and Incyte. YG is an employee of Novartis Pharma AG. DS is a current AbbVie employee and current shareholder in AbbVie stocks. MS is an employee of Novo Nordisk A/S and holds shares in Novo Nordisk. LMY provided consultancy for Sanofi Genzyme South Africa on two occasions in 2021 relating to genetic testing in Gaucher’s Disease (April 2021) and a conference lecture on genetic testing in cardiac clinics (Sept 2021). KD, MO and EB are staff members of the Berlin Embryotox Center of Clinical Teratology and Drug Safety in Pregnancy which is financially supported by the German Federal Institute for Drugs and Medical Devices (BfArM). TC receives research funding from the following industry sponsors and a foundation: Amgen, AstraZeneca; GlaxoSmithKline; Janssen Pharmaceuticals; Pfizer, Inc.; Regeneron; Hoffman La-Roche-Genentech; Genzyme Sanofi-Aventis; Takeda Pharmaceutical Company Limited; Sanofi; UCB Pharma, USA; Leo Pharma, Sun Pharma Global FZE; Gilead; Novartis; and the Gerber Foundation. EvP is an Editorial Board member of Drug Safety but was not involved in the original selection of the target journal, selecting the peer reviewers for the manuscript, nor any of the subsequent editorial decisions. Ethics approval: Not applicable. Consent to participate: Not applicable. Consent for publication: Not applicable. Availability of data and materials: May be made available on request, please contact the corresponding author. Code availability: Not applicable. Author contributions: JLR, DJL and LMY conceptualised the study; JLR, LMY and AO developed the study protocol and the Delphi consensus collection materials; JLR and AO acted as co-ordinators of the Delphi process with guidance from LMY; AM, MS, UW, JLR and YG drafted the statistical analysis plan and the preliminary recommendations; all authors participated in the Delphi process; JLR and AO finalised the documentation of the final recommendations; JLR wrote the first draft of the manuscript; all authors provided critical comments to finalise the manuscript. All authors have read and approved the final version.

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