| Title: |
Clinical and population‐based study design considerations to accelerate the investigation of new antiretrovirals during pregnancy |
| Authors: |
Brummel, Sean; Stringer, Jeff; Mills, Ed; Tierney, Camlin; Caniglia, Ellen; Colbers, Angela; Chi, Benjamin; Best, Brookie; Gaaloul, Myriam El; Hillier, Sharon; Jourdain, Gonzague; Khoo, Saye, H; Mofenson, Lynne; Myer, Landon; Nachman, Sharon; Stranix-Chibanda, Lynda; Clayden, Polly; Sachikonye, Memory; Lockman, Shahin |
| Contributors: |
Harvard T.H. Chan School of Public Health; Harvard University; Université de Caroline du Nord à Chapel Hill = University of North Carolina Chapel Hill (UNC-Chapel Hill); University of North Carolina System (UNC); Perelman School of Medicine; University of Pennsylvania Philadelphia; Radboud University Medical Center Nijmegen (RadboudUMC); Skaggs School of Pharmacy and Pharmaceutical Sciences San Diego; University of California San Diego (UC San Diego); University of California (UC)-University of California (UC); Rady Children's Hospital; University of California (UC); Medicines for Malaria Venture Geneva (MMV); University of Pittsburgh (PITT); Pennsylvania Commonwealth System of Higher Education (PCSHE); Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC); Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD Occitanie )-Université de Montpellier (UM); University of Liverpool; Elizabeth Glaser Pediatric AIDS Foundation; University of Cape Town; State University of New York (SUNY); University of Zimbabwe (UZ); Brigham & Women’s Hospital Boston (BWH); Harvard Medical School Boston (HMS); SL was supported by K24 AI131928. SSB, CT and SN: Overall support for the International Maternal Pediatric Adolescent AIDS Clinical Trials Network (IMPAACT) was provided by the National Institute of Allergy and Infectious Diseases (NIAID) with co-funding from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) and the National Institute of Mental Health (NIMH), all components of the National Institutes of Health (NIH), under Award Numbers UM1AI068632-15 (IMPAACT LOC), UM1AI068616-15 (IMPAACT SDMC) and UM1AI106716-15 (IMPAACT LC), and by NICHD contract number HHSN275201800001I. |
| Source: |
EISSN: 1758-2652 ; Journal of the International AIDS Society ; https://hal.science/hal-04980565 ; Journal of the International AIDS Society, 2022, 25 (S2), pp.6. ⟨10.1002/jia2.25917⟩ |
| Publisher Information: |
CCSD; BioMed Central (2008-2012); International Aids Society (2008-); Wiley (2017-) |
| Publication Year: |
2022 |
| Collection: |
Université de Montpellier: HAL |
| Subject Terms: |
viral suppression; treatment; paediatrics; intervention; clinical trials; ARV; [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases; [SDV.MHEP.GEO]Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics; [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology; [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie |
| Description: |
International audience ; Introduction : Pregnant women are routinely excluded from clinical trials, leading to the absence or delay in even the most basic pharmacokinetic (PK) information needed for dosing in pregnancy. When available, pregnancy PK studies use a small sample size, resulting in limited safety information. We discuss key study design elements that may enhance the timely availability of pregnancy data, including the role and timing of randomized controlled trials (RCTs) to evaluate pregnancy safety; efficacy and safety outcome measures; stand‐alone protocols, platform trials, single arm studies, sample size and the effect that follow‐up time during gestation has on analysis interpretations; and observational studies. Discussion : Pregnancy PK should be studied during drug development, after dosing in non‐pregnant persons is established (unless non‐clinical or other data raise pregnancy concerns). RCTs should evaluate the safety during pregnancy of priority new HIV agents that are likely to be used by large numbers of females of childbearing age. Key endpoints for pregnancy safety studies include birth outcomes (prematurity, small for gestational age and stillbirth) and neonatal death, with traditional adverse events and infant growth also measured (congenital anomalies are best studied through surveillance). We recommend that viral efficacy be studied as a secondary endpoint of pregnancy RCTs, once PK studies confirm adequate drug exposure in pregnancy. RCTs typically use a stand‐alone protocol for new agents. In contrast, master protocols using a platform design can add agents over time, possibly speeding safety data ascertainment. To speed accrual, stand‐alone pregnancy trial protocols can include pre‐specified starting rules based upon adequate PK levels in pregnancy; and seamless master protocols or platform trials can include a pregnancy PK and safety component. When RCTs are unethical or cost‐prohibitive, observational studies should be conducted, preferably using target trial emulation to ... |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
info:eu-repo/semantics/altIdentifier/pmid/35851758; PUBMED: 35851758; PUBMEDCENTRAL: PMC9294861 |
| DOI: |
10.1002/jia2.25917 |
| Availability: |
https://hal.science/hal-04980565; https://hal.science/hal-04980565v1/document; https://hal.science/hal-04980565v1/file/Journal%20of%20the%20International%20AIDS%20Society%20-%202022%20-%20Brummel%20-%20Clinical%20and%20population%E2%80%90based%20study%20design%20considerations%20to.pdf; https://doi.org/10.1002/jia2.25917 |
| Rights: |
http://creativecommons.org/licenses/by/ ; info:eu-repo/semantics/OpenAccess |
| Accession Number: |
edsbas.7F264AB0 |
| Database: |
BASE |