Inclusion of key populations in clinical trials of new antituberculosis treatments : current barriers and recommendations for pregnant and lactating women, children, and HIV-infected persons
Date
2019
Journal Title
Journal ISSN
Volume Title
Publisher
Public Library of Science
Abstract
ENGLISH ABSTRACT: Pregnant women, children < 15 years old and, HIV-infected persons contribute
approximately 20% of the global tuberculosis (TB) burden, with an estimated 216,000,
1,000,000, and 1,040,000 cases each year, respectively, yet these populations are currently
largely excluded from TB clinical trials, leading to suboptimal treatment and poor
access to new therapeutics.
• Special considerations in these populations include specific TB disease spectrum and
severity, lower sensitivity of commonly used TB diagnostic tests, potential differential
drug dosing and treatment responses, drug–drug interactions, and challenges in acquiring
high-quality data through clinical trials.
• To counter the automatic exclusion of pregnant and lactating women that currently pervades
the TB trial landscape, early discussions among trialists, pharmaceutical companies,
maternal–child clinical experts, ethicists, and regulatory bodies are needed to
address risks, benefits, and compelling rationale for inclusion. Reconsenting women
when pregnancy occurs on a trial to allow continuation of study drug by informed
choice is a practical and valuable approach to expand the currently limited evidence
base.
• Children tend to have less severe, often paucibacillary TB disease and may respond better
to treatment than adults. Consequently, trials of shorter, less intense TB treatment
regimens in children are needed; pharmacokinetic and safety studies should be initiated
earlier and involve age groups in parallel rather than in an age-de-escalation approach.
More rapid development of child-friendly drug formulations is needed.
• All HIV-infected populations, including those with advanced disease, who are likely to
be the intended population of the TB therapy, should be involved in Phase IIb and/or Phase III trials, as appropriate, to maximize knowledge of treatment, toxicities, drug–
drug interactions, and outcomes.
Description
CITATION: Gupta, A., et al. 2019. Inclusion of key populations in clinical trials of new antituberculosis treatments : current barriers and recommendations for pregnant and lactating women, children, and HIV-infected persons. PLoS Medicine, 16(8):e1002882, doi:10.1371/journal.pmed.1002882.
The original publication is available at https://journals.plos.org/plosmedicine
The original publication is available at https://journals.plos.org/plosmedicine
Keywords
Antitubercular agents, Clinical trials of drugs, Lactation, HIV-positive persons, Antibacterial agents -- Children
Citation
Gupta, A., et al. 2019. Inclusion of key populations in clinical trials of new antituberculosis treatments : current barriers and recommendations for pregnant and lactating women, children, and HIV-infected persons. PLoS Medicine, 16(8):e1002882, doi:10.1371/journal.pmed.1002882