Evidence map›Paper›PMID 40993799›Full record

ArticleTrials2025

Comparison of methods for identifying the optimal treatment duration in randomized trials for antibiotics.

Suzanne M Dufault, Brian H Aldana, Patrick P J Phillips

Abstract readComparative Study
In one paragraph

Article in Trials, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

3 authors.

Suzanne M DufaultDivision of Biostatistics, Department of Epidemiology and Biostatistics, University of California, San Francisco, CA, USA. suzanne.dufault@ucsf.edu.ORCID http://orcid.org/0000-0002-6316-6548
Brian H AldanaUCSF Center for Tuberculosis, San Francisco, CA, USA.
Patrick P J PhillipsUCSF Center for Tuberculosis, San Francisco, CA, USA.

Funding

Statistical and Data Management Center (SDMC), AIDS Clinical Trials Group (ACTG)UM1AI068634 · NIAID · HARVARD UNIVERSITY D/B/A HARVARD SCHOOL OF PUBLIC HEALTH · PI Marlene Ann Cooper, Michael David Hughes · 2011 to 2026
$246.6M
UCSF-UCB Tuberculosis Research Advancement Center (TRAC)P30AI168440 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI JEFFERY S COX, PAYAM NAHID · 2022 to 2026
$5.8M
Tuberculosis Research and Mentorship Program (TB RAMP II)R25AI147375 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Elizabeth Fair, PAYAM NAHID · 2020 to 2026
$2.8M
NIAID NIH HHS P30 AI168440NIAID NIH HHS R25 AI147375NIAID NIH HHS UM1 AI068634NIH/NIAID P30:P30AI168440NIH/NIAID R25:1R25AI147375
6 · The paper itself

Abstract

backgroundThe optimal duration of antibiotic treatment must strike a delicate balance: it must be long enough to achieve desirable efficacy yet short enough to prevent the development of toxicities, adverse events, and mitigate other arduous aspects related to patient burden. Historically, the approach used to determine duration of antibiotic treatment has been inefficient, severely impacting the refinement of therapeutics for tuberculosis (TB) where treatment duration, and its complications, can be extensive. Many of the challenges in duration-ranging have parallels and proposed solutions in the field of dose-ranging where the literature is substantially more established and where the traditions of qualitative, pairwise comparison studies have been replaced with model-based approaches. Such methods are more efficient and allow for interpolation between the doses observed.

methodsThis work examines the utility of cutting-edge dose-finding methods (such as MCP-Mod) for duration-ranging of TB treatments. We compare the operating characteristics of the adapted model-based duration-ranging methodologies against standard qualitative methods for the purposes of estimating optimal duration and describing the duration-response relationship, using a simulation study motivated by a Multi-Arm Multi-Stage Response Over Continuous Intervention (MAMS-ROCI) clinical trial design. We explore three specific targets: (1) power to detect a duration-response relationship, (2) ability to accurately reproduce the duration-response curve, and (3) ability to estimate the optimal duration within an acceptable margin of error.

resultsWe find that model-based methods outperform standard qualitative comparisons on every target examined, particularly when the sample size is constrained to that of a typical Phase II trial.

conclusionsWe conclude that the success of the next era in TB therapeutics duration evaluation trials, and antibiotics duration-ranging more broadly, will meaningfully rely on the ability to simultaneously pair innovative model-based statistical methods with re-imagined study designs such as MAMS-ROCI.

Indexed as

Anti-Bacterial AgentsAntitubercular AgentsRandomized Controlled Trials as TopicResearch DesignTuberculosisComputer SimulationDose-Response Relationship, DrugDrug Administration ScheduleHumansTime FactorsTreatment OutcomeAnti-Bacterial AgentsAntitubercular AgentsAntibioticsDuration-rangingMCP-ModTuberculosis

Identifiers

PMID40993799
PMCPMC12462354

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.