Trial reportBMC medicine2016
Limited role of culture conversion for decision-making in individual patient care and for advancing novel regimens to confirmatory clinical trials.
Trial report in BMC medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to 2 registered trials, which are not on this map. Cited by 44 papers, 4 of them syntheses that pooled 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.
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.
A Randomised Placebo - Controlled Double Blind Trial Comparing 1) a Two Month Intensive Phase of Ethambutol, Moxifloxacin, Rifampicin, Pyrazinamide Versus the Standard Regimen (Ethambutol, Isoniazid, Rifampicin, Pyrazinamide) and 2) a Treatment Shortening Regimen Comparing Two Months Moxifloxacin, Isoniazid, Rifampicin, Pyrazinamide Followed by Two Months Moxifloxacin, Isoniazid, Rifampicin Versus the Standard Regimen (Two Months Ethambutol, Isoniazid, Rifampicin, Pyrazinamide Followed by Four Months Isoniazid and Rifampicin) for the Treatment of Adults With Pulmonary Tuberculosis
Candidate Clinical Correlate of Prognostic Outcome for TB Study
Who cites it
44 citing papers in PubMed, 4 syntheses or guidelines pooled it, 76 citations in OpenAlex.
- Pooled it
- Treatment Effect Measures for Culture Conversion Endpoints in Phase IIb Tuberculosis Treatment Trials.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2021Pooled it
- A systematic review of endpoint definitions in late phase pulmonary tuberculosis therapeutic trials.Trials · 2021Pooled it
- Shortened treatment regimens versus the standard regimen for drug-sensitive pulmonary tuberculosis.The Cochrane database of systematic reviews · 2019Pooled it
- PET-CT outcomes from a randomised controlled trial of rosuvastatin as an adjunct to standard tuberculosis treatment.Nature communications · 2024Trial
- A pharmacometric multistate model for predicting long-term treatment outcomes of patients with pulmonary TB.The Journal of antimicrobial chemotherapy · 2024Trial
- A flexible multi-metric Bayesian framework for decision-making in Phase II multi-arm multi-stage studies.Statistics in medicine · 2024Trial
- Evaluation of six months sputum culture conversion as a surrogate endpoint in a multidrug resistant-tuberculosis trial.PloS one · 2018Trial
- Biomarkers of Tuberculosis Severity and Treatment Effect: A Directed Screen of 70 Host Markers in a Randomized Clinical Trial.EBioMedicine · 2017Trial
- A new trial design to accelerate tuberculosis drug development: the Phase IIC Selection Trial with Extended Post-treatment follow-up (STEP).BMC medicine · 2016Trial
- An Interactive Pharmacokinetic-Pharmacodynamic Framework to Evaluate Bedaquiline Dose Modifications in Adults With Tuberculosis.CPT: pharmacometrics & systems pharmacology · 2026Article
- Beyond culturability: VBNC-like and differentially culturableFrontiers in cellular and infection microbiology · 2026Review
- Association of T-Cell Profiles With Disease Severity, Drug-Induced Liver Injury, and Treatment Completion in Tuberculosis.The clinical respiratory journal · 2025Article
- Resolution of tuberculosis blood RNA signatures fails to discriminate persistent sputum culture positivity after 8 weeks of anti-tuberculous treatment.The European respiratory journal · 2024Article
- Developing biomarker assays to accelerate tuberculosis drug development: defining target product profiles.The Lancet. Microbe · 2024Review
- Therapeutic developments for tuberculosis and nontuberculous mycobacterial lung disease.Nature reviews. Drug discovery · 2024Review
- Does PET-CT Have a Role in the Evaluation of Tuberculosis Treatment in Phase 2 Clinical Trials?The Journal of infectious diseases · 2024Review
- Monitoring Live Mycobacteria in Real-Time Using a Microfluidic Acoustic-Raman Platform.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Early Microbiologic Markers of Pulmonary Tuberculosis Treatment Outcomes.Annals of the American Thoracic Society · 2023Article
- At Long Last: Short, All-Oral Regimens for Multidrug-Resistant Tuberculosis in the United States.Open forum infectious diseases · 2023Review
Corrections and comments
- Erratum issuedErratum to: Limited role of culture conversion for decision-making in individual patient care and for advancing novel regimens to confirmatory clinical trials.2016 · Crook, Angela [corrected to Crook, Angela M]
Authors and funding
9 authors at 6 institutions in 3 countries.
Funding
Abstract
backgroundDespite recent increased clinical trials activity, no regimen has proved able to replace the standard 6-month regimen for drug-sensitive tuberculosis. Understanding the relationship between microbiological markers measured during treatment and long-term clinical outcomes is critical to evaluate their usefulness for decision-making for both individual patient care and for advancing novel regimens into time-consuming and expensive pivotal phase III trials.
methodsUsing data from the randomized controlled phase III trial REMoxTB, we evaluated sputum-based markers of speed of clearance of bacilli: time to smear negative status; time to culture negative status on LJ or in MGIT; daily rate of change of log10(TTP) to day 56; and smear or culture results at weeks 6, 8 or 12; as individual- and trial-level surrogate endpoints for long-term clinical outcome.
resultsTime to culture negative status on LJ or in MGIT, time to smear negative status and daily rate of change in log10(TTP) were each independent predictors of clinical outcome, adjusted for treatment (p <0.001). However, discrimination between low and high risk patients, as measured by the c-statistic, was modest and not much higher than the reference model adjusted for BMI, history of smoking, HIV status, cavitation, gender and MGIT TTP.
conclusionsCulture conversion during treatment for tuberculosis, however measured, has only a limited role in decision-making for advancing regimens into phase III trials or in predicting the outcome of treatment for individual patients. REMoxTB ClinicalTrials.gov number: NCT00864383.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.