Format

Send to

Choose Destination
Clin Infect Dis. 2015 Aug 15;61 Suppl 1:S25-31. doi: 10.1093/cid/civ427.

Forecasting Accuracy of the Hollow Fiber Model of Tuberculosis for Clinical Therapeutic Outcomes.

Author information

1
Center for Infectious Diseases Research and Experimental Therapeutics, Baylor Research Institute, Baylor University Medical Center, Dallas, Texas Department of Medicine, University of Cape Town, Observatory, South Africa.
2
Center for Infectious Diseases Research and Experimental Therapeutics, Baylor Research Institute, Baylor University Medical Center, Dallas, Texas.
3
Critical Path Institute, Tucson, Arizona.
4
Center for Tuberculosis Research, Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, Maryland.

Abstract

BACKGROUND:

The hollow fiber system model of tuberculosis (HFS-TB), in tandem with Monte Carlo experiments, represents a drug development tool (DDT) with the potential for use to develop tuberculosis treatment regimens. However, the predictive accuracy of the HFS-TB, or any other nonclinical DDT such as an animal model, has yet to be robustly evaluated.

METHODS:

To avoid hindsight bias, a literature search was performed to identify clinical studies published at least 6 months after HFS-TB experiments' quantitative predictions. Steps to minimize bias and for reporting systematic reviews were applied as outlined in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Publications were scored for quality of evidence. Accuracy was calculated using the mean absolute percentage error, then summated with weighting assigned by sample size and quality-of-evidence score. Given the lack of a gold-standard tuberculosis DDT, the forecasting accuracy of a completely unreliable tool was also calculated from 1000 simulated experiments for a random or "total guesswork" model.

RESULTS:

The quantitative forecasting accuracy (95% confidence interval [CI]) for the "total guesswork" model was 15.6% (95% CI, 8.7%-22.5%); bias was -0.1% (95% CI, -2.5% to 2.2%). Twenty clinical studies were published after HFS-TB experiments predicted optimal drug exposures and doses, susceptibility breakpoints, and optimal combination regimens. Based on these clinical studies, the predictive accuracy of the HFS-TB was 94.4% (95% CI, 84.3%-99.9%), and bias was 1.8% (95% CI, -13.7% to 6.2%).

CONCLUSIONS:

The HFS-TB model is highly accurate at forecasting optimal drug exposures, doses, and dosing schedules for use in the clinic.

KEYWORDS:

Monte Carlo experiments; drug development tool; hollow fiber system; predictive accuracy; tuberculosis

PMID:
26224769
DOI:
10.1093/cid/civ427
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Silverchair Information Systems
Loading ...
Support Center