TB-PACTS data platform application statistics:

Project Researchers: Callum Taylor

Institution: University of Glasgow

Access Approval Date: September 25, 2017

Brief Description of Proposed Research:

Exploratory project, aiming to use machine learning techniques to predict likelihood of successful treatment for Tuberculosis. Initial plans are for an exploratory project, to see if it is possible to use routinely collected clinical data to accurately predict likelihood of successful treatment. If this stage is successful, plans would be to develop a prospective study to test these predictive models on new data.

Project Researchers: Daniel Grint

Institution: School of Hygiene and Tropical Medicine

Access Approval Date: August 30, 2017

Brief Description of Proposed Research:

Building on the recently published article by Patrick Phillips detailing the Phase IIc STEP trial, my aim is to use the outcomes data from the RIFAQUIN trial to simulate whether a phase III trial would have been recommended based on a novel method of Phase IIc analysis. The motivation for the study is that many researchers are now interested in undertaking Phase IIc studies, yet the methodology for declaring success and suggesting progression to Phase III study is not clear. The work will help to inform sample size calculations for several studies currently in the design phase. The data sharing platform is essential for this purpose so that we may use real data in our simulations.

Project Researchers:  Vitoria Cattani 

Institution: Oswaldo Cruz Foundation – Fiocruz

Access Approval Date:  05/02/2017

Brief Description of Proposed Research:

Integrated individual-level data will allow the linkage between drug exposure and outcomes data as well investigation of variables predicting exposure and/or outcome. As a reseacher in the field of TB/HIV at the National Institute of Infectology Evandro Chagas/Fiocruz (Rio de Janeiro, Brazil), this project is expected to support my doctorate dissertation. Results are expected to be published in disease-area conferences and journals related to infectious disease, tuberculosis and pharmacometrics. The Principal Investigator, one the researchers of the National Institute of Infectology Evandro Chagas/Fiocruz, will be confirmed within the next weeks.

Project Researchers:  Heather Murton

Institution: QuantuMDx

Access Approval Date:  03/16/2017

Brief Description of Proposed Research:

QuantuMDx are developing a point of care cell concentration and molecular diagnostics platform with initial focus of Tuberculosis.  The test aims to diagnose and then reflex to drug susceptibility testing.  The drug targets to be included in the panel are not yet finalized and with are working with St Georges University hospital to develop and optimize the assay.  Access to clinical trial data will not only be of benefit to the development of our assay but to provide a better understanding of clinical trials in this space as we progress towards our own.

Project Researchers:  Dave Anderson

Institution: Syte Logix, Inc.

Access Approval Date:  02/07/2017

Brief Description of Proposed Research:

Research involves leveraging a new data analytics platform that visually explores correlations and relationships between disparate data sets and attributes, to find and map possible new markers that can highlight new areas of exploration and research.  The goal of this research application would be to leverage this data set, and build a single repository that can manage both the structured and the unstructured aspects of this data, and apply visualization analytics across this data in an attempt to find previously unexplored relationships and causality across seemingly unrelated data.

Project Researchers:  Alvarez-uria, Gerardo

Institution: RDT HOSPITAL

Access Approval Date:  01/03/2017

Brief Description of Proposed Research:

Study the optimal initial treatment for HIV infected patients with advanced tuberculosis. In particular, We are interested in the synergy of high dose of rifampicin and streptomycin, and the possible inhibitory effect of isoniazid and ethambutol during the first days of treatment, which are the most important to reduce mortality in HIV infected patients. We have some clinical data from our cohort study, and we believe that the data from TB clinical trials would be very useful for us to clarify possible toxicities due to TB drugs and to investigate microbiological endpoints of different TB regimens. We hope that these data will be helpful in the clinical management of our patients and in developing new research hypotheses.

Project Researchers:  Kyomugisha Aman

Institution: The AIDS Support Organization

Access Approval Date:  11/15/2016

Brief Description of Proposed Research:

Characterize ART treatment failure in TB patients to improve outcomes.

The database will provide a dataset of valuable anonymous patient information to enable analysis of project requirements.

Project Researchers:  Petra Silva

Institution: Federal University of Rio Grande

Access Approval Date:  11/04/2016

Brief Description of Proposed Research:

Understanding the evolution of resistance. Results have suggested that efflux can be involved with drug resistance, so the use of adjuvants that inhibit this mechanism would be considered. Our knowledge about the role of efflux in drug resistance is related to classical drugs and combination. We believe that any platform that can add information about drug resistance is important for our goals.

Project Researchers:  Laura Via

Institution: NIAID

Access Approval Date:  11/01/2016

Brief Description of Proposed Research:

We are interested in looking at outcomes (time to sputum conversion, sputum status at treatment end, cure or relapse) in the context of a specific class of angiotensin II receptor antagonists.

Among the three trials, there may be enough subjects taking this class of drugs to see if they have an affect on outcome in a case controlled analysis design.

Clifton Barry (NIH) and Rakesh Jain (Harvard and Mass General Hospital) are PI’s on the project where I am investigating this class of drugs affects in animals models of TB.

Project Researchers:  Dr. Iain Gardner

Institution: Certara

Access Approval Date:  09/26/2016

Brief Description of Proposed Research:

The goal of this project is to enhance the currently available version of the physiologically-based pharmacokinetic model for the TB-infected lung, with patient-level data from the three Phase III clinical trials integrated as part of the TB-PACTS database. The PBPK model was developed in conjunction with CPTR.

These data will be used as part of a robust external validation exercise for the model predictions.

Dr. Iain Gardner will be the PI for this effort.

Project Researchers:  Tan Doan

Institution: University of Melbourne

Access Approval Date:  08/24/2016

Brief Description of Proposed Research:

Project aims to link pharmacokinetics and pharmacodynamics to health economics to optimize the treatment of tuberculosis (TB) that is resistant to at least two anti-TB drugs, isoniazid and rifampicin (multi-drug resistant TB, MDR-TB). This project will focus on the Asia-Pacific region, where more than half of the global MDR-TB cases occur and the majority of imported MDR-TB cases in Australia come from. Combining PK-PD and health economics will provide strong evidence-base for designing optimal TB treatment strategy to improve patient outcomes.

Project Researchers:  Morris Muliaditan

Institution: University College London

Access Approval Date:  07/28/2016

Brief Description of Proposed Research:

Information from the three pivotal Phase III trials will be used to support the development of an integrated clinical trial simulation framework for the evaluation of study design and dose selection of anti-tuberculosis drugs.

Project Researchers: Muhammad Babar

Institution: Osh State University, Kyrgyzstan

Access Approval Date: 7/25/2016

Brief Description of Proposed Research:
Research on TB drug efficacy. Remove the flaws from DOTS project.

Management of TB patients, monitoring of DOTS and training doctors on TB DOTS.
Researcher will be evaluating drug susceptibility data, concomitant medications information, adverse event information, treatment adherence information, co-morbidities, treatment outcomes, HIV co-infection information, CD4 counts and TB disease symptoms.

Project Researchers:  Thomas Peppard

Institution: Western Michigan University

Access Approval Date:  06/28/2016

Brief Description of Proposed Research:

This application is linked to the “Quantitative Model of Bacterial Dynamics” project.

The safety data captured as part of the TB-PACTS data platform will support the development of a safety data repository, which will allow the development of a benchmark for expected adverse events associated with the SOC regimen used in the control arms of the phase III trials REMox, OFLOTUB and RIFAQUIN. Such a benchmark will provide the foundation to understand the comparative safety of novel candidate regimens against TB.

Project Researchers: James Johnston

Institution: Queen’s University

Access Approval Date: 06/17/2016

Brief Description of Proposed Research:

The overall goal of our research to conduct an individual patient data (IPD) meta-analysis, based on high quality RCTs published from March 1st, 1996 to March 1st, 2016, in order to assess independent clinical and microbiological factors associated with relapse in the standard WHO 6-month TB
Specific objectives:
1. To examine the association between baseline cavitary disease/2-month sputum culture positivity and disease relapse in people treated with a 6-month first line therapy.
2. To examine the association between specific co-morbidities, microbiologic and treatment factors with relapse.

Project Researchers:  James Kerwin

Institution: University of Liverpool

Access Approval Date:  06/07/2016

Brief Description of Proposed Research:

The data will be used by consortium partners, in conjunction with other similar datasets, for development and validation of different  mathematical/statistical models of Phase II bacteriological response, which will ultimately form one module of the modelling framework for drug development envisaged by PreDiCT-TB. This framework is intended to form an platform for effective simulation of future clinical trials.

Project Researchers: Sunita Rehal

Institution: University of Leicester

Access Approval Date: 06/06/2016

Brief Description of Proposed Research:

PhD project to develop a framework for future phase III tuberculosis trials with a non-inferiority design. Develop a framework for future phase III tuberculosis trials with a non-inferiority design. To investigate the impact of excluding patients from the per-protocol analyses has had. Further, the data will enable researcher to develop what the most appropriate primary analysis is for tuberculosis trials, which will influence the design for future non-inferiority tuberculosis trials.

Project Researchers: Lori Dodd

Institution: University of Washington

Access Approval Date: 06/06/2016

Brief Description of Proposed Research:

Provide a clear picture of the extent to which culture and baseline factors modify risk of relapse, which is a quantity of interest to clinicians and trialists. Explore the associations of baseline variables and culture conversion status on the risk of poor outcome.

Project Researchers: Norbert Heinrich

Institution: Technical University of Munich

Access Approval Date: 05/19/2016

Brief Description of Proposed Research:

To elucidate a possible effect of DMPA on human TB and TB therapy, the large number of patients with clinical endpoints available. The TB-PACTS study repository will provide a unique opportunity to analyze a correlation of DMPA use with trial endpoints; including clinical endpoints such as unfavorable long-term outcome, but also surrogate markers such as time to sputum culture conversion, and changes in patient weight during treatment.

Project Researchers: Federica Fregonese

Institution: Padova University, Italy

Access Approval Date: 05/19/2016

Brief Description of Proposed Research:

The proposed research is an Individual patient data (IPD) meta-analysis on treatment outcome for patients with mono- or poly isoniazid resistant (INH-R) TB. Objectives are:

The proposed study aims to find correlates of successful treatment for INH-R TB, with specific focus on

1. Addition of a later generation fluoroquinolones and/or addition of an injectable in the first 2-3 months to accelerate microbiologic conversion and allow shortening of therapy;
2. Optimal duration of treatment with regard to timing of microbiologic conversion;
3. Impact of intermittent therapy early versus in continuation phase;
4. Differences in outcomes between HIV infected and uninfected patients.

Project Researchers: Roland Berard

Institution: Certara Strategical Consulting

Access Approval Date: 04/21/2016

Brief Description of Proposed Research:

Integrated data from three pivotal quinolone phase III trials will provide the necessary information on combined individual-level to develop a quantitative linkage between TTP parameters and relevant clinical outcomes.

Project Researchers: Payam Nahid

Institution: University of California, San Francisco

Access Approval Date: 04/18/2016

Brief Description of Proposed Research:

Complete aggregate and IPD data analysis for outcomes of patients with non-cavitary disease treated with a 4-month FQ substitution regimen. TB-PACTS aggregate data (minimal requirement) will be used to conduct stratified analyses by HIV status and individual patient data to address the question of whether a 4-month daily, FQ for EMB regimen can be used successfully in non-cavitary pulmonary TB.

Project Researchers: Rada Savic

Institution: University of California, San Francisco

Access Approval Date: 04/18/2016

Brief Description of Proposed Research:

Integrated data from three pivotal quinolone phase III trials will provide the necessary information on combined individual-level to develop a non-linear mixed effect modeling analysis to identify predictors of time-to-cure/relapse, by incorporating clinical, demographic, microbiological and pharmacological data.

Project Researchers: Rada Savic

Institution: University of California, San Francisco

Access Approval Date: 04/18/2016

Brief Description of Proposed Research:

Integrated data from three pivotal quinolone phase III trials will provide the necessary information to develop a quantitative model of bacterial dynamics, as expressed by CFU and TTP values (where captured) over time, while quantifying the relevant sources of variability.

Project Researchers: Stewart Chang, Bradley Wagner

Institution: Institute for Disease Modeling

Access Approval Date: 04/18/2016

Brief Description of Proposed Research:

Systematic review of factors associated with treatment success in tuberculosis.

The primary goal of the research is to determine factors associated with a successful treatment outcome in tuberculosis.

Project Researchers: Damion Dooley

Institution: BC Centre for Disease Control

Access Approval Date: 04/11/2016

Brief Description of Proposed Research:

This research will help validate the Genomic Epidemiology Ontology (GenEpiO) that covers vocabulary necessary to identify, document and research foodborne pathogens and associated outbreaks.  The OWL working group produces World Wide Web Consortium (W3C) language recommendations.