CPTR 2014 Rapid DST Workshop Report Day 1
Day One: September 22, 2014
Welcome – Objective of Meeting
Speaker: Marco Schito, Henry Jackson Foundation (HJF), TB Clinical Research Branch, DAIDS, NIAID, NIH
Marco Schito welcomed participants to the CPTR Rapid Drug Susceptibility Testing (DST) 2014 Workshop and shared the goals for the meeting:
- Develop work plans and goals for the CPTR Rapid DST work teams
- Increase collaborative efforts across the sectors: pharmaceutical, diagnostics, clinicians, academia, advocacy, funders, regulators, others
- Present plans for the TB drug Resistance Data Platform
- Provide networking opportunities for workshop participants
- Foster new ideas and potential efforts
He also presented an overview of the current landscape for rapid drug susceptibility testing (DST), including target product profiles (TTPs). After reviewing the NIH’s Genomic Data Sharing (GDS) policy, he highlighted future opportunities for the community, including exploring new drug entities, publications for World TB Day, and an upcoming conference on Next-generation Sequencing (NGS) Technology.
See Marco Shito’s presentation and video.
CPTR Rapid Drug Susceptibility Testing Roadmap
Speaker: Debra Hanna, Critical Path Institute
Debra Hanna provided an overview of the CPTR Rapid DST Consortium, including the objectives for the group and its Working Group structure:
- Accelerate the development of new, safe, and highly effective regimens for TB by enabling early testing of drug combinations
- Accelerate the development of a clinically useful, regulatory approvable, WHO-qualified in vitro diagnostic assay for rapid drug susceptibility testing of TB to facilitate drug development and rational use of new drug regimens
She reviewed the consortium’s overall progress since 2013 and then honed in on the focus, purpose, and accomplishments of each working group. She also shared future milestones for the group for 2015-2017:
- RDST Data Use Agreements and Data Requests developed [4Q 2014]
- Complete the Data Platform architecture & conduct beta testing [4Q 2015]
- Data Platform available for RDST Consortium Members [early 2016]
- Data Platform launch [mid-2016]
See Debra Hanna’s Roadmap presentation and video.
Clinical Pathogen Genome Sequencing
Speaker: Lynn Bry, Center for Clinical and Translational Metagenomics
Lynn Bry focused on the expanding role for genome analyses and where its use is appropriate. Bry discussed the role of Clinical Laboratory Improvement Amendments (CLIA) labs and how they are evolving. She shared results and findings from a clinical case study from culture to sequencing. The presentation also covered recommendations for what governments and other agencies can do to better use and integrate these techniques into their work, including leveraging existing programs and structures, increasing standards for vendors, ramping up educational efforts, and providing clinical training programs for specialists.
Rapid DST Data Sharing Platform Session
Objective: Provide a comprehensive overview of the RDST data sharing platform, discuss challenges & opportunities, and discuss the regulatory perspective.
TB Drug Resistance Database
Moderator: Angela Starks
- Introduction & Objective
Speaker: Angela Starks, Centers for Disease Control and Prevention (CDC)
Angela Starks gave an overview of the rationale for, and progress toward, a CPTR TB Drug Resistance database currently in development. She described the background for the project, the work to date, and early decisions that had been undertaken in the effort.
See Angela Starks’ video
- Database Architecture & Concept Plan
Speaker: Enrique Aviles, Critical Path Institute
Enrique Aviles provided more details on the TB Drug Resistance database, leading with examples of other data projects and the knowledge-sharing concept that has informed the effort. Aviles then described the RDST concept, provided examples of RDST data types and described the database architecture. He shared next steps for development, as well as the timeline through 2017.
See Enrique Aviles presentation and video.
- Validating DR SNPs—Expert Panel Engagement
Speaker: David Dolinger, FIND Diagnostics
David Dolinger discussed efforts to develop a database of regularly updated, validated resistance-associated mutations for m.tb, which will be data driven, developed by consensus, and can be utilized in a manner to positively affect patient treatment and validate and document drug resistance. Dolinger shared the precedents, potential and challenges for such a database, and the plans, roles and goals for an expert panel which will govern the project.
See David Dolinger’s presentation and video.
Current TB Sequencing Projects
- Data Challenges & Opportunities
Speaker: Stefan Niemann, Research Center Borstel
Stefan Niemann discussed some of the challenges to phenotypic and genotypic sequencing regarding mutations. Niemann also addressed questions on the relationship between mutations in the lab and patient response, as well as incentives for country-based contributors and research organizations to contribute data for the database.
See Stefan Niemann’s presentation.
- Importance of the genetic diversity within Mycobacterium canettii and the M. tuberculosis complex for the development of drug-susceptibility assays
Speaker: Claudio Koeser, University of Cambridge
Claudio Koeser shared suggestions for improving DST based on recent research, including checking for cross-resistance, using solid and liquid media, and evaluating across varied geographical samples in early-stage development. Koeser discussed the need to scale more intensive and complete testing for current and new therapies against resistance.
See Claudio Koeser’s presentation.
Workgroup Breakout Sessions
Assay Development Workgroup Session
This breakout session discussed the varying costs, drivers of costs, and the general consensus on how the pricing of new technologies needs to be addressed. With varying characteristics, there is no simple formula in order to determine cost. The drivers of cost that need to be taken into consideration include making suitable tests, ease of use, drugs, reproducibility and infrastructure. The group concluded that making information more available to industry on TPPs, markets and market projects, and increasing transparency are key components to this work.
Economic and Impact Modeling Workgroup Session
This workgroup reviewed updates and progress since the group’s previous meeting, which included developing frameworks of models, publication of the “first principles model,” shifting focus to PaMZ in light of REMox TB results, and recognizing that modeling certainty is a major issue. Current issues for the group include efforts to understand the drivers of resistance and upcoming publications soon to be submitted. The group spent time discussing the first principles model in more detail and outlined upcoming plans for various models. They discussed key priorities emerging from the discussions and recent research, and potential next steps for the working group.
Enabling Sciences Workgroup Session
This workgroup discussion was focused on the discovery and validation of the molecular basis for resistance and correlation of resistance to clinical outcomes. The group discussed needs, including access to drugs/isolates and outcome data with strains, limiting the number of DST methods, standardizing strains from other regions of the world, and further evolved and updated bio banks. The group also discussed the RDST database. Key take-aways included a focus on genotypic and phenotypic data and the timing of data collection as it relates to the monitoring of clinical outcome.
Surveillance Workgroup Session
This workgroup discussion focused on the need for, and challenges to, obtaining high quality surveillance data. The group examined the WHO database project, the largest thus far based on phenotypic data. A discussion focused on how data is currently obtained and stored, and the challenges to obtaining accurate and current data as the TB community grows in scope and depth. Currently, few standards exist for language, numbering system, etc. However, the WHO plans to discuss data-gathering from published works and sequencing technologies next year.
Workgroup Plenary Session
All workgroups reconvened in a plenary session to discuss the outcomes, challenges, and recommendations from the preceding breakout session with the full workshop audience.
Moderators: Marco Schito, Claudia Denkinger. See moderators Marco Schito and Claudia Denkinger’s presentation and video.
- Assay Development Workgroup
Presenter: Claudia Denkinger, FIND Diagnostics
Claudia Denkinger presented the highlights of the workgroup breakout session on assay development. The discussion focused largely on the varying perspectives towards costs and the challenges and considerations on pricing. Suggestions for solving these challenges included making information more available to the industry on TPPs, markets and market projects; creating more discussion platforms; and increasing transparency.
See Claudia Denkinger’s video.
- Economic Assessment & Impact Modeling Workgroup
Presenter: David Dowdy, Johns Hopkins University
David Dowdy presented the efforts of the workgroup thus far – which included exploring the role of mixed infections, modeling possible effects of different DST strategies, and modeling the impact of the DST – and next steps. He shared the group’s longer-term goal of considering the broader impact of DST as a tool to facilitate drug development, as well as key questions that the group is considering.
See David Dowdy’s video.
- Enabling Sciences Workgroup
Presenters: Barry Kreiswirth, Rutgers University; Jamie Posey, CDC
The presenters reminded the group of the mission and purpose of the working group, which focuses on the discovery and validation of the molecular basis for resistance and correlation of resistance with clinical outcome. Kreiswirth shared the data needs of the working group and the ways in which new data would continue to influence all of the working groups, as well as the RDST database.
See Barry Kreiswirth and Jamie Posey’s video.
- Surveillance Workgroup
Presenter: Matteo Zignol, World Health Organization (WHO)
Matteo Zignol focused on how to best gather quality surveillance data. The workgroup looked at the current WHO database and the need to strengthen surveillance data via phenotypic DST.
See Matteo Zignol’s video.