Speaker: Jan Gheuens, Bill & Melinda Gates Foundation
Jan Gheuens opened CPTR’s 2016 Workshop by reminding the audience of the principles and mission of the CPTR Initiative, stressing the urgency of accelerating the development and availability of new TB combination therapies and noting the role of partnership and coordination in achieving the mission. Gheuens placed the aims of the initiative within the context of the World Health Organization’s End TB Strategy, remarking that CPTR must succeed on its goals to make the achievement of the broader WHO goals possible. Gheuens went on to note the progress made within the initiative, specifically the expansion of work, including the increasing role of diagnostic work within CPTR, and to thank all those who have contributed to the success and growth of CPTR to date.
The Critical Path to TB Regimens: Mapping our Progress and Future Plans for Success
Speaker: Debra Hanna, Critical Path Institute
Debra Hanna began her remarks by recognizing the growth of CPTR, including the addition of key new partners, and articulating the importance of the initiative. Hanna referenced significant recent milestones and successes of CPTR, including the launch of the ReSeq TB data platform, TB Pacts Phase III clinical trial database, and establishment of CDISC Data Standards. The participants were reminded that the tools developed by CPTR are for use by the community, and therefore the work, and this workshop itself, are interactive and improved by feedback. Hanna called for the community to engage with CPTR to help ensure that the initiative is developing what the community deems important and useful, and that the tools and their use is understood by those for whom they are created. The address closed by looking forward to future goals and additional expected progress for the year.
Speaker: Mark Sulkowski, Johns Hopkins University
Mark Sulkowski played an integral role in the profound advancement of hepatitis C treatment over recent decades. His keynote address detailed the similarities between combination therapy development for hepatitis C and the challenges and opportunities facing the advance of TB therapies. Sulkowski covered subjects including regulatory issues and guidelines, proving the importance of each drug within an experimental regimen, and the benefits and unique dynamics of a regimen development approach. In what emerged as a key theme of the workshop, Sulkowski also stressed the importance of meeting the needs of a product’s end-users and pushing innovation beyond drug development and throughout the entire continuum of patient care. The keynote ended with a lively question and answer session.
Improving Translation in TB Drug Development through Quantitative Modeling
Moderator: Klaus Romero, Critical Path Institute
Applying Quantitative Pharmacology Platforms in TB Drug Development: Best Practices for When and How
Speaker: Dan Hartman, Bill & Melinda Gates Foundation
Dan Hartman spoke about using data to make early and confident go/no-go decisions in product development. He stressed the importance of making objective decisions based on data and discussed the importance of using tools and models to aid decision-making, articulating the processes of acquiring data, analyzing it, and applying that information to make decisions. Hartman referenced the TB-PACTS clinical trial database tool as an example of a CPTR innovation that can aid in this process.
Envisioned Impact in TB Drug Development of a Physiologically-Based Pharmacokinetic Platform
Speaker: Iain Gardner, Simcyp
Iain Gardiner discussed the role physiologically-based PK modeling can play in predicting drug activity, ADME, and drug-drug interactions. These benefits mean that it can be used to help inform and optimize dosing strategies. Gardner presented modeling tools and compared their conclusions to information known about moxifloxacin.
Evidence-Based Validation of Pre-Clinical Drug Development Tools: Next Generation Work with Hollow Fiber System TB and In Vivo Pharmacology Models
Speaker: Eric Nuermberger, Johns Hopkins University
Eric Nuermberger addressed the opportunities to improve understanding and predictability between preclinical and late stage clinical research outcomes. One way to make advances in this area is through improved preclinical models. Nuermberger acknowledged CPTR’s work in this area, citing the hollow fiber system model in particular. His presentation explained the working of the model, how it can be integrated with other research tools and strategies, and details some of the ongoing studies making use of the model.
Lessons to be Applied from Recent Phase III TB Trials
Speaker: Christian Lienhardt, World Health Organization (WHO)
Over recent years, three individual drug substitution trials were unable to achieve a shortened TB treatment regimen. Christian Lienhardt’s presentation focused on the learnings to be gleaned across these trials. He raised questions regarding the predictability of preclinical models and whether researchers are using the correct endpoints in earlier trials to predict outcomes of future research. Liendhardt makes note of the new TB-PACTS database, which includes data from all three of the aforementioned trials, and discusses its potential value. When data from each trial is examined more closely, one can see differences in measurements and outcomes among different patient subpopulations and across liquid versus solid media. By combining data from multiple trials, TB-PACTS helps add power to that data to improve the validity of trends witnessed among smaller groups within a trial.
Collaborative Registration Pilot Efforts: Learning an Application to TB Drugs and Regimens
Speaker: Mac Lumpkin, Bill & Melinda Gates Foundation
Mac Lumpkin opened his presentation by noting the challenges of the regulatory landscape for new TB therapies, especially in TB-endemic countries and when dealing with resource constraints. He referenced work done by the Bill & Melinda Gates Foundation to better understand the timelines for regulatory approval of new products in key endemic countries including China, India, and several countries in sub-Saharan Africa. He then introduced the World Health Organization’s Collaborative Regulation Procedure as a tool that can potentially speed up these processes in low- and middle-income countries.
Overview of World Health Organization Collaborative Registration Procedure
Speaker: Milan Smid, World Health Organization (WHO)
Milan Smid began by establishing the context for this pilot program and the value of WHO Prequalification. He went on to discuss how collaborative registrations can help local regulators benefit from already organized and completed scientific evaluations of a specific product, and discussed the incentives for both WHO and countries to participate in the process. Smid then shared experiences of countries currently participating in the program and noted that 80% of registrations under the procedure have been completed within 120 days. He concluded the presentation by providing an update on ongoing revisions to the process.
Perspective from Participating Regulatory Authority
Speaker: Sabine Haubenreisser, European Medicines Agency
Haubenreisser offered perspective on principles and priorities important to the EMA when evaluating products, and discussed the agency’s mechanisms for sharing and exchanging information. She went on to cover EMA’s participation in WHO’s Collaborative Registration Procedure, specifically discussing “Article 58,” which involves collaboration with the WHO and national regulatory authorities.
Perspective from Participating Sponsor
Speaker: Mercè Caturla, Janssen
Mercè Caturla articulated Janssen’s experience participating in the stringent regulatory agency pilot procedure from the sponsor’s perspective. She noted that certain steps within the registration process were potentially accelerated, but some aspects of the procedure offered opportunity for improvement, specifically noting the coordination between countries and the program itself. Ultimately, through the procedure, Janssen received its first approval in fewer than 90 days and most approvals for which it applied in less than a year.
National Regulatory Authorities’ Perspectives on the Procedure
Speaker: William Wekwete, Medicines Control Authority of Zimbabwe
William Wekwete discussed the benefits and challenges of participating in the procedure as a representative of a national regulatory authority. Authorities from the ZaZiBoNa region have worked to asses 150 products together, so he is experienced in collaborative registration. Wekwete discussed the value of the procedure, but also acknowledged challenges, such as the adaptation of data from product evaluations in the United States or Europe for local populations. Wekwete cited communication to address unique country needs as an area of the process that could be improved, and proposed additional plans, workshops, and strategy meetings as tools that can help address this issue.
Evaluating Community Engagement Practices in TB Research
Speaker: Steve Wandiga, Kenya Medical Research Institute
Wandiga opened the session by reminding the audience the importance of community engagement efforts as a core element of TB research, for both the researchers and community. He reinforced the fact that engagers continue try to determine the tools most helpful in both improving community engagement efforts and evaluating its impact.
Development and Roll-Out of Monitoring & Evaluation (M&E) Toolkit
Speaker: Stephanie Seidel, TB Alliance
Stephanie Seidel began by acknowledging CPTR’s critical role in facilitating the collaboration of various groups involved in community engagement (CE) efforts to advance and enhance tools to ensure best practices and unified standards in the field. Unified standards help enable the development of tools to measure the impact of CE efforts. Seidel then presented the “Engagement for Impact” website and toolkit, detailing its capabilities, aims, and its recent roll-out.
Implementing M&E Tools
Speaker: John Mdluli, Aurum Institute
John Mduli recounted Aurum Institute’s experiences implementing the M&E tools at the site level, reiterating the need to demonstrate the impact of CE work to improve performance, track progress, and attract donor support for such efforts. Mdluli looked forward to how the data captured from the M&E tools can be used in the future.