The Food and Drug Administration (FDA) recently gave a presentation on how the agency “Promotes Partnerships to Accelerate Medical Product Development.” The presentation was given by ShaAvhrée Buckman-Garner, MD, PhD, Director of FDA’s Office of Translational Sciences, in the Center for Drug Evaluation and Research (CDER). The presentation focused on:
- How FDA encourages broad stakeholder efforts to generate drug development tools
- How FDA respond sto a rapidly changing scientific landscape
- How FDA incorporates the patient’s voice?
- How FDA collaborates with other regulatory agencies toward greater concurrence in regulatory requirements in areas of unmet medical need?
- What are the benefits of such collaborations, especially between the US and EU? and
- How does FDA measure success?
Garner noted that there is general agreement that the development of evaluative tools is a “tremendously neglected area.” She noted that “better science is needed to both predict and assess safety and efficacy of investigational products.” She said that major causes of failure in Phase 3 clinical development include:
- Lack of effectiveness against placebo or active control
- Unexpected drug toxicity; or
- Commercial non‐viability (not better than existing therapy)
Accordingly, she emphasized the need for new evaluative tools. She pointed out that while there are a large amount of biochemical/molecular knowledge, there are few ways to assess the state of a whole organism and impact of interventions at the organism level. She recognized that “most assessment tools are not standardized so [there is] limited ability to compare one experiment to another.” She also noted that there is “little insight into sources of variability of treatment response, even for current therapies.
As a result, most clinical development programs are “brute force” empirical efforts: extremely costly and time‐consuming, she noted.
Garner pointed to several programs and achievements FDA has had with regard to advancing drug approval, such as the agency’s “Advancing Regulatory Science at FDA Report ,” Identifying CDER’s Science and Research Needs Report from July 2011, published by CDER’s Science Prioritization and Review Committee (SpARC), as well as
The Critical Path Opportunities List and Report.
Nevertheless, she discussed the future of FDA’s drug approval framework, first noting “Predicting, Measuring, and Improving Efficacy Needs.” In this regard, she said that FDA and stakeholders need:
- New endpoints
- New trial designs
- Use of biomarkers to subset disease (prognostic or response predictors)
- Use of patient‐reported outcomes; and
- Conducting natural history studies to understand disease course—particularly in rare diseases
Garner noted that CDER and FDA have already taken a number of steps to catalyze movement from “concept to action.” For example, examples of collaborative efforts include the
- Cardiovascular Safety Research Consortium (CSRC) (official site)
- International Serious Adverse Events Consortium (iSAEC)
- Biomarkers Consortium
- Clinical Trials Transformation Initiative (official site)
- Critical Path Institute
- Predictive Safety Testing Consortium (PSTC)
- Patient Reported Outcomes (PRO) Consortium
- Coalition Against Major Diseases Consortium
- Critical Path to TB Drug Regimens
- Polycystic Kidney Disease (PKD) Consortium
- Multiple Sclerosis Outcome Assessments Consortium
- Electronic Patient-Reported Outcome (ePRO) Consortium
- Coalition for Accelerating Standards and Therapies (CFAST)
– Analgesic Clinical Trials Translation, Innovation, Opportunities and Networks (ACTTION) Initiative
Garner also discussed Drug Development Tool (DDT) Qualification Activities, which includes clinical outcome assessment; Biomarkers; and animal models (animal rule)
The FDA director next discussed FDA’s work on Innovative Clinical Trial Designs Guidance Development, which include:
- DesignsAdaptive Trial Designs (draft published)
- Non-inferiority Trial Designs (draft published)
- Multiple Endpoint Analysis (in development)
- Enrichment Designs (draft published) (see our story)
- Treatment of Missing Data (in development)
Additional Topics include:
- Meta-Analysis Approaches for Efficacy and Safety Data (in development); and
- Qualification Process for Drug Development Tools (draft published)
She also discussed the need for FDA to create an Integrated Workforce and to train this work force, which should include members from:
- Clinical Investigation
- Drug Development
- Regulatory Science
- Medical Informatics/Computational Science; and
- Statistics
The concept, Garner said, is to create integrated training hubs for online/deployable content and training for international investigators, regulators, etc.
Next, she discussed how stakeholders can collaborate with other regulatory agencies more effectively. Several options include:
- Data Sharing, for example, the CPath-IMI-Biomarkers Consortium—renal biomarkers
- Cooperation re: Data Sharing, such as sharing plans and coordinating activities between international partners
- Share Best Practices
- Coordinate data requests for DDT Qualification submissions
- Share Discussion of Key Initiatives/Activities and Outcomes
- Joint liaisons to key initiatives
- PSTC and SAFE-T Consortium
- Remove Redundancy–Proactive sharing of strategy and plans
- Build Collaborative IT Platforms
Garner then discussed how FDA and stakeholders should measure success with these new collaborations. She said that FDA will measure success based on:
- The number of approvals of new medical therapies
- Development of new guidance
- Integration of novel biomarkers into regulatory review processes
- Proactive sharing of pre-competitive data
- Development of data warehouses based on standardized data in order to leverage prior knowledge
- Streamlined coordination of information among international regulators
In mentioning current and previous success, Garner pointed to the number of drug approvals in 2012. Through Nov 30, in Calendar Year (CY) 2012, CDER had received 34 NME applications.
Ultimately, Garner proposed that FDA and stakeholders “create collaborative platforms which provide a global mapping of Public Private Partnership (PPP) activities. Such activities would have an Internal aspect, which allows an interface for PPPs to collaborate and share information safely, as well as an external aspect, which allows potential stakeholders to identify efforts to support. Garner said that the benefits from such a proposal will allow PPPs to identify current efforts for collaboration internationally and target gaps for future development.