Core Competencies

Critical Path Institute (C-Path) serves as a neutral third party to enable multiple stakeholders across the spectrum of medical product development to work together in a pre-competitive consortium model in order to drive innovative tools and methods which help to de-risk decision making in the development and regulatory review process. This makes C-Path a unique source of expertise working to achieve many of the objectives outlined in the FDA’s report “Innovation / Stagnation – Challenge and Opportunity on the Critical Path to New Medical Products.”


Regulatory qualification of preclinical, and clinical biomarkers and novel methodologies for safety, efficacy, and trial enrichment Development and qualification of clinical outcome assessment tools Development of quantitative modeling and simulation tools Regulatory acceptance of nonclinical tools for medical product development Impact on Regulatory Science Forming and managing large international consortia Provision of large-scale data solutions for scientific research Clinical data standards development



Regulatory qualification of preclinical, and clinical biomarkers and novel methodologies for safety, efficacy, and trial enrichment

C-Path leads the way in regulatory qualification of biomarkers. C-Path was the first organization to qualify biomarkers with the US Food and Drug Administration (FDA), European Medicines Agency (EMA), and Japan’s Pharmaceutical and Medical Devices Agency (PMDA). The following C-Path consortia have successfully qualified biomarkers with regulatory agencies.



Development and qualification of clinical outcome assessment tools

By working with multiple stakeholders (e.g., patients, regulators, clinical advisors, industry scientists, measurement experts) in the US and around the globe, C-Path is a leader in the development and qualification of patient-reported outcome measures and other clinical outcome assessment (COA) tools.  C-Path’s Patient-Reported Outcome (PRO) Consortium provides a collaborative framework for the qualification of COA tools that can be used to support medical product labeling claims. The Electronic Patient-Reported Outcome (ePRO) Consortium works closely with the PRO Consortium to make the PRO instruments emerging from its therapeutic area working groups available in multiple modes of data collection.  While other COA tools are in development or other stages of qualification, the following PRO measures have obtained FDA qualification:



Development of quantitative modeling and simulation tools

The discipline of modeling and simulation has been a key area of expertise for C-Path since its inception. The vision of C-Path’s Quantitative Medicine <link> team is to transform drug development through methodological innovation and Model-Informed Drug Discovery and Development (MID3). C-Path’s Quantitative Medicine team also works to drive innovation in MID3 through partnerships with leading groups and organizations in the field, and through collaborations with societies such as the International Society of Pharmacometrics. The development of these tools is possible thanks to the standardized integration of clinical and data analytical knowledge to solve bottlenecks in the drug development process. C-Path collaborated with scientists in industry to develop the first endorsed quantitative drug development platform:

C-Path’s Quantitative Medicine team directly led the development of the disease progression model that supported the qualification of dopamine transporter imaging as an enrichment biomarker for trials in early motor Parkinson’s disease. Currently, the team is developing disease progression models for Parkinson’s disease, Duchenne muscular dystrophy, and mild cognitive impairment (a pre-dementia stage in Alzheimer’s disease), as well as several new quantitative drug development tools for tuberculosis, and the model-based biomarker qualification of four auto-antibodies as prognostic biomarkers for trials in type-1 diabetes.



Regulatory acceptance of nonclinical tools for medical product development

In addition to the competencies described above, C-Path also has capability in developing and providing evidence packages to regulators for in vitro tools and other atypical (or non-traditional) tools. In vitro tools are critically important in earlier phases of drug development to facilitate decision making regarding compound, dose, combination regimen selection and more. In vitro tools can also be utilized in clinical diagnosis and pathogen detection. Surveillance of pathogen resistance is another application with which C-Path has expertise.



Clinical data standards development

C-Path’s core competency in clinical data standards development enables the effective aggregation of large datasets and helps expedite the regulatory review process. C-Path has a close and long-standing relationship with the Clinical Data Interchange Standards Consortium (CDISC). CDISC is a recognized standards-setting organization and CDISC standards are required for new NDA and IND submissions to the FDA. C-Path worked with (CDISC) to develop the first therapeutic area data standards and has led the efforts in many others since then including Alzheimer’s disease, Parkinson’s disease, polycystic kidney disease, tuberculosis, multiple sclerosis, Duchene’s muscular dystrophy and others. Approved data standards are published for use by the scientific research community on CDISC’s website.



Provision of large-scale data solutions for scientific research

C-Path’s Data Collaboration Center (DCC)  was instituted to provide large-scale data solutions for scientific research. This DCC team has more than a decade of experience in data standards development, platform development, platform hosting, data curation, stewardship of patient-level data privacy, data security, and access control methodologies. The DCC’s work takes place in a neutral, non-competitive environment, and utilizes appropriate data standards. C-Path has developed and continues to maintain databases for Alzheimer’s disease, Parkinson’s disease, polycystic kidney disease, tuberculosis, Duchenne muscular dystrophy, kidney safety biomarkers, multiple sclerosis and other disease areas.

Information about three different types of databases C-Path developed are listed below this. For a complete list, visit the DCC Projects site.

  1. Genetic sequencing of pathogens
  2. Collection of nonclinical and clinical biomarker data
  3. Integrating patient level data



Forming and managing large international consortia

C-Path is an expert in pre-competitive collaboration and is a trusted, neutral entity in regulatory science that excels in forming, managing, and facilitating large international consortia.   Stakeholders include industry, regulatory and other governmental agencies, non-governmental organizations, patient groups, and academia world-wide.

C-Path’s ability to drive toward focused goals is key to its extraordinary competence in overseeing large consortia through technical, scientific, legal, regulatory, and project management expertise enabling the achievement of regulatory acceptance of drug development tools or novel methodologies. Each consortium collaborator is encouraged to share data that promotes the advancement of a wide variety of cross-cutting and disease-specific drug development tools and innovative methodologies.



Impact on Regulatory Science

C-Path focuses on the advancement of regulatory science through multiple avenues beyond qualification.  This includes the development of points to consider white papers representing consensus among experts and stakeholders within a consortium.  These papers are informative to regulatory authorities as they work to develop regulatory guidance documents.  Furthermore, C-Path has provided public feedback on numerous draft guidance documents released for comment by both FDA and EMA.

C-Path has been instrumental in leading the movement within the scientific community to more clearly articulate the level of evidence necessary to achieve qualification, one of the most challenging issues in the drug development tool qualification process.  In April 2016, key stakeholders including FDA CDER, C-Path, and the Foundation for the National Institutes of Health Biomarkers Consortium (FNIH BC) held a workshop to develop an evidentiary criteria framework for safety biomarker qualification.  The resulting white paper delineated the proposed framework and provided specific examples of its applicability to clinical safety biomarkers. In June 2017, C-Path and the Duke Margolis Center for Health Policy held a public conference to bring together key stakeholders to discuss a draft framework outlining criteria and best practices for biomarker assay performance expectations and validation. A draft white paper was prepared in advance of the public forum, and input was solicited after the conference.  Currently, the framework is being utilized by biomarker qualification stakeholders to evaluate assay acceptability in ongoing and planned biomarker qualification projects.