TABLE 5.

Key Elements of CARRA-CoRe Governance Plan

Principle	Challenge Addressed	CARRA-CoRe Solution
Formal role for patients, families, and patient advocates in governance	Ensuring governance appropriately reflects the social contract to protect the safety of patients	Steering Committee membership includes family/patient advocates and the Advocacy External Advisory Committee reviews progress and future directions, making recommendations as indicated.
Formal industry role in governance and scientific design	Protecting industry interests in decision-making and scientific design	The Industry Sponsor Advisory Committee appoints 2 Steering Committee members as well as ad hoc industry experts to advise the SOC (see below) on study design.
Independent scientific oversight	Ensuring a process to mitigate potential conflicts of interest	The SOC is solely responsible for scientific design, study conduct, and analysis without formal industry or other private or public membership. Scientific participation from industry is assured through the ISAC providing input to the SOC to manage conflicts of interest among industry participants with competing products. The Scientific EAC reviews the scientific progress and direction, making recommendations where indicated.
Efficient policies and procedures for data quality and monitoring	Balancing high-quality data collection and management with efficient and less costly data verification and monitoring procedures	Efficient policies and procedures optimize data integrity through use of electronic monitoring where appropriate, supplemented with routine and for cause on-site monitoring.a
Reliable adverse event adjudication and reporting	Ensuring a reliable process for efficient detection and management of adverse events	The SOC is responsible for the evaluation, adjudication, and appropriate notification and reporting of all serious adverse events and events of special interest. Adjudication will include subspecialty experts as necessary. Validated definitions of pediatric SAEs and events of interest are being developed with international partners.
Risk attribution in the presence of multiple exposures	Balancing patient care needs requiring treatment adjustments with interpretation of adverse events in the context of multiple exposures over time	Fair and transparent policies and procedures developed by the SOC with input from industry govern analyses of serious adverse events in the context of multiple exposures, risk windows, and other approaches.
Long-term follow-up	Implementing processes and procedures to follow participants who relocate or transfer to adult care	The Long-Term Follow-Up Group within the DCRI Clinical and Data Coordinating Center manages a centralized communication repository, including confidential contact information for participants. Efforts to harmonize a validated set of outcome tools and patient-reported outcome measures that can be used across the lifespan are underway. In addition, the protected contact repository will facilitate potential future linkage to large administrative and billing databases including the Centers of Medicare and Medicaid Services, pharmacy databases, insurance databases, cancer registries, death index, and other registries and resources.
Patient confidentiality	Assuring the highest level of personal health information protection	Participants’ personal health information is sequestered from clinical data at the sites or by the Long-Term Follow-Up Group (Honest Broker)31
Data access and sharing	Insuring responsible and transparent stewardship of data analysis and dissemination and publication of results	Policies and procedures are under development to govern data access, analysis, utilization, dissemination and publication of results to guarantee meeting safety and regulatory requirements and responsible conduct of research.
Management of intellectual property and antitrust issues	Balancing protection of public safety with intellectual property interests and antitrust issues	The Steering Committee is responsible for overseeing potential conflicts regarding ethical and regulatory reporting of safety issues with intellectual property or antitrust issues.

^aThe FDA agreed to this monitoring approach in concept, and the approach is generally consistent with that described in the FDA’s draft monitoring guidance issued in August 2011 and a letter from the Division of Pulmonary, Allergy, and Rheumatology Products, Office of Drug Evaluation II, Center for Drug Evaluation and Research, FDA, regarding CARRA-CoRe monitoring plan dated December 21, 2010.