FDA’s Clinical Investigator Course Cosponsored by FDA’s CDER, Office of Medical Policy and The Duke University School of Medicne Good Clinical Practice (GCP) Key Topics Bridget Foltz Office of Good Clinical Practice Topics • Investigator responsibilities • Clinical Investigator financial disclosure • Expanded access to and charging for investigational drugs and devices • Resources Investigator responsibilities • Both 21 CFR Part 312 and 812 hold the clinical investigator (CI) responsible for the conduct of the study at the study site • Lack of appropriate study oversight by the CI is a commonly cited noncompliance in bioresearch monitoring (BIMO) inspections Investigator responsibilities • FDA final guidance document issued October 2009 • Guidance covers: – Appropriate delegation of study tasks – Appropriate training of study staff – Supervision of staff, including contracted personnel – Subject protections, including necessary medical care Investigator responsibilities • Appropriate delegation of study tasks – Any individual to whom a task is delegated must be qualified by education, training, and experience (and state licensure where relevant) – Individuals delegated must meet any protocol specified requirements – Listing of tasks and individuals delegated should be maintained Investigator responsibilities • Appropriate training of study staff – Familiarity with protocol and specific tasks – Knowledge of applicable regulations and HSP and GCP principles – Individuals competent or trained to cover tasks assigned – Updates and additional training provided as needed Investigator responsibilities • Supervision of staff, including contracted personnel – The level of supervision should be appropriate to the staff, the nature of the trial, and the subject population – A supervisory plan should include routine meetings with study staff and procedures for determining appropriate completion of delegated tasks – Oversight extends to SMO staff, CI-contracted providers (radiologists, labs), and medical device engineers Investigator responsibilities • Subject protections, including necessary medical care – Reasonable medical care for study- related medical problems – Provision of access to appropriate medical care when specialized care is required – Adherence to the study protocol Clinical investigator financial disclosure • 21 CFR Part 54 – final regulation issued 1998 • Investigators and sub-investigators (those who play a significant role in the conduct of the study) are required to supply information (+ spouse and dependent children) • Requires reporting to the study sponsor prior to participation in the study and updates yearly, as needed, until one year after study completion Clinical investigator financial disclosure • Requires applicant of a marketing application/permit to – Certify that there are no financial arrangements with each investigator or – Disclose specific financial arrangements with study investigators and what was done to minimize bias Clinical investigator financial disclosure Disclosable arrangements 1.Compensation where the value could be affected by the study outcome (e.g., royalties) 2.Significant Payments of Other Sorts (SPOOS) – i.e., not including the payments for conducting the study – to either the investigator or the institution (e.g., grants, equipment, retainers for on-going consultation, honoraria) Clinical investigator financial disclosure Disclosable arrangments (cont.) 3.Proprietary interest in the product, such as a patent, trademark, copyright, or licensing agreement 4.Equity interest in a publicly traded company whose value >$50,000 or Equity interest such as ownership interest or stock options whose value cannot be readily determined through reference to public prices Clinical investigator financial disclosure • OIG inspection in 2009 • Recommended – Greater accountability of CIs, sponsors, and FDA – Additional guidance/training for FDA review staff – Follow-up during CI and sponsor inspections Clinical investigator financial disclosure • Final guidance issued February 26, 2013 • Specifically, the guidance describes: – Disclosure requirements – Responsibilities of various parties – Further explanation of terms used in regulations – How FDA will review financial disclosure information • Describes FDA’s policy to publicly post FDA’s reviews summarizing financial disclosure information related to an approved marketing application Expanded access • Long history of providing access outside of study participation – Emergency use – Treatment INDs/IDEs • FDAMA (1997) provides for access to experimental therapies for individuals and small groups of patients with serious or immediately life-threatening diseases Expanded access – investigational drugs • August 13, 2009 – final expanded access regulation issued • Strives to balance competing issues –。