MRCT Center Post-Trial Responsibilities Framework Continued Access to Investigational Medicines I. Guidance Document December 1, 2016 Version 1.0 MRCT Center Guidance for Post-Trial Responsibilities – Version 1.0, December 1, 2016 Page 1 Post-Trial Responsibilities Framework: Continued Access to Investigational Medicines Guidance Document Table of Contents I. EXECUTIVE SUMMARY .......................................................................................................................... 4 II. BACKGROUND ................................................................................................................................... 11 Section 1: Introduction ........................................................................................................................................ 11 A. History, scope and purpose of the Framework ...................................................................................... 11 B. Approach and Process ........................................................................................................................... 14 Section 2: Terminology and Definitions ............................................................................................................. 15 A. Post-trial terminology ............................................................................................................................ 15 B. General terminology .............................................................................................................................. 18 Section 3: Existing Reference Guidance ............................................................................................................. 18 A. Declaration of Helsinki ......................................................................................................................... 19 B. The Council for International Organizations of Medical Sciences (CIOMS) ....................................... 20 C. Additional sources of guidance ............................................................................................................. 21 D. Summary ............................................................................................................................................... 23 Section 4: Ethical Principles ............................................................................................................................... 24 A. General ethical considerations in biomedical research in concert with PTR duties .................................. 24 B. Nonmaleficence ......................................................................................................................................... 24 C. Autonomy .................................................................................................................................................. 25 D. Justice ........................................................................................................................................................ 25 E. Beneficence ................................................................................................................................................ 28 Section 5: Stakeholder Roles .............................................................................................................................. 28 Table 1. Primary roles of stakeholders................................................................................................................ 29 III. MRCT GUIDANCE FOR CONTINUED ACCESS TO INVESTIGATIONAL MEDICINES ................. 33 Section 1: Paradigm – Stages, Criteria and Stakeholder Responsibilities .......................................................... 33 Section 2: General Guidance .............................................................................................................................. 33 A. Stages of Continued Access to an Investigational Medicine ................................................................. 33 B. Criteria for Continued Access to an Investigational Medicine.............................................................. 35 1. Criteria ................................................................................................................................................... 35 MRCT Center Guidance for Post-Trial Responsibilities – Version 1.0, December 1, 2016 Page 2 2. Justification for Criteria ......................................................................................................................... 36 a) Risk of death or serious harm if treatment is withdrawn .................................................................. 36 b) Benefit and risk determination .......................................................................................................... 37 c) Suitable therapeutic alternatives ....................................................................................................... 37 d) Other ways to access treatment ......................................................................................................... 38 e) Adverse effects to the research viability ........................................................................................... 38 f) Eligible population ........................................................................................................................... 39 3. Criteria for Providing Medical Care and Infrastructure .................................................................... 40 4. Stakeholder Roles and Responsibilities ............................................................................................ 40 Section 3: Specific Guidance .............................................................................................................................. 41 A. Planning Stage of a Clinical Trial ......................................................................................................... 41 B. Access to the Investigational Medicine ................................................................................................. 46 1. Overarching Responsibility: Assess Benefit and Risk ........................................................................... 46 2. Responsibilities Over the Time Course of a Clinical Trial .................................................................... 46 3. How long do the responsibilities last? .................................................................................................... 52 4. How should phase of product development be addressed? .................................................................... 53 C. Access to Accompanying Medical Care ................................................................................................... 55 1. Who is responsible? ................................................................................................................................ 55 D. Access to Required Infrastructure .............................................................................................................. 58 1. What are the responsibilities? ................................................................................................................. 59 2. Who is responsible? ................................................................................................................................ 60 3. How long will the responsibilities last? .................................................................................................. 60 4. How will specific conditions be addressed? ........................................................................................... 60 Section 4: Special Considerations ....................................................................................................................... 62 A. National Laws and Regulations ................................................................................................................. 62 B. Reimbursement .......................................................................................................................................... 63 C. Research Participant’s Access to Post-trial Research Data ........................................................................ 64 References ........................................................................................................................................................... 65 APPENDIX ......................................................................................................................................................... 69 Writers and Reviewers of PTR Framework and Toolkit .................................................................................... 69 Post-trial Responsibilities Workgroup ................................................................................................................ 70 MRCT Center Guidance for Post-Trial Responsibilities – Version 1.0, December 1, 2016 Page 3 I. EXECUTIVE SUMMARY The MRCT Center Post-trial Responsibilities: Continued Access to an Investigational Medicine Framework outlines a case-based, principled, stakeholder approach to evaluate and guide ethical responsibilities to provide continued access to an investigational medicine at the conclusion of a patient’s participation in a clinical trial. The Post-trial Responsibilities (PTR) Framework includes this Guidance Document as well as the accompanying Toolkit. A 41-member international multi-stakeholder Workgroup convened by