MRCT Center Return of Aggregate Results to Participants Guidance Document Framework F r a m e w o r k Version 3.1 22 November 2017 Return of Aggregate Results Guidance Document Table of Contents RETURN OF AGGREGATE RESULTS WORK GROUP MEMBERS ........................................................... 4 ABBREVIATIONS .................................................................................................................................. 7 EXECUTIVE SUMMARY ........................................................................................................................ 9 1. INTRODUCTION ............................................................................................................................. 13 1.1 Purpose ................................................................................................................................................. 13 1.2 Document Scope .................................................................................................................................. 13 1.3 How to Use This Document ................................................................................................................. 15 2. OVERVIEW OF PLAIN LANGUAGE SUMMARIES FOR TRIAL PARTICIPANTS ................................. 17 2.1 Background .......................................................................................................................................... 17 2.2 Challenges ............................................................................................................................................ 22 2.3 Role and Involvement of the IRB/REC ................................................................................................. 25 2.4 Basic Principles ..................................................................................................................................... 27 3. ORGANIZATIONAL PROCESS AND LOGISTICS ............................................................................... 30 3.1 An Organization-Wide Process for Results Sharing ............................................................................. 30 3.1.1. Level and Scope of Plain Language Summaries .......................................................................... 30 3.1.2. Method(s) of Delivery .................................................................................................................. 31 3.1.3. Responding to Participant Follow-Up Queries ............................................................................ 35 3.1.4 Timing of PLS ................................................................................................................................. 36 3.1.5 Prior Publication and Timing of PLS ............................................................................................. 39 3.1.6 Coordinating PLS Among Study Sites ........................................................................................... 39 3.1.7 Ensuring Integration and Sustainability of PLS ............................................................................ 41 3.2 Process and Logistics for Study-Specific Results Sharing .................................................................... 41 3.2.1 Before the Study Starts ................................................................................................................ 42 3.2.2 During Study Donduct .................................................................................................................. 44 3.2.3 After All Data for the Primary Endpoint Has Concluded and (Often) After the Study Ends ....... 50 4. CONTENT OF PLS .......................................................................................................................... 53 4.1 General Principles ................................................................................................................................ 53 4.2 Levels of Personalization for Result Summaries .................................................................................. 55 4.2.1. General Overview of Study Results ............................................................................................. 55 4.2.2. Results by Study Arm (“Group”) see 75 .......................................................................................... 56 4.2.3. Study Results for Each Individual see 75 ......................................................................................... 56 4.2.4. Incidental Findings see 75 ............................................................................................................... 56 4.3 Essential Sections for Plain Language Summaries (PLS) ...................................................................... 57 General Information About the Clinical Trial ........................................................................................ 58 4.4 Cultural Literacy ................................................................................................................................... 61 MRCT Center Return of Aggregate Results Guidance Document Page 2 November 22, 2017 | Version 3.1 © MRCT Center 4.4.1 Translation of Plain Language Summaries ................................................................................... 61 4.4.2 Cultural Review of Plain Language Summaries ............................................................................ 62 4.4.3 Cultural Review of Return Processes ........................................................................................... 62 4.5 Templates for Plain Language Summaries (PLS) .................................................................................. 62 5. SPECIAL CONSIDERATIONS ........................................................................................................... 64 5.1. Trials That Close Early ......................................................................................................................... 64 5.2 Observational, Long-Term Follow-Up, Registry, and Extension Studies ............................................. 64 5.3 Studies That May Not Warrant Return of Results ............................................................................... 65 5.4 Notification of Results to a Third Party Who Was Designated by the Participant ............................. 66 5.5 Vulnerable Populations ........................................................................................................................ 66 5.6 Legally Authorized Representatives and Other Designated Parties ................................................... 67 5.7 Return of Results in the Event of Participant Death ........................................................................... 67 5.8 Assent for Return of Results to Children ............................................................................................. 68 6. FUTURE DIRECTIONS .................................................................................................................... 68 7. CONCLUSIONS ............................................................................................................................... 70 8. APPENDICES .................................................................................................................................. 71 1 - Key Terminology in this Document ....................................................................................................... 72 2 - Timing of Return of Results .................................................................................................................. 75 3 - Health Literacy Principles ...................................................................................................................... 77 4 - Health Literacy Missouri Best Practices for Numeracy ........................................................................ 82 Key Tables Table 1 Key Milestones for Clinical Trial Data Sharing ..................................................................... 18 Table 2 Suggested Timing for Returning Results ............................................................................. 38 Table 3 Summary of Essential Elements for Inclusion in the PLS .................................................... 57 MRCT Center Return of Aggregate Results Guidance Document Page 3 November 22, 2017 | Version 3.1 © MRCT Center RETURN OF AGGREGATE RESULTS WORK GROUP MEMBERS CORE WRITING GROUP Version 2.1 Carmen Aldinger Multi-Regional Clinical Trials Center of Brigham and Women’s Hospital and Harvard (MRCT Center) Barbara E. Bierer MRCT Center/ Brigham and Women’s Hospital / Harvard Medical School Deborah Collyar Patient Advocates In research Rebecca Li MRCT Center/ Brigham and Women’s Hospital / Harvard Medical School Laurie Myers Merck & Co., Inc. KEY CONTRIBUTORS Recognizing those who contributed specific content, templates or examples that are included within this guidance document Behtash Bahador CISCRP* Alla Digilova MRCT Center (currently Morgan Lewis) Elizabeth Frank Dana Farber Cancer Institute Barbara Godlew The FAIRE Company, LLC Zach Hallinan CISCRP* (currently Duke University) Barbara Kress Merck & Co. David Leventhal Pfizer Inc. Craig Lipset Pfizer Inc. Mary Ann Plummer TransCelerate BioPharma Inc Sandy Prucka Eli Lily & Co. Zachary Shapiro MRCT Center MRCT Center Return of Aggregate Results Guidance Document Page 4 November 22, 2017 | Version 3.1 © MRCT Center Additional thanks go to: • Deborah Collyar and Laurie Myers who participated