It’s Just a Little Change; Oh and It’s Time to Renew! How to submit amendments and renewals

1. It’s Just a Little Change; Oh and It’s Time to Renew!How to submit amendments and renewals Human Investigation Committee Human Research Protection Program Yale University

2. Federal regulations and Yale University policy require continuous approval of a research study • When the study’s approval period has expired, all research activity must stop unless the HIC finds that it is in the best interest of individual subjects to continue

3. Always use the most recent Request for Renewal form (Form5R), which can be found here: http://www.yale.edu/hrpp/forms-templates/biomedical.html • Submit Form5R in addition to all supporting documents (HIC application, consent forms, etc) 2 months prior to the lapse date

4. How many copies for paper submission? • General rule is 2 x Form5R and 2 x documents that need to be revalidated (protocol, consent forms) and 1 x sponsor documents • Once approved, recruitment materials, ROI forms and HIPAA RAF forms do not need to be submitted for renewal • Refer to ‘HOW MANY COPIES’ document on the HRPP website

5. What about electronic submissions? • Check Quick Guides on Coeus website • Submit only e-Form5R if other protocol documents are approved electronically and live in Coeus • Once electronic, protocols stay electronic

6. Tips for successful renewal • Fill out the entire form • Do not copy and paste from previous year e.g. ‘Progress of the study to date’ question • Make sure the enrollment numbers are correct • If subject enrollment has not progressed, explain why

7. When is an amendment necessary? • Any change to a protocol, consent form, or advertisement • If it’s a change, it’s an amendment

8. Expedited Amendments • An Expedited Amendment is: A proposed change in research related activities that does not materially affect an assessment of the risks and benefits of the study or does not substantially change the specific aims or design of the study • An expedited amendment can be reviewed by a regulatory reviewer in the office

9. Examples: • An increase or decrease in number of subjects targeted for enrollment • Change in the amount of subject payment • Grammatical changes/changes to sentences • Addition of recruitment materials • Change in Study Personnel • Minor clarifications of previously disclosed information • Other minor changes that do not affect the risk level

10. Full Committee Amendments • A Full Committee Amendment is: A proposed change in research-related activities that does materially affect the assessment of the risks and benefits of the study or substantially change the specific aims or design of the study • Full Committee amendments are reviewed at a Committee meeting

11. Examples: • Broadening the range of inclusion criteria • Alterations in the dosage or route of administration of study drug • Extending substantially the duration of exposure to the test material or intervention • The addition of serious unexpected adverse events or other significant risks to the Informed Consent Document

12. Change in Study Personnel • Make sure that the person to be added has HIPAA and current HSPT training and COI disclosure on file • Do not submit protocol at the time of personnel amendment • Electronic personnel amendments do not require amendment forms in Attachments • Remember that personnel may not participate in study activities without required training

13. Change in Principal Investigator • A change in Principal Investigator requires a form called Amendment to Change Principal Investigator • The form requires signatures of the outgoing and incoming PI AND Department Chair • All documents must be updated to reflect the change in PI (e.g. Protocol application, consent form, HIPAA RAF) • Responsibility to subjects: • Active participants in a study must be notified that there is a change in PI • Notification must be documented

14. What to include in the Amendment Request Form • Who requested change: sponsor vs. PI • What documents are affected • The number of subjects that are enrolled and number of subjects that are still receiving study intervention • Whether the change affects risk to subjects • Description of changes with RATIONALE behind them • Page numbers and sections of the protocol/consent forms/other documents where changes have occurred

15. The changes should be itemized in the form (one form for multiple changes) • Supporting documentation should be provided e.g. sponsor letter referencing the change, the IND report • Changes need to be indicated by using Track Change function

16. How many copies for paper submission? • 2 x amendment request forms • 1 x documents with track changes • 2 x clean documents that need HIC signature/stamp • 1 x supporting documentation e.g. sponsor protocols, other Committees’ approvals, etc.

17. What about electronic submissions? • Check Quick Guides on Coeus website • The general rule is to submit amendment request form and any supporting documentation as NEW documents in Attachments • Documents that are affected by the amendment need to be saved on top of the previously approved versions via AMEND button

18. NO changes can be implemented until reviewed and approved by the HIC • EXCEPTION: An Investigator may make a modification to research activities to avoid an immediate hazard to the participant but must report this to the HIC within 10 working days

19. When can amendments be submitted? • Amendments have to be submitted and approved before changes are implemented • Amendments can be submitted with reapproval requests if happening at the same time (Renewal and Amendment in Coeus) • Amendments should be combined when possible Note that if there is a pending amendment, you cannot submit another amendment. • We can’t approve an amendment request if the protocol is not in approved status

20. Cancer Center Amendments • Cancer Center amendments cannot be accepted without a PRC letter (either administrative memo of no-need for review or approval letter). Personnel amendments no longer need PRC approval EXCEPT for change of PI • It is necessary to thoroughly fill out the appropriate PRC amendment request form, and provide the rationale

21. Consent Addenda • Consent addenda may be necessary to inform currently enrolled subjects of new information, risks, or other changes that may affect their decision to participate in the study

22. Who to call/email with questions? • You can email us at ysmhic@yale.edu or hrpp@yale.edu • You can call us at 785-4688 • All inquiries are triaged to correct regulatory teams

23. Questions? Thank you!