1. GCRC Advisory Committee Evaluating Projects for GCRC Use Dr. Jules L. Dienstag, Chair Evaluating Projects for GCRC Use Dr. Jules L. Dienstag, Chair

2. 2 OrganizationOrganization The Committee is responsible to the GCRC Principal Investigator, Dr. James J. Mongan, President, Massachusetts General Hospital The Committee is responsible to the GCRC Principal Investigator, Dr. James J. Mongan, President, Massachusetts General Hospital Dr. Jules L. Dienstag, Chair Principal Investigator Dr. Peter Slavin GCRC Advisory Committee Dr. Jules L. Dienstag, Chair Program Director Dr. David M. Nathan Co-Director Dr. Anne Klibanski

3. 3 PurposePurpose Supervise and reviews the operations of the GCRC Sets general policies Evaluates projects for GCRC use Responsible for assuring implementation of existing NIH policies Periodically reviews GCRC operations to ensure optimal resource allocation Supervise and reviews the operations of the GCRC Sets general policies Evaluates projects for GCRC use Responsible for assuring implementation of existing NIH policies Periodically reviews GCRC operations to ensure optimal resource allocation

4. 4 The Protocol Review Process

5. 5 Understanding the Protocol Review Process Protocol is Received from Study Team At the same time the Investigators protocol is being reviewed by the HRC, the GCRC Advisory Committee reviews the protocol as well. Or HRC approval may already have been granted when the GCRC reviews the protocol. Protocol is Received from Study Team At the same time the Investigators protocol is being reviewed by the HRC, the GCRC Advisory Committee reviews the protocol as well. Or HRC approval may already have been granted when the GCRC reviews the protocol. Step 1 Step 2 Step 3 Step 4 Step 5 Step 6 Step 7 Step 8 Step 9 Finished

6. 6 Understanding the Protocol Review Process Protocol is distributed by the GCRC Administrative Office to all appropriate reviewers Protocol is distributed by the GCRC Administrative Office to all appropriate reviewers Step 1 Step 2 Step 3 Step 4 Step 5 Step 6 Step 7 Step 8 Step 9 Finished

7. 7 THE CLOCK STARTS A template (Critique Sheet) for each evaluator to access and place their comments on is placed on the network drive X:\GCRCM_PU\SPIDS FOR REVIEW - DRAFT Review of proposal is to be completed within 10 “working” days from day of distribution Efforts are made to identify two scientific reviewers from the GCRC Advisory Committee A protocol nurse and bionutritionist are assigned to the study. Understanding the Protocol Review Process Step 1 Step 2 Step 3 Step 4 Step 5 Step 6 Step 7 Step 8 Step 9 Finished

8. 8 Understanding the Protocol Review Process Reviews are returned to Committee within the required 10 business days “NO CONCERNS” – If you have completed the review and are satisfied with the protocol, type “NO CONCERNS” by your discipline. – After the designated review period, the file is moved to a read-only area of the network and no additional changes are permitted X:\GCRCM_PL\PROTOCOLS - FINAL VERSION. – If no safety-related concerns are identified, the investigator may challenge any concerns addressed after the appropriate review period. Reviews are returned to Committee within the required 10 business days “NO CONCERNS” – If you have completed the review and are satisfied with the protocol, type “NO CONCERNS” by your discipline. – After the designated review period, the file is moved to a read-only area of the network and no additional changes are permitted X:\GCRCM_PL\PROTOCOLS - FINAL VERSION. – If no safety-related concerns are identified, the investigator may challenge any concerns addressed after the appropriate review period. Step 1 Step 2 Step 3 Step 4 Step 5 Step 6 Step 7 Step 8 Step 9 Finished

9. 9 When Reviewing Projects When Reviewing Projects Please respect the Committee’s commitment to the investigator to complete the review in the established timeframe

10. 10 Understanding the Protocol Review Process – The GAC Editor will review the comments with 24 hours * Dr. David Nathan* Dr. Anne Klibanski – The purpose of the Editor is to ensure that comments are listed in the appropriate areas on the Critique Sheet, and for completeness of the review. – The GAC Editor reserves the right to alter, move or delete comments – The GAC Editor will review the comments with 24 hours * Dr. David Nathan* Dr. Anne Klibanski – The purpose of the Editor is to ensure that comments are listed in the appropriate areas on the Critique Sheet, and for completeness of the review. – The GAC Editor reserves the right to alter, move or delete comments Step 1 Step 2 Step 3 Step 4 Step 5 Step 6 Step 7 Step 8 Step 9 Finished Critique Sheet is Submitted to the GAC Editor

11. 11 Understanding the Protocol Review Process – The investigator will review and respond at their earliest convenience. Step 1 Step 2 Step 3 Step 4 Step 5 Step 6 Step 7 Step 8 Step 9 Finished The Critique Sheet is Submitted to the Principal Investigator (RESPONSE MEMO)

12. 12 Understanding the Protocol Review Process – If you have completed the review and are satisfied with the investigators response, promptly notify the Committee by calling (617) 726-6886 or by emailing ffortune@partners.org (A response must be received) – If your initial concerns are not addressed in the investigators response, the reviewer may notify the Committee in writing (email ffortune@partners.org) or direct your additional concerns to the PI directly for clarification before giving final approval. – Extensions are granted by the Chair to address concerns involving research volunteer safety. – If you have completed the review and are satisfied with the investigators response, promptly notify the Committee by calling (617) 726-6886 or by emailing ffortune@partners.org (A response must be received) – If your initial concerns are not addressed in the investigators response, the reviewer may notify the Committee in writing (email ffortune@partners.org) or direct your additional concerns to the PI directly for clarification before giving final approval. – Extensions are granted by the Chair to address concerns involving research volunteer safety. Step 1 Step 2 Step 3 Step 4 Step 5 Step 6 Step 7 Step 8 Step 9 Finished The response from the Principal Investigator is distributed to the initial reviewers (QUERY LETTER)

13. 13 Understanding the Protocol Review Process – Barring evaluator objections, the protocol is conditionally approved subject to final approval at the next meeting of the GCRC Advisory Committee. Step 1 Step 2 Step 3 Step 4 Step 5 Step 6 Step 7 Step 8 Step 9 Finished Protocol is conditionally approved within 7 business days once all information has been collected and addressed satisfactorily

14. 14 Understanding the Protocol Review Process Investigator is required to introduce their study at an in-service (Protocol Meeting) to the GCRC Staff. The protocol nurse assigned to the study will set up a protocol meeting with the study team. The study may enroll patients after the in-service. Investigator is required to introduce their study at an in-service (Protocol Meeting) to the GCRC Staff. The protocol nurse assigned to the study will set up a protocol meeting with the study team. The study may enroll patients after the in-service. Step 1 Step 2 Step 3 Step 4 Step 5 Step 6 Step 7 Step 8 Step 9 Finished

15. 15 Understanding the Protocol Review Process Protocol is submitted to the GCRC Advisory Committee for final approval at the next scheduled meeting Protocol is submitted to the GCRC Advisory Committee for final approval at the next scheduled meeting Step 1 Step 2 Step 3 Step 4 Step 5 Step 6 Step 7 Step 8 Step 9 Finished

16. 16 Communicating with the Committee (617) 726-6886 (phone) (617) 724-3299 (fax) E-Mail: E-Mail: ffortune@partners.orgffortune@partners.org Web Site http://www.mgh.harvard.edu/GCRC Network Drive Protocols Pending Evaluation – X:\GCRCM_PU\SPIDS for Review - Draft Evaluated Protocols – X:\GCRCM_PL\Protocols - Final Version (617) 726-6886 (phone) (617) 724-3299 (fax) E-Mail: E-Mail: ffortune@partners.orgffortune@partners.org Web Site http://www.mgh.harvard.edu/GCRC Network Drive Protocols Pending Evaluation – X:\GCRCM_PU\SPIDS for Review - Draft Evaluated Protocols – X:\GCRCM_PL\Protocols - Final Version

17. 17 Evaluating Projects for GCRC Use Responsibility of Each Reviewer To provide constructive feedback within their purview that reflect the – Rights & Responsibilities – Values of the GCRC program. To provide constructive feedback within their purview that reflect the – Rights & Responsibilities – Values of the GCRC program.

18. 18 When Reviewing Projects When Reviewing Projects Remember who the readers are – First-time users of the GCRC program – New investigators – Seasoned investigators – Your colleagues – GCRC Leadership – Committee’s Chair – Principal Investigator – National Institutes of Health Your comments should reflect this large diversity Remember who the readers are – First-time users of the GCRC program – New investigators – Seasoned investigators – Your colleagues – GCRC Leadership – Committee’s Chair – Principal Investigator – National Institutes of Health Your comments should reflect this large diversity

19. 19 When Reviewing Projects When Reviewing Projects Present the comment as a question Example: “Some provision should be made for blinding the investigators to the DEXA results until the study is complete”. The question should have been presented to the investigator as: Does the investigator believe that a provision should be made for blinding themselves and their study team to the DEXA results until the study is complete?

20. 20 When Reviewing Projects When Reviewing Projects Add Your Question to the Appropriate Area The following question added to the scientific section, should have been added to the core laboratory section: The reason for measurement of IGF-1 in both the core lab and in chemistry should be stated in the protocol (Notice the concern was not presented as a question...) The following question added to the scientific section, should have been added to the core laboratory section: The reason for measurement of IGF-1 in both the core lab and in chemistry should be stated in the protocol (Notice the concern was not presented as a question...)

21. 21 When Reviewing Projects Number Your Questions Example “Is the primary endpoint percent change in bone density form baseline at 6 months or 12 months? In either case how will the other time point and the 9 month time point be analyzed? Is the comparison of rhIGF-1 plus Actonel and Actonel at 6 or 12 months?” The questions should have been presented to the investigator as: 1. Is the primary endpoint percent change in bone density form baseline at 6 months or 12 months? 2. Referring to the question above, how will the other time point and the 9 month time point be analyzed? 3. Is the comparison of rhIGF-1 plus Actonel and Actonel at 6 or 12 months?” Number Your Questions Example “Is the primary endpoint percent change in bone density form baseline at 6 months or 12 months? In either case how will the other time point and the 9 month time point be analyzed? Is the comparison of rhIGF-1 plus Actonel and Actonel at 6 or 12 months?” The questions should have been presented to the investigator as: 1. Is the primary endpoint percent change in bone density form baseline at 6 months or 12 months? 2. Referring to the question above, how will the other time point and the 9 month time point be analyzed? 3. Is the comparison of rhIGF-1 plus Actonel and Actonel at 6 or 12 months?”

22. 22 When Reviewing Projects When Reviewing Projects Provide the reader with clarity In the following example the principal investigator was not sure if the comment is a suggestion or a request: “Since the 4-day food record requires active participant compliance, it is recommended that the consent include a phase such as “the participant will agree to document food intake for 4 days and bring completed food records to the baseline, 3m, 6m, 9m, and 12m visits”. Please change consent accordingly.” Again, notice the concern was not presented as a question… Provide the reader with clarity In the following example the principal investigator was not sure if the comment is a suggestion or a request: “Since the 4-day food record requires active participant compliance, it is recommended that the consent include a phase such as “the participant will agree to document food intake for 4 days and bring completed food records to the baseline, 3m, 6m, 9m, and 12m visits”. Please change consent accordingly.” Again, notice the concern was not presented as a question…

23. 23 When Reviewing Projects When Reviewing Projects Avoid Pronouns Because many people review each protocol, make comments and add responses, evaluators and investigators must use clear identifiers when commenting. Avoid Pronouns Because many people review each protocol, make comments and add responses, evaluators and investigators must use clear identifiers when commenting.

24. 24 When Reviewing Projects When Reviewing Projects Ensure the Review is Complete A common mistake is to not review the Physician’s Orders that accompany the protocol but rather wait until the in-service. all documents The Committee asks that all documents (e.g., Physician’s Orders, Consent forms, drug labels) are reviewed when submitted to the reviewers and that all concerns are stated at that time before they give final approval to Faith Fortune. Ensure the Review is Complete A common mistake is to not review the Physician’s Orders that accompany the protocol but rather wait until the in-service. all documents The Committee asks that all documents (e.g., Physician’s Orders, Consent forms, drug labels) are reviewed when submitted to the reviewers and that all concerns are stated at that time before they give final approval to Faith Fortune.

25. 25 Frequently Asked Questions Frequently Asked Questions It states that the evaluator is to “provide constructive feedback within their purview”. What is my purview? – For scientific reviewers, the Committee has developed a brief and helpful guide – For GCRC staff, please contact your immediate supervisor. What if I have a concern but it is considered outside of my purview? – Contact your immediate supervisor who can direct you to speak to the evaluator responsible for that area. The protocol was distributed while I was on vacation/out of the office. I don’t believe I have time to evaluate the protocol. What do I do? – You need to obtain an extension from the Chair. Typically extensions are granted to address a research volunteer safety-related concerns. Does the Committee allow expedited reviews? – Provisions are made for urgent studies with an unexpected opportunity to study unusual research patients. In these instances, the Committee will provide information for an ad hoc review process. Where are the evaluations maintained? – The evaluations are maintained on the GCRC network drive. For assistance accessing files please contact Faith Fortune It states that the evaluator is to “provide constructive feedback within their purview”. What is my purview? – For scientific reviewers, the Committee has developed a brief and helpful guide – For GCRC staff, please contact your immediate supervisor. What if I have a concern but it is considered outside of my purview? – Contact your immediate supervisor who can direct you to speak to the evaluator responsible for that area. The protocol was distributed while I was on vacation/out of the office. I don’t believe I have time to evaluate the protocol. What do I do? – You need to obtain an extension from the Chair. Typically extensions are granted to address a research volunteer safety-related concerns. Does the Committee allow expedited reviews? – Provisions are made for urgent studies with an unexpected opportunity to study unusual research patients. In these instances, the Committee will provide information for an ad hoc review process. Where are the evaluations maintained? – The evaluations are maintained on the GCRC network drive. For assistance accessing files please contact Faith Fortune