The Secret to Preparing Documents for a Smooth Approval Process Research Compliance Administration Training Presentation Wednesday, July 18, 2007 Presenter:Heather Kemp, MBA Research Compliance Coordinator

Tabled Studies v. Provisionally- Approved Studies  Studies are tabled when the Board requests descriptive responses relating to the design or safety of the study.  Studies are provisionally-approved when the Board makes proscriptive recommendations relating to the content or design of the study documents.  On average, the IRB gives provisional or final approval to 75% of studies they review each month; only 25% are tabled.

Provisional Approval Statistics  The RCA Processes an average of 22 provisionally-approved new studies each month for the Biomedical Boards (IRB-02, 04, and 05).  Even Distribution: IRB-02: Average of 9 Provisions per New Study IRB-04: Average of 6 Provisions per New Study IRB-05: Average of 8 Provisions per New Study

“Top Five” Selection Process We reviewed 95 files that were provisionally-approved in the months of March – July, 2007, in order to determine the five most common provisions in each study document.

* The only substitute for the IUPUI online test is documentation of Human Subjects Training at a facility that is a member of the Council on Governmental Regulations from Investigators who are not at an IUPUI affiliated institution. Summary Safeguard Statement 1.Spelling or grammar errors and inconsistencies in the document 2.Section XXI – Co-Investigators A.Lacking Co-Investigator Acknowledgements B.Co-Investigators who had not passed the online IUPUI Human Subjects Protection Test* 3.Section III – Subjects A.Failing to sufficiently justify why you are excluding patient populations (i.e., Spanish-speaking subjects) B.Incomplete I/E list C.Plan to obtain Assent is not sufficient D.Number of subjects being enrolled locally (cases and controls)

Summary Safeguard Statement (Cont’d) 4.Section V – Study Procedures A.Lack of detailed information regarding repositories and/or banked samples B.Failure to list the amount of blood to be drawn at each visit and total for the study C.Incomplete procedures list 5.Section XIX – Conflict of Interest A.The RCA Office will only be reviewing COI disclosures for Investigators listed in Section XIX.A and XIX.B. B.Please indicate if investigators are from Clarian, St. Vincent, or another hospital/facility that is not required to submit COI forms (IUPUI, VAMC, Wishard).

Recruitment Checklist 1.Recruitment Plan does not adequately address how all populations will be recruited and/or is inconsistent with other study documents  For Example: The multi-center protocol states that one of the inclusion criteria is that all subjects must be under the age of 65, but you’re only planning to enroll subjects 18 and under. Ensure that all study documents state explicitly that locally the Investigator will only be enrolling subjects who have not yet reached their eighteenth birthday. 2.Waiver of Authorization for Recruitment section not fully completed 3.Spelling or grammar errors

* The content of the ICS must be consistent with all other study documents (Protocol, CIB, SSS). Informed Consent Statement 1.Phrases/Words not written in 8 th -grade language  For Example: Anemia, Cardiac arrhythmia, CT, MRI, EKG, ECHO, De- identified data, Genetic testing, DNA, Lab value abnormalities (“elevated liver enzymes”)  Tip: Ensure that the content of your document flows for easy readability by utilizing lists, timelines, headings and tables appropriately 2.Spelling or grammar errors and inconsistencies in the document 3.Study procedures missing or not clearly stated* 4.Risks section incorrect or incomplete* 5.Costs of participating in the study not clearly stated A.“Costs” section missing completely B.Not clear on who is responsible for costs of study procedures/materials, most importantly the study drug

Authorization Form 1.Study title listed on document 2.Blanks not filled in (Sponsor/CRO names and PI address) 3.Expiration date not checked 4.Accessing institutions not checked 5.Form not submitted for review

Assent Form 1.Document does not provide subjects with any additional information 2.Document does not list the subjects’ total duration of participation in the study 3.Document written in a confusing manner, the order of sections does not flow for easy reading 4.Changes made that are inconsistent with the template found on the RCA website  Tip: Do not make any unnecessary changes to the Assent document from that which is found online at the RCA website. 5.Not listing all study procedures

Protocol 1.Spelling or grammar errors and inconsistencies in the document 2.Incomplete Data Safety Monitoring Plan  Tip: If the Protocol references a DSMB Charter, the study will not be approved until the IRB reviews this document. 3.Requires a Sample Size justification 4.Insufficient justification for inclusion/exclusion criteria 5.Missing preliminary or pilot data from previous studies

CIB or Other Study Documents 1.Missing CIB or Package Insert for drugs (comparator, concomitant) 2.Radiation Safety or SRC approval letter missing 3.GCRC protocol insufficient to address subject safety requirements 4.Need letters of support from participating affiliates  For Example: Wishard Health Services (if using Midtown); IUMG Community Health Centers that are not listed on an FWA letter, Other hospitals or facilities that do not have their own IRB

Advertisements or Other Items to be Seen By Subjects 1.Items that were referenced in the ICS were not submitted to the IRB for review 2.Telephone scripts asking more than minimal questions in screening and not written so that they can be read verbatim 3.No plan indicated for how the study team will ensure that documents are received and/or completed  For Example: Educational/Instructional documents regarding study procedures or requirements for continued participation 4.Compensation not consistent with what is stated in other study documents 5.Pre-randomized subjects must be told to which group they are being randomized

Tips for Success 1.Ask another colleague to read your study documents 2.Practice good version control and naming conventions 3.Proof your prior to submitting the documents to ensure you have included all the documents in the right version 4.Respond to the pre-review suggestions and questions in a timely manner 5.Adhere to the templates provided on the RCA website

Recommended Naming and Version Control Styles  File Naming Convention: (IRB Study No.) – PI Name – Document Type – MM.DD.YY Document Types: SSS, RCT, ICS, AUT, AST, CIB, AD Example: “ – Kemp H – AUT – ”  Version Control in Footers: No subject initial lines Version date of ICS (MM/DD/YYYY) – to be updated every time a change is made Do not delete “IRB Rev.” dates in the footer  Version Control in Use: During the pre-review process, please make all changes to the version of documents that are returned by the RCA staff, not versions saved on your computer

Final Approval Documents  What is returned to you via ? Final Approval Letter Signed DRA (Scanned in and converted to PDF format) Informed Consent, Authorizations and Assent Statements with IRB Approval stamps Advertisements (Recruitment letters, Flyers, Print or video advertising copy, OCR web site Trial Listing form) Recruitment Checklists (only if you requested and were granted a waiver of Authorization for recruitment)  What is reviewed, but not returned after approval? Information to be seen by potential subjects (Telephone scripts, Questionnaires, Patient diaries) SSS, CIB, Recruitment Checklists without waivers of Authorization