1. CRF Harmonization and Standardization Preparation for a Round 5 CRF Review Dianne M. Reeves, RN, MSN, National Cancer Informatics Program Neesha Desai, Essex Management June 12, 2012

2. Background CTWG Vision Statement Enhance the best of all the components of the NCI- supported clinical trials system to develop a cooperative enterprise built on a strong scientific infrastructure and a broadly engaged coalition of critical stakeholders

3. Background Establish a Comprehensive Community-Accessible NCI Clinical Trial Database Promote System Harmonization & Interoperability between NCI’s Clinical Trials systems Establish Core Library of Standardized Case Report Forms (CRFs) through Stakeholder Consensus (called out in red font) Develop a Credentialing System for Investigators and Sites

4. Workgroup Process 1NCI CBIIT staff collects existing CRFs and creates an inventory of content 2Working group, NCI Cooperative Groups and NCI divisions aggregate and identify common content to retain, resolves discrepancies, and achieves harmonization 3Working group reviews and partitions content as Mandatory, Conditional, Optional, or non-harmonized 4Working group, with CBIIT curator matches data elements to all questions and achieves consensus on final list of elements 5Module is distributed for community review. 6Working group reviews and responds to changes from community review and CBIIT staff review content to insure the use of standards. 7A participant for each of the NCI cooperative groups approves any content that has changed since the initial review. 8Biostatistician reviews and approves for Cooperative Groups 9CTROC reviews and approves module 10Pilot

5. CRF Question Partition Categories Mandatory: A data collection variable that must be on the CRF (e.g., a regulatory requirement (if applicable)). Must be used. Conditional: A data collection variable that must be collected on the CRF for specific cases that may be dictated by local or sponsor defined business rules. Optional: A data collection variable that is available for use if needed. Usually collected due to the design of the protocol, like in instances where marital status or educational level are important indicators in a study. Non-harmonized: A data collection variable that is, by consensus, to primarily belong to a different CRF module or is not belonging to any defined module. NCIP CRF Standardization Process

6. Hypothetical Assembly of a Disease History and Prior Therapies CRF (for electronic) using caBIG® standardized CRF Modules Header module Outcomes Insert Mandatory, Conditional CDEs (if applicable), select Optional CDEs as desired. Staging/Extent of Disease Agents (Prior/Post Therapies) Agents (Prior/Post Therapies) Sign Off/Footer ~~NOTE: fields may be collected automatically by system through user login/authentication and e-signatures ~~ Insert Mandatory, Conditional CDEs (if applicable), select Optional CDEs as desired. Disease History and Prior Therapies {Study ID}, {PI), {Course#},{Patient ID}, {Institution ID} ~~NOTE: fields may be collected automatically by system ~~ *Prior Agent Name {*date type}Therapy Start Date {*date type}Therapy Stop Date {*dose type}Total Dose *Unit Disease status Stage TNM Primary Site Metastatic Sites *Disease response Date of response assessment Created by Lara Fournier, OHSU, March 2009

7. Hypothetical Assembly of a Disease History and Prior Therapies CRF (for paper) using caBIG® standardized CRF Modules

8. CRF Roadmap 8

9. CRF Round 5 Modules Diagnosis Microscopic Histology Response Survival Lost to Follow-up Follow-up Progression CT Image Acquisition CT Imaging Agent Image Administration RECISTv1.1 Diagnosis Diagnosis Gross Tumor Diagnosis Metastasis

10. Goals of the CRF Review Evaluate the content for appropriate inclusion in the module Evaluate the content for correct definitions of variables Analyze the content for missing variables Evaluate the proposed content partition for correctness Evaluate if conditionality rules are complete/clear Evaluate the permissible values (when present) for accuracy and completeness Editorial changes – spelling, wording of a definition

11. Reviewer Responsibility Each Reviewer represents an organization Your feedback must be aligned with your organizational requirements Each organization is a stakeholder in this initiative Items that challenge harmonization require sufficient detail to achieve resolution

12. Review Process Open the CRF Round 5 multi tab spreadsheet. * Each module is on a separate tab Reference the following materials while reviewing: –CRF Review Goals –CRF Review Process –CRF Roadmap –CRF Wiki: https://wiki.nci.nih.gov/display/CRF/CRF+Harmonization+and+Standardization –CRF Round 5 Community Review Page https://wiki.nci.nih.gov/display/CRF/CRF+Round+5+Wiki Enter in your comments in the CRF Round 5 spreadsheet Reviewer Comments Column. Comments can be captured at the element level, and/or for a single permissible value. Send the completed spreadsheet to your Neesha Desai Neesha.Desai@nih.gov Neesha.Desai@nih.gov

13. Consideration : Partition rules Mandatory –The element must be included on the CRF. There is an expectation that if the data exists or can be recovered, it will be entered. There may be skip patterns or dependencies that make the completion of an element unnecessary. Conditional –The element is needed on the form based on certain protocol level rules. These may include: Disease rules – staging systems for different types of cancer Phase of study or multi-trial study needs Requirements like stratification and randomization Ask yourself ‘When would I not use this variable?’ When is something NOT conditional – items like Male/Female, or ‘Date of Death’

14. Consideration : Partition rules Optional –Needed usually for study-specific design requirements. ‘If you need it, this is the best one to use’. Not Harmonized –Variables that do not fit into the module, or don’t belong in ANY module.

15. Next Steps Review of Round 5 content begins week of December 2 Review sheets to be posted on CRF wiki Posting will be announced to all reviewers Please respond to the review by mid-December if at all possible -Comments through the first week of January acceptable Typically three rounds of reviews have been needed 15

16. Reference Material Contact Dianne Reeves, Associate Director, Biomedical Data Standards, NCIP –Dianne.Reeves@nih.govDianne.Reeves@nih.gov Contact Neesha Desai, Project Manager, NCIP, Essex Management –Neesha.Desai@nih.govNeesha.Desai@nih.gov NCI CRF Harmonization and Standardization Wiki –https://wiki.nci.nih.gov/display/CRF/CRF+Harmonization+and+St andardizationhttps://wiki.nci.nih.gov/display/CRF/CRF+Harmonization+and+St andardization