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1 DEVELOPING EFFECTIVE CASE REPORT FORMS MAKING YOUR CRF WORK FOR YOU CONFLICT OF INTEREST DISCLAIMER No conflict of interest to disclose PRESENTED BY ROXANNE WARD CLINICAL RESEARCH PROGRAM MANAGER, KSG OCTOBER 17, OBJECTIVES Understand the different types of CRF s Understand relationship between protocol and CRF Understand how a well designed CRF can promote accurate data collection/entry and analysis Learn methods to ensure accurate data collection and transcription Discuss process of data correction, data management tips Have some fun! 3 4 What is the most important tool in a research study outside the protocol? Case Report Form! The tool that is designed and used to collect your data! PURPOSE OF CRF Collect raw data Facilitate monitoring or auditing Expedite data processing Reviewing, editing, analyzing 1

2 TYPES OF CRF S Paper Electronic Web-based (aka Electronic CRF or ECRF) Becoming more common Examples: OpenClinica, REDCap (Research Electronic Data Capture*) WHAT TYPE OF CRF PAPER OR ECRF? Paper CRF ECRF Small sample size Large sample size Few sites Multiple sites Small budget Regulated studies, i.e. Industry *More to come on REDCap!!! 7 8 LET S START AT THE BEGINNING - RESOURCES OHRI Standard Operating Procedures SOP s Clinical Data Management SOP 014_06 Case Report Form Design SOP 100_04 Data Management Plan SOP 103_03 Database Set-up SOP 104_03 Database Maintenance and Management SOP 105_03 ADDITIONAL RESOURCES Clinical Data Interchange Standards Consortium CDISC Facilitate the regulatory-compliant acquisition, archive and interchange of metadata and data for clinical research studies. Clinical Data Acquisition Standards Harmonization (CDASH) - Recommended basic standards for collection of clinical trial data Society for Clinical Data Management SCDM Advance the discipline of clinical data management Certification as CCDM Good Clinical Data Management Practices - GCDMP 9 10 DATA MANAGEMENT PLAN Study specific document that outlines all aspects of data management from start to study completion - Outlines functional roles within data management process and who is responsible for those roles - Ensures conformity to local, national and international regulations and guidelines - Reference document, communication tool WHO DEVELOPS THE CASE REPORT FORM? Research Coordinator Investigator Data manager Statistician Data Entry personnel Others content experts

3 RELATIONSHIP BETWEEN CRF & PROTOCOL Ideally design simultaneously with protocol What data will be collected? Will need to meet the objectives of the protocol Primary and secondary objectives Every variable on CRF should be justified by protocol Primary & secondary objectives and safety endpoints Avoid collecting extraneous data ANATOMY OF A CASE REPORT FORM Inclusion/Exclusion Criteria Demographics Previous History Baseline Data on procedures/patient s condition Medications Adverse Events Outcomes/Follow-up DEVELOP A LIBRARY OF STANDARDIZED FORMS Facilitates process of developing CRFs Standardizes process Increases uniformity of content across trials Minimizes errors in coding, data entry Facilitates analysis Decreases cost DESIGNING CRFS GENERAL CONSIDERATIONS Questions/Prompts are clear, concise Take into account: Flow of study procedures Where is information coming from? Organization of medical chart Paper or Electronic, varies by site Perspective of person completing the CRF Who is completing the CRF? Training Paginate, Numbered Sections Group items into sections with headings Use numbering system to identify relevant items Identify Version #/Date in footer or header if Paper CRF Identify Protocol Version that CRF refers to Paper CRF forms printed on one side only Align checkboxes consistently throughout Use vertical checklists instead of horizontal When collecting the same data at different time points (i.e. different visits) Appearance of forms should be identical Same data points collected, using same terminology, same units Use separate forms for different visits

4 Use Forced (Closed-System) Responses Avoid Check if present For questions with multiple response options force a Yes or No response for each option Control format of response Date: DD/MMM/YYYY = / / Decimal placement - Weight:. kg Avoid blank items All items should be filled in If item does not apply N/A, ND, UNK Meaning of N/A, ND or UNK should be consistent throughout Use consistent codes/logic and questions throughout Example: Abnormal = Yes Normal = Yes Ensure Question/Response format is consistent throughout Placement and use of Yes/No/None/Other/Not Applicable should be the same throughout Provide form-completion instructions Specify how you want date formats recorded Use same format throughout Specify how you want any errors dealt with EXAMPLE Case Report Forms: CRF Completion Instructions General Instructions At the top of each page, enter your Center number, the Subject s number and the Encounter number Enter dates in the format dd / mmm / yyyy (i.e. October 22, 2012 is 22 / Oct / 2012) Enter times according to the 24 hour clock in the format HH:MM (i.e. 4 pm is entered 16:00) EXAMPLE Case Report Forms: CRF Completion Instructions Do not write in shaded areas If data is not applicable, not known, illegible, or incorrect, enter N/A. There should be no blank spaces. Use only black ink If you enter a value and realize that it is incorrect, please put a line through it, date and initial it and enter the correct value EXAMPLE: RW

5 ACCURATE DATA COLLECTION Limit referential questions Phrase questions in the positive Indicate if questions are mutually exclusive Example: Check ALL that apply Select ONLY ONE category from the list below Provide Other option EXAMPLE: REFERENTIAL QUESTION Does the patient have an underlying RESPIRATORY System disorder? yes no If Yes, indicate type of Respiratory Disorder ( all that apply) Asthma yes no Cystic Fibrosis yes no Chronic Upper Airway Disease yes no Other yes no Describe: EXAMPLE: MULTIPLE RESPONSE ACCURATE DATA COLLECTION Provide the reason that patient was not approached for consent (check all that apply)? Not Applicable Age (too young) yes no Sedated yes no Decreased LOC yes no Hemodynamically unstable yes no Other yes no Avoid calculations Enter raw data needed for scores/calculations Examples: Length of stay Duration of mechanical ventilation Scores/Scales QOL EXAMPLE ORDER OF RANGES Lowest ph: Highest ph:. or N/A. or N/A Highest Total C0 2 :. or N/A Lowest Total C0 2 :. or N/A Lowest ph: Highest ph:. or N/A. or N/A Lowest Total C0 2 :. or N/A Highest Total C0 2 :. or N/A ACCURATE DATA COLLECTION Avoid use of free text difficult to analyze Collect data only once Define measurable items

6 EXAMPLE DEFINE MEASURABLE ITEMS CONFIDENTIALITY Was the patient hypotensive? Yes No Was the patient hypotensive? Yes No Hypotension Persistent hypotension as defined by age, lasting 15 minutes and not responsive to standard treatment: Age 1 month to 6 months old: SPB < 60 mmhg Age > 6 months to < 2 yrs old: SBP < 70 mmhg Age 2 to 12 yrs old: SBP < 80 mmhg Age > 12 to < 17 yrs old: SBP < 90 mmhg 31 NO identifying information on CRF Avoid DOB instead use age Example: Age: Years Months Each CRF should be assigned a number that is linked to a subject: Subject Enrolment List (Name and CRF #) If electronic password protected If paper access limited to research personnel Encrytion Tool 32 NOW WHAT? CRF SUBMISSION Pilot test the CRF on pre-determined number of cases Ease of data collection Analyze data collected are you answering your questions? Duration of time to collect data Make revisions based on pilot testing Avoid making changes to CRF once implemented Who signs off/approves the CRF? The person completing it The Investigator For Multi-Centre studies: Courier, fax, electronic If courier copy, send original Track when CRF received, entered DATA CLEANING Activities to assure completeness, validity and accuracy of data Types of errors Source data, transcription errors, data entry errors Systematic versus Random error

7 DATA CLEANING EDIT CHECKS CHANGES TO DATA Manual review Front-end When CRF received and entered Computer checks Front-end or Back-end To identify out-of-range values, missing etc Frequencies, boxplots, Means, Min-Max Double entry of % of cases (I.e. 10%) Data Queries Need to know who changed what data & when Use Form to clarify data point Change made to copy of CRF as well as original initialed and dated All changes tracked EXAMPLE DATA QUERY FORM COMMON PITFALLS Lab units Specify units differ between institutions Dates Calculation of time between dates Percentages 0.2 = 20% OR 0.2%? Medications Dose versus Rate Mg versus mg/kg versus mg/kg/hr TAKE HOME MESSAGE: The CRF is the most important tool that you have. A well developed CRF will enable accurate data collection, prevent transcription errors, facilitate data cleaning and analysis. A poorly designed CRF is Questions? Garbage in = Garbage out!