1. Design of Case Report Forms

2. RDC/RDE (Remote Data Capture,
Case Report Form
..CRF
Official clinical data-recording document or tool used in a clinical study
The Case Report Form is a data-reporting document used in a clinical study. Its purpose is to collect the study data in a specific format that allows for efficient analysis.
Data from clinical trials is also collected using computerized Case Report Forms. This is referred to as Remote Site Monitoring (RSM) or Remote Data Entry (RDE). If RSM/RDE is utilized, data is generally entered onto paper workbooks, then input on computer screens which mimic the format of a paper CRF. Data can then be electronically transferred to Pfizer.
PAPER
RDC/RDE (Remote Data Capture,
Remote Data Entry)

3. Purpose in accordance with the protocol
Collects relevant data in a specific format
in accordance with the protocol
compliance with regulatory requirements
Allows for efficient and complete data processing, analysis and reporting
Facilitates the exchange of data across projects and organizations esp. through standardization

4. CRF Relationship to Protocol
Protocol determines what data should be collected on the CRF
All data must be collected on the CRF if specified in the protocol
Data that will not be analyzed should not appear on the CRF

5. CRF Development Guidelines Collect data with all users in mind
Collect data required by the regulatory agencies
Collect data outlined in the protocol
Be clear and concise with your data questions
Avoid duplication
Request minimal free text responses

6. CRF Development Guidelines (con’t) allows for computer summarization
Provide units to ensure comparable values
Provide instructions to reduce misinterpretations
Provide “choices” for each questions
allows for computer summarization
Use “None” and “Not done”

7. CRF Development Guidelines (con’t)
Collect data in a fashion that:
allows for the most efficient computerization
similar data to be collected across studies
CRF book needs to be finalized and available before an investigator starts enrolling patients into a study
Take the time to get it right the first time

8. Elements of the CRF Three major parts: Header Safety related modules
Efficacy related modules
Module block of specific questions
CRF module(s) make up a single CRF page
CRF Book series of CRF pages
The term CRF indicates a single CRF page. A series of CRF pages makes up a CRF Book, and one CRF book is completed for each subject enrolled in a study.

9. Header Information MUST HAVES Key identifying Information Study Number
Site/Center Number
Subject identification number

10. Creating Safety Modules
Usually come from a standard library
Select modules appropriate for your study
Keep safety analysis requirements in mind
Safety Modules usually include
Demographic
Adverse Events
Vital Signs
Medical History/Physical Exam
Concomitant Medications
Patient Disposition

11. Efficacy Modules
Designed for each therapeutic area based on the protocol
Considered to be “unique” modules and can be more difficult to develop
Use existing examples from similar protocols where applicable
Consider developing a library of efficacy pages
Design modules following project standards for data collection

12. Creating Efficacy Modules
Follow general CRF design guidelines
Use pages or modules from the therapeutic library
Define diagnostics required
Include appropriate baseline measurements
Repeat same battery of tests
Define and identify
key efficacy endpoints
additional tests for efficacy

13. Importance of Standard CRFs
Prepares the way for data exchange
Removes the need for mapping during data exchange
Allows for consistent reporting across protocols, across projects
Promotes monitoring and investigator staff efficiency
Allows merging of data between studies
Provides increased efficiency in processing and analysis of of clinical data

14. CRF Development Process
Drafts CRF from protocol
CRF Designer
CRF Review Meeting
Comments back to designer
Reviewers
CRF Designer
The slide shows an overview of the CRF development process.
One of the first decision points is to determine which CRA Book format to use. There are two types of formats; one format is designed to retrieve data upon treatment completion (log form), and the other is designed to retrieve data on a visit-by-visit basis.
To help with the design, you can access Pfizer’s library of standard CRF pages for collecting safety and demographic data. You can select a template that is appropriate to the needs of the study. Using a template facilitates the assembly of the CRF.
With appropriate approval from your group, you may make changes or edits to the safety templates to meet the specific needs of the study.
Date requests on the CRF pages which collect efficacy or, for Phase I studies, pharmacokinetic or pharmacodynamic data must parallel the protocol.
After drafting any new or unique efficacy or pharmacokinetic/pharmacodynamic pages, it is a good idea to send them to one or two sites that will be conducting the study and ask the site personnel for feedback.
Updates CRF to incl. comments
Review and Sign off
Coordinate printing and distribution
Site
CRF Book

15. CRF Development Process
Responsibility for CRF design can vary between clinical research organizations (CRA, data manager, specialty role)
Include all efficacy and safety parameters specified in the protocol using standards libraries
To collect ONLY data required by the protocol
Work with protocol grid/visit schedule
The CRA is responsible for designing the CRF Book to parallel the efficacy and safety parameters indicated in the protocol.

16. CRF Development Process
Interdisciplinary review is necessary
each organization has its own process for review/sign-off
Should include relevant members of the project team involved in conduct, analysis and reporting of the trial
Begins
As soon in the study prep process as possible
The CRA is responsible for designing the CRF Book to parallel the efficacy and safety parameters indicated in the protocol.

17. CRF Development Process
Review Team (example)
Project Clinician
Lead CRA
Lead Statistician
Lead Programmer
Lead Data Manager
Others
Database Development, Dictionary Coding, Standards
CRF development should begin as soon as possible in the study preparation process. However, some CRF pages, such as those relating to efficacy or pharmacokinetics and pharmacodynamics, cannot be finalized until the final protocol has been completed.
Draft CRFs are usually reviewed by the clinician, statistician and group leader. There also may be a CRF Review Committee that includes clinical staff as well as Data Management personnel.

18. CRF Development Process
After the CRF book is approved
Initiate the process for printing
Note: the Protocol must be approved before the CRF book is approved and printed
After it is printed
Stored according to organizational guidelines
Printed and distributed to research sites
After the CRF Book has been approved, the process for printing the document is initiated. The completion of this process will vary. After the CRFs have been finalized and printed, a copy of the CRF Book is sent to: Central Files (CRF Librarian), Statistician, Data Coordination Group.

19. Properly Designed CRF + Components/All of the CRF pages are reusable
Saves time
Saves money +

20. Poorly Designed CRF Data not collected
Database may require modification
Data Entry process impeded
Need to edit data
Target dates are missed
Collected too much data – Wasted resources in collection and processing

21. The Case Report Form How do we use it?
Collect data from the investigational sites
Helps project team and study site team
Reminder to investigator to perform specific evaluation
CRA uses to verify protocol is being followed and compare with source documents
Biometrics uses it to build database structures, develop edit checks and programming specs
The CRA and Clinician will monitor the data recorded on the CRFs. Although the purpose of the CRF is to collect data, it also helps the study site team and you perform your jobs.
The CRF acts as a reminder to the investigator to perform specific evaluations and you can use the CRF to verify that the protocol is being followed (i,e, correct evaluations are being conducted at the appropriate time) and subject safety is being maintained.

22. The Case Report Form e.g.. APR ...Used for Subject tracking
Data analysis and reporting
Reports to FDA on subject safety
e.g.. APR
Promotional materials
New Drug Application submissions
Support of labeling claims
Articles in medical journals
CRFs collect all subject data required by the protocol and are used for subject tracking and data analysis. The data that is collected is very important, because it is the basis for making decisions about the drug, its benefits, risks, and potential marketability.
Biometricians/Statisticians and Data Management personnel analyze and report the data recorded on the CRFs in the final study reports for the clinical trial. This data is used for reports to the FDA on subject safety (e.g. serious adverse events, annual progress reports, is included in promotional materials and is submitted in NDAs.
Additionally, the data from the clinical trial may be used to support labeling claims for the drug or may be published in medical journals. So it is critical that the data be accurate and completes

23. Electronic CRFs The use of RDC is increasing
In general, the concepts for the design of electronic CRFs/RDC screens are the same as covered for paper
Electronic CRFs will impact the following:
Review of CRF is different (screen review)
No need to print and distribute paper