A Case Report Form (CRF) is an electronic or paper document which is used in a clinical trial to record the protocol and required information about each participant. It enables efficient and complete data collection, processing, analysis and reporting. It is the main tool that Investigators use to collect information from clinical trial participants which is why there needs to be one completed CRF for each participant.
The Sponsor-Investigator puts together the CRF Completion Guidelines and ensures that the site staff have received training before collecting, entering and reviewing data.
All users are given a unique username and password to gain access to the CRF and the trial database. The Principal Investigator assigns permissions to each user which includes ‘data entry’ or ‘data view only’. Permission to access the data must be in accordance with the consent given by participants.
The CRF should be completed soon after each participant's initial visit which ensures that information can be followed up on while the participant is easily accessible.
All the data should be collected with users in mind and the requirements set out by regulatory agencies. The questions should be as clear and concise as possible to prevent any duplication.
Relationship to Protocol
The clinical trial protocol determines what kind of data should be collected - all the information found in the CRF should be specified by the protocol. Any data that will not be analyzed shouldn’t be included in the CRF.
Elements of a CRF
A Case Report Form consists of three main parts: a header, a safety-related module and an efficacy-related module.
The header must contain key identification information including a study number, a site number and a participant ID number.
Consists of the key safety analysis requirements found in the protocol which includes demographic information, adverse events, medical history, physical exam, deaths, drop-outs and eligibility confirmation.
The protocol outlines the elements which are required in the efficacy modules. The elements of this module include the key efficacy endpoints of trial, additional tests to measure efficacy, how lesions will be measured and requited diagnostics.
CRF Development Process
The development of the CRF begins as soon as the development process begins. The responsibility of the design varies between Clinical Research Organizations, Clinical Research Associates, Data Managers, Research Nurses and Database Development.
The only data collected for the CRF should be what is required by the protocol- nothing more, nothing less. An interdisciplinary review is needed for every CRF:
- Each company has its own process for review.
- Should include the relevant staff members involved in the conduct, analysis and reporting of the clinical trial.
Properly and Poorly Designed CRFs
An effective CRF allows for components to be reused across the clinical trial, saving time and money.
A poorly designed CRF is one that is missing requested data or has unnecessary information meaning that it requires edits and modifications throughout the clinical trial.
For a CRF to be completed, it needs to have:
- Completed sections including headers with identifying items.
- Relevant modifications.
- A record of adverse events and specific documentation for any serious adverse events.
The data needs to be collected from the relevant source documentation (medical records) and entered into the CRFs by study personnel. Only designated members of the clinical trial staff are allowed to record or edit data in the CRFs.
Important Tips for Completion
- The CRF Completion Guidelines should be followed to ensure that each CRF is accurate and completed in a timely manner.
- Make sure the appropriate protocol, Investigator, and participant identifying information is included in the header.
- Ensure the data is entered in the correct data field (provide boxes or lines to make it clear where the answers should be entered).
- Use the appropriate units of measurement.
- Be consistent.
- Double-check spelling and grammar.
- Watch for transcription errors.
- Use the comment section to expand on any answer (be as concise as possible).
- Use consistent formats, font style and font sizes.
- Visual cues (boxes) which indicate the place and the format of data to be recorded.
- Use check boxes.
- Separate columns with thick lines.
- Use precoded answer sets (male/female, yes/no and mild/moderate/severe, etc) wherever possible.
Electronic CRF (eCRF)
- Ensures data integrity.
- Provides an audit trail for data changes.
- Ensures data preservation (automatic back-ups).
- Essential identification information (protocol ID, site code and participant ID) will be generated from the first page to all other pages ensuring no duplication.
- Linking data between 2 or more pages is easy.
- There’s always the threat of losing valuable data due to software malfunction or if the eCRFs aren’t backed up successfully.
Confidentiality and Security
To protect confidential participant and clinical trial data, eCRFs must be stored on secure servers with restricted access, while paper CRFs must be stored in a secure location. Regular backups and archiving for future copies must be utilized.
Freezing the Database
Once the data has been finalized, it is necessary to lock the database which protects the integrity of the collected data and prevents any unauthorized edits from being made.