Clinical research tools: What is a CRF (Case Report Form)?

What is a CRF in clinical trials?

In medical terms, CRF stands for case report form. A CRF is a document that is used to compile all protocol-related information for each participant in a clinical trial. This data can include everything from participants’ personal information to study visit results to treatment outcomes and side effects experienced. CRFs are integral for standardizing data collection and for sharing data across sites and between investigators and sponsors.

What is the purpose of a CRF in clinical research?

The primary purpose of the CRF is standardized data collection and recording, to ensure that complete information is collected for all participants in the same format. A CRF allows the investigators and sponsors to hold all important details about the participants in a clinical trial in one place, which is important for regulatory affairs as well as drawing conclusions from trial data.

The clinical trial sponsor/investigator is responsible for creating a study-specific CRF template that appropriately captures all data involved in or required by the study protocol. They will prepare CRF completion guidelines, and ensure that the staff at each study site is properly trained with respect to filling in this data. The sponsor/investigator is also responsible for managing, reviewing, and validating CRFs. Designing a good CRF is a complex and nuanced task, and has been called an art; it requires significant planning, attention to detail, and consideration of the study protocol and various stakeholders.

What does a case report form consist of?

One CRF is created for each participant, and will contain all information that is collected and intended to be analyzed, as per the unique study protocol. Information that will not be analyzed should be excluded from the CRF. The CRF should be designed in such a way that data is entered consistently and completely for all participants; it will thus be fairly detailed in terms of how data should be entered. Although different studies will require different data fields in CRFs, parts of well-designed CRFs can often be used by sponsors across various trials. CRFs can vary in length, depending on the complexity and length of the trial.

A CRF form includes three major parts: a header, a safety module, and an efficacy module. The header specifies important identification details such as site, participant ID, and study numbers. The safety module covers principal safety analysis criteria outlined in the protocol, including fatalities, drop-outs, demographic data, medical histories, eligibility validation, adverse events, and physical examination records. The efficacy module concerns endpoints and additional tests that are used to assess treatment efficacy in the study protocol.

Before the site personnel transfers CRF data to the sponsor for reporting and analysis, it is often de-identified to keep the patient's identity anonymous. Each patient is assigned a study number, and certain personal information, attributes, or even the treatment group may be anonymized in order to avoid potential bias in the interpretation of results.

New developments in CRFs

There are challenges associated with manual data entry and standardization that commonly lead to issues with data integrity, completeness, and organization in paper-format CRFs if not properly controlled. In most clinical trials, a monitor is tasked with CRF data validation to check for errors and ensure accuracy and consistency of the data. This is a time-consuming task.

eCRF: Electronic case report forms

As technology and digitalization continue to revolutionize clinical research processes, many clinical researchers have switched from paper CRFs to electronic CRFs, or eCRFs. An eCRF contains the same data as a traditional CRF, but is filled out and stored electronically. This can help address manual data entry errors and streamline the data validation process. However, there is an ongoing debate over whether paper CRFs or eCRFs are better. Let's look at the main advantages and disadvantages of eCRFs relative to paper-format CRFs:

Advantages

Faster: Filling out an eCRF may be quicker and easier, especially as some aspects can be automated in specialized eCRF software solutions
Reduced error: eCRFs can be created in such a way so as to minimize the possibility of data entry errors (field validation)
Built-in validity checks: Built-in validation features in some eCRF solutions allows for rapid identification of missing data, inconsistencies, or unexpected values, which can facilitate data validation tasks and improve data quality

Disadvantages

Complexity of setup and installation: It will likely be necessary to utilize third-party software or design a program and/or workflow to manage the eCRFs. This will require an adjustment away from traditional methods and a learning curve for staff using the system. The system will need to be installed at all trial sites involved in a study as well as centrally for real-time data capabilities and organization.

Initial investment costs: In relation to the above point, there may be a one-off cost or monthly payment for the eCRF management software. Nonetheless, the costs are likely to be offset by the improved efficiency and data consistency.

Artificial intelligence and machine learning in CRFs

Artificial intelligence and machine learning are being leveraged to transform how CRFs are filled out in clinical trials. These technologies can be involved in automation techniques to enable batch data entry of critical patient information into eCRFs quickly and automatically.

Tips for designing error-proof CRFs

As mentioned, the CRF needs to be designed carefully in order to capture all essential data for the study and maximize data consistency and validity. Here are a few expert tips for designing high-quality case report forms:

Be explicit: Provide instructions that are as detailed as possible to ensure data consistency
Mark instructions clearly: Leverage italicized, bold, or otherwise stand-out format
Work from the study protocol: Follow a hypothetical patient through the entire study process to ensure that all data expected from the protocol is provided for in the form
Provide explicitly clear instructions regarding ‘skip patterns’ that are easily visible and logical to follow
Include clearly defined and separate lines, fields, or boxes for each expected answer/entry.
Reduce free text fields - include as much guidance as possible for data input. E.g.: Avoid: Date of birth: __________ Better: Date of birth: dd/mm/yyyy
For paper CFRs, utilize multi-sheet NCR forms to ensure identical copies of the CRF
Use consistent formatting (font, style, size) throughout the case report form - i.e., one style for instructions, another style for titles/headings, and another yet for example data
In eCRF tools or electronic databases, activate built-in validity checks and flags for improperly entered/missing data

Conclusions

High-quality CRFs are key to successful clinical trial patient data management. Careful planning and design of the CRF template is important for optimizing data consistency, validity, and accuracy, which in turn facilitates data sharing and regulatory affairs, optimizes data organization, and streamlines analysis of study data and results. eCRFs are increasingly adopted in clinical trials as they can help reduce errors and minimize manual work while maximizing data consistency and its associated benefits.