If you want to:
- expand your knowledge of CRFs in clinical trials
- understand the difference between traditional CRFs and eCRFs
- learn the dos and don’ts of CRF design
…you’ve come to the right place! Let’s start with the basics.
What are case report forms?
A case report form is a printed or electronic document designed to record all patient information that’s required by the sponsor during a clinical trial.
An electronic CRF (eCRF) is an electronic version of the traditional CRF, that can be stored in cloud-based systems such as clinical metadata repositories (CMDRs) or Electronic Data Capture (EDC) systems. The terms ‘CRF’ and ‘eCRF’ tend to be used interchangeably, and they’re also referred to simply as ‘forms’.
CRFs play a crucial role in helping to assess the safety and efficacy of clinical products. For a study to be successful, the data collected must be correct and complete. This means that forms must be well planned with meticulous attention to detail. They must comply with the study protocol, and record its detail. They must also comply with regulatory requirements, such as those defined by the US Food and Drug Administration (FDA).
With improvements in technology over the last 20 years, there’s been a move away from traditional paper CRFs, towards creating and maintaining eCRFs using cloud-based systems like CMDRs and EDCs. While lots of organizations have embraced this change and witnessed the benefits, many are reluctant to get on board.
Why do organizations still use traditional CRFs?
Organizations feel more comfortable with a familiar process. They’re under time pressure to get studies live and meet the first patient in (FPI). Moving to a cloud-based system involves significant change, and organizations see change as a cause for uncertainty and risk. On top of that, there are some misconceptions around switching to a cloud-based system, that deter organizations from making the change.
We’ve analyzed three common misconceptions below:
Belief 1: It’s more cost-effective to use traditional CRFs in clinical trials.
“With traditional CRFs, there’s a low start-up cost and no monthly license fees to pay. A lot of training is needed to be able to switch to cloud-based systems and use eCRFs.”
Fact 1: Using eCRFs for studies can be much more cost effective.
It actually costs more to continue using text documents or spreadsheets, rather than switching to a CMDR. Why? Because time means cost. Traditional CRFs need to be created manually each time, which takes longer. Then there’s the annotated CRFs, which need to be done from scratch for every form and study.
There’s also a higher likelihood of data errors with traditional CRFs because formats can’t be enforced and collected data must be manually entered into a computer. Generally, only small companies running small studies find traditional CRFs to be cost effective.
In comparison, standardized eCRFs can be reused, which creates efficiencies; they’ve already been reviewed and approved by stakeholders, and you know that they capture clear and valid data.
Belief 2: Data stored in text documents or spreadsheets is safer.
“Using a secure centralized location, like a vault, keeps data safe.”
Fact 2: Creating and maintaining CRFs using text documents and spreadsheets can be tedious and error-prone. Content in text documents can become corrupted or unintentionally altered by users. Locating the latest version of a CRF that has been approved by all stakeholders can be tricky. On the other hand, EDCs use encryption to secure data both in transit and when stored, in addition to off-site encrypted backups. With EDCs, access is restricted and there’s a full audit trail for traceability.
Belief 3: Making the move to using eCRFs and EDCs requires a lot of software training.
“Training takes up a lot of time. We already have tight deadlines and as a result, are under pressure. There’s no need for software training to create text documents or spreadsheets.”
Fact 3: There’s less training required than you think. Using a cloud-based system that automates the process of creating eCRFs saves lots of time. Some training is required to get started, but the time saved in the long term makes it far more efficient.
Using eCRF design software typically gives you access to a technical support team. Plus, these days EDCs are much more user-friendly and have built-in help and support.
|Myth X||Fact ✓|
|Traditional CRFs are more cost effective||It actually costs more to continue using text documents or spreadsheets, rather than switching to electronic CRFs.|
|Traditional CRFs are more secure||Content in text documents can get corrupted or unintentionally altered by users. With eCRFs, access can be restricted and there’s a full audit trail of changes.|
|Moving to eCRFs/implementing an EDC requires a lot of training time||There’s less training required than you think, and using a cloud-based system that automates the process of creating eCRFs saves lots of time.|
To recap, studies can be automated and speeded up, which means time and cost efficiencies. Data is nice and secure. And there’s training and support for onboarding and beyond.
But, there’s something equally as important to a successful submission to the FDA, and that’s CRF and eCRF design.
Designing CRFs in clinical trials
Good CRF design is essential for a successful submission, and for getting clinical products to market quickly.
We’ve found that organizations often struggle with the following design challenges:1. Creating forms that are consistent
2. Collecting precise data
3. Creating user-friendly forms
Here are some best practice steps to overcome these challenges:
- Do proper planning early on in the study. This should be done by a team of people that includes data management, biostatisticians, and clinicians.
- Define clear objectives and stick to them – what information are you required to gather?
- Maintain standardized forms – that way, you can reuse the form over and over.
- Get user feedback. It’s best to build this into the design and maintenance process.
- Provide form completion guidelines with specific instructions to reduce data entry issues and ambiguities. This helps investigators fill in forms correctly and ensure that data is accurately captured for analysis.
Below, we’ve listed some dos and don’ts to help you create a well-designed form that can be reused again and again.
Well-designed forms must:
- Gather data that is complete, accurate, and high quality
- Avoid duplication
- Be well structured, simple, uncluttered and user-friendly
- Be unambiguous and allow for accurate data entry; use coded lists to limit answers to approved responses only and avoid open-ended questions
- Minimize the use of free-text responses or ‘check all that apply’
- Avoid gathering more data than what’s needed
- Include clear guidance using prompts and instructions
- Use consistent formats, fonts, and font sizes across all forms
- Include consistent headers
- Specify units of measurement
- Use visual clues to show how questions are to be answered (for example, the date format, and the number of decimal places)
- Keep related questions together in sections
For paper CRFs, include page number. Avoid circling answers, and make it clear which questions are mandatory.
Example of a poorly designed form
Where it went wrong:
X There’s no guidance given for responses.
X There are no controlled terms to guide the investigator. That means responses are open to interpretation.
X No measurement units are stipulated (is height measured in inches or meters?). This can also make mappings more complex.
X Many questions on a CRF are mapped to variables in SDTM (Study Data Tabulation Model) datasets down the line. Allowing free text responses can create a considerable challenge when it comes to mapping and converting data from its raw state to SDTM datasets.
Example of a well-designed form
Why it works:
✔ Clear guidance is provided.
✔ Questions are divided into logical sections.
✔ Use of controlled terminology ensures there’s a limited choice of answers and helps prevent unnecessary queries.
✔ The content of each terminology complies with the National Cancer Institute (NCI) standards which makes future mapping easier.
✔ Allowable measurement units are indicated to allow for accurate conversion into appropriate units.
We’ve covered the background to CRFs in clinical trials, and some common design challenges. Now, we’ll take a look at another submission essential: annotated CRFs.
What are annotated CRFs?
Annotated CRFs are a key submission deliverable, a mandatory requirement of the FDA. Each form in a study contains markings or annotations. These annotations map data points on forms to the name of datasets, and variables within those datasets. In other words, “each CRF should provide the variable names and coding for each CRF item included in the data tabulation datasets” as stated by the FDA guidelines.
The FDA stipulates that a set of blank annotated CRFs be submitted in a PDF document called “blankcrf.pdf”. This document helps the FDA reviewer find the origin of variables in the SDTM datasets.
You can read more about why it’s a good idea to switch to automated CRF annotations.
Here’s an example of an annotated CRF in ryze.
Creating good quality annotated case report forms (CRFs) takes time and attention to detail. While it can feel overwhelming, there is industry and regulatory guidance to help you get it right. Read our blog about the guidance that’s available to help ensure you’re meeting the requirements.
Why should CRFs be standardized?
Standardization means consistency, compliance, and reusability. It means creating forms that cover everything your stakeholders need. The investigator, data manager, biostatisticians and data entry personnel can all review and approve the standardized form. This means it can be used again and again, saving time on both design and approval in future studies. And, annotations don’t need to be manually done on each form in the study – they’re standardized in line with requirements right from the get-go!
You can also reuse edit checks – a process which normally takes a lot of time and resources. So, for all your studies, you’ll have a pre-approved and well-designed CRF that’s user friendly, captures consistent data, and results in clear and valid datasets down the line.
How ryze can help...
ryze, our clinical trial automation software lets you create forms from scratch, or upload your existing forms and store them in our clinical metadata repository. Once your forms are standardized, you can quickly and easily find, share, update, preview and reuse them across other standards and studies - including annotations and edit checks.
You can also see how eCRFs look and work for leading EDCs in ryze - including Rave and InForm/Clinical One. In other words, you can preview exactly how forms look before building your EDC. This in itself speeds up the approvals process. Then once eCRFs are approved, you can automatically build your EDC from ryze with just one click!
As soon as you start working with us, you’ll have access to technical support, training, and your own dedicated account manager. We’ll help you to get set up and walk you through the ryze platform.
Not only were we one of the first ever CDISC members over 18 years ago, today we’re active members of the CDISC XML Technology team, and our friendly experts regularly speak at industry events. This means that we when it comes to standards and legislation, we really know our stuff. So working with us means you’ll benefit from the very latest industry standards knowledge.
If you want to learn more about CRF design, why not download our guide to common case report form design issues and how to solve them? Our guide also includes a CRF design checklist to keep you on track!
Author's note: this blog post was originally published in January 2021 and has been updated for accuracy and comprehensiveness.
About the author
Customer Success Manager | Formedix
Gilbert joined Formedix nearly ten years ago as a technical writer. The system knowledge he gained from content development, together with his existing customer service skills, marked him out for transition to the Professional Services (PS) team.
Gilbert has worked with the PS team for over four years, providing both CDISC-based training and software training, as well as support and consultancy services to Pharmaceutical, Biotechnology and Clinical Research Organizations. He helps organizations build studies faster and to a higher quality by making their clinical trial design and regulatory submissions far more efficient.
Today, as Customer Success Manager, Gilbert’s focus is to ensure customers maximize the benefits they can achieve from ryze by overcoming their challenges and achieving their goals.