Author: Gilbert Hunter
What’s the background on CRFs?
A Case Report Form (CRF) is a printed, optical, or electronic document designed to record all of the protocol required information to be reported to the sponsor on each trial subject. CRFs play a crucial role in helping to assess the safety and efficacy of clinical products.
An electronic CRF (eCRF) is an electronic version of the traditional CRF stored in cloud-based systems such metadata repositories or Electronic Data Capture (EDC) systems. Both CRF and eCRF tend to be used interchangeably, and they’re also referred to as forms.
An annotated CRF is a blank CRF with annotations that document the location of the data with the corresponding names of the datasets and the names of those variables included in the submitted datasets. Annotated CRFs are part of the mandatory CDISC submission deliverables to the U.S. Food and Drug Administration (FDA).
For a study to be successful, data collected must be correct and complete. To be correct and complete, forms must be well planned with meticulous attention to detail. They must comply with the study protocol, and record its detail. And, they must also comply with regulatory requirements, such as those defined by the FDA.
Over the last 20 years, with improvements in technology, there’s been a move towards creating and maintaining eCRFs using cloud-based systems. While a lot of organizations have embraced this change and witnessed the benefits, many are reluctant to get on board.
Why organizations still use traditional CRFs
Organizations like having 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 huge changes and can cause uncertainty. So it’s a risky undertaking. On top of that, there are a few misconceptions that deter organizations.
Here are 3 misconceptions around moving to a cloud-based system:
- Using traditionally-designed CRFs for studies is more cost effective.
“There’s a low clinical study 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.”
- Data stored on text documents or spreadsheets is safer as it’s in a secure centralized location.
“Using a secure centralized location, like a vault, keeps data safe.”
- 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. So additional training will take up time we can’t afford. There’s no need for software training to create text documents or spreadsheets.”
Why cloud-based systems are better
In the long run, it’s been proved that using EDCs and eCRFs provides much greater advantages than using traditional methods.
Here’s why the misconceptions above have proved to be false:
- Using eCRFs for studies can be much more cost effective.
It actually takes more effort and cost to continue using text documents or spreadsheets, rather than using a clinical metadata repository and reusing standardized eCRFs. Why? More time means more costs. It takes much longer to create traditional studies, and you can’t easily reuse the CRFs because they need to be created manually each time. Plus, annotations need to be done from scratch for every single text document or spreadsheet. There’s a much higher likelihood of data errors because data formats can’t be enforced and collected data must be manually re-entered into a computer. This is the main reason for costs being higher. It’s generally only small companies running small studies that are more cost effective using traditional CRFs.
- Data stored in a cloud-based system is more secure than on text documents or spreadsheets.
Creating and maintaining CRFs using text documents and spreadsheets can be tedious and error-prone. Locating the latest version of a CRF that has been approved by all stakeholders isn’t as easy as it sounds. Content in text documents can get corrupted or unintentionally altered by other users.
EDCs have encryption that secures data both in transit and when stored, as well as off-site encrypted backups. Access is restricted, and there’s a full audit trail.
- There’s not as much training required as you think.
Using a cloud-based system that automates the process of creating eCRFs saves lots of time. Yes, some training will be needed to get started, but the time saved for current and future studies makes up for it many times over. Using a cloud-based system like ryze means you’ll have access to help and support from our professional services team, as well as a dedicated account manager, and access to training. We can help get you set up and walk you through our platform. These days, EDCs are much more user friendly than they used to be. So training is a fairly quick process. And EDCs have built-in help and support.
This is all great. Studies can be automated and speeded up. Data is nice and secure. Training doesn’t take too long, and it’s cost effective. But, if you don’t have good CRF design in clinical trials, then successful submission to the FDA is unlikely, or will take a lot longer, even using cloud-based automated systems.
CRF design & eCRF design
Forms that are well-designed are essential for a successful clinical trial submission and getting clinical products to the market.
Well-designed forms must:
- Gather data that is complete, accurate, and high quality.
- Avoid duplication.
- Be well structured and easy for the user to complete.
- Be unambiguous and allow for accurate data entry. For example, using coded lists to limit answers to questions. And avoid open-ended questions.
- Avoid gathering more data than what’s needed.
- Be consistent, well laid out, uncluttered, simple, and user friendly.
What to keep in mind at design time
To capture data correctly, here are some things to think about:
- Clear guidance using prompts and instructions should be included.
- Formats, fonts, and font sizes should be the same across all forms.
- The layout should be simple and uncluttered.
- Questions should be clear, precise, and easy to understand.
- Include consistent headers.
- Specify units of measurement.
- Visual cues should be used to show how questions are to be answered. For example, the date format, and the number of decimal places.
- Minimize the use of free-text responses or “check all that apply”.
- Keep related questions together in sections.
- For paper CRFs, include page numbering. Avoid circling answers, and make it clear which questions are mandatory.
Example of a poorly designed form
There’s no guidance given for responses in the form above. There are no controlled terms to guide the investigator. That means responses are open to interpretation. Many questions on a CRF are mapped to variables in SDTM (Study Data Tabulation Model) datasets. Allowing free text question responses can provide a considerable challenge when mapping and converting data from its raw state to SDTM.
No measurement units are stipulated (is height measured in inches or meters?). This can also make mappings more complex.
Example of a well-designed form
Clear guidance is given on the CRF. Questions are divided into logical sections.
Use of controlled terminologies ensures there’s a limited choice of answer and helps prevent unnecessary queries. The content of each terminology complies with the National Cancer Institute (NCI) standards which makes mapping easier. Allowable measurement units are indicated to allow for accurate conversion into appropriate units.
CRF design & eCRF design challenges
3 common design challenges that typically come up:
- Creating forms that are consistent.
- Collecting precise data.
- Creating user-friendly forms.
To overcome these challenges there’s a number of things you can do:
- Do proper planning, and start it early on in the study. This should be done by a team of people that include data management, biostatisticians, and clinicians.
- Define clear objectives and stick to them.
- Maintain standardized forms.
- Get user feedback. It’s best to build this into the design and maintenance process.
- Apply best practices.
- Provide form completion guidelines to reduce data capture and data entry issues. This helps investigators fill in forms correctly by providing step by step guidance, and uses clear specific instructions.
If you’re interested, you can find out about using ODM and CDASH for CRF design.
Now that CRF and eCRF design are covered, the next thing to look at is annotating CRFs.
Why are annotated CRFs so important?
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.
Why should CRFs be standardized?
It’s important to standardize forms so that stakeholders such as the investigator, data manager, biostatisticians, data entry personnel, etc. have their needs met. CRFs must be user friendly and capture consistent data, that’s clear and valid.
Standardizing CRFs means you can reuse them. That’s a huge efficiency gain. They’ve already been reviewed and approved, so they’ll be consistent, and of high quality. And, annotations don’t need to be manually done on each form. You can also reuse edit checks that normally take lots of time and resources to do. So, not only is it a huge time and resource-saving, it’s a lot less hassle!
How we can help...
Our clinical trial automation software ryze 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 reuse them across other standards and studies, including annotations and edit checks. It’s easy to find, share, and update your forms. And you can preview them in different formats as you design them, as well as being able to see how they look and work in leading EDCs including Rave and Clinical One. Plus we integrate 100% with Rave! CRF, EDC, and CDISC validation are built-in, so you don’t have to worry about being compliant. You can find more about creating your CRF designs and EDC designs in ryze.
You can read about how a clinical metadata repository can help with data quality and you can read about important aspects you should consider before implementing one.
If you want to see the ryze platform in action, you can book an online customized demo. Or, if you just want to find out a bit more, you can set up a call or contact us to tell us about your particular challenges or requirements.
There’s also the option of a free trial which includes 6 hours of free training to get you up and running!