aCRFs are a mandatory requirement of the FDA, and therefore a key submission deliverable for any clinical trial. Creating quality annotated case report forms (aCRFs) takes time and attention to detail.
So, it’s important to understand what regulatory and industry guidelines are out there, to ensure your aCRFs meet the requirements.
What are annotated CRFs?
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.
According to the FDA Study Data Technical Conformance Guidelines, “each CRF should provide the variable names and coding for each CRF item included in the data tabulation datasets”.
For more information about CRFs, read our blog: Everything You Need to Know About CRFs in Clinical Trials.
Regulatory requirements for annotated CRFs
So how do you create submission-ready aCRFs?
There are two documents published by the FDA that include requirements applicable to annotated CRFs.
We’ve highlighted some key points from both documents below. We recommend that you download and review each PDF thoroughly, to ensure adherence to requirements.
FDA’s study data technical conformance guide section 4.1.4.6 lays out guidance for providing regulatory submissions electronically, as follows:
- aCRFs should be submitted ideally at the same time a protocol is submitted.
- The aCRF should be in PDF format and should have the file name ‘acrf.pdf.’
- aCRF should include treatment assignment forms, if relevant, and should map each variable on the CRF to the corresponding variables in the datasets or database.
- For each CRF item, include the variable names and coding.
- When data is recorded on the CRF but are not submitted, the CRF should be annotated with the text ‘NOT SUBMITTED.’ Include an explanation in the relevant reviewer’s guide stating why these have not been submitted.
FDA’s portable document format (PDF) specifications guide; as the annotated CRF is a PDF, it is subject to the specifications in this document.
The following technical requirements are applicable to the formatting of annotations on CRFs – this list includes some key requirements but is not exhaustive. Review the PDF download for a full list of technical requirements for submitted PDFs, including guidelines for page layout and document navigation.
- Submitted PDF files should be in PDF versions 1.4 through 1.7, PDF/A-1 and PDF/A-2 and readable in Adobe Acrobat.
- Documents should not be password protected.
- Only standard fonts should be used at 9-12pt, and any non-standard fonts should be fully embedded. You can see a full list of standard fonts in the PDF download.
- It’s recommended that text should be black, but blue is permitted for hyperlinks.
- The PDF should be text searchable and should include a contents table featuring hyperlinks to bookmarked pages.
Industry requirements for annotated CRFs
In addition to the regulatory requirements for annotated CRFs, you should also be aware of industry requirements from the Clinical Data Interchange Standards Consortium (CDISC).
These are laid out in the following documents:
CDISC’s annotated CRF SDTM guidelines
CDISC’s metadata submissions guidelines (MSG)
Below, we’ve summarized some key points as recommended by these documents. We do advise that you review the PDF downloads, which contain detailed guidance.
- The aCRF should be bookmarked in two ways ‒ chronologically and alphabetically.
- The aCRF must not contain any blank pages.
- Each domain that is represented on a page should have its own annotation on the upper left side of the CRF page with the 2-letter domain code and domain name.
- If more than one domain exists on a page, each domain annotation, and all its variables, should be color-coded.
- All text in the annotations that represent variable and domain names should be capitalized. If possible, the annotations should not obstruct any text on the CRF page.
- It should include additional collection documents (e.g. questionnaires, diaries, lab print outs) if these data are NOT transcribed into the CRF.
Automating annotated CRFs
With traditional, manual annotated CRFs, you can spend a lot of time and effort:
- ensuring compliance
- identifying all annotations to be added for disparate sources
- editing the font and color of the annotations
- adding links and bookmarks and applying changes – and often, there can be multiple rounds of changes to accommodate!
This traditional process is not only time consuming; it can result in human error and a reduction in quality of your annotations.
If you find this is the case for your current process, why not consider automating annotated CRFs to make the job a little easier?
The benefits of automating annotated CRFs:
- They’re quicker and easier to create than manual versions.
- You can achieve higher quality and more consistent annotations.
- Easily make color, position, and text consistent.
- Reuse your standardized annotations across different studies.
- Easily edit forms and annotations.
- And there’s no need to redo bookmarks – this is done automatically!
Find out how Pinnacle 21 Enterprise can help you automate your aCRF design.
If you’re feeling overwhelmed by the challenge of creating compliant CRFs, why not download our best practice guide to CRF design?