Electronic Signature Application Questions
There is quite a bit of information by the FDA and others about what it means to apply an electronic signature.
Here are the questions around electronic signatures that I hear most often:
- Should the electronic signature be applied to all pages in the electronic CRF?
- Should the electronic signature be applied to Adverse Events, and Study Completion as typically done on paper?
- Should electronically transmitted laboratory data be electronically signed?
- What happens if pages are electronically signed and the data changes?
- What if a page is electronically signed, then a query is added to the page?
Consider the functionality of the electronic data capture system being used when determining how you will use electronic signatures. For example, in BioClinica Express, electronic CRF pages can be signed at the page level, visit level or patient level. When signing at the patient level, all underlying pages for that patient receive the electronic signature. When signing at the visit level, all underlying pages for the visit receive the electronic signature.
Quite often, companies new to EDC want to put the disclaimer 'My signature indicates that all information entered into the Case Report Form by myself and/or my associates is correct to the best of my knowledge' at the end of the completion page and sign only that page as they do in paper. This method does not take advantage of the features in EDC.
Best Practice Recommendations for Applying Electronic Signatures When Using EDC
Here are some best practice recommendations for applying electronic signatures when using electronic data capture, assuming all regulatory requirements have been met:
Make sure your EDC system checks that the investigator has electronically signed all required pages and that the signature date is later than any data change date.
If you're not planning on signing off on the entire case book at one time, take into consideration that data changes may be made after a subset of the forms are signed. For example, if the investigator signs off on a study termination form and adverse event forms ONLY, the data related to these items may change after signature. The only way to realize the form requires resigning is to compare the dates of data changes to the signature dates. This is not ideal.
Cleaning as you go is always recommended. By cleaning visits or entire patients in an ongoing way at the end of the study, there is minimal cleaning to do prior to lock:
For long studies, consider having the investigator sign off each visit or cycle after it is complete, source verified, queries answered, and data management has reviewed. This ‘clean as you go' concept will allow for concerns to be addressed while the study is ongoing, providing a faster lock time at the end of the study. All pages in the visit or cycle should be electronically signed.
In shorter studies, the investigator should review and sign the entire patient record as the patient completes the study. It is not recommended to wait until all patients are completed, but to ‘clean as you go.'
To summarize, determining how you will be applying electronic signatures and how these will be checked for completeness should be part of the overall data-cleaning plan and may be dependent on the functionality of the EDC system being used.
How do you utilize electronic signatures with electronic data capture? What benefits and/or challenges have you encountered? I look forward to your comments.