An eCRF (electronic case report form) is basically a digital questionnaire used to collect data about a clinical study and research participants. The data collected in eCRFs is what biostatisticians analyze to draw a conclusion from a study, so to properly evaluate whether the endpoints of the clinical trials have been met.

There are different types of e-CRFs. Usually, an electronic case report form (eCRF) is a digital, sometimes web-based, questionnaire for collecting data about a study participant. There are many routes data can take into the eCRF. It may be:

• manually entered by a clinical research coordinator; 
• provided directly from the study participant herself; 
• uploaded in bulk; or 
• transferred directly by integrating with an external data source (e.g. imaging database, via API, etc.). 

eCRF Validation: General Considerations

The validation of eCRF is of foundamental importance. Clinical data needs to be properly collected with a high level of confidence towards security and confidentiality of these data. To properly consider the importance of computer system validation, you may consider, for example, the EMA Notice to Sponsor published in 2020 in relation to SW validation. In this document, for example, it is clearly reported that:

The sponsor is ultimately responsible for the validation of the computerised system and for providing adequate documented evidence on the validation process. Sponsors shall be able to provide the GCP inspectors of the EU/EEA authorities with access to the requested documentation regarding the qualification and validation of computerised systems irrespective of who performed these activities.

At the end of the document, it is also mentioned the following:

It is not acceptable to use computerised systems in clinical trials for which the validation status is not confirmed or for which appropriate documentation on system validation cannot be made available to GCP inspectors.

In fact, as we have already been discussing, software validation is one of the key activities related to Good Clinical Practice and many different standards are regulation may apply, such as GAMP-5 and 21 CFR Part 11: both these standards and regulations are essential for an efficient validation of eCRF. Other regulations may apply, for example GDPR and related considerations.

GAMP-5 is in fact a very powerful guideline and methodology used to perform computer system validation, especially for application in the life science sector, such clinical trials / clinical operations.

eCRF Validation Documentation

Validation is a procedure for testing and checking all system functions. Its purpose is to confirm that the eCRF and in general the Electronic Data Capture is configured correctly and meets all requirements.

Validation is defined as the culmination of evidence that a system does what it claims to do and will continue to do so.

The development of an eCRF itself starts with the final study protocol; once the specific objectives of the study has been determined, the structure of the eCRF can be defined, i.e. the names and characteristics of all CRF items and corresponding database tables.

For that purpose, a structure plan is created which is reviewed and approved – by all involved parties – before set-up and validation of the eCRF structure within the development environment of the EDC system.

Once the structure of the eCRF is finalized, the criteria for online and offline plausibility checks are defined. Upon review and approval of the data validation plan, the implementation and validation of the online edit checks and e-mail alerts can be performed within the development environment of the Electronic Data Capture system.

In summary, to properly perform validation activities one the eCRF, the following documentation shall be prepared:

• Data Validation Plan
• CRF/eCRF matching report
• Test case report

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