No experiment is said to be complete until the results had been published or otherwise reported. It becomes even more important when the research directly involve human. Clinical research not only directly involves human subjects but can also affect human health if the reporting is not performed properly. And for proper reporting, proper data collection is very important.
In 70% clinical trials data collection is done manually through paper CRF in which Investigators manually record data on source documents and copy the same to the CRFs. Clinical monitors from CRO/sponsor verify the data and send the CRFs to CDM team. Paper CRF usually has an audit trail that is visible directly on the CRFs. Changes to individual fields are indicated with a single-line cross out, with the changed data appended along with the signature or initial of the person making the change, a date and perhaps a reason for change. Comments are written in the margin of these CRFs. Data clarification forms are appended to the CRF and contain the questions and responses that generated the change. This time honored format creates a complete case record with audit trail that is familiar to regulatory reviewers and investigators.
Though paper CRF gives an accurate, reliable and complete data, it is a laborious process and takes time for collecting CRF from investigational site, performing data entry and validation, and raising and resolving queries via Data Clarification Form (DCF). This has direct impact on time for drug to come in market. This suggested the idea of real time data management tools. Hence technology and innovation is used to its full extent and Electronic Data Capture (EDC) comes into limelight. The concepts for the design of electronic CRF are same as covered for paper.
EDC technology is expected to improve efficiency and accuracy of data, speed up decision making process and reduce cost. It resulted in a reduction of paper consumption and load on clinical monitors to manage such huge volume of paper. This paradigm has reduced the risk of damage of CRF during transit. It is due to these reasons EDC is preferred to traditional method.
GCP and 21 CFR Part 11 require validation for a software system used for processing clinical data. System validation includes user requirement specifications, functional specification, design specifications, implementation and testing. 21 CFR Part 11 defines the criteria under which electronic records and electronic signatures are considered to be trustworthy, reliable and equivalent to paper records. Part 11 has requirements to implement controls including audits, system validations, audit trails, electronic signature and documentation for software and systems involved in processing electronic data that are a) required to be maintained by FDA rules and b) demonstrate compliance to a predicted rule.
In electronic CRF, investigator enters data and signs electronically for accuracy, reliability and completion of all data points. It assembles data from multiple tables into a single Web page. However, the investigator later can add, modify or delete data in the EDC system in future at any time-point, until the electronic CRF are locked and no more updating is permitted. Investigator at this point should sign for the changes made to electronic CRF data points which were entered or changed. At the end, Investigator has to sign for all data entries, modifications or deletions as he is owner of that clinical data. This is why signing by the investigator is so important in electronic data capture.
Audit trails and comments are not found in the margins of an eCRF- they are viewable through links from the CRF and also are simply user-friendly representations of data tables. Electronic CRF is not just a repository but is designed to allow the backend systems to perform efficiently. The forms have built in edit checks and no longer accept entered data. POPs will appear if there is any error in entry/incorrect value. Query management can be done within minutes as opposite to paper CRF. Queries can be managed through computer user interface rather than paper based clinical trial. We can raise query directly on website and monitor can log on the query message and provide his resolutions there. Since high quality data are available at the time of data entry by the study site, biostatistician can review and analyze very early. As a result almost all statistical programs are completed before the visit of last patient.
Roles of data management staffs that have changed with the arrival of eCRF:
There is no doubt that electronic data capture is the future as it increases the speed of data processing and assures high quality data with lower error than paper CRF of Clinical Research. However, deployment of these advances should be implemented carefully as it requires consideration of desired outcome and the needs of people involved in the process.
Representing
Genelife Clinical Research - Clinical Data Management Department
In 70% clinical trials data collection is done manually through paper CRF in which Investigators manually record data on source documents and copy the same to the CRFs. Clinical monitors from CRO/sponsor verify the data and send the CRFs to CDM team. Paper CRF usually has an audit trail that is visible directly on the CRFs. Changes to individual fields are indicated with a single-line cross out, with the changed data appended along with the signature or initial of the person making the change, a date and perhaps a reason for change. Comments are written in the margin of these CRFs. Data clarification forms are appended to the CRF and contain the questions and responses that generated the change. This time honored format creates a complete case record with audit trail that is familiar to regulatory reviewers and investigators.
Though paper CRF gives an accurate, reliable and complete data, it is a laborious process and takes time for collecting CRF from investigational site, performing data entry and validation, and raising and resolving queries via Data Clarification Form (DCF). This has direct impact on time for drug to come in market. This suggested the idea of real time data management tools. Hence technology and innovation is used to its full extent and Electronic Data Capture (EDC) comes into limelight. The concepts for the design of electronic CRF are same as covered for paper.
EDC technology is expected to improve efficiency and accuracy of data, speed up decision making process and reduce cost. It resulted in a reduction of paper consumption and load on clinical monitors to manage such huge volume of paper. This paradigm has reduced the risk of damage of CRF during transit. It is due to these reasons EDC is preferred to traditional method.
GCP and 21 CFR Part 11 require validation for a software system used for processing clinical data. System validation includes user requirement specifications, functional specification, design specifications, implementation and testing. 21 CFR Part 11 defines the criteria under which electronic records and electronic signatures are considered to be trustworthy, reliable and equivalent to paper records. Part 11 has requirements to implement controls including audits, system validations, audit trails, electronic signature and documentation for software and systems involved in processing electronic data that are a) required to be maintained by FDA rules and b) demonstrate compliance to a predicted rule.
In electronic CRF, investigator enters data and signs electronically for accuracy, reliability and completion of all data points. It assembles data from multiple tables into a single Web page. However, the investigator later can add, modify or delete data in the EDC system in future at any time-point, until the electronic CRF are locked and no more updating is permitted. Investigator at this point should sign for the changes made to electronic CRF data points which were entered or changed. At the end, Investigator has to sign for all data entries, modifications or deletions as he is owner of that clinical data. This is why signing by the investigator is so important in electronic data capture.
Audit trails and comments are not found in the margins of an eCRF- they are viewable through links from the CRF and also are simply user-friendly representations of data tables. Electronic CRF is not just a repository but is designed to allow the backend systems to perform efficiently. The forms have built in edit checks and no longer accept entered data. POPs will appear if there is any error in entry/incorrect value. Query management can be done within minutes as opposite to paper CRF. Queries can be managed through computer user interface rather than paper based clinical trial. We can raise query directly on website and monitor can log on the query message and provide his resolutions there. Since high quality data are available at the time of data entry by the study site, biostatistician can review and analyze very early. As a result almost all statistical programs are completed before the visit of last patient.
Roles of data management staffs that have changed with the arrival of eCRF:
- Data entry task shifted to site personnel/investigator
- Data review/cleaning became a joint venture of site personnel/investigator, clinical monitor and CDM team
- Trainer is needed in CDM to impact training functionality of EDC software
- Clinical monitors to perform source data verification which is a QC task,
- CDM members have to generate extra manual review listings and perform this task manually
- Clinical monitors or data management team to address/resolve technical issues faced by site personnel/investigators.
There is no doubt that electronic data capture is the future as it increases the speed of data processing and assures high quality data with lower error than paper CRF of Clinical Research. However, deployment of these advances should be implemented carefully as it requires consideration of desired outcome and the needs of people involved in the process.
Representing
Genelife Clinical Research - Clinical Data Management Department
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