The Electronic Informed Consent Has Arrived

The informed consent process is based on a trusted interaction between a study subject and the clinical research investigator. In 1991, the “Federal Policy for the Protection of Human Research Subjects,” based on the HHS 45 CFR part 46 subpart A and known as the “Common Rule,” was issued by 15 federal departments and agencies.¹ The last revision of the Common Rule was in 2009.

FDA regulations concerning the protection of human subjects are codified in 21CFR Part 50,² and in March 2015, FDA issued a Draft Guidance on Electronic Informed Consent.³ The draft guidance was prepared by the Office of Medical Policy (OMP) in the Center for Drug Evaluation and Research (CDER), the Office of Good Clinical Practice (OGCP) in the Office of Medical Products and Tobacco, in coordination with the Center for Biologics Evaluation Research (CBER) and the Center for Devices and Radiological Health (CDRH).

The following are points to consider when designing and using an electronic informed consent form (eICF):

Point 1: Operational Considerations

If a subject cannot or does not want to sign the informed consent form (ICF) electronically, there should be the option for the clinical research site to document in any electronic data capture (EDC) system that a paper process was used. Likewise, if a stand-alone eICF system is used via a dedicated tablet, for example, there should be ways to seamlessly “inform” the EDC system that the eICF has been signed. For web-based eICF systems that are fully integrated with EDC systems, access to the data entry screens should be controlled until the signature process is finalized. In the world of Bring Your Own Devices (BYOD), access to the eICF should also be browser independent.

Point 2: Roles and Responsibilities

When using an eICF, the clinical research site and companies sponsoring the clinical trial should clearly define the eICF process as well as the roles and responsibilities of each stakeholder in standard operating procedures (SOPs) and in the study protocol. For example: How is version control managed? How are different languages managed? Who is hosting the eICF software application? How is website access controlled? How are questions created and answered? What happens if the website is down temporarily? Who is managing the user accounts?

Point 3: Subject Authentication

Attribution, as well as binding of the contents within the eICF to the electronic signature and the signatory, must also allow for the eICF to be compliant with the electronic recordkeeping and electronic signature requirements found in 21 CFR Part 11,^4,5 and the FDA Guidance for Industry on Computerized Systems Used in Clinical Investigations.⁶

When a study subject electronically signs the ICF, there must be confidence that the signature can be attributed to the actual person participating in the clinical trial, and that the subject cannot repudiate the signature once invoked. For example, there must be a verification step to assure that the person signing the eICF is the actual person participating in the clinical trial, and it is not possible to delete the signature. Because technology is always changing and subject authentication can be addressed in multiple ways, wisely, the FDA did not require a specific authentication process in the draft guidance, but left it up to the sponsor to decide. While sponsors could assess technology tools associated with user authentication, especially for remote and virtual clinical trials, costs or complexity should not be added to the ICF process.

Point 4: Keep it Simple

As we introduce eICF systems, there may be a tendency to make the eICF process more complex than needed. Some may want to create videos to assist in the process or require tests to assess comprehension. While these approaches may add to the success of eICF implementation, we must be aware of unintended consequences especially when the eICF is used in global multicenter studies, when just managing versions and multiple languages within and between sites can be daunting.

Point 5: Monitoring Efficiencies

When Signing the ICF Electronically It is common practice for CRAs and regulators to document that each and every study subject signed the correct version of the ICF. Imagine the time, cost savings and other efficiencies if there was a simple validated online report to track the time and date of each electronic signature.

Point 6: Accessibility

After signing the ICF, the study subject must have access to the eICF and it should be printable. For printing, a .pdf file is preferable as it can be printed with any computerized system supporting an Adobe reader.

Point 7: Source Document Control

Since the eICF is a source document, it should be under the control of the clinical site as would be a paper copy. To accomplish this, the eICF should be stored in an electronic repository with user management and access controlled by the study site.

Jules T. Mitchel is President, Target Health Inc. and Jonathan Helfgott is Coordinator of the Regulatory Science Graduate Program at Johns Hopkins University.

References

1. Part 46: Protection of Human Subjects http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.html
2. 21 CFR Part 50; Protection of Human Subjects. Code of Federal Regulations, Title 21, Volume 1. Revised, April 1, 2015. (https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?CFRPart=50)
3. FDA Draft Guidance Use of Electronic Informed Consent in Clinical Investigations, March 2015. http://www.fda.gov/downloads/drugs/guidancecomplianceregulatory information/guidances/ucm436811.pdf
4. FDA Guidance For Industry. Part 11, Electronic Records; Electronic Signatures - Scope and Application, August 2003. http://www.fda.gov/downloads/RegulatoryInformation/Guidances/ucm125125.pdf
5. 21 CFR Part 11. Code of Federal Regulations http://www.ecfr.gov/cgi-bin/text-idx?SID=c654e9b1077d05f0b0bb0fbdd45f00b8&mc=true&tpl=/ ecfrbrowse/Title21/21cfr11_main_02.tpl
6. Guidance for Industry Computerized Systems Used in Clinical Investigations, May 2007 http://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation /guidances/ucm070266.pdf