e-Consent has the Potential to Replace the Paper Informed Consent Process

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e-Consent has the potential to replace the paper Informed Consent process

By Mourin Patnaik

Informed consent (IC). It may be just a data point in the Case Report Form (CRF) for Data Management, but it means a
whole lot for the Clinical Operations. In this article we will understand what a traditional IC process is and why the next
era of clinical trials is talking about electronic IC or e-Consent.
Among the 13 principles of the International Conference on Harmonization (ICH) Good Clinical Practice (GCP), the
third principle talks about safeguarding the right, safety and wellbeing of the trial subjects.[1] This is ensured by the
Investigator selecting the right patient, assessed using the study’s inclusion and exclusion criteria, and by receiving a
signed and dated IC from the trial subjects.

IC IS IMPORTANT… BUT WHY IS IT SO IMPORTANT?

IC is ethically essential in clinical research to respect a person’s rights to decide whether participation in the research
is compatible with their interests, including their interests in protection from exploitation and harm. In the process of
IC, participants are given an opportunity to understand relevant information about research participation and to make
a voluntary choice. Required by ethical guidelines and regulations, unless explicitly waived by institutional review
boards, IC is thus a means of protecting the rights and welfare of participants while they contribute to the advancement
of knowledge.[2]
The term IC is not just about obtaining a handwritten signature from the subject or the subject’s legally authorized
representative (LAR) on a written IC form, but also involves providing a potential subject with adequate information
about the research. This is to allow for an informed decision about the subject’s voluntary participation in a research
study.
The ideal IC process involves an ongoing, interactive conversation between the participant and the research site
personnel, responsive research staff who have been trained in best practices. The IC process should be supported by
a detailed IC document that provides critically relevant information to aid in the decision to participate in a study.[3, 4]

PAPER IC OR E-CONSENT? WHICH ONE TO PREFER?

In the paper-based process, IC is obtained by an investigator who presents the potential participant with information
regarding a new therapeutic, diagnostic, or prophylactic intervention and then asks the participant to read and sign a
detailed written consent document. This traditional prototype may soon become outdated.[5]
Over the past 50 years, the IC process has become increasingly regulated and standardized, while the challenges
remain persistent and hard to overcome. Consent forms are increasingly long and complicated, obscuring important
details, and are often designed to serve the interests of institutions and sponsors. What is generally observed is that
participants often have a limited understanding of study information even when they have signed a consent form.
Technological advances driving changes in research methods and information practices have influenced how we think
about IC, which raises the possibility of new approaches to IC and innovative options for obtaining it.
Having worked as a monitor before, some of the common issues that we face on site during review of paper IC forms
are:
• Failure to re-consent on a timely manner when new information is available. Waiting for the next subject visit means
new information on the investigational product (IP) or study procedures is not shared with the study participants in a
timely manner.
• New enrolled subjects are consented on expired forms or unapproved forms. Long recruitment periods, frequent
protocol amendments, and consent form changes may all lead to consent being collected on outdated forms.
• Principle investigator or co-investigator inadvertently misses signing/ dating the IC form.
• Failure to provide full copies of the form to the subject.
• Keeping only the last page of the consent document in the investigator site files.
• Enrolling a subject from a different region, not understanding the preferred language and not using a proper
interpreter to ensure the subject’s rights are protected before providing his consent for participation.
• Changes made to the consent documents by hand without IRB approval (e.g., crossed out information about
procedures, increased amount of payment).
Paper-based consent may result in an additional work burden due to frequent human contact. E-Consent may be the
solution to this and the other mentioned IC concerns.

E-CONSENT! THE WAY AHEAD…

E-Consent systems are gaining momentum and attracting considerable interest as healthcare providers increasingly
apply information technology and management to plan and deliver high-quality and cost-effective healthcare. These
systems can ensure that patients are informed about the consequences of clinical intervention and are also aware that
their personal health information might be used for research purposes. E-Consent is real-time and the patient can
view the conditions of consent and create an audit trail of when each version was read and acknowledged.
Digitalization has changed the way people live in today’s world. It has also transformed the way research is conducted.
We are slowly moving to becoming paperless and all information is constantly at our fingertips. Health information
is stored electronically. Technology and the advances in health sciences bring in innovative ways of implementing IC.
Applications, tablets, videos, interactive computers, robots, personal digital assistants, mobile phones/ smartphones,
and wearable technology can each help to modernize, alter, and improve methods of IC. Technologies permit broad
standardization and easy updating of information, ready use of creative graphics, the means for remote interactive
discussions, and documentation of the process. Investigators can use technologies to provide information, interact
with participants, answer questions, and assess understanding on an ongoing basis. Available consent toolkits
featuring visual interactive approaches aim to make IC more participant-centered and less focused on signing legal
documents. Technologies allow for methods of IC that are modern, GREEN, interactive, and dynamic.

E-CONSENT! IS IT THE SAME PAPER CONSENT, MADE AVAILABLE ELECTRONICALLY?

While we say, industry is making advancements with e-Consent, it does not mean merely moving the same paper
document to an electronic page. This would mean long and complex information being presented in an electronic
medium. Clicking an agreement box at the end without engaging with the audience or having a discussion would be
the equivalent to signing a consent form without reading it. It is a challenge with e-Consent to verify that the people
who are consenting have the capacity to consent and are who they say they are (authentication). It is important that
the e-Consent interaction is brief, engaging, and informative about the risks and benefits in a way that enables the
participants’ decision making.[6]
Participants can sign electronically, using passwords known only to the participant or using a fingertip on a mobile
device. When e-Consent is performed remotely, the identity of the person who is giving the consent can be confirmed
in one of several ways, such as digital signature, username and password, or biometrics. Participants receive a copy of
the completed e-Consent form electronically on an electronic storage device or via email. If the copy provided includes
one or more hyperlinks to information on the Internet, the hyperlinks should be maintained and information should be
accessible until study completion.
Signed e-Consent records must be stored securely (e.g., encrypted to protect privacy, with audit trails to track any
changes). It’s of utmost importance that the e-Consents are readily available during an audit or inspection. Also from
a regulatory standpoint, it is important that the system that houses the e-Consents is in line with the parameters
outlined by the FDA in their guidance of December 2016, as well as 21 CFR Part 11, and ICH GCP E6 R2.[6, 7, 8, 9]

RISKS OF E-CONSENT

Although e-Consent can be beneficial in many aspects there are certain challenges in its implementation as well:
• Initial development of an e-Consent process can be costly, but reuse of templates can save money in subsequent
studies.
• e-Consent has been accepted by central institutional review boards in the United States, however launching a multisite
trial can be challenging because local institutional review boards may be unfamiliar with e-Consent or may want
modifications.
• Obtaining IC on smartphones raises several unique challenges and limitations. The most challenging one is that there
is no face-to-face confirmation of identity. For example, it is possible that one person could sign in to confirm identity
and another could carry the device.
• The smaller screen size of smartphones adds a considerable challenge to the e-Consent process in that multiple
consent screens are required to review all the key consent components.
• We also need to consider the strata of the society or population we are considering when we use e-Consent. Not
every participant would be familiar using a computer or application to provide consent. It is also an ethical challenge
if certain segments are incapable to provide consent due to issues related to access or cost of smartphones or data
connectivity.
• Videos and quizzes add time to read the consent form and the subject might not be willing to take quizzes.

CONCLUSION

The e-Consent process has evolved since its inception and is still evolving, with the potential to break through the
constraints of a traditional clinical trial. Some of the challenges of a traditional clinical trial being patients somewhat
willing to participate, trials delayed due to slow enrollment, and patients becoming disengaged and dropping out of
studies. At a time when the entire clinical research industry continues to have a paradigm shift from conventional
trials to e-Clinical trials, e-Consent is a tailored option that can be provided to subjects offering them flexibility and
encouraging participation. It can help a subject participate in a clinical trial and can also help the subject get more
involved/ engaged in the clinical trial, thus ensuring study enrollment and compliance. This has the potential to have
a direct impact on subject retention for long-term trials. Researchers should definitely evaluate whether e-Consent
may benefit their studies by considering the study design, research population, cost and the participating sites. [10]

REFERENCES
1. “INTEGRATED ADDENDUM TO ICH E6(R1): GUIDELINE FOR GOOD CLINICAL PRACTICE E6(R2),” International Conference on
Harmonization, E6 Good Clinical Practices Section 2.3, Version 09Nov2016, Accessed 27Nov2018,
https://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Efficacy/E6/E6_R2__Step_4_2016_1109.pdf.
2. “Informed Consent for Clinical Trials,” U.S. Food and Drug Administration, Accessed 27Nov2018, www.fda.gov/ForPatients/
ClinicalTrials/InformedConsent/ucm20041763.htm?source=govdelivery&utm_medium=email&utm_source=govdelivery.
3. Lokesh P. Nijhawan, Manthan D. Janodia, B. S. Muddukrishna, K. M. Bhat, K. L. Bairy, N. Udupa, Prashant B.
Musmade, “Informed consent: Issues and challenges,” J Adv Pharm Technol Res. 2013 Jul-Sep; 4(3): 134–140. doi:
10.4103/2231-4040.116779PMC.
4. “Use of Electronic Informed Consent, Guidance for Institutional Review Boards, Investigators and Sponsors,” U.S. Food and
Drug Administration, Dated December 2016, Accessed 27Nov2018, www.fda.gov/downloads/drugs/guidances/ucm436811.pdf
5. Faden, R.R. and Beauchamp, T.L., A History and Theory of Informed Consent (New York and Oxford: Ox-ford University Press,
1986), Accessed 27Nov2018, https://books.google.co.inbooks?hl=en&lr=&id=jgi7OWxDT9cC&oi=fnd&pg=
PA3&dq=paper+informed+consent+or+electronic+informed+consent&ots=ZhJOXQgO4&sig=cbvzbwg8qpU6Gy0kNGBxg
Gw5-SE#v=onepage&q=paper%20informed%20consent%20or%20electronic%20informed%20consent&f=false.
6. Enrico Coiera, Roger Clarke, “e-Consent: The Design and Implementation of Consumer Consent Mechanisms in an Electronic
Environment,” J Am Med Inform Assoc. 2004 Mar-Apr; 11(2): 129–140. doi: 10.1197/jamia.M1480.
7. Tassé, A.M. and Kirby, Emily, “Is written informed consent outdated?” European Journal of Public Health, Volume 27, Issue 2,
1 April 2017, Pages 195–196, https://doi.org/10.1093/eurpub/ckw197
8. “FDA and OHRP Issue Final Guidance on the Use of Electronic Informed Consent,” The University of Iowa, Accessed
27Nov2018, hso.research.uiowa.edu/fda-and-ohrp-issue-final-guidance-use-electronic-informed-consent
9. “Part 11, Electronic Records; Electronic Signatures — Scope and Application,” United States Code of Federal Regulation,
CFR Part 11, U.S. Food and Drug Administration, Accessed 27Nov2018, www.fda.gov/regulatoryinformation/guidances/ucm125067.htm
10. Shenoy P. “Electronic informed consenting: A boon to modernize consenting process,” Perspect Clin Res, 2015;6:173-4.
http://www.picronline.org/text.asp?2015/6/4/173/167091

AUTHOR BIOGRAPHY
Mourin Patnaik comes with an overall 8 year of Clinical Research experience. She is currently working as an
Associate Data Team Lead in Clinical Data Management at IQVIA.
Mourin holds B-tech degree in Biotechnology along with a PGD in Clinical Research. Prior to joining IQVIA Data
Management, she has worked as a Clinical Research Associate for 3yrs in Novo Nordisk & Clintec which gives her a
dual experience in understanding both the Clinical & Data Management processes well. In her experience as a CRA
she has been a part of FDA audit and Regulatory inspections. She started her career with Eli Lilly & Company dealing
with pharmaceutical product marketing & branding.

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