When it comes to choosing e-signatures in global trials, sponsors often face a difficult decision: whether to use a qualified e-signature (QES) or a standard e-signature (AES). QES is the highest bar available for electronic consent, carrying full legal equivalence to a wet-ink signature backed by identity verification through a qualified trust service provider (QTSP). However, its use is not a one-size-fits-all solution and requires careful consideration of several factors.
Under eIDAS in the EU, QES is mandated in certain jurisdictions, while in others it is preferred or simply accepted. Sponsors must evaluate not just the letter of the regulatory requirement but also local authority expectations when determining the appropriate signature approach. This is because regulatory expectations can extend beyond what’s formally permitted, and sponsors may still face regulatory scrutiny even if AES is accepted.
Country Requirements
Country requirements are a critical factor in determining whether to use QES or AES. Sponsors must assess the regulations in each jurisdiction where the study will take place and determine whether QES is mandated, preferred, or accepted. If QES is mandated, it must be used, but if it is preferred or accepted, sponsors must weigh the benefits and drawbacks of each approach.
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In jurisdictions where AES is accepted, regulatory bodies may still lean toward or informally expect QES in practice. Sponsors must therefore consider not just the formal regulatory requirements but also the informal expectations of local authorities. This requires a thorough understanding of the regulatory environment and the ability to manage complex regulatory frameworks. Study teams need to carefully examine the rules and expectations in each country to make an informed decision.
Study Risk Profile
The study risk profile is another important factor to consider when choosing between QES and AES. High-risk indications or studies subject to significant regulatory scrutiny may benefit from the stronger, third-party-verified identity foundation provided by QES. This is because QES provides a high-quality audit trail that can help to prevent disputes over identity verification.
However, if the risk of an identity dispute is low, deploying AES may be the more practical choice. AES can reduce costs and avoid additional delays for participants before their first visit. They must carefully weigh the benefits and drawbacks of each approach and consider the specific needs of their study.
Participant Population
The participant population is a critical factor to consider when choosing between QES and AES. QES requires identity verification, which can be a challenge for certain populations, such as remote or low-literacy populations without reliable access to identification documents. Additionally, patients with physical conditions that make it difficult to interface with a camera may struggle to complete the identity verification process.
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They must consider the operational realities of their study and determine whether QES is feasible for their participant population. This may involve assessing the availability of identification documents, the literacy level of participants, and the ability of participants to complete the identity verification process.
Operational Feasibility
Operational feasibility is the final factor to consider when choosing between QES and AES. Sponsors must assess whether their sites are set up to handle QES and whether site staff have the necessary training and resources to manage the process. This includes evaluating the ability of site staff to handle the authentication handoff and provide support to participants who encounter difficulties with the identity verification process.
Sponsors must also consider the technology and systems required to support QES and whether they can be configured to enforce the correct modality for each country and population. This may involve establishing a documented wet-ink fallback for participants who cannot complete ID verification and providing clear training on how staff should manage exceptions.
By considering these four dimensions – country requirements, study risk profile, participant population, and operational feasibility – sponsors can make an informed decision about whether to use QES or AES in their global trials. It is not a question of whether QES is better than AES, but rather which approach is best suited to the specific needs of the study.
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The framework for choosing between QES and AES should be documented before enrollment starts, with a clear decision matrix that outlines the reasoning behind the choice of signature method for each country and population. This document should be owned jointly by regulatory affairs and clinical operations, as the decision sits at the intersection of both functions.
Once the signature approach has been determined, it should be translated into site-level instructions that provide clarity on how to execute the designated signature method. This includes providing a one-page job aid that walks coordinators through the process step-by-step, in plain language. Coordinators should not be expected to decide between AES and QES at the point of care; that decision should have already been made upstream.
Finally, sponsors should configure the technology and define fallbacks to ensure that the correct modality is used for each country and population. This includes establishing a documented wet-ink fallback for participants who cannot complete ID verification and providing clear training on how staff should manage exceptions. By taking a strategic and thoughtful approach to choosing between QES and AES, sponsors can ensure compliance, reduce risk, and improve the overall efficiency of their global trials.
