Why It’s More Complex Than It Sounds
One common (and underestimated) source of delay in clinical trial agreements isn’t negotiation but execution. Everyone says: “Just send it via DocuSign.” In reality, it’s often not that simple.
Not all “signatures” are the same.
We tend to use terms like electronic and digital interchangeably, but they don’t always mean the same thing:
- Electronic signature: a broad concept (e.g., DocuSign, Adobe Sign, even a scanned PDF sent by email in some contexts). While platforms like DocuSign and Adobe may use digital signature technology (e.g., cryptographic keys and certificates), in many jurisdictions (including the U.S.) they are still generally treated as “electronic signatures” from a legal standpoint.
- Digital signature: a specific type of electronic signature that uses cryptographic keys and certificates to verify identity and integrity.
- Wet-ink signature: the traditional physical signature.
To make things more confusing, in some countries “digital signature” is used as a legal term of art (often meaning a certified cryptographic signature), while in others, it’s used loosely to mean any electronic signature. Same words, different meanings depending on jurisdiction.
Why this matters in global studies.
Execution requirements are not harmonized across countries, or even across sites within the same country. You can have one site accepting DocuSign, another requiring wet ink, and a third requiring a certified digital signature all within the same city, country, and study.
Italy as a good example:
Italy is one of the clearest illustrations of this complexity. Depending on the site, you may encounter:
- Acceptance of standard electronic signatures (e.g., DocuSign).
- Requirement for wet-ink signatures.
- Requirement for PAdES-compliant digital signatures.
What is PAdES?
PAdES (PDF Advanced Electronic Signatures) is a European standard for digital signatures applied to PDFs. It aligns directly with the EU eIDAS Regulation (EU No 910/2014), which classifies electronic signatures into Simple (SES), Advanced (AdES), and Qualified (QES) tiers, with QES carrying the same legal weight as a handwritten signature across all EU member states. It also relies on (a) qualified digital certificates, (b) identity verification of the signatory, and (c) a signature embedded directly into the PDF.
In practice, this often means:
- The signatory must have a qualified digital certificate issued by a recognized provider.
- In Italy, this typically requires registration/verification within the Italian system or through an accepted EU provider.
And then there’s the duty stamp requirement. Separate from the signature itself, Italy also requires duty stamps (marca da bollo) on many contracts. These are typically applied every 4 pages and are not actually a signature requirement, but a tax requirement. This is satisfied physically with paper stamps or digitally through approved processes. This is an important distinction: even a perfectly executed digital signature does not replace the duty stamp requirement.
Practical reality.
What this means in practice:
- In many cases (usually with the exception of specific legal documents such as real estate deeds) the signature method is purely a legal preference –not an enforceability requirement.
- It’s an operational requirement tied to the site and/or country.
- Getting it wrong can delay execution significantly.
A practical approach.
At ICE Global, when supporting CTA negotiations we adapt the execution method site-by-site and we proactively prepare for even the extraordinary scenario if we can (and if it’s going to save time at a low or non-existing extra cost).
In Italy, where required, we can:
- Execute agreements under power of attorney on behalf of the sponsor.
- Use PAdES-compliant signatures.
- Facilitate digital duty stamp handling in an efficient manner.
Additional practical considerations.
Beyond the signature itself, there are often additional execution requirements that can impact timing if not anticipated early, such as:
- Providing supporting documentation (e.g., corporate certificates, powers of attorney, authorization letters) which can in many cases carry their own legal nuances as well.
- Notarization or apostille requirements in certain jurisdictions.
- Verification of signatory authority.
These are not always consistently required and, in many cases, may be more of a “nice to have” than a strict legal requirement. A key part of the process is understanding when these steps are truly necessary versus when they can be reasonably challenged or streamlined to avoid unnecessary time, effort, and cost.
Being prepared for these scenarios — and knowing when to push back — can make a meaningful difference in execution timelines.
The takeaway.
Execution is often treated as the “last step.” In reality, it should be planned as part of the strategy from the beginning. Because in global trials, the question isn’t “Can we sign this electronically?” It’s: “How does this specific site need this agreement to be executed?”
If you have more questions, the team at ICE Global is here to help. You can contact us here or by email at [email protected] or visit our website at www.iceglobalconsulting.com.