It may sound posh, but a Clinical Trial Agreement’s (CTA) life looks pretty much as a human’s. CTA is born from the template, then its childhood period is filled with the site-specific adaptations ending up in a turbulent adolescence period of negotiation and execution. A grownup CTA becomes quite mature and self-sufficient, and often becoming cluttered with Amendments at some timepoints of its life. Here is where the allegory ends.

While preparing an Amendment the negotiator should bear in mind that the Amendment may be something of the same ‘age’ as the ‘parent’ CTA – we mean the effective date. Surely, in no way the Amendment can be valid until it is signed by all the parties, but in many jurisdictions it is up to the parties to decide when the terms of the Amendment become valid – it can be after or before the execution (or ‘birthday’ if we proceed with the allegory).

Let’s review some real-life examples:

• Site’s name/address/banking details/other details is/are changed when the CTA was already finalised and partially signed. This can be sensitive, but depending on the severity of such change, the parties can proceed with signature of the CTA agreeing to sign the Amendment after on (if at all needed) to reflect such change. In this case it is highly likely the Amendment’s effective date should be set as the effective date of the ‘parent’ CTA.

• During the long and tough negotiation a Protocol amendment was issued resulting in the budget change. The negotiator faces a tough choice: whether to proceed with the finalisation of the negotiated CTA with the ‘old’ budget, or restart the negotiation with the new budget version. It is really a difficult decision that shall be taken together with the project team. If, say, budget changes don’t affect screening visit and another visits weeks after it, it can be preferable to sign the old-budget CTA to start the study as soon as possible, and sign the CTA Amendment afterwards. This will ensure the patients’ treatment starts without delays and the site will be paid on time. Again, the CTA Amendment in this case will likely have the same birthday as the ‘parent’ CTA.

• Paradoxically, the above situation with the Protocol Amendment can result in the ‘delayed’ CTA Amendment effective date. Let’s say there is plenty of time before the Protocol amendment is implemented, but it is available, it is ‘technical’ and the parties know for sure it will be approved by the Regulatory Authority / Ethics. It is not ideal, but the decision can be made to execute the CTA Amendment which will note that it will come into effect after all approvals are in place.

• Error in the CTA. It happens on variety of reasons, which may be quite complex situation. If an error results in the CTA Amendment, effective date of such agreement may have to be set as the effective date of the CTA.

Amazingly, a bunch of factors influence something one could have never paid enough attention to, which could lead to huge consequences. CTA Amendment’s effective date is evidently something sensitive and depends on the the plenty of de-jure and de-facto aspects, which in turn directly influence the CTA’s life. It is critical to have the local expertise while making the decision on the CTA Amendment’s birthday to avoid further CTA Amendments. Compared to the humans, the difference is the-more-the-better principle could work for humans, but it never works for the CTAs – here the allegory ends again. 🙂