InfoCRG_Article №13_Execution of Clinical Trial Agreements

Overview

According to regulations it is required that all Parties conducting particular Clinical Trial are legally bound with contractual arrangements (agreements).

There are various agreements between the Parties involved in Clinical Trials, but one of the most important is a Clinical Trial Agreement (hereinafter referred to as “CTA”).

CTA is a legally binding agreement, approved and signed by all applicable Parties, that manages the relationship between a Sponsor, Investigational Site (hereinafter simply referred to as “Site”), and Investigational Team (e.g., Principal Investigator, Sub-Investigator, Study Coordinator etc.), and outline each Party's responsibilities and obligations for the Clinical Trial.

CTA should be fully executed the latest at the moment of Site Initiation Visit and not doing so while completing Clinical Trial related activities (especially Subjects’ recruitment) will be a serious violation which could have legal and regulatory consequences.

Aim

This article aims to briefly introduce the process of CTA execution (from the moment of template creation until its signing by all Parties).

Process

In general, the process of CTA execution can be broken down into the following steps which are later described in more detail:

1. Creation and approval of CTA template
2. Review & negotiation of CTA between all applicable Parties
3. Signing the CTA by all applicable Parties.

In the course of Clinical Trial there might be situations requiring changes/modifications to initial fully signed CTA, in such cases a CTA amendment is usually being created and signed in written.

Step 1: Creation and approval of CTA template

This step typically includes:

• Creation of CTA template from the scratch (if not available)
• Agreement on the use of either Sponsor’s or Contract Research Organisation’s (CRO) available CTA template (in some cases Site may utilise their own CTA template)
• Adaptation of agreed CTA template to the country-specific and Clinical Trial Protocol requirements, including making it multi-lingual (e.g., English-Ukrainian).

Depending on the signatory Parties CTAs could be of the following types (non-exhaustive list):

• Site – Sponsor and/or CRO
• Investigator (or Sub-Investigator or Study Coordinator) – Sponsor and/or CRO
• Site – Investigator – Sponsor and/or CRO.

Below is a non-exhaustive list of important information/topics that need to be covered in CTA template:

1. Number of CTA, if applicable (for referencing and other purposes)
2. Effective Date of the CTA (explicit information from which date the CTA will be considered as legally binding for all signatory Parties)
3. Information on contracting Party (e.g., name, type of legal entity, legal address, tax ID, etc.)
4. Clinical Trial Protocol title and number
5. If CRO is a signatory to CTA then information on how Sponsor authorised CRO to manage Clinical Trial (e.g., on the basis of corresponding Power of Attorney)
6. Purpose of CTA
7. Functions, rights, and obligations in a particular Clinical Trial of each Party to CTA, including location(s) of Clinical Trial conduct
8. Information on provided Investigational Medicinal Product/Medical Device and its handling up to return or destruction (for “Clinical Trial” purposes only)
9. Information on provided Clinical Trial equipment (if applicable) & materials and their handling up to return or destruction (for “Clinical Trial” purposes only). In case Site uses their own equipment for Clinical Trial then it should be stated that this equipment should be properly maintained, calibrated and that the documentation confirming this should be available
10. Requirements of laws, regulations on Clinical Trial conduct and Data Privacy protection including applicable references
11. Important obligations on direct access to Clinical Trial source documents, handling of protocol deviations, reporting of safety events etc.
12. Obligations on receipt of all necessary Clinical Trial authorisations and ongoing regulatory reporting/notifications
13. Obligations on Clinical Trial related insurance
14. Obligations to allow inspection/auditing of Clinical Trial related activities at Site
15. Obligations on handling of Clinical Trial data (e.g., Case Report Forms), including timelines for data entry and responding to queries, if any
16. Obligations on handling Subject Clinical Trial files (binders) and Investigator Site Files, including Pharmacy Files as applicable
17. Confidentiality provisions, Intellectual Property and Publications requirements
18. Indemnity and limitations of Liability
19. Term of agreement and termination considerations (including due to cancellation/discontinuation of the Clinical Trial)
20. Site budget (including per Subject fees, Site set-up & archiving fees, fees for procedures etc)
21. Payment considerations (currency, frequency, timelines, taxation, commissions & withholding if any) and banking details
22. Contact details for Notices and how they will be transmitted (e.g., via regular mail, e-mail etc)
23. Force majeure provisions
24. Place of jurisdiction and applicable governing law

25.? Statement on prevailing language (if the CTA is multi-lingual)

26.? Statement on how changes/modifications to the text of CTA will be processed

27.? Statement on what provisions will survive the termination of CTA (if any) and for which duration

28.? Signature requirements and applicable Signature fields.

Step II: Review & negotiation of CTA between all applicable Parties

As soon as CTA template is prepared and approved it is being sent to Site for filling of required information (e.g., Site name, addresses, contact persons, banking details), content review and acceptance. Legal Departments of each Party (as applicable) are heavily involved in this process.

Usually, Principal Investigator is a recipient of all applicable CTAs and acts as a facilitator in the process of review and negotiation of CTAs from the Site’s end. On the other hand, CRO is usually acting as a CTA facilitator between Site and Sponsor.

Rounds of review & negotiation last until the moment when CTA text is acceptable for all Parties and could proceed to sign-off.

Step III: Signing the CTA by all applicable Parties

CTAs may be signed wet-ink or electronically (e.g., using DocuSign) depending on what was agreed within the text of CTA.

If wet-ink signed the Parties exchange the original counterparts in an agreed consequent manner until all required Parties will put their signature. In such cases the CTA is executed is several counterparts which are equal to the quantity of signatory Parties, so each of them receives their signed original copy.

The use of electronic signatures greatly facilitates the signing of CTAs and the duration of the period between final CTA text and its full execution. ?

Carpathian Research Group capabilities

CRG as a CRO has supported multiple Sponsors in creation, review, negotiation & execution of CTAs for the smooth set-up and initiation of Clinical Trial Sites.

Information on all other Clinical Trial services that we provide could be found at www.crg.global

You can contact us at [email protected]