Adaptive clinical trials in the US are complex exercises in management tasks, social collaboration, and clinical patient care. Delegation of duties must occur at all levels and throughout all phases of the process. But how does a sponsor (particularly a foreign sponsor) retain the appropriate level of control while still facilitating the necessary collaboration?
Perhaps most important is choosing the right Contract Research Organization (CRO) to whom you will delegate certain definable tasks in the clinical trial. An effective CRO will have experience working with the specific disease category or device type being studied. Prior experience with the research site is also beneficial, but at a minimum prior experience with the category of facility is a necessity (oncology center, cardiac unit, etc). Since the CRO will step into the sponsor shoes in a number of ways, it is essential that the CRO bring components of familiarity and expertise to the relationship.
After a CRO is selected, the critical issue of task delegation must be approached.21 CFR 312.52 permits transfer of sponsor obligations to a CRO. Any transfers of responsibility MUST be documented in writing. If not all of the sponsor responsibilities are transferred, the writing should contain a comprehensive list of all responsibility areas and specific whether the sponsor has retained responsibility or transferred responsibility. Although the regulations permit a "default" assumption — that a responsibility not transferred in writing is retained — we've found that the best way to ensure the sponsor and CRO are communicating and on the same page is to document all areas and not rely on the "default."
So what tasks should be retained and which should be transferred to a CRO? It obviously depends upon the circumstances, including the strengths and skills of sponsor staff, CRO staff, and experience of the principal investigator. Below is a list of the general categories of clinical trial responsibility that the sponsor may transfer. The sheer size and scope of tasks needed to accomplish a compliant clinical trial in the U.S. favors task delegation and good project management.
- Trial Design: efficacious and safest manner
- Trial Management, Data Handling and Record Keeping: developing systems to handle
- QA/QC: implement QA and QC systems
- Medical Direction: have experts available for questions
- Investigator Selection: appropriate, qualified investigators, trained in protocol and product
- Allocating Responsibility: delegating tasks and documenting the delegation
- Financing: document financial arrangements with investigators; secure adequate liability coverage
- Submissions to Regulators: all submissions, ensure all approvals in place before initiating trial
- Secure IRB Review and Approval
- Information on Product: usually in form of Investigator Brochure
- Manufacturing, Labeling and Supplying investigative product
- Providing Record Access to Regulators
- Safety Information: safety evaluation and notification to regulatory authorities
- AE reporting: serious and unexpected adverse drug reactions, to investigators, IRB and regulators
- Monitoring: selection, training and oversight of monitors.
- Auditing: establishing an audit plan, selecting auditors and approving audit procedures.
- Dealing with Non-Compliance: prompt corrective action, including terminating investigators if needed
- Suspension or Termination of a Trial (if warranted)
- Trial Reporting: to IRB and regulatory authorities