First-in-human and early phase clinical trials must meet a wide range of criteria. They must be scientifically justified and clearly designed. They must consider the patient population involved and their needs, including safeguarding patients and ensuring proper oversight.
Regulators are looking for clear scientific rationale and robust justification on dose escalation and dosing strategy, they want evidence of study monitoring, and they expect good supporting data. They are not just assessing the proposed study, but also whether there is sufficient detail and clarity to show trial consistency and to demonstrate safe implementation of the trial.
Why do sponsors run into difficulties?
All these expectations mean sponsors must be prepared, but, invariably, many run into difficulties. One of the most common issues we have witnessed are problems with protocol preparation. This can occur when documents are developed under time pressure.
Fragmented data collection is another recurring problem where the nonclinical, clinical and CMC (chemistry, manufacturing, and controls) data are not fully aligned or summarised in a cohesive manner across the submission package.
Inconsistency with the structured fields is another challenge that arises when documents are uploaded to the Clinical Trials Information System (CTIS). And, more generally, we see limited understanding of the regulatory expectations leading to deficiencies with submissions.
All these issues can, and very often do, result in requests for information (RFIs).
How can sponsors avoid common pitfalls?
In our experience, the best way to avoid common pitfalls is to prioritise the high impact areas. For example, ensure your protocol is complete, robust and in alignment with other key documentation including the Investigator’s Brochure (IB), the Investigational Medicinal Product Dossier (IMPD), and the informed consent forms. Consistency across your key documentation should be a priority.
One message we reiterate to clients is that it’s not just about having the right data but also presenting that data clearly and consistently and in line with regulatory requirements. Sponsors often run into problems if the content is in incorrect sections. A thorough review of your application can prevent numerous RFI’s.
Think about the regulatory language that needs to be included in your protocol. Are the reporting requirements complete? Are there gaps in your safety monitoring plans? Is there sufficient detail in your study design? Are there issues with your document structure?
All of these are important questions to consider before submission in order to reduce your risk of receiving avoidable RFI’s, which will delay your clinical trial approval.
“Regulators are looking for justification on dose escalation and dosing strategy, they want evidence of study monitoring, and they expect good supporting data.”