How Labcorp Drug Development Can Support Strategic Submission Planning
The European Union Clinical Trial Regulation 536/2014 (EU-CTR)1, which will be implemented on January 31, 20222, aims to enable more efficiencies in clinical trials, but will also impact legacy processes. Our team at Labcorp Drug Development is here to support strategic submission planning and provide guidance on common operational challenges. This article provides an overview of the potential study submission scenarios for meeting major milestones in clinical development plans.
Preparing for change
The harmonized submission process for countries within the European Union (EU) will introduce many benefits, including a unified study approval timeline, “centralized” communication via the Clinical Trial Information System (CTIS) portal and greater transparency of clinical trial data. While there are many efficiencies associated with the EU-CTR, drug development sponsors must analyze their processes and implement strategic thinking when initiating new studies.
At first glance, it may seem that the EU-CTR submission process is straightforward, with simultaneous submission of an application dossier consisting of Part I (core scientific documents) and Part II (national documents/considerations). In reality, it is more complex.
The submission process will depend upon a study’s planned geographic footprint and key study milestones. For example, will your study include countries outside of the EU, the planned first subject first visit (FSFV) milestone and how many sites need to be identified, as well as the ease of finding those sites.
While there are many different approaches to consider, Figure A highlights several potential submission strategies.
Figure A: Examples of Study Submission Scenarios
Consider a study with multiple regions. If the United States is included, then a United States site will most probably provide the FSFV milestone and may relieve some of the pressure of the timing of the EU submission. In this case, Scenario 1 may be the best approach for the EU submission strategy. Here, all countries and all sites in the EU are identified before the Part I and Part II submissions are made.
Scenario 2 (and Scenario 4)
If the proposed study geography relies upon the EU providing the FSFV milestone, then the submission strategy may need to be more complex, particularly if facing an aggressive FSFV milestone. In such a situation, Scenario 2 may be appropriate. Accordingly, the Part I submission will identify all the countries a sponsor plans to include in the study.
It is important to note that the initial Part II submission may only include a subset of those countries—and a subset of sites planned for those countries. This will allow sponsors to achieve their target FSFV milestone with an early cohort of sites while the remaining site identification continues in parallel.
Once sites are identified in the remaining countries, a second Part II submission is completed for those countries (but only after approvals are received from initial Part I and Part II submission). Additional sites can be added to the original Part II submitted countries by way of a Substantial Modification after the initial approval is received for that country.
This strategy should not be confused with the addition of extra EU countries (i.e., addition of countries not included in original Part I, which is depicted in Scenario 4). Scenario 4 is more likely to be employed part way through a study as a mitigation strategy if, for example, patient recruitment is slower than anticipated.
Scenario 3 may allow for a modest saving of time if a sponsor has its final core documents but faces a lengthy site identification process and no immediate need to achieve FSFV. In this case, a sponsor can submit Part I only, which will take a maximum of 106 days for review. During this time, site identification can be performed in parallel. The Part II submissions can then be made after Part I approval is received and all the sites are identified. The review of the Part II submissions will take a maximum of 81 days. This option is only worth considering if site selection is anticipated to take significantly longer than the maximum review cycle for Part I.
Designing a submission strategy to maximize efficiencies
While sponsors can consider any number of submission scenarios beyond these examples, it is helpful to understand the available options and the potential timelines when planning new studies. Aiming to be more than a partner for our clients, our team can provide guidance and help sponsors ensure their studies will meet the major milestones within a clinical development plan—and ultimately help life-changing treatments reach patients.
- European Union Clinical Trial Regulation (Regulation (EU) No. 536/2014); https://eur-lex.europa.eu/legal-content/EN/TXT/?uri=celex%3A32014R0536
- Official Journal of the European Union, 31 July 2021; https://eur-lex.europa.eu/legal-content/EN/TXT/PDF/?uri=CELEX:32021D1240&from=EN