Early feasibility studies are small clinical investigations that are conducted when developing medical devices. Generally they are carried out when the preclinical testing has been done, but the design hasn’t been finalised fully. They are often used to test high-risk devices where the benefit is higher than the risk to the patient.
Early feasibility studies are an important part of innovation development in medical devices. They allow first-in-human trials to be carried out on small numbers of people with time built in for testing and iterative improvements of the design.
Although it’s provided for under the international standard for clinical investigation of medical devices for human subjects, EFS are still not widely or uniformly used in Europe. That’s because there is no harmonised framework for how to implement or assess them, and often regulators are not familiar with them. Giuditta Callea of Bocconi University, who is the Principal Investigator of the project, says that there are many advantages to early feasibility studies, and that Europe shouldn’t shy away from this method of testing medical devices.
“You start generating evidence early, the competent authorities start to become aware of the technology very early and this technology will be tested on a limited number (10-15) of non-consecutive patients – while guaranteeing their safety – and the device can be changed if some element of it doesn’t work. If the early feasibility is successful, the technology will be investigated in a number of subsequent clinical investigations, for instance pivotal studies, before conformity assessment.”
IHI’s HEU-EFS project is delivering a harmonised framework for early feasibility studies to guide manufacturers, regulators and ethics committees on how best to approach and assess these studies. The second phase of the project –developing the framework, along with a series of templates and checklists – has just been completed. The last phase – piloting the framework in different scenarios, technologies and patient conditions – is about to begin.
Callea explained the main points of the framework, starting with eligibility criteria. “Not all technologies should undergo an EFS,” she explains. “To test the proposed framework, we decided to focus on breakthrough devices that address an unmet need, devices that help to enhance anatomical understanding, or a device that allows for a new or expanded intended user indication for patients.”
The next element of the framework is the methodological framework and timeline. HEU-EFS recommends early contact with regulators, discussing the new technology or medical device and trying to understand what studies are required. The idea is that early dialogues can lead to more complete, high-quality submission documentation, boosting the chances of success. For EFS, thanks to the pre-submission early dialogue, the project proposes shortening the validation phase and the review with the possibility to have a clock stop in case competent authorities require more information. The ideal timeframe put forward by the project anticipates a 30% decrease in the overall timeline compared to the current timelines of the medical device regulation.
Templates and checklists for success
HEU-EFS also developed a series of templates and checklists for teams planning on conducting early feasibility studies. Ranging from templates and checklists for i a clinical investigation plan and patient informed consent form to guidance for master clinical site agreement and insurance contract, the templates are for those teams who want to follow the project’s lead to the letter, while checklists are for those teams who need to follow different templates or processes. For instance, some competent authorities or ethics committees have their own templates that need to be used. The checklists provide a way to ensure that a team is including all the necessary steps in their EFS, even if not following HEU-EFS’ template.
“All these templates and checklists underwent an internal consultation,” says Callea. “These templates and checklists reflect the perspectives of academic organisations, HTA bodies, hospitals, clinicians, patient organisations, CRO, the industry, both large companies and SMEs.”
The templates and checklists can also be adapted for other purposes, Callea explains. While tailored to EFS in their current form, they could also be useful for other types of medical device regulation.
Launching pilots
HEU-EFS is now embarking on their pilot phase, where the framework developed by the project will be put to the test. Three pilots were developed by the project partners, but HEU-EFS also launched an open call for proposals to find other pilots. Four pilots are now in the initial launch phases, investigating a wide range of medical devices.
Building up a medtech ecosystem that supports early feasibility studies is a step in the right direction, says Callea, who points out that the USA already has embraced EFS.
“We are lagging behind, we are 15 years late with respect to the FDA. Many companies told us they would prefer to conduct early clinical investigations in Europe if possible. But we don’t formally have this possibility, we don’t have defined criteria,” she says.
The work of HEU-EFS will make carrying out EFS in Europe more feasible for medtech companies.
“We want to promote a friendly medtech system in the European Union, because it's beneficial from so many perspectives, from the patient perspective, from the policy makers perspectives, clinical sides. If we bring early clinical investigations in the European Union, we are also contributing to better skills and competencies of our PIs of clinical investigations, we are bringing R&D investments thus enhancing the EU single market competitiveness,” says Callea. “We believe that there are only pros. If we create a favourable environment, it's a benefit. It's a win, win, win, win, win.”