Karim Benali, M.D., Msc05.02.16
You’ve completed pre-clinical testing, but need clinical data about safety, design, or operation before moving forward with development. In other words, you’re likely in a position to conduct an early feasibility study (EFS) either in the United States or outside the U.S. (OUS).
The United States seems like an obvious location for conducting an EFS if U.S. FDA approval or clearance is the final goal. In reality though, this doesn’t happen as often as it should. According to a 2015 member and stakeholder survey from the Medical Device Innovation Consortium (MDIC), 53 percent of respondents’ companies initiated their EFS exclusively OUS in 2015.
Why Go OUS?
EFS studies require frequent iterations to the device design and study protocol that cannot occur without regulatory go-ahead. The perception is that the U.S. ecosystem has become increasingly uncertain and the process to bring technologies to market is much longer compared to other countries. For large companies, waiting on approval for a small change could lead to an inconvenient study delay. For the small and midsize companies that represent 80% of the U.S. medtech landscape, that same delay could tie up investment dollars and easily lead to bankruptcy.
On top of those temporal and financial restrictions, there is no definitive body of evidence that an overly stringent regulatory process in early development will improve device safety and increase patient benefit (Read the Boston Consulting Group report for more information).
Why then should a device manufacturer choose to conduct an EFS in the United States?
The Case for U.S. EFS
On the simplest of levels, conducting an EFS in the U.S. means that a manufacturer can acquaint the FDA with its technology early in development. Doing so builds a strong foundation of expertise and experience with the device within the FDA that helps de-risk the rest of the development process. There is also the potential in this scenario for the device to reach U.S. patients faster as the U.S. remains the global leader in medical innovation.
Furthermore, the United States is home to large numbers of key opinion leaders whose insight and experience can help manufacturers create better generations of their devices. U.S. Centers of Excellence combine cutting edge academic and industry knowledge that can be leveraged to improve protocols or device designs. With its large patient base and advanced healthcare system network, the U.S. is likely to offer a more adequate patient population when it comes time for study recruitment.
The FDA Wants You To
The FDA has made it a priority to bring EFS back to the U.S., as primarily evidenced by the 2013 release of the Investigational Device Exemptions (IDE) for Early Feasibility Medical Device Clinical Studies guidance. The guidance details several measures intended to ease regulatory burden for EFS, including the idea of “just-in-time testing”—which “departs from the custom of expecting exhaustive nonclinical testing prior to any clinical use” and “recognizes that comprehensive testing during early phases of development may add cost without return.” (For more information, review this FDA presentation). Also, under the guidance, sponsors can make simple changes to the device or protocol through a five-day notification process without having to obtain prior FDA approval. In addition to the guidance, FDA created EFS online learning modules and made a commitment to training reviewers in order to boost internal knowledge of EFS.
FDA’s efforts have worked to an extent. According to a September 2015 Clinical Trial Performance Update, the number of approved EFS IDEs rose from FY13 to FY15. From FY14 to FY15, the number of EFS IDEs received and approved nearly doubled. Still, the device industry is hesitating to pull the trigger on U.S. EFS. The MDIC Early Feasibility Survey showed that 57 percent of respondents had not initiated an EFS study in the U.S. in the past two years. While progress has been made and some success stories need to be highlighted, skepticism remains. The survey also showed that about 50 percent of the respondents would prefer to wait and see more success stories before committing to conducting EFS in the U.S.
Clearly, there is a need for education and awareness if we are to increase the number of EFS in the United States.
Top 5 Considerations for U.S. EFS
While the regulatory process is important, there are many other challenges to the EFS in the U.S. These include lengthy ethics committee review time, legal, funding, and reimbursement issues, all of which add more burden to an EFS in the U.S.
In an effort to provide tools to help sponsors navigate early feasibility studies, industry experts from the MDIC Early Feasibility Working Group created the Blueprint for Early Feasibility Study Success. The Blueprint addresses regulatory, IRB, legal, reimbursement, and other issues identified as barriers to EFS in the U.S. It available for download now as a draft version open to public feedback at mdic.org/EFSblueprint.
While the Blueprint covers much ground (and is encouraged reading), following are the top 5 considerations when contemplating a U.S. EFS.
A well-designed EFS should provide you with sufficient information to pursue your path to market and accelerate patient access to your device. As with any clinical study, the best way to minimize delays is to set expectations, clearly outline risk, and set shared goals among all stakeholders.
Increasing the number of early feasibility device studies conducted in the United States is a sure step to creating a favorable development ecosystem that, in turn, will foster innovation. To truly achieve our goal, it is imperative that medical device companies commit to conducting EFS in the United States. Tools such as the MDIC Early Feasibility Blueprint cannot solve the problem alone, but help to open the lines of communication between regulators, industry, advocacy groups, and patients.
Karim Benali, M.D., MSc, is chair of the MDIC Early Feasibility Working Group and lead author of the MDIC Blueprint for Early Feasibility Study Success. He is also the chief medical officer of Abiomed Inc.
The United States seems like an obvious location for conducting an EFS if U.S. FDA approval or clearance is the final goal. In reality though, this doesn’t happen as often as it should. According to a 2015 member and stakeholder survey from the Medical Device Innovation Consortium (MDIC), 53 percent of respondents’ companies initiated their EFS exclusively OUS in 2015.
Why Go OUS?
EFS studies require frequent iterations to the device design and study protocol that cannot occur without regulatory go-ahead. The perception is that the U.S. ecosystem has become increasingly uncertain and the process to bring technologies to market is much longer compared to other countries. For large companies, waiting on approval for a small change could lead to an inconvenient study delay. For the small and midsize companies that represent 80% of the U.S. medtech landscape, that same delay could tie up investment dollars and easily lead to bankruptcy.
On top of those temporal and financial restrictions, there is no definitive body of evidence that an overly stringent regulatory process in early development will improve device safety and increase patient benefit (Read the Boston Consulting Group report for more information).
Why then should a device manufacturer choose to conduct an EFS in the United States?
The Case for U.S. EFS
On the simplest of levels, conducting an EFS in the U.S. means that a manufacturer can acquaint the FDA with its technology early in development. Doing so builds a strong foundation of expertise and experience with the device within the FDA that helps de-risk the rest of the development process. There is also the potential in this scenario for the device to reach U.S. patients faster as the U.S. remains the global leader in medical innovation.
Furthermore, the United States is home to large numbers of key opinion leaders whose insight and experience can help manufacturers create better generations of their devices. U.S. Centers of Excellence combine cutting edge academic and industry knowledge that can be leveraged to improve protocols or device designs. With its large patient base and advanced healthcare system network, the U.S. is likely to offer a more adequate patient population when it comes time for study recruitment.
The FDA Wants You To
The FDA has made it a priority to bring EFS back to the U.S., as primarily evidenced by the 2013 release of the Investigational Device Exemptions (IDE) for Early Feasibility Medical Device Clinical Studies guidance. The guidance details several measures intended to ease regulatory burden for EFS, including the idea of “just-in-time testing”—which “departs from the custom of expecting exhaustive nonclinical testing prior to any clinical use” and “recognizes that comprehensive testing during early phases of development may add cost without return.” (For more information, review this FDA presentation). Also, under the guidance, sponsors can make simple changes to the device or protocol through a five-day notification process without having to obtain prior FDA approval. In addition to the guidance, FDA created EFS online learning modules and made a commitment to training reviewers in order to boost internal knowledge of EFS.
FDA’s efforts have worked to an extent. According to a September 2015 Clinical Trial Performance Update, the number of approved EFS IDEs rose from FY13 to FY15. From FY14 to FY15, the number of EFS IDEs received and approved nearly doubled. Still, the device industry is hesitating to pull the trigger on U.S. EFS. The MDIC Early Feasibility Survey showed that 57 percent of respondents had not initiated an EFS study in the U.S. in the past two years. While progress has been made and some success stories need to be highlighted, skepticism remains. The survey also showed that about 50 percent of the respondents would prefer to wait and see more success stories before committing to conducting EFS in the U.S.
Clearly, there is a need for education and awareness if we are to increase the number of EFS in the United States.
Top 5 Considerations for U.S. EFS
While the regulatory process is important, there are many other challenges to the EFS in the U.S. These include lengthy ethics committee review time, legal, funding, and reimbursement issues, all of which add more burden to an EFS in the U.S.
In an effort to provide tools to help sponsors navigate early feasibility studies, industry experts from the MDIC Early Feasibility Working Group created the Blueprint for Early Feasibility Study Success. The Blueprint addresses regulatory, IRB, legal, reimbursement, and other issues identified as barriers to EFS in the U.S. It available for download now as a draft version open to public feedback at mdic.org/EFSblueprint.
While the Blueprint covers much ground (and is encouraged reading), following are the top 5 considerations when contemplating a U.S. EFS.
-
Make sure you actually need to conduct an EFS
Sketch out a game plan for development including timelines, business goals, and expectations. Having a solid strategic device evaluation roadmap in place will make it easier to determine whether non-clinical methods are neither available nor adequate to provide the information needed. If that is the case, then it makes sense to go ahead with an EFS. (Remember that an EFS is not a regulatory requirement).
-
Know the EFS guidance and other relevant FDA materials
While FDA encourages sponsors to communicate early with the agency, the aforementioned guidance document is a “must read” reference to educate yourself. Understanding this guidance document will help companies maximize the quality of their interaction with FDA reviewers. The CDRH Learn Module offers suggestions for minimizing regulatory delays when interacting with FDA under the EFS program. Following is an example from the module of four chronological steps to take:- Contact the FDA EFS representative early
- Submit the initial pre-submission to share program goals, justification, and questions
- Submit additional pre-submissions that contain proposed non-clinical test programs, the investigational plan, and informed consent forms
-
Submit the IDE using proper submission assembly techniques
-
Understand “risk” and be prepared to make your case to IRBs
When preparing to interact with Institutional Review Boards (IRBs), read up on FDA 21 CFR part 50 regulations. Clear communication with IRBs (and to patients via informed consent forms) is even more imperative than usual because potential anticipated benefits are still uncertain and unforeseeable risks exist at this early stage of development. The potential benefits to patients can be mentioned, but don’t overstate the anticipated benefits.
-
Protect your intellectual property
Your device, your intellectual property (IP)? Not necessarily. Have you considered that a study institution may own the rights to any device modifications or improvements made during the study if someone from the institution had any input on those subjects? You’ve made a significant investment to get this far, so it’s important that you protect your work. Each site may have a different policy regarding what’s yours and what’s theirs, as well as differing IP rights for an IDE study as compared to other studies. Consider a confidentiality or non-disclosure agreement before you discuss the study, study device, or protocol with the investigator or study institution.
-
Understand everything that could possibly go wrong in your study and select the sites that can deal with it
A famous investigator, world-renowned hospital, or a state-of-the-art facility does not mean that a site is qualified for your EFS. In other words, each EFS requires a de novo assessment of the type of investigator and site that will fit that study’s specific needs and potential outcomes. Consider building a list of 10 to 15 potential pre-selected sites for consideration. But first ask yourself if the site, its investigator, staff, and facilities are fully equipped, communicative, and flexible enough to handle the unknowns and “what ifs” associated with EFS studies. If not, strike it from the list. Then use a weighted Pugh Matrix to objectively compare and rank the sites for the actual study.
A well-designed EFS should provide you with sufficient information to pursue your path to market and accelerate patient access to your device. As with any clinical study, the best way to minimize delays is to set expectations, clearly outline risk, and set shared goals among all stakeholders.
Increasing the number of early feasibility device studies conducted in the United States is a sure step to creating a favorable development ecosystem that, in turn, will foster innovation. To truly achieve our goal, it is imperative that medical device companies commit to conducting EFS in the United States. Tools such as the MDIC Early Feasibility Blueprint cannot solve the problem alone, but help to open the lines of communication between regulators, industry, advocacy groups, and patients.
Karim Benali, M.D., MSc, is chair of the MDIC Early Feasibility Working Group and lead author of the MDIC Blueprint for Early Feasibility Study Success. He is also the chief medical officer of Abiomed Inc.