RE:Regarding the FDA Approval Process An excerpt from my November 11th post:
In the case of pivotal stage trials for therapeutic devices, the FDA’s statutory directive is to show valid scientific evidence to determine whether there is reasonable assurance that the device is safe and effective. Valid scientific evidence comes from:
- well controlled studies
- partially controlled studies
- objective trials without matched controls
- well documented case histories
- reports of significant human experience
From all the factors listed above, only once has the primary endpoint of the many studies Helius Medical has conducted over the last decade not reached statistical significance. Therefore, from all the factors listed above, one in a single trial has not been met, but I acknowledge it probably is the most important one.
The main mitigating factor is the impact of the low frequency device on the results, which I have put forward was imposed by the FDA during the trial design, and thus the whole trial has been designed around this possibility (e.i. patients that have plateaued in their physical therapy).
Doing some quick research, I could find several Class II devices that were approved by the FDA after not meeting their primary endpoint, which I will be sharing in greater detail in later posts.
The following is a list of the common factors between all these cases:
- In all those cases, the application was first reviewed by an “Advisory Committee” assembled from non-FDA industry experts and scientists.
- Purpose: “The Committee reviews and evaluates data concerning the safety and effectiveness of marketed and investigational devices for use in the neurological system and makes appropriate recommendations to the Commissioner of Food and Drugs.
- In all cases, the Committee agreed that the benefits of the device outweighed the risks for use in patients
- Note that a recommendation only requires a majority of the Committee members to vote in favor of the approval, and not a unanimous vote.
- Below you can find a number of direct quotes from company and regulatory press releases for devices that did not meet their primary endpoint and which were subsequently approved by the FDA:
- Described as “mostly positive review by the agency’s advisory committee”
- “Most panelists agreed that potential benefits of using the device outweigh any risks and said that despite the lack of clear clinical benefit”
- “Advisors to the US Food and Drug Administration (FDA) agreed today that the device, is safe and likely effective, paving the way for the approval of the first such device in the United States. Most, despite concerns about the lack of clear clinical benefit, said they themselves would want to have the device in place if they underwent such a procedure”
- “they believe the totality of the data suggests that it may be of benefit and they would want it on the market. That’s despite the fact that the pivotal trial met its primary safety endpoint but did not meet its primary efficacy endpoint”.
- “The panel recommended the device for approval based upon the totality of the data from earlier trials and other information. The lone dissenting panel member said that this lack of complete data and the fact that it technically did not meet its primary endpoint were his reasons for voting against approval.”
- In many of these cases, serious adverse events reported in the clinical study included nausea, pain, vomiting and surgical complications.
- Recall, the PoNS device has proven to have no serious adverse events
- The devices were described as “transformative technology”
- The devices addressed an unmet need and a large population
- The FDA considered the clinical study and the Panel’s recommendations
- The FDA required a post approval study to be conducted over several years