The development of health care products and devices that could benefit patient care is underpinned by industry and manufacturer innovation. In the United States, the Food and Drug Administration (FDA) is responsible for ensuring the safety and efficacy of drugs, biological products, and medical devices. Typically, the FDA regulatory process for interventional drugs can last many years, involving initial testing and development, completion of phase I-III trials (assessing patient risk while aiming for a specific therapeutic goal), and review with postmarketing observation. Accelerated pathways exist and are increasingly used, but even then, substantial evidence is usually (not always) collected either pre or at least postmarketing. Conversely, for devices, the supporting evidence is almost always thin for both preapproval and postmarketing, with relatively few exceptions. Many devices are approved or cleared and remain in the market with absolutely no evidence of their merits.
Figure 1 shows the different FDA pathways for device approval and clearance. Excluding humanitarian exemptions and investigational approvals, the 2 main pathways are Premarket Approval (PMA) and the Premarket Notification (501[k]). There are 3 risk categories (class III-I) for new regulated devices. , Only approximately 9% of devices approved in the United States have been class III (high risk), whereas most (53%) have been class II (moderate risk), and many (40%) have been class I (low risk). Only 20-40 new devices go through the PMA pathway annually, whereas 510(k) applications are approximately 100 times more frequent.
FDA device approval pathways. The humanitarian device exemption pathway is uncommon and pertains to devices for rare conditions (<8000 people affected); only 86 such devices have been approved ( https://www.fda.gov/medical-devices/hde-approvals/listing-cdrh-humanitarian-device-exemptions ). The investigational device exemption pathway is a fast approval pathway (30-day clock) for all devices that need to be tested in clinical trials, so that the testing can be done, and hundreds are granted each year.
A class III (high-risk) device supports or sustains human life, is of substantial importance in preventing impairment of human health, or presents a potential, unreasonable risk of illness or injury, and usually requires following the PMA pathway, although in some cases a 510(k) may suffice. A search on the FDA’s medical device database revealed that there are currently 19 class III dental products that include, but are not limited to, endodontic sterilizers, root canal fillings, denture adhesives, bone grafting materials, and temporomandibular joint prostheses. Successful PMA approval is dependent on the availability of high-level scientific evidence (prospective data with controls or randomized controlled trials) demonstrating that the device is safe and effective for its intended use. However, manufacturers can apply for new devices to be reclassified as either class II (moderate risk) or class I (low risk), which require just a 510(k), if they can demonstrate that their device is substantially equivalent to a pre-existing legally marketed device (predicate) in terms of safety and effectiveness. No orthodontic products are currently in the list of class III approvals, but one wonders whether some of them are listed under class II clearance, with just 510(k) requiring higher standards of evidence.
A 510(k) for equivalence practically requires no data to be submitted if the device has the same intended use and same technological characteristics as the predicate. The manufacturer can make the case that the technological characteristics remain the same, even if the modifications are substantial. If technological characteristics clearly differ, then the device should not raise different questions of safety and effectiveness, and the manufacturer should submit information demonstrating that the device is as safe and effective as the legally marketed device. Importantly, the device is not requested to have any advantage (superiority) over the predicate, and the quantity and quality of information that demonstrates equivalence can be very limited.
The 510(k) application to the FDA is required at least 90 days before the device is marketed. The predicate must not currently be under review and must have previously received either PMA or 510(k) clearance. Many 510(k) applications pertain to devices that are modifications of a previously marketed device. From a manufacturer’s perspective, this is beneficial, as it facilitates the faster introduction of their device into the marketplace without incurring additional costs or the time required to conduct studies. Tens of thousands of devices, including many dental devices, have benefited from the fast, streamlined 510(k) features.
However, concerns have been raised about the FDA 510(k) process. A central concern pertains to safety and effectiveness. The new device is considered substantially equivalent in safety and effectiveness to a previously marketed device, despite the absence of high-quality clinical evidence to support these claims. If included in the application, treatment estimates and subsequent regulatory decisions tend to be based on low-quality data. In addition, there appears to be no time limit in terms of when the substantially equivalent predicate was approved and cleared. A need for greater transparency when selecting historical comparators and predicates has been advocated. Furthermore, for devices that are modifications of a previously approved device, manufacturers could introduce higher charges without evidence that the newer device yields improved outcomes compared with the previous iteration.
Overall, the FDA approach is more facilitative of device approvals than the European counterpart, which has had the Medical Device Regulation in place since May 2021. For devices, the United States benefits from the FDA’s centralized system, whereas Europe still relies on dozens of local Notified Bodies. However, although the Medical Device Regulation also uses a 3-class classification, in Europe, more devices are classified as class III, and many class II devices require supporting evidence comparable to that of class III devices. Moreover, postmarketing requirements, including documentation of use and studies to be conducted, tend to be more demanding in Europe than in the United States. Despite these differences, in both systems, many devices pass successfully through the regulatory process and maintain their approval and clearance status in the absence of good evidence of their benefits, or even in the presence of evidence against their risk-benefit ratios, let alone evidence of poor cost-effectiveness. For all products, once approval or clearance is granted, it is difficult to revoke. Therefore, it is important to make sure that the original approval or clearance is appropriate.
Within the orthodontic specialty, device manufacturers typically classify new devices as class II (moderate risk) and pursue the 510(k) process. Examples of these approval applications are shown in Figures 2 and 3 . ,
Premarketing Notification (510[k]) application for Invisalign palatal expander: screenshot information from FDA.
Premarketing Notification (510[k]) application: screenshot from the FDA clearance letter for ORMCO SPARK.
In the first example ( Fig 2 ), both primary (the Invisalign aligner system, Align Technology, Inc) and secondary (Hyrax expansion screw, Dentauraum, Inc) predicate devices had previously received 510(k) clearance. The date of submission was September 18, 2023, and clearance was issued within 88 days (December 15, 2023). The results of the stated early feasibility study and real-world data were not available in the application. The absence of independent FDA-approved scientific evidence on the effectiveness of the device does not seem to deter Align Technology, Inc from stating in advertisements: “The Invisalign Palatal Expander System is the only FDA-cleared, removable palatal expander that’s just as effective as traditional expanders”. A similar example is the clearance of the ORMCO SPARK aligner appliance (Ormco, Orange, Calif), in which the product clearance was based on the Invisalign system as the predicate, again without any supporting clinical data.
The lack of a mandatory clinical testing requirement in the 510(k) clearance process may itself be the primary driver of the large number of orthodontic products introduced into the marketplace without prior testing of clinical effectiveness. , Once cleared, high-quality postmarketing studies are often not pursued at all. When high-quality studies are conducted, the new product is often shown to have no effect on clinical efficiency and outcomes. For instance, supplemental vibrational force devices (eg, AcceleDent, OrthoAccel Technologies, Inc) have been shown, contrary to advertising claims, not to affect the rate of tooth alignment, the rate of space closure, the treatment duration, or the total number of visits during fixed appliance therapy. ,, Interestingly, as of December 1, 2022, the AcceleDent company is no longer operating as a business. Similarly, claims by the ORMCO Damon system (Ormco) on improved efficiency and shorter treatment times were not confirmed by independent postmarketing clinical trials.
One may also question why only substantially equivalent performance is required. To justify any additional financial costs to patients and clinicians, any new device or product should demonstrate superior performance on key outcomes (better effectiveness and/or fewer harms) compared with existing devices. Conversely, after clinical testing, the existing device (predicate) may show equivalence or superiority to the new device, raising the following question: Why should we introduce a newer device? The introduction of new devices and products into the marketplace without prior robust, independent clinical testing results in financial gain for the industry without any positive effects for patients. It seems that the burden is shifted from the industry to health care and practitioners, who are called to use untested products directly on their patients. Under such circumstances, any approval or clearance should be seen as a signal that profit can be made, rather than as a reassurance that a product (device or other) has merit with a favorable risk-benefit ratio.
Improving this situation would require endorsing higher standards of required evidence—both pre and postapproval—for a large number of medical devices, including dental devices, and the willingness to remove large numbers of already approved/cleared devices. However, such transformational changes may meet with resistance and may be slow or even impossible to implement. In the meantime, practitioners and other health care stakeholders should be aware of the situation and be cautious when scrutinizing the use of devices, especially expensive ones with no good evidence to support their use.
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