Dataset Information

FDA approval of cardiac implantable electronic devices via original and supplement premarket approval pathways, 1979-2012.

ABSTRACT: The US Food and Drug Administration (FDA) evaluates high-risk medical devices such as cardiac implantable electronic devices (CIEDs), including pacemakers, implantable cardioverter-defibrillators, and cardiac resynchronization therapy devices, via the premarket approval (PMA) process, during which manufacturers submit clinical data demonstrating safety and effectiveness. Subsequent changes to approved high-risk devices are implemented via "supplements," which may not require additional clinical testing.To characterize the prevalence and characteristics of changes to CIEDs made through the PMA supplement process.Using the FDA's PMA database, we reviewed all CIEDs approved as original PMAs or supplements from 1979 through 2012. For each supplement, we collected the date approved, type of supplement (panel-track, 180-day, real-time, special, and 30-day notice), and the nature of the changes. We calculated the number of supplements approved per PMA and analyzed trends relating to different supplement regulatory categories over time. For supplements approved via the 180-day regulatory pathway, which often involve significant design changes, from 2010-2012, we identified how often additional clinical data were collected.From 1979-2012, the FDA approved 77 original and 5829 supplement PMA applications for CIEDs, with a median of 50 supplements per original PMA (interquartile range [IQR], 23-87). Excluding manufacturing changes that do not alter device design, the number of supplements approved each year was stable around a mean (SD) of 2.6 (0.9) supplements per PMA per year. Premarket approvals remained active via successive supplements over a median period of 15 years (IQR, 8-20), and 79% of the 77 original PMAs approved during our study period were the subject of at least 1 supplement in 2012. Thirty-seven percent of approved supplements involved a change to the device's design. Among 180-day supplements approved from 2010-2012, 23% (15/64) included new clinical data to support safety and effectiveness.Many CIED models currently used by clinicians were approved via the PMA supplement process, not as original PMAs. Most new device models are deemed safe and effective without requiring new clinical data, reinforcing the importance of rigorous postapproval surveillance of these devices.

SUBMITTER: Rome BN

PROVIDER: S-EPMC4142419 | biostudies-literature | 2014 Jan 22-29

REPOSITORIES: biostudies-literature

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FDA approval of cardiac implantable electronic devices via original and supplement premarket approval pathways, 1979-2012.

Rome Benjamin N BN Kramer Daniel B DB Kesselheim Aaron S AS

JAMA 20140101 4

<h4>Importance</h4>The US Food and Drug Administration (FDA) evaluates high-risk medical devices such as cardiac implantable electronic devices (CIEDs), including pacemakers, implantable cardioverter-defibrillators, and cardiac resynchronization therapy devices, via the premarket approval (PMA) process, during which manufacturers submit clinical data demonstrating safety and effectiveness. Subsequent changes to approved high-risk devices are implemented via "supplements," which may not require a ...[more]

PMID: 24449317

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Project description:BackgroundThe FDA approves novel, high-risk medical devices through the premarket approval (PMA) process based on clinical evidence supporting device safety and effectiveness. Devices subsequently may undergo postmarket modifications that are approved via one of several PMA supplement review tracks, usually without additional supporting clinical data. While orthopaedic devices cleared via the less rigorous 510(k) pathway have been studied previously, devices cleared through the PMA pathway and those receiving postmarket PMA supplements warrant further investigation.Questions/purposesWe asked: What are (1) the types of original orthopaedic devices receiving FDA PMA approval, (2) the number and rate of postmarket device changes approved per device, (3) the types of PMA supplement review tracks used, (4) the types of device changes approved via the various review tracks, and (5) the number of device recalls and market withdrawals that have occurred for these devices?MethodsAll original PMA-approved orthopaedic devices between January 1982 and December 2014 were identified in the publically available FDA PMA database. The number of postmarket device changes approved, the PMA supplement review track used, the types of postmarket changes, and any FDA recalls for each device were assessed.ResultsSeventy original orthopaedic devices were approved via the FDA PMA pathway between 1982 and 2014. These devices included 34 peripheral joint implants or prostheses, 18 spinal implants or prostheses, and 18 other devices or materials. These devices underwent a median 6.5 postmarket changes during their lifespan or 1.0 changes per device-year (interquartile range, 0.4-1.9). The rate of new postmarket device changes approved per active device, increased from less than 0.5 device changes per year in 1983 to just fewer than three device changes per year in 2014, or an increase of 0.05 device changes per device per year in linear regression analysis (95% CI, 0.04-0.07). Among the 765 total postmarket changes, 172 (22%) altered device design or components. The majority of the design changes were reviewed via either the real-time review track (n = 98; 57%), intended for minor design changes, or the 180-day review track (n = 71; 41%), intended for major design changes. Finally, a total of 12 devices had FDA recalls at some point during their lifespan, two being for hip prostheses with high revision rates.ConclusionsRelatively few orthopaedic devices undergo the FDA PMA process before reaching the market. Orthopaedic surgeons should be aware that high-risk medical devices cleared via the FDA's PMA pathway do undergo considerable postmarket device modification after reaching the market, with potential for design "drift," ie, shifting away from the initially tested and approved device designs.Clinical relevanceAs the ultimate end-users of these devices, orthopaedic surgeons should be aware that even among high-risk medical devices approved via the FDA's PMA pathway, considerable postmarket device modification occurs. Continued postmarket device monitoring will be essential to limit patient safety risks.

Project description:ImportanceMany patients and physicians assume that the safety and effectiveness of newly approved therapeutic agents is well understood; however, the strength of the clinical trial evidence supporting approval decisions by the US Food and Drug Administration (FDA) has not been evaluated.ObjectivesTo characterize pivotal efficacy trials (clinical trials that serve as the basis of FDA approval) for newly approved novel therapeutic agents.Design and settingCross-sectional analysis using publicly available FDA documents for all novel therapeutic agents approved between 2005 and 2012.Main outcomes and measuresPivotal efficacy trials were classified according to the following design features: randomization, blinding, comparator, and trial end point. Surrogate outcomes were defined as any end point using a biomarker expected to predict clinical benefit. The number of patients, trial duration, and trial completion rates were also determined.ResultsBetween 2005 and 2012, the FDA approved 188 novel therapeutic agents for 206 indications on the basis of 448 pivotal efficacy trials. The median number of pivotal trials per indication was 2 (interquartile range, 1-2.5), although 74 indications (36.8%) were approved on the basis of a single pivotal trial. Nearly all trials were randomized (89.3% [95% CI, 86.4%-92.2%]), double-blinded (79.5% [95% CI, 75.7%-83.2%]), and used either an active or placebo comparator (87.1% [95% CI, 83.9%-90.2%]). The median number of patients enrolled per indication among all pivotal trials was 760 (interquartile range, 270-1550). At least 1 pivotal trial with a duration of 6 months or greater supported the approval of 68 indications (33.8% [95% CI, 27.2%-40.4%]). Pivotal trials using surrogate end points as their primary outcome formed the exclusive basis of approval for 91 indications (45.3% [95% CI, 38.3%-52.2%]), clinical outcomes for 67 (33.3% [95% CI, 26.8%-39.9%]), and clinical scales for 36 (17.9% [95% CI, 12.6%-23.3%]). Trial features differed by therapeutic and indication characteristics, such as therapeutic area, expected length of treatment, orphan status, and accelerated approval.Conclusions and relevanceThe quality of clinical trial evidence used by the FDA as the basis for recent approvals of novel therapeutic agents varied widely across indications. This variation has important implications for patients and physicians as they make decisions about the use of newly approved therapeutic agents.

Project description:ImportanceMedical device companies submit premarket approval (PMA) statements to the US Food and Drug Administration (FDA) for approval of the highest-risk class of devices. Devices indicated for the pediatric population that use the PMA pathway have not been well characterized or analyzed.ObjectiveTo identify and characterize high-risk devices with pediatric age indications derived from PMA statements.Design, setting, and participantsIn this cross-sectional study of PMA statements, those statements containing the words indicated or intended for medical devices listed in the FDA PMA database as of February 2020 were retrieved. Age indications were manually annotated in these approval statements via PubAnnotation. Based on the PMA identification from the PMA statements, device metadata including product codes, regulation numbers, advisory panels, and approval dates were queried.Main outcomes and measuresThe main outcome was discernment of the distribution of devices indicated for the pediatric population (neonate, infant, child, and adolescent). Secondary measures included outlining the clinical specialties, device types, and lag time between the initial approval date and the first date of an approval statement with a pediatric indication for generic device categories.ResultsA total of 297 documents for 149 unique devices were analyzed. Based on the manual age annotations, 102 devices with a pediatric indication, 10 with a neonate age indication, 32 with an infant age indication, 60 with a child age indication, and 94 with an adolescent age indication were identified. For indications for patients from age 17 to 18 years, the number of devices available nearly doubled from 42 devices to 81 devices. Although more than half of the surveyed devices had a pediatric age indication, many were available only for a limited range of the pediatric population (age 18-21 years). For indications for patients from age 0 to 17 years, the mean (SD) number of clinical specialties at each age was 7.27 (1.4), and 12 clinical specialties were represented from ages 18 to 21 years.Conclusions and relevanceIn this cross-sectional study on device PMA statements, a gap was identified in both quantity and diversity of high-risk devices indicated for the pediatric population. Because the current scarcity of pediatric devices may limit therapeutic possibilities for children, this study represents a step toward quantifying this scarcity and identifying clinical specialties with the greatest need for pediatric device innovation and may help inform future device development efforts.

Dataset Information

FDA approval of cardiac implantable electronic devices via original and supplement premarket approval pathways, 1979-2012.

Publications

FDA approval of cardiac implantable electronic devices via original and supplement premarket approval pathways, 1979-2012.

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