Medical Devices: FDA Ordered Postmarket Studies to Better Understand Safety Issues, and Many Studies Are Ongoing
Published: 2015-09-30T00:00:00

Fast Facts:

Highlights:
section_title: Why GAO Did This Study
paragraphs: Americans depend on FDA—an agency within the Department of Health and Human Services (HHS)—to oversee the safety and effectiveness of medical devices sold in the United States. FDA's responsibilities begin before a new device is brought to market and continue after a device is on the market. As part of its postmarket efforts, FDA may order manufacturers to conduct two types of studies: (1) postapproval studies, ordered at the time of device approval, and (2) postmarket surveillance studies, generally ordered after a device is on the market.
GAO was asked to report on the characteristics and status of postmarket studies. This report describes (1) the types of devices for which FDA has ordered a postapproval study and the status of these studies, and (2) the types of devices for which FDA has ordered a postmarket surveillance study and the status of these studies. GAO analyzed FDA data—including data on medical specialty and study status as of February 2015—for (1) postapproval studies ordered from January 1, 2007, through February 23, 2015, and (2) postmarket surveillance studies ordered from May 1, 2008, through February 24, 2015. These represent the time periods for which FDA reported consistently tracking study data. GAO also reviewed documents, such as FDA guidance, and interviewed FDA officials.
HHS provided technical comments that were incorporated, as appropriate.
section_title: What GAO Found
paragraphs: Fifty-six percent of the 313 medical device postapproval studies—studies that are ordered at the time of device approval—the Food and Drug Administration (FDA) ordered from January 1, 2007, through February 23, 2015, were for cardiovascular devices and most were making adequate progress. Postapproval studies are ordered to obtain additional information not available before devices are marketed, such as a device's performance over the course of long-term use. In terms of study design, 69 percent of the 313 postapproval studies ordered were prospective cohort studies—that is, studies in which a group using a particular device was compared to a second group not using that device, over a long period of time. Most (72 percent) of the postapproval studies were ongoing as of February 2015, 20 percent of studies were completed, and 8 percent were inactive because, for example, the device is no longer marketed. Ongoing postapproval studies that GAO reviewed had been ongoing for an average of a little more than 3 years; FDA considered most of them (182 studies) to be progressing adequately and the rest (43 studies) to have inadequate progress or to otherwise be delayed. According to FDA officials, a key reason for a study's delay may be limited patient enrollment in the postapproval study. On average, manufacturers completed postapproval studies in about 3 years, with the longest study taking almost 7 years, for the studies that GAO reviewed.
Ninety percent of the 392 medical device postmarket surveillance studies FDA ordered from May 1, 2008, through February 24, 2015, were for orthopedic devices and devices such as certain kinds of implantable surgical mesh following concerns with these types of devices, and many were consolidated into ongoing studies. Unlike postapproval studies, FDA may order postmarket surveillance studies at the time or after a device is approved or cleared for marketing—for example, if FDA becomes aware of a potential safety issue. Safety concerns about metal-on-metal hip implants, including potential bone and tissue damage from metal particles, led to an increase in such studies ordered in 2011. Forty percent of the 392 ordered studies were for implanted surgical mesh and other devices used in general and plastic surgery and obstetrics and gynecology procedures. FDA ordered most of these studies in 2012, following safety concerns associated with implanted surgical mesh, such as severe pain. Eighty-eight percent of the postmarket surveillance studies GAO analyzed were inactive as of February 2015. Inactive studies include those that were consolidated (108 studies), meaning that a manufacturer was able to combine an order for a postmarket surveillance study with other related study orders into a single study, such as combining studies of multiple device models into a single study; and those that were inactive for other reasons, such as if the order was for a device that is no longer marketed. The remaining 12 percent of the postmarket surveillance studies were either still ongoing (40 studies) or completed (8 studies). Of the 40 ongoing studies, more than half were progressing adequately, according to FDA, and had been ongoing for an average of a little less than 3 years; the rest were delayed and had been ongoing for an average of about 4 years as of February 2015. According to FDA, postmarket surveillance studies may be delayed for reasons similar to postapproval studies, such as difficulty enrolling patients into the study.

section_title: Letter
paragraphs: Americans depend on the Food and Drug Administration (FDA)—an  agency within the Department of Health and Human Services (HHS)—to  oversee the safety and effectiveness of medical devices sold in the  United States. FDA’s responsibilities for medical devices begin before a  new device is brought to market and continue after a device is on the  market. As part of its premarket efforts, FDA reviews submissions for  thousands of new medical devices filed each year to decide whether they  should be allowed to be marketed in the United States. As a part of its  postmarket efforts, FDA may use a variety of tools to monitor marketed  devices, including ordering manufacturers to conduct postmarket studies  of medical devices.
Section 522 of the Federal Food, Drug, and Cosmetic Act authorizes FDA to require a  manufacturer to conduct postmarket surveillance of certain medical devices. See   21 U.S.C. § 360l. For this report, we refer to the studies required under this authority as  postmarket surveillance studies. the course of long-term use. In contrast, postmarket surveillance studies  are designed to obtain additional information about devices and are  generally ordered after they are on the market.receives reports of potential safety concerns related to a marketed  device, the agency may order a manufacturer to conduct a postmarket  surveillance study.
The agency identified as a priority achieving the following goal: assure the appropriate  balance between premarket and postmarket data requirements to facilitate and expedite  the development and review of medical devices, particularly high-risk devices of public  health importance. Department of Health and Human Services, Food and Drug  Administration, 2014-2015 Strategic Priorities: Center for Devices and Radiological  Health, accessed August 4, 2015,  http://www.fda.gov/downloads/AboutFDA/CentersOffices/OfficeofMedicalProductsandTob acco/CDRH/CDRHVisionandMission/UCM384576.pdf. these studies, including whether FDA ensures that these studies are  completed.
You asked us to report on the postmarket studies of medical devices  ordered by FDA. This report examines  1.  the types of devices for which FDA has ordered a postapproval study  and the status of these studies, and  2.  types of devices for which FDA has ordered a postmarket surveillance  study and the status of these studies.
To examine the types of devices for which FDA has ordered a  postapproval study and the status of these studies, we analyzed data  provided by FDA from its Center Tracking System for postapproval  studies ordered from January 1, 2007, through February 23, 2015.  Specifically, we analyzed the number of postapproval studies ordered by  FDA, the characteristics of the studies ordered during this time frame,  including the medical specialty in which the device is used (e.g.,  cardiovascular), the study design (e.g., randomized clinical trials), the  data source (e.g., newly collected data), and the premarket review  process through which the device was approved. We also analyzed  these data for the status of postapproval studies as of February 23, 2015,  and determined how long these studies had been ongoing or how long it  took to complete them.
To examine the types of devices for which FDA has ordered a postmarket  surveillance study and the status of these studies, we conducted a similar  analysis as we did for postapproval studies, except that we analyzed  FDA’s data for postmarket surveillance studies ordered from May 1, 2008,  through February 24, 2015. We did not analyze study design and data  source for postmarket surveillance studies because FDA had not  completed updating its database with data on these characteristics at the  time of our review.
For both objectives, we reviewed relevant laws and regulations and FDA  policy and guidance documents, and we interviewed knowledgeable FDA  officials about how the agency maintains data on postmarket studies for  medical devices. We also assessed the reliability of the data by, for  example, comparing data provided to us by FDA with the agency’s  publicly available data on study status. We determined that these data  were sufficiently reliable for our purposes.
We conducted this performance audit from May 2015 to September 2015  in accordance with generally accepted government auditing standards.  Those standards require that we plan and perform the audit to obtain  sufficient, appropriate evidence to provide a reasonable basis for our  findings and conclusions based on our audit objectives. We believe that  the evidence obtained provides a reasonable basis for our findings and  conclusions based on our audit objectives.
subsections: section_title: Background
paragraphs: FDA may order a postapproval study for a device at the time FDA  approves that device for marketing through its premarket approval (PMA)  process or its humanitarian device exemption (HDE) process (for devices  that treat rare diseases or conditions).the length of a postapproval study, but according to FDA guidance, the   There are no statutory limits on  device manufacturer and FDA agree on the study plan, which includes a  study design (e.g., randomized clinical trial or other study design), the  study’s data source, and time frame for when the manufacturer will  complete required reports.
In contrast, FDA may order a postmarket surveillance study at the time of  approval or clearance for certain devices or any time thereafter as long as  certain criteria are met. (See table 1.) FDA may order a postmarket  surveillance study not only for PMA and HDE devices, but also for  devices that are cleared through the less stringent 510(k) premarket  notification process—also known as the 510(k) process. FDA may order  postmarket surveillance studies if failure of the device would be  reasonably likely to have serious adverse health consequences, and such  studies may be ordered when FDA officials identify an issue with a device   FDA is  through adverse advent reports or reviews of scientific literature.authorized to order postmarket surveillance studies for a duration of up to  36 months, but the time frame may be extended if the manufacturer and  FDA are in agreement. Additionally, FDA may order a study with a longer  duration if the device is expected to have significant use in pediatric  populations and an extended period is necessary to assess issues like  the impact of the device on children’s growth or development.
Manufacturers must periodically report to FDA information on these  postmarket studies such as the progress of the study. Table 2 describes  the various status categories that apply to postmarket studies.
section_title: FDA Ordered Most Postapproval Studies for Cardiovascular Devices and Most Were Making Adequate Progress
subsections: section_title: FDA Ordered Most Postapproval Studies for Cardiovascular Devices and Most Were Designed as Prospective Cohort Studies
paragraphs: Cardiovascular devices, such as stents and heart valves, accounted for  56 percent of the 313 postapproval studies ordered from January 1, 2007,  through February 23, 2015. Orthopedic and general and plastic surgery  devices were the second and third most common subjects of  postapproval studies, respectively. FDA also ordered postapproval  studies for another 11 medical specialties, which are included in the other  category. (See table 3.)
The number of postapproval studies for cardiovascular devices varied  from year to year, with the most cardiovascular device studies ordered in  2008 and 2012. (See fig. 1.) In general, FDA orders a postapproval study  to obtain specific information on the postmarket performance of or  experience with an approved device. For example, the increase in the  number of postapproval studies ordered for cardiovascular devices in  2008 reflects that FDA has required that each new implantable  cardioverter defibrillator lead undergo a postapproval study.
Other includes devices for ophthalmic (e.g., intraocular lens); obstetrics and gynecology   (e.g., permanent birth control system); gastroenterology-urology (e.g., gastric banding system);  anesthesiology (e.g., computer assisted personalized sedation system); clinical chemistry   (e.g., artificial pancreas device system); dental (e.g., bone grafting material); ear, nose, and   throat (e.g., implantable hearing system); general hospital (e.g., infusion pump); microbiology   (e.g., human papillomavirus test); neurology (e.g., intracranial aneurysm flow diverter); and   pathology (e.g., breast cancer detection test).
The PMA process is the more stringent of FDA’s premarket review processes and  requires the manufacturer to supply evidence providing reasonable assurance that the  device is safe and effective before the device is legally available on the U.S. market.
February 23, 2015, were for devices approved through the PMA  process.
In terms of study design, more than two-thirds (69 percent) of the   313 postapproval studies ordered during the timeframe we examined  were prospective cohort studies—that is, studies in which a group   using a particular device was compared to a second group not using   that device, over a long period of time. (See fig. 2.) For example, one  postapproval prospective cohort study was designed to follow patients  who received a certain type of breast implant over a 10-year period and   to collect information on complications as they occur.
Additionally, postapproval studies were conducted using a variety of data  sources, including newly collected data and medical device registries.  Nearly two-thirds (196 studies) of the postapproval studies we examined  relied upon new data collected by the manufacturer; and about one-third  (98 studies) used data collected from registries—that is, a data system to  collect and maintain structured records on devices for a specified time  frame and population.maintained by the manufacturer or another organization, such as a   (See table 4.) Registries may be created and  medical specialty’s professional association. For example, FDA has  established a National Medical Device Registry Task Force to further  examine the implementation of registries in postmarket surveillance.  According to FDA, registries play a unique role in the postmarket  surveillance of medical devices because they can provide additional  detailed information about patients, procedures, and devices. For  example, registries can help assess device performance by collecting  information on patients with similar medical conditions.
section_title: Most of the Postapproval Studies FDA Ordered Were Ongoing and Making Adequate Progress, According to FDA
paragraphs: About 72 percent of the postapproval studies we examined (or 225 of the  313 studies ordered) were categorized as ongoing as of February 2015.  An additional 20 percent were completed and the remaining 8 percent  were inactive. (See fig. 3.)
Further analysis of FDA data on the 225 ongoing postapproval studies  showed 81 percent (or 182 studies) to be progressing adequately, while  the remaining 19 percent (43 studies) were delayed as of February 2015.  The 182 ongoing postapproval studies considered to be progressing  adequately—that is, the study was pending, the protocol or plan was  pending, or progress was adequate—had been ongoing for an average of  37 months, or a little over 3 years.
Similarly, the 43 ongoing postapproval studies considered to be  delayed—that is protocol/plan overdue, or progress inadequate—had  been ongoing for an average of 39 months or a little over 3 years.  Delayed studies include studies for which FDA had not approved a study  plan within 6 months of the PMA approval date (3 studies) or studies  which had begun, but had not progressed as intended (40 studies).
According to FDA officials, a key reason for a study’s delay may be  limited patient enrollment into the postapproval study. FDA officials said  they work with manufacturers to address manufacturers’ inability to enroll  patients, in part, by suggesting different strategies to improve enrollment,  such as hiring a dedicated person for recruitment or reducing the cost of  the study device to make it competitive with conventional treatments.
Twenty percent (or 62 studies) of the 313 postapproval studies were  categorized as completed as of February 23, 2015—that is, FDA  determined that the manufacturer had fulfilled the study order and had  closed the study. As table 5 shows, on average, these completed  postapproval studies took about 36 months, or 3 years, with the longest  study taking almost 7 years. The remaining 8 percent (or 26 studies) were  categorized as inactive. Postapproval studies that are considered inactive  include studies that, for example, involve a device that is no longer being  marketed or the study’s research questions are no longer relevant.
section_title: FDA Ordered Most Postmarket Surveillance Studies for Orthopedic, General/Plastic Surgery, and Obstetrics/ Gynecology Devices and Many Were Consolidated into Ongoing Studies
subsections: section_title: FDA Ordered Most Postmarket Surveillance Studies for Orthopedic, General/Plastic Surgery, and Obstetrics/Gynecology Devices Resulting from Concerns about Metal-on- Metal Implants and Certain Kinds of Implantable Surgical Mesh
paragraphs: FDA ordered 392 postmarket surveillance studies, half of which   (196 studies) were for orthopedic medical devices, from May 1, 2008,  through February 24, 2015. In 2011 alone, FDA ordered 176 studies   for orthopedic devices following safety concerns about metal-on-metal   hip implants, including potential bone or tissue damage from metal  particles. (See fig. 4.) An additional 40 percent (or 158 studies) of the  postmarket surveillance studies FDA ordered were for devices used in  general and plastic surgery and obstetrics and gynecology procedures.  FDA ordered 121 postmarket surveillance studies for devices in these  medical specialties in 2012, following safety concerns about the use of  implanted surgical mesh used for urogynecologic procedures, such as  severe pain. About 10 percent of the postmarket surveillance studies  were for devices in other medical specialties.
Other includes general hospital (e.g., intravascular administration set), cardiovascular (e.g., vena  cava filter), dental (e.g., temporomandibular joint implant), immunology, neurology, ophthalmic, and  physical medicine devices.
Between May 1, 2008, and February 24, 2015, about 94 percent of the  postmarket surveillance studies ordered were for devices cleared through  the 510(k) premarket notification process.regarding metal-on-metal implants and implantable surgical mesh used  for urogynecologic procedures that arose after the devices were cleared  through the 510(k) process, according to FDA officials.
section_title: Most of the Postmarket Surveillance Studies FDA Ordered Were Inactive, and Many of Those Had Been Consolidated into Ongoing Studies
paragraphs: About 88 percent of the postmarket surveillance studies we examined (or  344 out of 392 studies) were categorized as inactive. (See fig. 5.) A study  might be categorized as inactive, for example, because it had been  consolidated, meaning that a manufacturer was able to combine an order  for a postmarket surveillance study with other related study orders into a  single study. For example, if FDA issued 22 orders for postmarket  surveillance studies for different models of metal-on-metal implants from  a single manufacturer, the manufacturer could combine all of the orders  into a single study covering all of the devices, and the other 21 orders for  postmarket surveillance studies would be categorized as consolidated  and considered inactive. About 31 percent (or 108 studies) were inactive  because they had been consolidated into another study.
Another 31 percent of the inactive studies (or 107 studies) were  categorized by FDA as either terminated, meaning the study was no  longer relevant because, for example, the manufacturer changed the  indication for use that was the subject of the postmarket surveillance  study, or withdrawn by FDA because the manufacturer demonstrated the  objective of the study using publicly available data and FDA agreed with  the results. The remaining 38 percent (or 129 studies) were categorized  as other—that is, the status does not fit in another category because, for  example the device is no longer being marketed. However, according to  FDA officials, if the manufacturer does begin marketing the device again,  then it will have to conduct the study.
The inactive category for postmarket surveillance studies includes studies with one of four FDA study  statuses: (1) other—that is, the study status does not fit another category, because, for example, the  device is no longer being marketed or is being redesigned; (2) consolidated—that is, the study was  one of many postmarket surveillance studies ordered and the manufacturer, with the approval of  FDA, consolidated these multiple studies into a single study; (3) terminated—that is, studies that were  terminated by FDA because they were no longer relevant (e.g., the manufacturer changed the  indication for use that was the subject of the postmarket surveillance study); or (4) withdrawn—that is,  studies that were withdrawn because the manufacturer demonstrated the objective of the study using  publicly available data and FDA agreed with the results.
While 88 percent of the postmarket surveillance studies in our analysis  were inactive, the remaining 12 percent (or 48 studies) were either still  ongoing or completed as of February 24, 2015. Specifically, 10 percent  (or 40 studies) were categorized as ongoing, while 2 percent (or   8 studies) were completed. Of the 40 ongoing postmarket surveillance  studies, more than half were progressing adequately, while the rest   were delayed. Further analysis showed the following:
The 21 ongoing postmarket surveillance studies that FDA considered  to be progressing adequately had been ongoing for an average of   33 months, or about 2.7 years. (See table 6.)
The 19 ongoing postmarket surveillance studies that FDA considered  to be delayed had been ongoing for an average of 49 months or about  4 years. Delayed studies included studies for which FDA had not  approved a study plan within 6 months of ordering the study or studies  that had begun but were not progressing as intended. According to  FDA, postmarket surveillance studies may be delayed for reasons  similar to postapproval studies, such as difficulty enrolling patients into  the study.
Regarding the eight completed postmarket surveillance studies, the  average length of time to complete the study—that is, the time from   the study order to the date FDA determined that the manufacturer had  fulfilled the study order and had closed the study—was about 29 months  or 2.4 years. FDA generally may order a manufacturer to conduct a  postmarket surveillance study for up to 36 months unless the  manufacturer and FDA agree to an extended time frame.
section_title: Agency Comments
paragraphs: We provided a draft of this report to the Secretary of Health and Human  Services. HHS provided technical comments that were incorporated, as  appropriate.
As agreed with your office, unless you publicly announce the contents of  this report earlier, we plan no further distribution until 30 days from the  report date. At that time we will send copies to the Secretary of Health  and Human Services, appropriate congressional committees, and other  interested parties. In addition, the report will be available at no charge on  the GAO website at http://www.gao.gov.
If you or your staff have any questions about this report, please contact  me at (202) 512-7114 or crossem@gao.gov. Contact points for our  Offices of Congressional Relations and Public Affairs are on the last page  of this report. GAO staff who made major contributions to this report are  listed in appendix I.
section_title: Appendix I: GAO Contact and Staff Acknowledgments
subsections: section_title: GAO Contact
section_title: Staff Acknowledgments
paragraphs: In addition to the contact named above, Kim Yamane, Assistant Director;  Britt Carlson; Carolyn Fitzgerald; Sandra George; Cathleen Hamann; and  Gay Hee Lee were major contributors to this report.