BMJ raises concerns about FDA
post-approval surveillance of medical devices
3 Nov 2010
A British Medical Journal (BMJ) investigation
published today raises concerns about the ability of the US Food and
Drug Administration (FDA) to monitor the ongoing safety of medical
devices through post-approval surveillance .
The report by Jeanne
Lenzer, a medical investigative journalist in New York, and Shannon
Brownlee from the Dartmouth Institute for Health Policy and Clinical
Practice in New Hampshire, looks at the FDA’s approval of a device to
prevent or reduce seizures in patients with epilepsy who do not respond
to drug treatment.
The device, manufactured by Cyberonics, is
implanted under the skin and sends electrical impulses to stimulate the
vagus nerve in the neck. It was approved by the FDA in 1997 on the
condition that Cyberonics carried out a post-approval study to examine
the safety of the device.
“However, in the 13 years since the
device was approved in the US, more than 900 deaths have been reported
to the FDA, and it is still not clear what impact, if any, the device
has had on patient mortality,” say Lenzer and Brownlee. They point out
that, although Cyberonics conducted the requisite post-approval study,
the FDA did not specifically require the company to submit mortality
Lenzer and Brownlee argue that the FDA’s failure to request
and rigorously monitor mortality data related to the vagus nerve
stimulator “is but one example of the gap in post-approval surveillance
of medical devices.” A recent review showed that less than one third of
devices approved under FDA’s premarket approval process had been
evaluated in a randomised study.
They also question the FDA’s
ability to detect potentially unsafe devices through its harms database
(Manufacturer and User Facility Device Experience — MAUDE) and cite a finding that many post-approval studies “are not conducted or
conducted so poorly as to be meaningless”. One of the problems mentioned
is that manufacturers themselves can decide whether a device is
connected with a negative outcome. Even when a device is connected, 39%
of events are reported late — which could be years after the event.
The FDA gave the
references to five additional post-approval studies as evidence of the
device’s safety. But Lenzer and Brownlee say that these studies do not
establish that the device wasn’t responsible for deaths because none of
them reported mortality data.
In 2005, the FDA approved the vagus
nerve stimulator for the treatment of depression, despite the
recommendation against approval by its own scientists. The company has
also suggested that the stimulator might have a role in treating
obesity, stroke, traumatic brain injury, and other conditions, and has
taken out patents for these potential therapies.
The gaps in
post-approval monitoring of the vagus nerve stimulator are emblematic of
the FDA’s surveillance of all devices, say the authors. Yet they believe
many of the problems have relatively easy fixes. For example, the FDA
could make better use of the FDA’s database to detect potential safety
issues by requiring manufacturers to regularly submit data on the number
of active devices.
An independent review panel could also be
appointed to decide whether certain adverse outcomes could be excluded
from reporting, instead of allowing the manufacturer to make those
decisions. And, as the FDA has suggested, mechanisms to limit widespread
uptake of new devices could be put in place so that fewer patients are
harmed if it ultimately turns out that newly approved devices are
flawed, they conclude.
In an accompanying editorial, Professor
Jerry Avorn from Harvard Medical School argues that “the standards for
device approval and surveillance have fallen far below those for drugs,
and even those that would be dictated by common sense” .
points to a “notoriously inadequate approach” in the vital area of
postmarketing safety surveillance, and calls for surveillance activities
to be placed at a higher and more independent position within regulatory
Important lessons can be learnt from drug regulation, he
says, including mandatory recording of all installed devices on clinical
databases and better systems to review new products.
1. Lenzer J, Brownlee S. Why the FDA can’t protect the public?
2. Editorial. Regulation of devices.