What are the FDA Approved Medical Devices

FDA: New criticism of drug and medical device approval procedures

Boston / New Haven / Silver Springs - Most models of pacemakers and defibrillators implanted today have been approved by the US FDA without clinical testing. In the opinion of critics, the FDA often tends to make quick decisions when it comes to drugs. Two studies in the US-American Ärzteblatt examine the approval practice of the US regulatory authority. An employee of the authority defends the approval process.

There have been two spectacular recalls of implantable cardioverters / defibrillators (ICD) in recent years. Both times, well-known US companies, Medtronic and St. Jude Medical, which also sell their devices in Germany, were affected. And both times, defects in electrodes were affected, which are supposed to give the patient's heart muscle the life-saving electrical impulses to end a ventricular arrhythmia.

In October 2007, Medtronic had to recall devices with Sprint Fidelis electrodes, and in December 2011 St. Jude Medical withdrew ICDs with Riata electrodes from the market. In both cases, it was found that the manufacturers made modifications to the devices without retesting the devices in clinical trials. This is also not legally necessary, as the US authorities allow manufacturers to make modifications to devices that have already been approved if they notify the authorities of this. The FDA then promises a short-term review.

The approval of medical devices by the FDA takes place via what is known as “premarket approval” (PMA). Today it usually requires a clinical study, although this was by no means the rule in the past. In Europe, medical devices can still be imported without clinical testing via a CE certificate, which critics see as a security gap.

In the case of medical products, it is common to keep changing the structure and design. In the USA, a supplementary approval or “supplement” is then required. Most cardiac implantable electronic devices (CIED) - in addition to ICDs, conventional pacemakers and devices for cardiac resynchronization therapy - that are implanted today are modifications.

According to research by Benjamin Rome from Brigham and Women’s Hospital in Boston, there are 77 CIEDs approved since 1979, no less than 5,829 PMA “supplements” or a median 50 per CIED (JAMA 2014; 311: 385-391). The number has increased in recent years, according to Rome. For every CIED today, there would be an average of 2.6 changes per year in the design and construction of the devices.

Manufacturers must report any changes to the FDA; new clinical tests are usually not required. According to research by Rome, they were only carried out in 23 percent of the so-called "180-day supplements". The "180-day supplements" are an approval variant for which the FDA reserves an examination period of 180 days. The withdrawn Fidelis electrode had been introduced as a “180-day supplement”, with the Riata electrodes the manufacturer even received a “real-time supplement”, for which the FDA only briefly checks, in real time, whether the Change could pose a potential risk to the patient.

Having every small change verified by a new clinical study would certainly stunt technical progress in the medical device field. Rome is also of the opinion that most of the modifications do not endanger the safety of the devices. However, as the two recalls show, the process has its pitfalls.

The approval of drugs in the USA (and also in Europe) always requires clinical studies. The FDA has fixed standards for this. According to Leonard Sacks from the FDA's Center for Drug Evaluation and Research in Silver Spring (near Washington), only one drug (valdecoxib in 2005) had to be withdrawn from the market due to safety concerns after approval in the past twelve years.

2009: 181 drug safety issues
However, Sacks does not mention the fact that there were several voluntary withdrawals and a number of indication restrictions. In 2009 alone, the FDA acted 181 times on drug safety issues, including 25 black box warnings and 19 contraindications, as Steven Goodman of Stanford University notes in the editorial.

Sacks, on the other hand, emphasizes the high standards of the exam (JAMA 2014; 311: 378-384). In the years 2001 to 2012, half of the applications for new drugs initially failed, he writes. And of the other half, only every second remedy made it in a follow-up application. The manufacturers needed an average of 435 days to submit the missing data. According to Sacks, frequent deficiencies in marketing authorization applications relate to the choice of dose and the endpoints, which do not always describe clinically relevant benefits for the patient. Occasionally, the drugs fail because they are less effective than drugs that have already been approved.

Nicholas Downing from the Yale Center for Outcomes Research & Evaluation (CORE) in New Haven, on the other hand, paints a less rosy picture of drug approval by the FDA (JAMA 2014; 311: 368-377). His analysis of 188 new drugs launched in the seven years between 2005 and 2012 found that manufacturers only had data from a single clinical trial on a third of the applications, even though the FDA required a minimum of two trials. In other studies, Downing complains that the number of participants is too small, the duration and the choice of laboratory parameters as the endpoint.

Only about 40 percent of all new active ingredients have been compared with an already approved drug. The health care researcher is generally disappointed with the quality of the drug approval. The population expects the FDA to make new drugs safe and effective. Based on the investigation, however, there are doubts that these expectations will always be met, says Downing in the press release. © rme / aerzteblatt.de