For patients with a high risk of cardiac-related death, implantable cardioverter-defibrillators (ICDs) are usually a demonstrably favorable alternative to medication. Rather than taking medication, an ICD is implanted in a patient and will monitor the patient’s heartbeat. When an irregularity is detected, the ICD will administer a shock which should correct it. During implantation, the ICD is connected directly to heart by thing wires, called leads.

In December 2007, Medtronic, a major manufacturer of defibrillator leads, was forced to recall their latest model of leads, the Sprint Fidelis, because of reports of lead fractures. If fractured, the ICD is unable to function properly, and may either give unnecessary shocks or none at all. Clearly, this creates a significant health risk for patients in need. The danger becomes worsened by the fact that the surgery to remove or replace the leads is not without risk. In a March 2009 investigation by the New York Times, it was reported that at least 13 people were likely killed due of the faulty leads or during surgery to replace the defective leads.

Since the initial recall, the rate of failures has continually increased. So much so, UBS Analysis’ predict that the rate of failure at four years could be as high as 30%. This would be an astounding failure rate and will jeopardize patient health, and many patients would be required to undergo medium-risk surgery to replace the wires.

The monumental failure of the Sprint Fidelis brings to light FDA’s failings in its approval processes. When a company makes a minor change to an FDA approved device, it must seek new approval from the FDA. However, the threshold for a supplemental device is lower and the FDA has a much higher tendency to approve this type of device as opposed to new device applications. Because of this, companies have an incentive to seek approval of new devices claiming they have only been slightly altered from an already approved device.

When Medtronic released the Sprint Fidelis series, Medtronic advertised it as the next generation of lead wires. The Sprint Fidelis was advertised as thinner and easier to implant compared to the Sprint Quattro. It replaced their previous line of wires, the Sprint Quattro line. Despite the seemingly significant changes, Medtronic claimed to the FDA that the changes from the Sprint Quattro were only minor. Shortly after, the FDA approved the Sprint Fidelis based its approval of the Sprint Quattro. So while Medtronic told the FDA the changes were only minor, it went on to flaunt the changes as significant improvements over the previous line of leads.

The severity of this disaster only worsens as more patients experience failures. This situation reiterates the need for significant FDA reform. In this case, the FDA needs to ensure that a manufacturer is not advertising “significant improvements” to the public while declaring the changes only minor to the FDA. And in the least, the FDA must do a better job at thoroughly reviewing supplemental applications before approving them.  After all, sometimes the changes aren’t so minor.

Read the rest of this entry >

Dr. Rita Redberg and her colleagues at the UCSF Medical Center have published a startling report regarding the FDA’s approval of cardiovascular drugs. According to the report, from 2000-2007 the FDA approved 78 cardiovascular devices with relatively little evidence.

In fact, nearly two thirds of the pre-market approvals were supported only by a single research study. Additionally, only 27% were randomized tests, and only 14% were approved.  Only 5%, or 4 out of 78, used more than one blinded, randomized studies. Nearly nine in ten of the studies relied on surrogate endpoints, which are sometimes misleading.

These numbers and statistics mean that the FDA approved a significant number of cardiovascular devices based on only one report. And many of the reports used it its approval were based on clinical methods widely considered inadequate.

While new surgical procedures do not require any FDA approval and new drugs have strict approval requirements, devices fall somewhere in between the two. Dr. Redberg suggests that the standards of device approvals should be higher than drugs, because "because [devices] are implanted and cannot simply be discontinued, as drugs can."

Less than strict approval requirements for devices affects a significant number of recipient patients, since once a device is approved the manufacturer almost always begins encouraging widespread use. Meanwhile, the GAO recently reported that the while the FDA is improving its post-market procedures, it is still understaffed and ill equipped to pull approved drugs and devices from the market quickly when necessary.

This has created a troubling situation: inadequate device approval requirements, and a deeply flawed post-market monitoring system. This is all the more reason that the FDA needs substantial reform, and it needs it soon.

Read the rest of this entry >

The Government Accountability Office (GAO) has compiled a report looking at the steps the FDA has been taking to improve communication between the internal offices of the FDA, in an effort to protect the public from dangerous drugs released on the U.S. market. The GAO found some FDA efforts towards this goal, including having done or planning to:

·         Improve communication between the Office of Surveillance and Epidemiology (OSE, once called Office of Drug Safety) and Office of New Drugs (OND).

·         In 2010, implement new data systems facilitating quicker access to outside data, in order to facilitate “timeliness, quality, and analysis of reports of adverse events associated with human drug use.”

·         Improve funding for private contracts to provide external data for speedier access.

But is this enough? Within the FDA, scientists in the OND are tasked with reviewing, and ultimately approving, new drug applications. These same scientists are also the ones who (generally) make the determination whether to pull the same drugs off the market. Meanwhile, the OSE monitors the drug’s side-effects on the market and compiles patient complaints. However, the OSE doesn’t have much say in whether the drugs should be pulled from the market. Many outsiders would point to this bureaucratic setup as improper – to have the same scientists which approved the drug also have to be the ones puts the public at risk.

Additionally, the GAO reports that both the OND and OSE are understaffed. Both offices’ employees cite the inability to meet their responsibilities. According to the GAO the OSE must double its employees in the next year in order to keep up with workload. All of this means that both the OND and OSE are understaffed and overworked; and as a result are unable to fulfill their responsibilities.

It’s important to remember that the GAO is fully independent of the FDA, the pharmaceutical industry, and trial lawyers. In fact, it’s an investigative arm of Congress, funded by taxes. There is no incentive for the GAO to fabricate or exaggerate in any direction, and their reports should be taken as truthful and honest. Knowing this makes their reports about the inadequacies of the FDA all the more alarming. While the GAO reports the FDA is going in the right direction, it still has a tremendous amount of ground to make up. And the FDA needs to do much more to distance itself from the pharmaceutical industry. And until this happens, some Americans are at risk of taking FDA-approved medications which should not be on the market.

Read the rest of this entry >

The American Recovery and Reinvestment Act allocated $1.1 billion dollars to coordinate research and guide investments in comparative research funded by the Act. Some critics suggest that a whole lot of money could have been saved just by looking to the FDA.

Dr. Lisa Schwartz and Dr. Steven Woloshin have co-authored a New England Journal of Medicine article titled Lost in Transmission – FDA Drug Information That Never Reaches Clinicians, in which they talk about the fallacies of the current system, and possible ways to correct it.  Primarily, on the journey from clinical trials to FDA approval to the production of a drug label, potentially vital information is lost.  For example, the FDA approved the drug Rozerem in 2005 to treat chronic insomnia, but in one phase 3 clinical trial, the drug failed to provide any benefit at all for this condition.   In fact, a memo created by the FDA’s own medical review team debated whether to even approve the drug since the insignificant benefits provided by the drug may be outweighed by its potential side effects, but Rozerem was eventually approved.  Obviously, knowing this background information would certainly appear to have an effect on a doctor’s enthusiasm to prescribe the drug, and a patient’s willingness to take the drug. Unfortunately, though, this type of important information is not placed on the FDA’s approved drug label, so none of it is clearly communicated to the public.

To its credit, the FDA has issued new guidelines about drug labeling, such as including phase 3 trial results and other effectiveness data, but this information is not mandated as it should be.  In the case of Rozerem, the effectiveness data is still absent even after the label was updated. Bottom line - more needs to be done.

The FDA is currently undergoing a pilot test of a “drug fact boxes” which would include a succinct table of effectiveness data such as reviews and labels. This would give doctors more pertinent information about drugs and also allow patients to make a more educated decision before they take a new medication. The FDA is still debating internally how to use these “drug fact boxes.”

There are other potential alternatives, but the authors concisely (and correctly) conclude, “Whatever approach the agency adopts, it needs a better way of communicating drug information to clinicians. We don’t need to wait for new comparative-effectiveness results in order to improve practice. We need to better disseminate what is already known.”

Read the rest of this entry >