How the FDA Approves New Drugs

There has been a 90% increase in the number of serious adverse drug event reports received by the Food and Drug Administration (FDA) over the last four years. In the first quarter of 2012, the FDA received nearly 60,000 reports alone. The report’s adverse reactions fall into four basic categories: (1) new drugs; (2) widely used drugs; (3) suspect drugs; and (4) drugs that are being used now more than in the past. The reports are submitted by the actual drug manufacturers rather than consumers.

For example, in the world of high-stakes pharmaceuticals, there has been a longing to replace Coumodin. For the last fifty years, Coumodin has been the go to blood thinner for millions of patients. Coumodin’s two biggest drawbacks are that it requires constant medical monitoring to insure proper dosage and that the drug does not interact well with other medications.

Two drugs were recently approved by the FDA to finally replace Coumodin. Enter the blood thinners Dabigatran etexilate capsules sold as Pradaxa and Rivaroxaban sold as Xarelto. For some reason, the FDA expedited approval of Pradaxa under its Fast Track Program approval process, based upon the manufacturer’s promise that the no medical monitoring was necessary for a single primary dose. The Fast Track Program expedites the approval of medications designed to fulfill serious unmet medical needs, before the testing is complete. The benefit is obvious when a drug may provide relief for patients with limited time and options. The risk however, is that important safety questions often go unanswered.

The only disclosed drawback would be the cost; about 15 times more than generic Coumodin. The FDA’s limited approval for long term use by patients with atrial fibrillation to prevent strokes is unlike the European Medicines Agency which approved it for short term use to prevent blood clots in patients undergoing artificial knee or hip implantation. Like Coumodin, Pradaxa and Xarelto are anticoagulant blood thinners designed to lengthen the time it takes the blood to clot. Aspirin on the other hand, is an antiplatelet drug that prevents blood cells called platelets to form a clot.

In less than a year, Pradaxa became a block buster drug for its manufacturer Boehringer Ingelheim by capturing 28% of the market. Regrettably, the rushed approval process has resulted in too many stories with tragic endings. According to the Philadelphia Inquirer, Pradaxa has been associated with 3,781 reported adverse reactions, including 542 deaths and 2,367 hemorrhages. Particularly at risk are elderly patients in their 80’s who report the greatest number of controllable bleeds. And unlike Coumodin, there is no antidote to stop a patient from bleeding out.

Shortly after the debut of Pradaxa, the FDA expedited the approval of Rivaroxaban sold as Xarelto. Xarelto succeeded in convincing the FDA to approve it not just for AFib patients, but also for bedridden patients recovering from artificial hip implant and knee replacement surgeries. Like Pradaxa, this is a once-a-day-drug that does not require the same blood level monitoring as Coumodin.

A clinical trial involving 14,000 patients showed that while Xarelto were no worse off than those who took Coumodin. The reporters acknowledged most of the Coumodin patients were not optimizing the drug. The review also noted that if Xarelto was really worse than Coumodin, it’s use could lead to increased bleeding injuries and death. The reviewers also advised that the rate of clinically relevant bleeding was very high – fifteen percent - making the drug the riskiest outpatient drug treatment on the market, according to the Institute for Safe Medication Practices’ Quarter Watch. The FDA’s senior management disagreed with the findings and approved Xarelto.

In the first quarter of 2012 alone there have already been 356 reports of serious bleeding injuries or deaths associated with Xarelto. Unlike Pradaxa’s, Xarelto tends to affect younger patients in their mid 60’s who took the drug for short-term use after hip replacement surgery. In addition, there have been a high number of pulmonary embolisms reported; the precise event the drug was designed to prevent.

I have represented consumers and their families for over 20 years in cases against pharmaceutical giants, such as Johnson and Johnson and Bayer, for defective and dangerous prescription drugs and medical devices. Many of our clients are shocked to learn that the FDA itself does not test drugs but instead relies upon the drug manufacturers to report the findings of their own clinical research. This is called the Pre-Clinical Research Stage. Usually, these drugs are tested on animals with the results compiled into an application to the FDA.

If the application is positive, Phase 1 testing begins on a limited number of both healthy humans and sometimes patients. During this period, the drug’s efficacy and side-effects are evaluated in a structured setting. Assuming the results are positive overall, the drug moves to Phase 2 testing on a larger group of subjects, typically several hundred patients. Subsequently, the drug moves to Phase 3 where it is given to hundreds to thousands of people.

These clinical trials are overseen by Institutional Review Boards that are comprised of pharmaceutical industry experts and lay people charged with protecting the wellbeing of the participants. Once the clinical testing is complete, the manufacturer makes a formal application for approval of the new drug to the FDA. This is called a New Drug Application, or NDA. The NDA includes all tests and the results of all clinical trials on both the animals and humans, details on the manufacturing process and proposed labeling. To be approved, the NDA must pass a balancing test by demonstrating that the benefits of the drug outweigh its risks, and that it is safe and effective for human use.

The prescription drug and medical device approval process can and should take years. President Obama’s Administration has a policy with the FDA to encourage growth and innovation in drug development. This is an admirable goal that we should all appreciate. However, as a Miami lawyer who sues prescription drug manufactures, I strongly urge the FDA to slow down and not allow innovation and corporate profit to outweigh consumer safety.