Four Approval System Failures

Earlier in the chapter, I examined several dramatic failures on the part of the FDA to withdraw drugs from the market until the passage of years and even decades, despite mounting reports of potentially fatal adverse effects. This section examines how long it can take before flagrant adverse effects are even noted in the drug label. 

NMS (see chapter 4) provides an example of how a devastating, common disorder can be wholly missed in the clinical trials during the approval process. It also illustrates how long it can take drug companies and the FDA to give formal recognition to such a disorder. 

NMS is a potentially fatal reaction to neuroleptic drugs such as Haldol, Prolixin, Risperdal, Zyprexa, Seroquel, and Abilify. It occurs at a relatively high rate, developing in somewhere from 1.4% to 2.4% of patients exposed to the older neuroleptics and at significant rates to patients exposed to the newer ones (chapter 4). By contrast, a reaction that occurs 1% of the time is considered common or frequent by FDA standards. This particular reaction is extremely dramatic and therefore not easily overlooked. Yet NMS was entirely missed in one study after another conducted by drug companies when applying for FDA approval of neuroleptic drugs. 

In 1986, nearly two decades after NMS had become an identifiable syndrome, the FDA at last began to force the drug companies to add the adverse drug reaction to their neuroleptic labels. Since the disease is fatal in approximately 20% of cases when it goes unrecognized and untreated, the failure to properly inform physicians cost many lives and untold suffering. 

There are important lessons from the history of NMS. First, for many years, neither the FDA nor the drug companies came close to fulfilling 

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