According to U.S. and European records, another one of the drugs approved based on research at Cetero's troubled Houston lab was a chemotherapy drug known as Temodar for Injection.
Temodar was originally approved in 1999 as a capsule to fight an aggressive brain cancer, glioblastoma multiforme. Some patients, however, can't tolerate taking the medication orally, so drug maker Schering-Plough decided to make an intravenous form of the drug.
To get Temodar for Injection approved, the FDA required what it called a "pivotal" test comparing the well-established capsule form of Temodar to the form injected directly into the bloodstream.
Cetero Houston conducted that test, comparing blood samples of patients who received the capsule to samples of those who got the injection to determine if the same amount of the drug was reaching the bloodstream. This test is crucial, particularly in the case of Temodar, where there was a question about the right dosing regimen of the injectable version. If too little drug gets into the blood, the cancer could continue to grow unabated. If too much gets in, the drug's debilitating side effects could be even worse.
Cetero performed the test between September 2006 and October 2007, according to documents from the European Medicines Agency, and FDA records indicate that same test was used to win approval in the U.S.
In 2011, the FDA notified Merck & Co., which had acquired Schering-Plough, about the problems with Cetero's testing. In April 2012, the FDA publicly announced that analyses done by Cetero during the time when it performed the Temodar work would have to be redone. But according to Merck spokesman Ronald Rogers, the FDA has not asked Merck for any additional analyses to replace the questionable study.
The FDA declined to answer specific questions about the Temodar case, saying to do so would reveal confidential commercial information. But Woodcock said that in some cases, drug manufacturers had submitted alternative test results to the FDA that satisfied the agency that no retesting was necessary for specific drugs.
The FDA never removed Temodar for Injection from the market. The European Medicines Agency also kept the injection form of the drug on the market, but the two agencies handled their decision in sharply different ways.
The EMA has publicly laid out evidence — including studies not performed by Cetero — for why it believes the benefits of the injection drug outweigh its risks. But in the United States, the FDA has kept silent. To this day, Temodar's label — the single most important way the FDA communicates the risks and benefits of medication — still displays data from the dubious Cetero study. (The label of at least one other drug, a powerful pain reliever marketed as Lazanda, also still displays questionable Cetero data.)
Woodcock said the agency hadn't required manufacturers to alter their labels because, despite any question about precise numerical precision, the FDA's overall recommendation had not changed.
In a written response to questions, Merck said it "stands behind the data in the TEMODAR (temozolomide) label." The company said it learned about "misconduct at a contract research organization (CRO) facility in Houston" from the FDA and that it cooperated with investigations by the FDA and its European counterpart. It said that Cetero had performed no other studies for Merck.