Anemia drugs made billions, but at what cost?

The trouble would arise as the drugmakers won FDA approval for vastly expanded uses, pushing it in larger doses, for milder anemia and for patients with a wider array of illnesses. Very quickly, the market included nearly all dialysis patients, not just the roughly 16 percent who required blood transfusions. The size of average doses would more than triple. And over the next five years, the FDA would approve it to treat anemia in patients with cancer and AIDS, as well as those getting hip and knee surgery.

The key to their marketing was the claim that the drugs at higher doses could make patients feel better. By 1994, the drug’s label, approved by the FDA, advertised a range of benefits: “statistically significant improvements for . . . health, sex life, well-being, psychological effect, life satisfaction, and happiness.”

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Those claims, withdrawn 13 years later because they did not meet new FDA standards for proof, would be the basis of television and print advertising campaigns, pitched to people with potentially fatal illnesses.

The drugs, according to one, offered “Strength for Life.”

But while ads touted the drugs’ virtues, some at the FDA had raised safety concerns. To address them, the drugmakers agreed to conduct two key safety studies.

The first was supposed to evaluate the drug’s “safety profile” and enrolled 2,100 patients. Scientists affiliated with Amgen published “interim” results in 1991 and 1993.

But the full safety results of the study were never published, and in later lists of safety investigations by the FDA and Amgen, there appears to be no reference to this study.

It’s not clear from the agency’s records how seriously anyone was taking the results, anyway. Amgen filed a “clinical study report” with the agency in 1995, and the company says its research commitment was fulfilled then. But the FDA did not deem the study completed until March 2004, almost 15 years after the company agreed to conduct it.

Neither Amgen nor the FDA would release a copy of the study report.

An FDA spokesman explained that the original report had been “misfiled” and that the agency has instituted tracking procedures to prevent that from happening.

A company spokesman said the report’s findings were consistent with what was known of the risks at the time.

The second promise of a safety report would arise as the drugs were being approved for cancer patients. In 1993, the companies agreed to conduct a study of whether the drugs might have “stimulatory effects” on tumor growth.

That year, Johnson & Johnson started a study of patients with small-cell lung cancer.

It was supposed to have 400 patients.

Eleven years later, the company said it was having difficulty recruiting them, having enrolled only 224. That meant it would be harder to reach statistically significant conclusions. Moreover, the FDA noted that in about 17 percent of the cases, data were missing.

With FDA approval, Johnson & Johnson halted the study, never finding evidence of clear dangers. But as Medicare researchers would later remark, the patients taking the drugs appeared more likely to die than those taking the placebo.