The New England Journal of Medicine is commonly regarded as one of the most esteemed journals in medicine and influences the practice of medicine around the world. But about two-thirds of its articles on new drugs are sponsored by pharmaceutical companies and most of those are co-written by their employees. The journal’s editors have put in place numerous safeguards to prevent bias. In some recent high-profile cases, some of those articles have either overstated the benefits or underestimated the risks of a sponsor’s drugs.
PUBLISHED: July 2000.
ARTICLE FINDINGS: Results of two trials of the heart drug. Natrecor, it concluded, “improves . . . clinical status” and is “useful.”
FUNDED BY: Drug maker Scios (now a subsidiary of Johnson&Johnson)
AUTHORS/EMPLOYEES: One of the co-authors was an employee.
Improves breathing in patients with congestive heart failure.
Reportedly reached $400 million in annual sales by 2004.
Even before the NEJM article, Food and Drug Administration reviewers who had seen the data from the two trials concluded that the link between the drug and clinical benefits is “tenuous.” They also cited “problems in the collection of these data,” which undermined their “independence and strength.” Last year — 11 years after the first article on the drug — NEJM published an article about a larger trial conducted by other researchers, which was funded by the company. The drug was ineffective in normal usage and “cannot be recommended for routine use in the broad population of patients.”
“We are proud to have completed the [second] study and to continue making Natrecor available for physicians to treat patients,” a Scios spokesman wrote.
PUBLISHED: August 1998.
ARTICLE FINDINGS: Results of a major trial of Epogen, an anemia drug that would become one of the bestselling in the nation. Among other things, the artcile suggested that the drug led to a better quality of life and and that “a higher . . . dose was not associated with higher mortality.”
FUNDED BY: Drug maker Amgen
AUTHORS/EMPLOYEES: Four of the authors were employees.
Treats anemia in chronic kidney disease patients and chemotherapy patients.
By 2005, sales reached $3 billion annually.
Earlier this year, a Washington University doctor reconsidered the data and discovered discrepancies. Although the original NEJM article suggested that a higher dose improved a patient’s quality of life, it omitted the fact that no such difference was detected between patients in the higher-dose and lower-dose groups. Moreover, while the paper said the risk of death and heart attacks was not statistically different between the higher-dose and lower-dose groups, the FDA said that the hazards are higher for patients getting the higher dose and that the result is statistically significant. The agency required that the company offer consumers a warning.
Amgen said that as the understanding of the drugs has evolved, the company “quickly and responsibly communicated these new findings.”
PUBLISHED: November 2000.
ARTICLE FINDINGS: Report of trial showing that Vioxx is less likely to cause gastrointestinal problems than a competitor. One of the co-authors was praised in a Merck company performance review as a “tireless defender” of the drug, court proceedings showed.
FUNDED BY: Drug maker Merck
AUTHORS/EMPLOYEES: Two of the authors were employees.
Reduces pain, inflammation and stiffness caused by arthritis, and manages acute pain in adults.
Worldwide sales in the early 2000s reached as high as $2.5 billion annually.
Five years after they published the Vioxx trial, the editors reported that critical information about “adverse cardiovascular events” had been omitted from the article and that the omission created “misleading” conclusions about the drug’s safety. Documents released as part of subsequent lawsuits showed that scientists planning the experiment had worried that their experiment would indicate a safety risk and “kill” the drug. The scientists discussed ways of designing the experiment so that the heart troubles would be less apparent — such as allowing aspirin and excluding patients with heart ailments, e-mails released in litigation show.
In 2004, Merck voluntarily removed Vioxx from the market.
In 2007, the company agreed to pay $4.85 billion to settle 27,000 lawsuits related to the drug.
PUBLISHED: December 2006.
ARTICLE FINDINGS: Study saying that Avandia lasted longer and that heart risks were similar to another commonly used medicine.
FUNDED BY: Drug maker GlaxoSmithKline
AUTHORS/EMPLOYEES: Four of the authors were employees.
Helps regulate blood glucose levels in patients with Type-2 diabetes.
Topped $3 billion in 2006.
Researchers at the Cleveland Clinic gathering and analyzed all the trial results involving Avandia that they could find. In a 2007 NEJM article, they reported that Avandia use elevated the risk of heart attack by more than 40 percent. After three years of debate, Avandia sales were restricted in the United States, and removed from the market in Europe.
GlaxoSmithKline issued a statement: “We firmly believe we acted responsibly in conducting the clinical trial program, in marketing the medicine, in monitoring its safety once it was approved for use and in updating information in the medicine’s labeling as new information became available.”
PUBLISHED: May 2010.
ARTICLE FINDINGS: Study on risk of unusual fractures of the thigh bone in patients taking the drug. No significant increase in thigh-bone fracture risks. Authors acknowledged it did not include enough patients for definitive conclusions.
FUNDED BY: Drug makers Merck and Novartis
AUTHORS/EMPLOYEES: Three of the authors were employees.
Treats bone loss in patients with osteoporosis. Includes brands such as Reclast and Fosamax.
A year later, an FDA review of data and studies concluded otherwise. The FDA said such fractures “appear to have a strong association” with bisphosphonates. The FDA added a warning about fractures on the drug label.
A Novartis spokesman said in a statement: “As clinical trials generate new safety and efficacy data, as in the case of atypical fractures potentially relating to bisphosphonates, we work with the FDA to update the labels, where appropriate, to provide information based on this evolving data.”
SOURCES: New England Journal of Medicine, Food and Drug Administration, company reports and statements.
GRAPHIC: Peter Whoriskey and Tobey/The Washington Post. Published Nov. 23, 2012.