Published online 11 November 2008 | Nature | doi:10.1038/news.2008.1219


Company sues researcher over unfavourable review

Biopure says meta-analysis harmed its product.

A biomedical researcher at the US National Institutes of Health has been sued for publishing a study that linked a class of blood substitutes to increased risk of heart attack and death.

Biopure, a company based in Cambridge, Massachusetts, accused Charles Natanson of making "false and defamatory statements" about the company's blood substitute, Hemopure, both in a study published in the Journal of the American Medical Association1 and in letters sent to health officials in the United Kingdom, Greece and South Africa.

Blood substitutes are meant to help alleviate the shortage of natural blood in many parts of the world.© JUPITERIMAGES/ BananaStock / Alamy

The study, published by JAMA in April, combined data from clinical trials of five blood substitutes, including Hemopure. All five products were haemoglobin-based blood substitutes designed to improve oxygen transport in patients with severe anaemia, and members of a class plagued by safety concerns. Several of the products studied had had trials terminated early for safety reasons. Hemopure had been approved for use only in South Africa, where the HIV epidemic has dramatically restricted blood supplies.

A bloody mess

On the basis of their analysis, Natanson and his co-authors concluded that the blood substitutes were associated with a 30% increase in the risk of death compared with control solutions, which varied among the studies. According to Biopure, Natanson then sent letters to countries with ongoing or planned clinical trials of Hemopure to alert them to his findings. Natanson declined interview requests for this story.

Biopure asserts that Natanson's analysis was so methodologically flawed that he could not conclude that Hemopure poses a health risk. In June, the company's lawyers sent Natanson a letter asking him to retract the paper. He stood by his findings.

On 10 October, Biopure filed the lawsuit in a US district court. About two weeks later, South African officials announced that they had pulled Hemopure from the market.

Biopure also notes that Natanson originally neglected to disclose his involvement in a provisional patent application for a technique to reduce the alleged harmful effects of haemoglobin-based oxygen carriers. He has since amended his conflict-of-interest statement and stated that he would not be listed as an inventor on the final patent application.

This is not the first of Biopure's problems with Hemopure. In 2003, the US Food and Drug Administration (FDA) expressed concerns about the safety of Hemopure, and halted plans for a clinical trial of the product in trauma patients. Two years later, the US Securities and Exchange Commission (SEC) sued three Biopure executives and the company for misrepresenting the FDA's concerns to investors. In August, Biopure's former head of regulatory affairs, Howard Richman, settled the case with the SEC, only to be indicted by a grand jury at the end of September for lying to the court about having terminal colon cancer to avoid testifying. The company's stock is currently trading at about 20 cents per share.

Company practice

Regardless of Biopure's legal foibles, the lawsuit against Natanson has some observers worried. Such lawsuits are highly unusual, says Jann Ingmire, director of media relations at JAMA. In 2000, Immune Response of Carlsbad, California, sued authors of a paper published by the journal that presented data showing that the company's therapeutic HIV vaccine had failed in clinical trials. Immune Response said the authors refused to include additional data that the company felt was favorable towards the vaccine, but later dropped the lawsuit.

Biopure's case is unlikely to succeed, says patent litigator Steve Keane in the San Diego office of the international law firm Morrison & Foerster. If a judge were to rule in Biopure's favour with respect to the JAMA article, Keane says, "it would be an unprecedented restraint on scientific speech."

Whether or not the lawsuit succeeds, some say that it sets a dangerous precedent that could be intimidating to researchers. "It puts these individuals who publish this work in the position of having to seek legal counsel," says Steve Nissen, a cardiologist at the Cleveland Clinic in Ohio, who has authored controversial meta-analyses pointing to safety risks of the diabetes medication Avandia (rosiglitazone) and the painkiller Vioxx (rofecoxib) and says he has never been threatened with a lawsuit. "It could have an enormous chilling effect on independent scientific inquiry." 

See related Editorial.

  • References

    1. Natanson, C., Kern, S. J., Lurie, P., Banks, S. M. & Wolfe, S. M. J. Am. Med. Assoc. 299, 2304–2312 (2008).
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