Pharma company demands retraction, damages in lawsuit against journal

A drug company that manufactures a painkiller used for surgery patients has sued an anesthesiology journal along with its editor and publisher and the authors of articles that it says denigrated its product unfairly.

In a complaint filed yesterday in U.S. District Court in New Jersey, Pacira Biosciences claims that “In the February 2021 issue of Anesthesiology, the ASA, reflecting a bias against EXPAREL amongst the editorial staff at Anesthesiology, published three articles, and other related content, that seriously disparage Pacira’s product EXPAREL,” an FDA-approved drug which they say is “a non-opioid pain medication proven to prolong post-surgery pain relief.” 

In seeking retractions, compensatory and punitive damages exceeding $75,000 — the threshold for U.S. federal court — and lawyers’ fees, the company’s attorneys at Latham & Watkins write:

The challenged journal articles, as well as the related podcast and Continuing Medical Education (“CME”) content on the ASA’s website, contain false and misleading conclusions, based on faulty scientific research that does not satisfy applicable standards within the scientific community. These conclusions create the false impression that EXPAREL—a drug approved by the FDA and used by over eight million patients over the past nine years—is not an effective pain medication. As a result, Pacira has suffered and will continue to suffer significant pecuniary harm as both existing and potential customers who have seen the disparaging articles, have either canceled contracts for EXPAREL, declined to purchase EXPAREL, or are considering removing EXPAREL from hospital formularies. 

The articles, which Pacira is demanding that the journal remove, and related content are:

• Perineural Liposomal Bupivacaine Is Not Superior to Nonliposomal Bupivacaine for Peripheral Nerve Block Analgesia: A Systematic Review and Meta-analysis
• Clinical Effectiveness of EXPAREL Administered by Infiltration or Peripheral Nerve Block to Treat Postoperative Pain: A Narrative Review
• Liposomal Bupivacaine: Effective, Cost-effective, or (Just) Costly
• The February 2021 Anesthesiology podcast and accompanying podcast transcript
• The February 2021 Continuing Medical Education (“CME”) quiz questions related to the February 2021 issue of Anesthesiology

Pacira argues in its suit that the authors of the papers “knew or recklessly disregarded the fact that [their] statements about EXPAREL were false or misleading,” and that some of them failed to disclose ties to a competitor.

The company also claims that Duke University’s Evan Kharasch, the editor in chief of the journal, “appears to have a significant bias against EXPAREL, in favor of opioids for treatment of pain.” They write:

On information and belief, Kharasch has also used his position as Editor-in-Chief to suppress information favorable to EXPAREL, in order to further his pro-opioid agenda. Pacira understands that Anesthesiology rejected publication of a letter to the editor that reported favorable experience with EXPAREL, and which expressed concern about the over-generalizations contained in the metaanalysis published in the February 2021 issue. 

Kharasch, who is a named defendant in the suit, said he could not comment on pending litigation. Nor would named defendant James Eisenach, a co-author of the meta-analysis and a former editor-in-chief of Anesthesiology. (Eisenach told us he learned about the lawsuit from our inquiry.)

The suit’s critiques get into the weeds, for example in describing one of the articles:

The authors also employ a flawed method known as “crude pooling” rather than the methodologically correct approach known as “stratified pooling.” Crude pooling can lead to inaccurate and misleading results that do not reflect trial outcomes. For this reason, this methodology is widely recognized as an incorrect method.

Exparel has come under scrutiny before, for its relatively high price compared to an older version of a related drug. And Pacira has sued the U.S. FDA over a warning letter that the agency issued about the way the company marketed the drug.

We asked two leading anesthesiologists for their takes on the suit, and got widely divergent responses. Steven Shafer, professor of anesthesiology at Stanford, and the former top editor of Anesthesia & Analgesia, told us that “the suit is without basis.” Shafer, who is a member of our parent nonprofit’s board of directors and noted that he is “an investor and advisor to Concentric Analgesics, which is developing an injectable long-acting analgesic that is a potential competitor to Pacira,, went on:

Pacira has a history of manipulating the reporting of its studies, as documented for the PILLAR study (see attached PILLAR study, the initial publication of the study design, my letter to the editor, and the non-response from the authors). The alteration of the analysis plan described in the attached letter to the editor demonstrates a lack of transparency and willingness to manipulate the study design to achieve a commercially desirable result.

Pacira performed multiple studies comparing Exparel to plain bupivacaine for FDA approval. Those studies failed to consistently demonstrate a benefit of Exparel over plain bupivacaine. Where did Pacira publish their multiple randomized controlled studies for FDA approval that failed to demonstrate a benefit of Exparel over plain bupivacaine? It appears to me that following FDA approval Pacira chose to only publish and promote their randomized controlled studies that showed a benefit over placebo, and did not publish the efficacy results of their studies that failed to show benefit over plain bupivacaine. If that is the case, how can Pacira claim to objectively represent the evidence that their product is superior to plain bupivacaine?

But Admir Hadzic, a prominent anesthesiologist who has practiced in the United States and Europe, has studied and used Exparel clinically, called the case “fascinating,” and said that it has: 

potentially significant ramifications for journals/publishers/researchers and industry alike. I think  [Pacira] are asking legitimate questions.

Hadzic, who is familiar with the literature on the drug, said that the meta-analysis did not include all positive peer-reviewed studies, while including some non-peer reviewed negative trials. He also objected to the 

repetitive implication in the articles that the company-funded research is by-definition ethically tainted. There are no grounds by which industry-sponsored studies should be labeled biased if they were peer-reviewed and published. That would mean that the studies of the Covid-19 vaccines, most of which were done timely only thanks to the industry [funding] could also be biased and/or unethical.  

Hadzic, the author of several textbooks on regional anesthesia, acknowledged the risks to publishers, journals and researchers should Pacira win its libel suit. But he argued that academia and industry have been in an unhealthy “tension” for some time and that the case could be seen as a “call for balance.”  

Although companies have certainly sought retraction of critical articles before, it is unclear how often companies sue, or threaten to, for that reason. Readers may recall cases involving Betty Dong and Nancy Olivieri. Richard Smith, former editor in chief of The BMJ and a member of our parent nonprofit’s board of directors, told Retraction Watch:

Libel is a poor way to settle scientific disputes. It is an expensive, time-consuming process where victory may not be determined by what is “true” but by who has the deepest pockets and the best lawyers. Scientific disputes are best conducted through debate, not least in the correspondence columns of journals.

He continued:

I received many threats of actions for libel as editor of the BMJ and after I left. We had the experience and insurance policy to resist them, but many smaller journals have neither. Many of the threats to the journal and me came from R K Chandra, a scientist whose extensive fraud is now well established. He used the threat of libel to stop his university taking action despite an internal investigation establishing his fraud. But a libel action he took against the Canadian Broadcasting Corporation proved his undoing when the case laid bare his fraud.

The BMJ was involved in one of the longest libel cases in British legal history in the 60s. It ran in court for weeks, generated huge bills for both the plaintiff and the journal, and was eventually settled out of court. In retrospect the plaintiff was trying to defend a process–giving general anaesthetics in dentists’ offices–that was abandoned as unsafe soon after the case.

Resorting to libel action is a high-risk expensive action–and is almost always inadvisable.

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