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News — A new study led by researchers at the Johns Hopkins Bloomberg School of Public Health found that makers and marketers of prescription opioid painkillers misused scientific evidence to advance five common and inaccurate claims about the safety and effectiveness of prescription opioids—including that they were not addictive.

The researchers found that 15 key scientific articles—letters to the editor, case reports, commentaries, original research, and reviews—were cited to support these unsubstantiated claims in more than 3,600 documents in the UCSF-JHU Opioid Industry Documents Archive (OIDA), a repository of millions of documents obtained from settlements arising from litigation with opioid manufacturers. A joint project between the University of California, San Francisco and Johns Hopkins University, is modeled on a tobacco industry archive developed by UCSF. The OIDA documents are publicly available to help understand industry’s role in the opioid epidemic and prevent future public health crises.

The , published online October 24 in the journal Health Affairs Scholar, is thought to be the first to use OIDA documents to capture the industry’s misrepresentations of scientific claims about opioid safety.

The authors note that the scientific articles used in their analysis are not meant to be an exhaustive representation of all the scientific literature the opioid industry used to influence audiences and markets.

“Our findings shed light on the opioid industry’s use of scientific publications to increase opioid sales and prescriptions and to disarm criticism,” says study corresponding author , MD, an assistant professor in the Bloomberg School’s Department of Health Policy and Management and the Johns Hopkins University School of Medicine’s Division of General Internal Medicine. “Hopefully this will inform efforts to better regulate products that may harm public health in the future.”

For their qualitative study, the researchers first identified five of the most widely used unsubstantiated claims about prescription opioids from a review of published literature. These claims were:

• Opioids are effective for the treatment of chronic, non-cancer pain.
• Opioids are “rarely” addictive as long as they are prescribed by a doctor to a patient with pain.
• Patients appearing to develop addiction to prescription opioids may have “pseudoaddiction.”
• No opioid dose is too high, and if a patient develops tolerance to opioids, the solution may be to further increase the dose to treat the pain.
• Screening tools can identify high-risk patients who will develop addiction in advance.

The researchers then identified 15 key scientific articles that industry used to support these five claims. Next, the research team ran keyword searches and the titles of the scientific articles through the OIDA database and found that they were cited in 3,666 documents, including teaching or training materials, knowledge brokering materials, articles or textbooks, regulatory filings, and emails.

Overuse of prescription opioid painkillers, starting in the late 1990s, helped trigger the ongoing opioid epidemic, which has claimed hundreds of thousands of lives in the United States since 1999. Nationwide, settlements with current and former opioid manufacturers, distributors, and pharmacies have so far totaled more than $50 billion. These settlement funds are being distributed to states, localities, and tribal nations for treatment and prevention programs. The settlement funds also support OIDA.

The prescription opioid industry not only used various marketing strategies to increase sales, but also marshaled seemingly valid scientific evidence to “manufacture doubt” about opioid dangers—much as the cigarette industry once did for its products.

The analysis illuminated several key strategies in this misuse of scientific literature. One was to misleadingly imply the relevance of a medical publication by listing it in the references section of documents for regulatory approval, but without citing its findings specifically. Another was to exaggerate a publication’s findings or apply them to unrelated settings, for example using findings from a study of acute pain to support the use of opioids for chronic pain. Yet another strategy was to not fully disclose authors’ conflicts of interest.

“The authors of some of these publications were consultants for the opioid industry, yet the use of these publications often obfuscated those conflicts,” Gupta says.

The industry cited these publications to support its claims in a variety of settings, including industry-sponsored continuing medical education courses, briefings to sales representatives, and presentations to patient advocacy groups. Unfounded claims based on these scientific publications often ended up being repeated in the documents of non-industry organizations—including doctors’ associations.

The findings, Gupta says, add to evidence that better regulatory safeguards are needed for potentially addictive pharmaceuticals as well as for any commercial product that may endanger public health.

“As the OIDA documents show, the opioid industry essentially worked from a ‘playbook’ that the tobacco industry once used and that the ultra-processed food, gambling, and other industries continue to use,” Gupta says. “So this is really a broad problem, and with limited industry oversight, it’s not an easy one to solve.”

The authors note that the study has limitations. The OIDA collection does not include Purdue Pharma documents. That settlement was overturned by the U.S. Supreme Court last year, and the fate of settlement payments and litigation documents remains unclear.

“” was co-authored by Ravi Gupta, Jason Chernesky, Anna Lembke, David Michaels, Cecília Tomori, Jeremy Greene, Caleb Alexander, and Adam Koon.

Disclosures: The Opioid Industry Documents Archive is supported in part through settlements of public interest lawsuits by states. Ravi Gupta, Jason Chernesky, and Adam Koon were supported in part by these funds during the conduct of this study. Anna Lembke has served as a paid plaintiffs’ expert in opioid litigation. Caleb Alexander co-directs OIDA; has served as a paid plaintiffs’ expert in opioid litigation; is a past chair of the Food and Drug Administration’s Peripheral and Central Nervous System Advisory Committee; and is a co-founding principal and equity holder in Stage Analytics. 

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