HOW A PAPER STOKED A CRISIS

Short ‘letter’ cited over 600 times in opioid research

The article is a single paragraph long, five sentences and 100 words, the bylines and pair of footnotes taking up almost as much space as the paper itself.

But there is new evidence that the curt research “letter” published in 1980 in one of the world’s most prominent medical journals has played a remarkable role in stoking North America’s deadly prescription-opioid crisis.

The blurb in the New England Journal of Medicine stated unambiguously that patients hardly ever become addicted to narcotic painkillers.

And it has been cited in other journal papers — usually positively — more than 600 times since it was published, a new Canadian study documents.

That would be highly unusual for a full-blown research paper and “unthinkable” for a letter, say the authors from Toronto’s Institute for Clinical Evaluative Sciences.

They found the citations peaked in the late 1990s and early 2000s, as the drug OxyContin was rolled out and specialists — often funded by opioid manufacturers — widely promoted the notion that narcotic painkillers were a safe, effective option for people with chronic, noncancer pain.

Such drugs had previously been reserved mainly for terminal cancer patients.

“It was critical to the genesis and propagation of the crisis,” said Dr. David Juurlink, lead author of the new study and a clinical toxicologist at Sunnybrook Health Sciences Centre. “The key thing about this paper … is that it was leveraged to destigmatize opioid use.”

Indeed, Canadians’ consumption of the medicines took off, making this country second only to the U.S. in per-capita ingestion of narcotics.

At the same time, addiction and overdose deaths have reached epidemic proportions, and what started as a medical phenomenon is now a thriving street practice, too.

“It really is a very powerful illustration of what I think is the greatest scandal in modern medical history,” Dr. Mel Kahan, an addictions expert at Toronto’s Women’s College Hospital, said about the new study. “This is a lesson. Thousands of people have died as a result of doctors’ prescriptions.”

Dr. Jeffrey Drazen, editor of the New England Journal, said the letter’s conclusions may have been somewhat overstated, but argued the main problem was how it was misinterpreted by others over the years.

Its posting on the journal website will now include a notice about that misuse and a link to the Juurlink article, he said in an interview.

But, Drazen added, “it’s impossible to know what role this has had in the opioid epidemic. It’s a very multi-faceted thing.”

The 1980 article by Dr. Herschel Jick and a colleague at the Boston University Medical Center, called “Addiction rare in patients treated with narcotics,” examined 11,882 patients with no history of drug-dependency who received at least one narcotic while in hospital. They found only four cases of addiction.

Yet the letter contained no information about the methodology used and measured addiction only by looking at hospital records, not assessing each patient carefully, noted Juurlink.

And then the paper was invoked in articles and talks as evidence for giving opioids long-term to patients with chronic pain — not just a few doses while in hospital, he said.

Jick himself later acknowledged that disconnect.

“If you read it carefully, it does not speak to the level of addiction in outpatients who take these drugs for chronic pain,” he told journalist Sam Quinones, author of a 2015 book on the opioid crisis.

The Canadian study found the paper was cited 608 times — 60-fold more often than other letters published the same year in the New England Journal of Medicine.

And in more than 70 per cent of cases, it was mentioned as affirmation that addiction was rare in patients taking opioids.

Such upbeat citations have dropped off lately. But just last year, a Korean study referenced the letter in touting use of the powerful opioid fentanyl for chronic pain.

The article was also cited by a 1995 editorial in the journal Canadian Family Physician — distributed to most family doctors in the country.

The journal found the one-paragraph study’s conclusions “persuasive,” and evidence that patients can take opioids over the long term without getting addicted.

Better research has since suggested that 5-10 per cent of people prescribed opioid painkillers for chronic pain get addicted, a “staggering” number given the millions taking them, said Juurlink.