We now have more proof that drug companies helped cause America’s opioid epidemic, which was associated with a record 47,600 opioid overdose deaths in 2017: A new study linked drug companies’ marketing for opioid painkillers to more overdose deaths.

Drug companies have for years spent billions of dollars to market their products to doctors, wooing physicians and other prescribers with speaking fees, free dinners, paid trips, and more. When pharmaceutical companies marketed their new opioid pills, like OxyContin, starting in the 1990s, they used many of these same tactics to convince doctors, contrary to the evidence, that the narcotics were safe and effective, persuading them to prescribe far more of the drugs.

The new study in JAMA Network Open looked at the potential link between marketing for opioids to doctors across the US and county-level opioid painkiller overdose deaths. The researchers found that where there was more marketing, there were more deaths.

The study, by researchers from Boston University, UC Davis, New York University, and Brown University, looked at more than 430,000 marketing payments, totaling $39.7 million, to nearly 68,000 doctors across the US between August 2013 and December 2015. They then looked at county-level data to see whether the payments had an effect on painkiller overdose death rates one year later. If the marketing led to more opioid prescriptions, and more opioid prescriptions led to more misuse, addiction, and overdoses, then you could expect to see painkiller overdose deaths rise in places that got more marketing.

That’s exactly what researchers found: The counties that got more marketing the year before saw more painkiller prescriptions and more overdose deaths.

“[T]he United States continues to vastly exceed the rest of the developed world in opioid prescribing, and many individuals with opioid use disorder are first introduced to opioids through a prescription,” the researchers wrote. “Our findings suggest that direct-to-physician opioid marketing may counter current national efforts to reduce the number of opioids prescribed and that policymakers might consider limits on these activities as part of a robust, evidence-based response to the opioid overdose epidemic in the United States.”

The cost of the marketing didn’t seem to have as much of an impact as the number of marketing interactions, suggesting that it’s not so much the financial impact as it is the marketer-to-doctor contact that has a significant effect on prescribers’ practices. For states (like New Jersey) that are trying to limit opioid marketing, understanding this dynamic is key to enacting the most effective policies.

“As evidence mounts that industry-sponsored meals contribute to increased prescribing, data suggest that the greatest influence of pharmaceutical companies may be subtle and widespread, manifested through payments of low monetary value occurring on a very large scale,” the researchers warned.

The study had some important caveats. For one, the researchers didn’t rule out reverse causation. It’s possible, for example, that marketers went to doctors who were already prescribing more opioids, since the marketers saw those doctors as reliable targets. In that case, it may not be that the marketing led to more prescriptions and overdose deaths, but that more prescriptions led to more marketing.

Another caveat: Opioid painkillers aren’t the sole driver of overdose deaths in the US — particularly as illegal opioids, like illicit fentanyl and heroin, have taken off — though they’re still involved in 40 percent of opioid overdose deaths, according to the study. Whether and how more opioid prescriptions may lead to other kinds of opioid overdose deaths needs to be studied further, the researchers cautioned.

The study also couldn’t differentiate between deaths caused by opioid painkillers that were prescribed to the victim and those that were illicitly obtained through, say, a family member or the black market.

Still, coupled with a study published in JAMA Internal Medicine last year, the findings are certainly suggestive — exposing one of the ways that drug companies likely helped cause the deadliest drug overdose crisis in US history.

There’s other evidence that opioid marketing helped cause the overdose crisis

The opioid epidemic can be understood in three waves. In the first wave, starting in the late 1990s and early 2000s, doctors prescribed a lot of opioid painkillers. That caused the drugs to proliferate to widespread misuse and addiction — among not just patients but also friends and family of patients, teens who took the drugs from their parents’ medicine cabinets, and people who bought excess pills from the black market.

A second wave of drug overdoses took off in the 2000s when heroin flooded the illicit market, as drug dealers and traffickers took advantage of a new population of people who used opioids but either lost access to painkillers or simply sought a better, cheaper high. And in recent years, the US has seen a third wave, as fentanyls offer an even more potent, cheaper — and deadlier — alternative to heroin.

It’s the first wave, though, that really kicked off the opioid crisis — and it’s where marketing for opioid painkillers is likely most relevant. (The study, however, could only look at recent data, because similar statistics don’t exist for prior years. So we don’t know if things are getting worse or better when it comes to marketing.)

Over the past few years, we’ve seen more and more reports about opioid companies aggressively marketing their products, even as it became clearer that the drugs weren’t the safe, effective alternative to other painkillers on the market that they claimed opioids to be.

Most recently, a filing in Massachusetts Attorney General Maura Healey’s lawsuit against Purdue Pharma, the maker of OxyContin, exposed how Richard Sackler, then Purdue’s president and part of the Sackler family that owns Purdue, was personally involved in some of those efforts. The filing claims that Sackler pushed to market OxyContin as a “non-narcotic” in other countries, even though it’s an opioid; Robert Kaiko, who created OxyContin, had to talk him down from the idea.

The company also allegedly overlooked excessive prescribing in the US, even as some of Purdue’s staff warned of pill mills that should have been reported to federal officials, Maia Szalavitz reported for Tonic.

Purdue countered that the filing “is littered with biased and inaccurate characterizations of these documents and individual defendants, often highlighting potential courses of action that were ultimately rejected by the company.”

Other reports, however, suggest opioid companies were widely irresponsible. As a group of public health experts explained in the Annual Review of Public Health, opioid companies exaggerated the benefits and safety of their products, supported advocacy groups and “education” campaigns that encouraged widespread use of opioids, and lobbied lawmakers to loosen access to the drugs. Purdue, as the maker of the then-new OxyContin, played a big role in these efforts, but so did companies like Endo, Teva, and Abbott Laboratories.

The result: As opioid sales grew, so did addiction and overdoses.

It’s not just that the drugs were deadly; they also weren’t anywhere as effective as Purdue and others claimed. There’s only very weak scientific evidence that opioid painkillers can effectively treat long-term chronic pain as patients grow tolerant of opioids’ effects — but there’s plenty of evidence that prolonged use can result in very bad complications, including a higher risk of addiction, overdose, and death. In short, the risks and downsides outweigh the benefits for most pain patients.

In some cases, drug companies faced consequences for their faulty claims. In 2007, Purdue Pharma and three of its top executives paid more than $630 million in federal fines for their misleading marketing. The three executives were also criminally convicted, each sentenced to three years of probation and 400 hours of community service.

And last year, with public pressure and scrutiny mounting, Purdue announced that it would stop marketing its opioids to doctors.

But Purdue and others may soon face bigger consequences. A judge in Cleveland has consolidated lawsuits against opioid companies in an attempt to reach a big settlement agreement. The hope is that an agreement would not only restrict marketing from opioid companies but also lead to a financial settlement that would pay for addiction treatment across the US.

The latest study in JAMA Open Network suggests that those steps, particularly marketing restrictions, could help reverse the current opioid crisis — and maybe prevent future crises as well.

For more on how to combat America’s opioid painkiller problem, read Vox’s explainer.

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