WASHINGTON — Amid a worsening opioid epidemic, the overdose-reversal drug naloxone has taken center stage. Fire and police departments across the country stock the drug; nonprofits aim to get it into the hands of millions of residents as a bystander intervention.

But a controversial new working paper has raised the question of whether the urgent push to expand naloxone access may be doing more harm than good.

The paper, published online last week, aimed to estimate the changes in behavior resulting from expanded naloxone access. Researchers found that after states passed naloxone access laws, opioid-related emergency room visits and opioid-related theft both rose, and no decrease was observed in opioid-related mortality. Their most troubling results came in the Midwest, where the researchers measured a 14 percent increase in opioid-related mortality attributable to expanded naloxone access.

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That, co-authors Jennifer Doleac and Anita Mukherjee said, illustrates that by reducing the likelihood of the worst outcome of opioid use — death — greater access to naloxone reduces disincentives for risky behavior.

At a time when naloxone access is viewed as an unambiguous benefit, the new paper elicited strong reactions.

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Specifically, many in life sciences and public health spheres, less accustomed to the publication of working papers that have not yet been peer-reviewed, were troubled by the moral implications of publishing research making such impactful claims.

“We expected some pushback from the public health community,” said Doleac. “We know that economists think differently about some issues than people in other disciplines. But the response has been a lot more hostile than I’d expected.”

The paper, titled “The Moral Hazard of Lifesaving Innovations,” contradicts previous research that has found expansion of naloxone access to have no effect on risky behavior. For instance, a recent National Institutes of Health study of two groups of heroin users found no increase in high-risk behavior resulted from increased naloxone access. And an economics paper from last year found that naloxone access laws typically resulted in a reduction in opioid-related deaths of between 9 and 11 percent.

Examining methodology

“I think what’s important for us to take into account is that this is not science in medical best practice,” said Dr. Leana Wen, Baltimore’s health commissioner, who issued a citywide prescription to any individual wishing to purchase naloxone last year and has been a vocal advocate for addiction response.

“The last thing that we need in the middle of an opioid epidemic is for information to come out that further stigmatizes addiction and can cost lives,” Wen said.“I think we have a duty to a higher burden of proof.”

Though the practice of publishing working papers is common in economics, the authors also plan to submit the paper for peer review.

“We took unusually long to post the working paper because we knew it would be so sensitive and [so that] we knew we got it right,” Doleac said. “Before we posted, we got a lot of feedback from people who are expert in this field. It seems like a lot of people are responding as if Anita and I whipped this up over the weekend. We’ve been working on this for two years.”

Wen also criticized the study for what she characterized as misleading methodology. For instance, authors used opioid-related emergency room visits to gauge population-level addiction trends, which Wen said is flawed partly because such visits could also rise in response to better public health campaigns informing drug users of how to seek treatment. And the study looked at a varied set of laws that Wen said likely had disparate impacts on actual naloxone access — making it difficult to draw sweeping conclusions.

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Plus, public health experts said, the need for naloxone has become more pronounced even in the two years the authors worked on the study, as the prevalence of fentanyl has led to more overdoses that are also more difficult to reverse.

“Given the substantial change in the riskiness of the drug supply, I think the overdose death numbers would have been been substantially higher had we not deployed naloxone to the extent we did,” said Chris Jones, the director of the National Mental Health and Substance Use Policy Laboratory.

Drug makers’ influence

The movement to make naloxone more widely available is moving quickly — so much so that the issue has become subject to the same influence-peddling that characterizes most health policy issues in Washington.

Kaleo, the manufacturer of Evzio, a popular injectable form of naloxone, disclosed $260,000 in lobbying on naloxone access in 2017. Adapt, the maker of the nasally administered Narcan, reported spending $300,000.

In an interim report, an opioid crisis commission empaneled by President Trump recommended the health secretary negotiate a reduced naloxone price for government entities — a strategy the Department of Health and Human Services has yet to indicate it will pursue.

In the meantime, manufacturers have worked to maintain their reputation as good actors, particularly after Kaleo drew criticism for hiking the price of a single device to $4,500. The company announced last summer that it had donated 250,000 units of its auto-injector to communities in the last two years.

But the authors of the latest study say that the wider effects of naloxone’s penetration deserve further examination.

“This is something we wrestled with, because neither of us think it would be better if we saved fewer lives,” Doleac said. “I think we tried very hard not to draw that conclusion. But broadening naloxone access as the policies are currently being implemented is not helping and in some places making it worse. To us, the takeaway is not to restrict access to naloxone — it’s that we need to make sure we are doing other things that address the root cause of the crisis.”