More opioid marketing to doctors was linked to an increase in opioid overdoses, according to a new study.

The research, published in JAMA on Friday, compared county-level data of marketing interactions doctors had related to opioids and the number of opioid overdose deaths. While the findings don’t mean that marketing opioids to HCPs explicitly caused an increase in deaths, the researchers found an association between the two data sets.

Researchers used three measures of opioid marketing: number of payments to doctors, marketing value in dollars, and number of physicians receiving marketing. The analysis found all three measures were significantly associated with increased opioid overdose deaths.

The mediating factor between marketing and overdose deaths is that more prescriptions are written when doctors receive more marketing, a finding that has been widely supported by previous research.

This study went a step further, said lead author Dr. Scott Hadland, a pediatrician and addiction medicine specialist at Boston Medical Center and Boston University School of Medicine, by linking the data beyond prescriptions to the overdose deaths themselves.

“We went into the work hypothesizing this would be the case,” Hadland said. “We suspected there would be a link. The thing that surprised us was the total dollar value of marketing was less important than the number of times a company interacted with the doctor.”

While large payments to doctors have been criticized, Hadland added that the smaller, but more frequent, marketing interactions had a larger effect on prescribing rates, based on these findings.

The researchers found opioid marketing dollars were highly concentrated in counties where there was a lower percentage of people younger than 65 and where race and ethnicity composition was mixed. Marketing payments were concentrated in counties with a higher prevalence of high school completion, greater unemployment, lower poverty, a higher median household income, lower income inequality, and metropolitan location. In the U.S., the Northeast was the region with highest concentration of opioid marketing, while the Midwest had the lowest.

Researchers noted that some of the association could be caused by reverse causality, where counties with high opioid-prescribing rates that were already experiencing more overdose deaths, were subsequently targeted by pharmaceutical company marketing.

The study used drug marketing data from the Centers for Medicare and Medicaid Services public open payments database and matched it with data from the Centers for Disease Control and Prevention’s data on opioid prescribing and overdose deaths.

Researchers used marketing data from August 2013 to December 2015 and prescribing and overdose data from August 2014 to December 2016. They included a one-year lag in the two data sets to ensure that the marketing dollars preceded the overdose deaths.

Dr. James Yeh, who has also conducted research on the effect of pharma marketing, said the results are consistent with other research on the issue that found that more marketing has led to more prescriptions. Yeh was not affiliated with this study.

“This is especially important as spending on pharmaceutical marketing has increased significantly in the past decade and more recently the focus on marketing by Purdue Pharma,” Yeh said, in an email. “The bigger questions to consider are: Is there a role for pharma based marketing to ‘educate’ physicians? There are objective alternatives such as academic detailing for physicians to be educated and learn about these drugs.”

The study suggests continued opioid marketing may be counteracting efforts to curb opioid prescribing. Hadland said that pharma companies, health systems, or lawmakers could work to limit the amount of marketing done for opioid products as another way to address the opioid crisis.

In 2017, more than 49,000 people died from opioid overdoses, including prescription opioids and synthetic opioids like fentanyl, according to the National Institutes of Health. Some opioid drugmakers have already ended the practice. Last February, Purdue Pharma, the maker of OxyContin, stopped marketing the drug to doctors.

“In the face of a national crisis, all options need to be on the table,” Hadland said. “Based on our study, there is a link between these marketing practices and overdose deaths. It’s important that we consider, at least for opioid products, whether there should be restrictions on marketing.”