Yet another study is out blaming prescription painkillers for an “epidemic” of overdose deaths in the United States and Canada. What sets this study apart from others, however, is that the authors openly acknowledge how weak the evidence is to support much of their research.

“Prescription painkiller overdoses have received a lot of attention in editorials and the popular press, but we wanted to find out what solid evidence is out there,” says lead author Nicholas King, a professor in the Biomedical Ethics Unit in the Faculty of Medicine at McGill University in Montreal, Quebec.

“Our review identified significant limitations in the evidence base for determinants of increased opioid-related mortality.”

King and his colleagues conducted a quantitative analysis — a study of studies — of 144 articles and reports dealing with opioid-related mortality. Of those, 47 studies were selected for further review and analysis.

“Few studies in our sample had a study design adequate for robust causal inference or tested the sensitivity of their results to methodological choices, and most studies focused on small populations or geographic areas. Researchers and decision-makers should exercise caution in drawing larger generalizations from this work,” King wrote.

Much of the evidence that researchers did find reliable has been reported before. Between 1999 and 2010, sales of prescription painkillers in the U.S. increased four-fold, while opioid consumption doubled in Canada.

During that period, mortality from overdoses of prescription opioids rose sharply in both countries, surpassing deaths from heroin and cocaine combined. In 2010, prescription opioids were blamed for 16,651 deaths in the United States, according to the Centers for Disease Control and Prevention.

But were opioids solely responsible for those deaths or were other factors involved?

“We found evidence for at least 17 different determinants of increasing opioid-related mortality, mainly, dramatically increased prescription and sales of opioids; increased use of strong, long-acting opioids like Oxycontin and methadone; combined use of opioids and other (licit and illicit) drugs and alcohol; and social and demographic factors,” said King.

“We found little evidence that Internet sales of pharmaceuticals and errors by doctors and patients — factors commonly cited in the media — have played a significant role.”

The findings point to a complicated public health problem in which physicians, users, the health care system, researchers, and the media all play a role — and sometimes add bias to the research.

One study reviewed by King and his colleagues claimed there was “evidence” that media coverage of the issue “often amounted to ‘inadvertent endorsements of prescription drug abuse,’ thus increasing the popularity of opioids.”

Several studies also speculated that media coverage led to “diagnostic suspicion bias,” causing medical examiners and coroners to screen more carefully for opioids as a cause of death, while ignoring or downplaying other causes.

“Determining exact cause of death is often difficult, particularly in cases involving methadone. Prescription data are proprietary, and data on adverse events are held privately,” King wrote.

“Identification of diversion and doctor shopping is particularly difficult because it generally relies on interviews with contacts or on proxies such as having a prescription in the preceding 30 days. Generalizing from specific studies to national trends or cross-national comparisons seems inadvisable given the population and regional variation in determinants of opioid-related mortality we found across studies.”

Although the research is not always reliable, there is no dispute that Americans and Canadians are the #1 and #2 consumers of prescription opioids in the world. Canada and the U.S. consume 99.9% of the world’s supply of hydrocodone, over 87% of oxycodone, 60% of morphine and over half of the methadone. Many of those drugs are unavailable in other countries.

And because of that, says King, the rest of the world should pay attention.

“As efforts are made to increase access to prescription opioids outside of North America, our findings might be useful in preventing other countries from following the same path as the U.S. and Canada,” he wrote.

The results of this research are published in the American Journal of Public Health, http://ajph.aphapublications.org/doi/abs/10.2105/AJPH.2014.301966