The Opioid Cohort Consortium (OPICO) to investigate the effects of using opioids on cancer risk - Summary Over the past twenty years, the use of prescription opioids among the American population has reached alarming levels, with over 17% of Americans using prescription opioids annually, leading to its designation as a public health emergency. In 2020, the International Agency for Research on Cancer (IARC) classified use of opium (natural source for many opioids) as carcinogenic to humans based on evidence for causing cancers of the lung, larynx, and bladder, and possibly pancreas and esophagus. This classification raises major concerns on how using prescription opioids may relate to subsequent cancer risk, as they are closely related to opium in terms of their composition and mechanisms of action. Prior efforts to assess the link between prescription opioids and cancer in humans have been limited by the lack of studies with prospectively collected data on both opioid use and confounders such as tobacco, alcohol, and chronic health conditions. We initiated the pilot phase of the Opioid Cohort Consortium (OPICO) in 2020, to overcome the existing methodological limitations by applying highly innovative multi- disciplinary approaches to leverage and harmonize data from (1) prospective cohort studies, (2) medication dispensing records, and (3) healthcare databases across multiple countries. In this R01 project, we will extend OPICO to leverage and harmonize existing data from 19 sources across the United States, Europe, and Australia to build a unique resource with high-quality data from more than 1.7 million individuals, including over 385,000 who used prescription opioids at baseline. In addition to harmonizing data on demographics, confounders, and cancer incidence, we will use healthcare records to assess participants’ comorbidities, and will use medication dispensing records to assess participants’ use of prescription opioids at baseline and during follow-up. OPICO will first address the hypothesis that use of prescription opioids is associated with increased risk for opium-related cancers, including lung, bladder, esophageal, pancreatic, and laryngeal cancers. Analyses will assess relationships with different aspects of opioid use including their strength, duration of action, and types. We will also assess dose-response relationships and will use multiple strategies to eliminate confounding and indication bias. Furthermore, we will apply novel statistical methods to account for opioid overdose deaths and variations in using prescription opioids over time. We expect OPICO to deliver robust and conclusive evidence on the relationship between opioids and cancer, and to generate an international resource that can support future studies on opioids and their long- term health effects. These findings would have a significant impact on developing national prevention strategies and targeted early detection policies to mitigate the future burden of the current opioid crisis.
