LAUSR

Pain is one of the most common symptoms of cancer and is often thought to be the most feared by patients with advanced disease. Cancer pain management, an often neglected component of oncological care, has been closely linked with the development of the modern hospice movement, with its focus on research and education, and the parallel development of palliative care. Dame Cicely Saunders, while volunteering at a London hospice in the middle of the 20th century, observed that the administration of regular morphine to patients with cancer resulted in improved pain control. Contemporaneously, the United Nations Single Convention on Narcotic Drugs was adopted in 1961 with the aim of ensuring access to “narcotics” for medical and scientific purposes while reducing the risk of their misuse and diversion. Cancer pain, especially in those with advanced disease, who, to this day, make up the majority of global patients with cancer, was deemed to be an appropriate medical indication. However, much of the global focus was on the war against drugs and not on improving access for medical purposes, and this resulted in poor management of cancer pain. In the 1970s, the World Health Organization (WHO) Cancer Unit placed increasing focus on cancer pain relief, and in 1986, it established the WHO pain ladder together with recommendations for the provision of palliative care. Despite these recommendations, a significant increase in opioid prescribing was not seen, even in high-income countries. Multiple barriers to the medical use of opioids were documented within patient, clinician, and regulatory populations primarily in the United States, but they were also confirmed in other places throughout the world. In association with these barriers, Cleeland et al with the Eastern Cooperative Oncology Group documented that at least 40% of patients with advanced cancer were undertreated for cancer-associated pain at major US cancer centers, with older, minority women less likely to receive appropriate care. This undertreatment was further seen with the spread of HIV/AIDS in the United States, which highlighted another population of patients needing aggressive palliative care. These individuals were an initial and important focus of the use of opioids for pain other than that caused by cancer, especially where there had been previous use of illicit opioids by many US patients with HIV/AIDS. Balance in opioid prescribing, based on both the intent and language of the Single Convention on Narcotic Drugs, led to the production and adaption of the WHO document Narcotic and Psychotropic Drugs: Achieving Balance in National Opioids Control Policy: Guidelines for Assessment in 2000. In the early 2000s, the US Drug Enforcement Agency, the Federation of State Licensing Boards, and the US Association of Attorney Generals worked to improve access to opioids and ensure balanced regulations for those for whom the prescription of opioids was deemed to be appropriate medical care. The consumption of opioids began to rise in the United States and other high-income countries as commercial products were produced and their prescription, no doubt encouraged by pharmaceutical industry marketing, spread beyond the cancer and HIV populations. In association with their increased availability, in the United States, there was a major and steady rise in the misuse and diversion of opioids with a significant increase in deaths associated with opioids, especially when they were taken with alcohol and/or benzodiazepines. The misuse and diversion were initially for prescribed opioids (but most commonly not by the patients for whom they were prescribed), and over time, this was followed by a surge in cheap illicit heroin imported from Mexico and now increasingly in illicit fentanyl and its analogues imported from China. There are multiple factors involved in the increased consumption of opioids in the United States and the associated increase in adverse events, including opioid-associated deaths: the prescribing of excessive quantities of opioids for the management of acute pain; the inadequate disposal of these medicines; the use, often regulated by insurance, of opioids for which physicians have had little training (eg, methadone); the increased use of opioids for noncancer and non–palliative care populations, which is often encouraged by inaccurate and fraudulent marketing by pharmaceutical companies (as determined by the Food and Drug Administration); fraudulent prescribing by physicians, including those at pill mills