The prescription of opioid analgesics represents a double-edged sword. On the one hand, opioid analgesics (e.g., morphine, oxycodone, fentanyl) have been shown to provide modest improvement in pain and function for patients with chronic non-cancer pain. On the other hand, prescription opioids may lead to opioid-induced algesia [
1,
2], addiction, or diversion, particularly at high doses (e.g., ≥ 200 mg morphine equivalents/day) [
3]. As such, prescription opioids are associated with serious and increasing public health problems, such as addiction treatment admissions and overdose death [
4].
Opioid prescribing within the context of chronic pain management
In 2011, the United States Institute of Medicine concluded that chronic pain, defined as pain that persists longer than 3 months, or beyond the expected duration of healing [
5], is a public health concern and should be treated as a disease itself [
6]. While estimates vary depending on survey methodology, nationally representative data from Canada, the USA, Germany, and other European countries indicates that 20 to 30% of adults (≥ 18 years of age) suffer with chronic non-cancer pain [
7‐
11]. The prevalence of chronic pain is higher among women [
12] and ethnic minorities [
13] and increases with age. Approximately 65% of community-dwelling seniors and 80% of older adults living in care facilities experience chronic pain, including cancer-related pain [
14].
The goal of pain management is to decrease pain and improve function while monitoring for adverse effects [
15]. In the late 1980s and early 1990s, the under-treatment of pain, including among patients with chronic non-cancer pain, garnered national attention in both the USA and Canada. A classic 1986 publication describing the treatment of chronic pain in 38 patients concluded that opioid pain relievers could be prescribed safely on a long-term basis [
16]. Further, a letter to the editor of the New England Journal of Medicine asserted that the rate of addiction in patients receiving opioids was low [
17]. This letter was heavily and uncritically cited as evidence that addiction was rare with long-term opioid therapy, many citing rates ≤ 1% [
18]. Despite low-quality evidence, these sources were widely cited to support the expanded use of opioid medication for the management of chronic pain [
4]. By the late 1990s, healthcare providers (HCPs) were encouraged by pharmaceutical companies and medical boards to be more proactive in treating all types of pain (e.g., acute, palliative, chronic) to alleviate suffering, including the prescription of opioid analgesics at relatively high doses for long durations [
19]. The potential adverse effects of long-term opioid use were under-appreciated and often based on beliefs that opioids were safe for extended use in patients with chronic pain with no known dosing threshold. Opioid prescribing increased in a marked linear fashion until 2013 when it began to plateau in the USA [
20] and Canada [
21].
Trends in opioid prescribing morbidity and mortality
The past two decades have been characterized by a linear increase in the prescription of opioid medications. A twofold increase in the consumption of hydrocodone and fivefold increase in the use of oxycodone was observed in the USA between 1999 and 2011 [
22]. Observational data show a mean increase from 180 mg morphine equivalents per person in the US population per year in 1997 to 710 mg per person per year in 2010 [
23]. This corresponded with a fourfold increase in the sale of prescription opioids [
23], a fivefold increase in drug treatment admissions for prescription opioids (from ~ 20,000 to ~ 120,000) [
24], more than a twofold increase in emergency department visits related to pharmaceutical opioids [
25], and a fourfold increase in opioid-related overdose [
26]. Although there is an undeniable rise in the availability of illicit opioids [
27,
28], it has also been argued that opioid-related mortality is directly associated with the increase in opioid prescriptions observed in Canada, the USA, Europe, the UK, Spain, France, and Australia [
21,
29‐
31]. Beyond the direct association, prescriber adjustment and tapering of opioid analgesics have been associated with risk of nonmedical use, morbidity, and mortality as individuals turn to illicit opioids in an attempt to manage their pain [
32].
A systematic review of data from the USA and Canada identified three interacting factors associated with opioid-related mortality: (1) prescriber behaviors, (2) patient characteristics, and (3) systemic determinants [
33]. Pertinent for this protocol, four ways that prescriber behaviors influence opioid-related mortality were elucidated. First, results from seven studies indicated that prescribing higher doses of opioids is associated with opioid-related mortality. Second, seven studies reported an association between more potent opioids, such as fentanyl, and opioid-related mortality. Third, 14 studies reported that the co-prescription of opioids with sedatives or more than one opioid was associated with the observed increase in opioid-related mortality. This was particularly relevant with the co-prescription of methadone which has a small window between therapeutic and fatal doses. Finally, eight studies reported that an increase in the number of opioid prescriptions played a role in opioid mortality through increased availability. The top quintile of prescribers was observed to issue opioid prescriptions 4.5 times more frequently than the next quintile and wrote the final prescription in 63% of opioid-related deaths [
34].
Clinical practice guidelines for the prescription of opioid medication
Clinical practice guidelines (CPGs) have been developed by several countries, including the USA [
35] and Canada [
2], to support evidence-based prescription of opioid medication for the management of chronic non-cancer pain. A systematic review of opioid prescribing CPGs identified 13 guidelines reporting on recommendations for the prescription of opioids for chronic pain between 2007 and 2013 [
36]. While there is between-guideline variability, clinical practice guidelines consistently recommend that HCPs (1) avoid doses ≥ 90–200 mg per day, (2) acquire additional training prior to prescribing methadone, (3) recognize risk of fentanyl patches, (4) titrate cautiously, and (5) reduce doses by at least 25 to 50% when switching opioid [
36]. Based on expert consensus rather than rigorous supporting evidence, CPGs also regularly support the use of risk assessment tools, written treatment agreements, and urine drug tests to mitigate risks.
Clinical inertia in the context of prescribing opioids for chronic pain management
Despite their widespread availability and strong evidence supporting the benefits of their use [
37‐
39], there is a long history of poor uptake of CPGs for chronic disease management by HCPs, with many studies reporting rates of non-adherence at or exceeding 50% [
40‐
42]. HCP non-adherence to CPGs is increasingly referred to as “clinical inertia” [
43]. Practically speaking, clinical inertia refers to a HCP’s decision not to initiate, intensify, titrate, or stop treatment despite an indication and recognition of the need to do so. Clinical inertia has most commonly been studied within the context of managing chronic diseases, such as diabetes, cardiovascular disease, hypertension, and dyslipidemia. Within this area, it has been estimated that clinical inertia is responsible for up to 80% of myocardial infarctions and strokes within the context of sub-optimally treated hypertension, diabetes, and dyslipidemia [
44].
Our team recently published a review of clinical inertia in the context of chronic disease management where we elucidated the factors associated with this behavior [
45]. In brief, clinical inertia is influenced by HCP factors (e.g., knowledge, agreement with guidelines, cognitive biases, motivation), patient factors (e.g., sociodemographics, medical history, lifestyle factors, treatment adherence), and system factors (e.g., time constraints, resources, setting) [
45]. System- and patient-level interventions are often mistakenly perceived as being more important or resulting in greater benefit than HCP-level interventions. This protocol will focus on HCP-related factors given that HCP influences (1) account for 50% of variability in clinical inertia [
44], (2) are less well understood than system- and patient-factors, (3) often require more sophisticated behavioral corrective interventions, (4) are particularly relevant given the difficult balance between under-prescribing within the context of pain management and over-prescribing within the context of aberrant use, and (5) partially address a priority identified by patients and clinicians who have taken part in a national chronic pain research priority setting process [
46].
It is difficult to estimate the impact of clinical inertia on pain, opioid-related morbidity, and mortality because of the relative paucity of available data. Consistent with other chronic diseases, the available evidence suggests that HCP adherence to opioid prescribing guidelines is less than optimal [
47]. For example, a survey of more than 200 physicians in Wisconsin reported that only 38% were aware of at least one clinical practice guideline for prescribing opioids in the management of chronic pain [
48]. Similarly, an assessment of HCP behavior in a sample of 1300 physicians and residents in Massachusetts reported only partial compliance with national opioid prescribing guidelines (e.g., 43% had a controlled substance agreement, 34% provided > 2 early refills, 63% utilized urine drug tests) [
49].
There are many reasons why HCPs deviate from CPGs. One obvious reason is insufficient knowledge. Many HCPs are unaware that evidence of long-term effectiveness for opioids is lacking [
4] or that risks include hyperalgesia [
50], androgen deficiency [
51], and serious fractures from falls [
52]. A study of more than 700 family physicians in Canada reported that only 40% of physicians correctly answered two of nine questions pertaining to knowledge of opioid prescribing [
53]. Inadequate training and a consequent lack of self-efficacy (i.e., a belief in one’s own ability to personally affect change) are other reasons. More than 70% of 636 family physicians in the province of Quebec surveyed did not feel confident that they could properly prescribe opioids for chronic non-cancer pain, despite 75% of the sample having received continuing education on the topic within the previous year [
54]. A similar study observed that 54% of primary care providers surveyed in Massachusetts did not feel sufficiently trained to prescribe opioids [
55]. Large volume and inaccessibility of guidelines also contribute to HCP deviation from CPGs. A qualitative study of 12 pain physicians in Ontario identified excessive length and poor formatting as a deterrent to the implementation of the 2010 CPGs for the safe and effective use of opioids for chronic non-cancer pain [
56]. An additional reason is fear; nearly 50% of 226 physicians surveyed in Wisconsin reported altering opioid prescribing practices (e.g., limiting refills, lowering dose, reducing prescribed quantity) due to fear of investigation by regulatory agencies [
48]. This is also problematic as it may lead to under-treatment of pain or use of an inappropriate opioid tapering schedule contributing to unnecessary suffering, such as aggressive tapering.
In summary, it is safe to assume that adherence to the current guidelines for the prescription of opioid medication for the management of chronic non-cancer pain will make no exception to the general observation that adherence to recommendations detailed in CPG is suboptimal, and would therefore benefit from interventions to improve adherence.