US Trends in Opioid Access Among Patients With Poor Prognosis Cancer Near the End-of-Life

PURPOSE

Heightened regulations have decreased opioid prescribing across the United States, yet little is known about trends in opioid access among patients dying of cancer.

METHODS

Among 270,632 Medicare fee-for-service decedents with poor prognosis cancers, we used part D data to examine trends from 2007 to 2017 in opioid prescription fills and opioid potency (morphine milligram equivalents per day [MMED]) near the end-of-life (EOL), defined as the 30 days before death or hospice enrollment. We used administrative claims to evaluate trends in pain-related emergency department (ED) visits near EOL.

RESULTS

Between 2007 and 2017, the proportion of decedents with poor prognosis cancers receiving ≥ 1 opioid prescription near EOL declined 15.5% (relative percent difference [RPD]), from 42.0% (95% CI, 41.4 to 42.7) to 35.5% (95% CI, 34.9 to 36.0) and the proportion receiving ≥ 1 long-acting opioid prescription declined 36.5% (RPD), from 18.1% (95% CI, 17.6 to 18.6) to 11.5% (95% CI, 11.1 to 11.9). Among decedents receiving opioids near EOL, the mean daily dose fell 24.5%, from 85.6 MMED (95% CI, 82.9 to 88.3) to 64.6 (95% CI, 62.7 to 66.6) MMED. Overall, the total amount of opioids prescribed per decedent near EOL (averaged across those who did and did not receive an opioid) fell 38.0%, from 1,075 morphine milligram equivalents per decedent (95% CI, 1,042 to 1,109) to 666 morphine milligram equivalents per decedent (95% CI, 646 to 686). Simultaneously, the proportion of patients with pain-related ED visits increased 50.8% (RPD), from 13.2% (95% CI, 12.7 to 13.6) to 19.9% (95% CI, 19.4 to 20.4). Sensitivity analyses demonstrated similar declines in opioid utilization in the 60 and 90 days before death or hospice, and suggested that trends in opioid access were not confounded by secular trends in hospice utilization.

CONCLUSION

Opioid use among patients dying of cancer has declined substantially from 2007 to 2017. Rising pain-related ED visits suggests that EOL cancer pain management may be worsening.

BACKGROUND

The United States is experiencing a crisis of opioid use disorder. Although the sources of this crisis are complex, an important contributing factor was the significant liberalization of opioid prescribing during the late 1990s and early 2000s.^1-4 In response, policymakers, health care organizations, and insurers enacted numerous regulations to curb inappropriate prescribing.^5-9 Examples include the widespread implementation of prescription drug monitoring programs (PDMPs),¹⁰ state- and insurance-mandated limits on the dose or quantity of opioid prescriptions,^7,9 and the 2016 Centers for Disease Control and Prevention guidelines on opioid use for chronic pain.⁵ As of 2017, these efforts helped achieve a 30% reduction in per capita opioid prescribing from its peak in 2010-2012.^2,4,11,12 Unfortunately, these prescribing reductions have not curbed overdose deaths, which have risen exponentially because of heroin and synthetic opioid overdoses.

CONTEXT

• Key Objective

• To identify trends in opioid utilization among patients with poor prognosis cancers near the end-of-life (EOL).

• Knowledge Generated

• Among 270,632 Medicare beneficiaries with poor prognosis cancers who died between 2007 and 2017, we observed a 34% reduction in opioid prescription fills, a 50% reduction in long-acting opioid prescription fills, and a 38% reduction in the total dose of opioids filled per decedent near the EOL. Over the same period, the proportion of decedents undergoing one or more pain-related emergency department visit near EOL increased by 50%.

• Relevance

• Among patients with terminal cancer, there have been substantial declines in opioid access and an increase in treatment of pain through the emergency department. More research is needed to determine the causes of these trends and to advocate for policies that balance the pain management needs of advanced cancer populations with broader societal concerns about opioid misuse disorder and opioid safety.

Restrictions on opioid prescribing may also have unintended consequences for patients with pain from advanced, incurable cancers.^13-15 More than three quarters of patients with advanced malignancies experience pain, with the highest symptom burdens occurring near the end-of-life (EOL).^16,17 Opioids are the cornerstone of managing moderate-to-severe cancer pain and are effective when used at appropriate doses.^18,19 Unfortunately, 30%-40% of patients with cancer pain receive analgesics that are insufficient for their pain severity.^20-24 Opioid regulations may therefore exacerbate the problem of cancer pain undertreatment.

Opioid prescribing by oncologists is falling at rates similar to generalists,^25,26 although patients with cancer are not the intended target of opioid regulations. However, it is unknown whether these trends in prescribing have translated into reduced utilization among patients dying of cancer, versus patients with early-stage cancers or cancer survivors—for whom the long-term risks of opioids are more relevant. To answer this question, we examined national trends in opioid use among Medicare beneficiaries with poor prognosis cancers near EOL and trends in pain-related emergency department (ED) visits as a potential indicator of undertreated pain.

METHODS

Data or Study Population

Using the Centers for Medicare & Medicaid Services (CMS) administrative data for a 20% random sample of beneficiaries, decedents with poor prognosis cancers were identified from January 1, 2007, through December 31, 2017—years spanning the initial recognition of the opioid crisis,^27,28 ensuing legislative reforms,^6,8 and declines in population-based opioid prescribing.⁴ We focused on decedents age ≥ 66 years who were continuously enrolled in fee-for-service Medicare Parts A, B, and D for ≥ 12 months before death. To examine those who likely died of cancer, instead of dying with cancer or a history of cancer, we identified decedents with one or more inpatient or two or more outpatient evaluation and management visits with an International Classification of Diseases Ninth Revision (ICD-9) or Tenth Revision (ICD-10) code for a poor prognosis cancer, adapted from a prior list of relevant diagnosis codes²⁹ to also include the 10 most common causes of cancer death reported by the American Cancer Society³⁰ and the National Vital Statistics System,³¹ and supplemented by ICD-9 or ICD-10 codes for highly lethal rare cancers (eg, gallbladder cancer and acute myeloid leukemia). Concurrent nonlymphatic metastatic codes were required for solid tumors frequently diagnosed at early stages (eg, breast, prostate, and colorectal). The Harvard Medical School institutional review board approved the study.

Outcomes

We identified all outpatient opioid prescriptions filled ≤ 30 days before death or hospice enrollment (for hospice enrollees), referred to hereafter as near EOL using Medicare Part D claims. The hospice period was excluded because hospice patients receive opioids within an EOL comfort pack—making it difficult to ascertain whether they are prescribed for pain or symptoms of active dying. Moreover, symptom medications are paid by the hospice benefit, not Medicare Part D. Opioid claims were identified from a comprehensive list of opioid National Drug Codes from the Centers for Disease Control and Prevention³² and supplemented by Red Book Online, excluding addiction treatments (eg, buprenorphine), cough suppressants (eg, guaifenesin-codeine), and parenteral opioids. Opioid potency was determined by multiplying the total dose of each prescription filled in the last 30 days by standard conversion factors,³² summed across all of a patient's prescriptions, and averaging to obtain a daily dose in morphine milligram equivalents per day (MMED). Given their distinct roles in cancer pain management, prescription fills were also examined separately for strong short-acting opioids (eg, immediate-release morphine, hydrocodone, oxycodone, and hydromorphone), weak short-acting opioids (eg, tramadol and codeine), and long-acting opioids (eg, extended-release morphine, methadone, and transdermal fentanyl). The average number of opioid prescriptions filled per decedent near EOL was calculated annually. Annual trends at the prescription level were also examined, including the mean days-supply and mean daily dose per prescription—calculated overall, and by medication type.

To examine potential consequences of poorly controlled pain, trends in overall and pain-related ED visits near EOL were examined. Visits were considered pain-related if a relevant ICD-9 or ICD-10 code (based upon pain diagnosis codes from the CMS OP-35 measure)³³ was present in the first four positions of the ED claim (Appendix Table A1, online only). ED visits for malignancy-associated pain (338.3 or G89.3) were examined separately as a sensitivity analysis. ED visits for nausea or vomiting were examined as a control condition, using diagnosis codes from the CMS OP-35 measure.

Patient Characteristics

The Medicare Beneficiary Summary File was used to identify age at death, documented sex, race or ethnicity (White, Black, or other), region (Northeast, South, Southwest, or West), and median household income at the ZIP code level. Prior diagnoses of 14 coexisting medical conditions possibly associated with receipt of an opioid prescription or ED utilization (using the Chronic Conditions Data Warehouse) were examined.

Statistical Analysis

Descriptive statistics characterized annual trends in the proportion of decedents filling ≥ 1 opioid prescription near EOL (overall and by opioid type), the proportion having ≥ 1 ED visit near EOL (overall, for pain and for nausea or vomiting), opioid potency among decedents filling ≥ 1 prescription, and the average total dose of opioids filled per decedent near EOL—averaged across those who did and did not fill an opioid. Bivariate linear probability models calculated absolute annual declines in EOL opioid access, using separate regression coefficients for 2007-2011 and 2012-2017 because of natural breakpoints in the data and because population-based opioid prescribing began declining in 2012.⁴ We then tested the statistical difference between these coefficients. Linear regression models examined annual trends in prescription-level outcomes including the number of opioid prescriptions filled per decedent near EOL, and the mean days-supply and mean daily dose per prescription.

We conducted multiple sensitivity analyses. First, we repeated analyses to assess opioid prescription fills in the 60 days and 90 days before death or hospice enrollment. To ensure that our main findings were not an artifact of secular trends in hospice utilization, we examined trends in EOL opioid access separately for decedents who ultimately enrolled in hospice, and those who did not. We also examined trends in opioid utilization in the 30 days before death, without censoring the hospice period. K.G. performed analyses using STATA software, version 16.1, and SAS software, version 9.4.

RESULTS

The cohort included 270,632 patients with poor prognosis cancers who died between 2007 and 2017 (Fig 1). Decedents' mean age was 77.3 (7.0) years, 51.8% were men, and 84.8% were White, 9.2% were Black, and 6.0% were of other races (Table 1). The most common cancer types were lung, colorectal, pancreatic, prostate, and breast. Overall, 166,962 patients (61.7%) enrolled on hospice before death, increasing from 57.1% in 2007 to 66.2% in 2017 (P_trend < .001). The mean hospice length of stay increased slightly from 14.9 days to 15.2 days between 2007 and 2017 (P_trend = .012). The mean days in a hospital or skilled nursing facility near EOL was 5.0 days, and stable over the study period (P_trend = .60).

FIG 1.

Flow diagram of study cohort: Medicare decedents with poor prognosis cancers (2007-2017). The study cohort was derived from administrative data from the Centers for Medicare & Medicaid Services 20% random sample of beneficiaries. Our final cohort included decedents age > 66 years with poor prognosis cancers who died between January 1, 2007, and December 31, 2017, with continuous fee-for-service Medicare part A, B, and D coverage ≥ 12 months before death. Patients living outside the United States or missing geographical data were excluded.

TABLE 1.

Patient Characteristics

Between 2007 and 2017, the proportion of patients with poor prognosis cancer filling ≥ 1 opioid prescription near EOL fell from 42.0% (95% CI, 41.4 to 42.7) to 35.5% (95% CI, 34.9 to 36.0; Fig 2A and the Data Supplement [online only])—declining faster from 2012 to 2017 (–1.1 percentage points per year; 95% CI, –1.4 to –0.9) than from 2007 to 2011 (–0.2 percentage points per year; 95% CI, –0.4 to –0.1; P < .001). The proportion filling long-acting opioids near EOL fell from 18.1% (95% CI, 17.6 to 18.6) to 11.5% (95% CI, 11.1 to 11.9)—also declining faster from 2012 to 2017 (–0.8 percentage points per year; 95% CI, –0.9 to –0.7) than from 2007 to 2011 (–0.5 percentage points per year; 95% CI, –0.6 to –0.4; P = .001). The proportion filling strong, short-acting opioids near EOL fell from 31.7% (95% CI, 31.1 to 32.3) to 28.5% (95% CI, 28.0 to 29.0)—being initially stable from 2007 to 2011 (0.3 percentage points per year; 95% CI, –0.2 to 0.9), and then declining 1.0 percentage points per year (95% CI, –1.2 to –0.8; P < .001) beginning in 2012. The proportion filling weak short-acting opioids near EOL fell from 8.4% (95% CI, 8.1 to 8.8) to 6.5% (95% CI, 6.2 to 6.8)—declining 0.6 percentage points per year between 2007 and 2011 (95% CI, –1.0 to –0.2), and then stabilizing after 2012 (0.1 percentage points per year; 95% CI, –0.0 to 0.2; P = .02).

FIG 2.

Annual trends from 2007 to 2017 in opioid prescription fills, opioid potency, and the total dose of opioids filled by decedents with poor prognosis cancers near the EOL. (A) The proportion of patients filling any opioid prescription, including weak short-acting opioids, strong short-acting opioids, and long-acting opioids in the 30 days before death or hospice enrollment. The inset shows the same data, on an enlarged y-axis. (B) The red line represents the mean total dose of opioids (in MMEs) provided to patients with poor prognosis cancers near EOL. This was calculated by summing the morphine equivalent dose of all opioid prescriptions filled by decedents near EOL in a given year, and dividing it by the number of decedents that year. The blue line represents the population mean daily opioid dose in MMED received by patients who filled ≥ 1 opioid prescription near EOL. Near EOL is defined as the last 30 days before death or hospice enrollment. EOL, end-of-life; LA, long-acting; MME, morphine milligram equivalents; MMED, morphine milligram equivalents per day; SA, short-acting.

Among patients filling ≥ 1 opioid near EOL, the population mean daily dose fell 24.5%, from 85.6 MMED (95% CI, 82.9 to 88.3) to 64.6 MMED (95% CI, 62.7 to 66.6) between 2007 and 2017 (Fig 2B, Data Supplement). Overall, the total dose of opioids filled by poor prognosis cancer decedents near EOL (averaged across those who did and did not receive an opioid) fell 38.0%, from 1,075 morphine milligram equivalents (95% CI, 1,042 to 1,109) to 666 morphine milligram equivalents (95% CI, 646 to 686) per decedent.

As shown in Figure 3A, between 2007 and 2017, the number of opioid prescriptions filled per decedent near EOL fell from 0.887 to 0.584—reflecting an annual decline of 4.1% (95% CI, –4.8 to –3.4). The number of long-acting opioid prescriptions filled per decedent fell by half, from 0.28 to 0.14—reflecting an annual decline of 6.3% (95% CI, –6.7 to –5.8; Fig 3B). The number of strong short-acting opioid prescriptions filled per decedent declined 1.3% annually (95% CI, –1.9 to –0.7) and the number of weak short-acting opioid prescriptions declined 0.5% annually (95% CI, –0.6 to –0.3). The mean daily dose per prescription fell 2.2% annually (95% CI, –2.4 to –2.0) for long-acting opioids, 1.9% annually (95% CI, –2.1 to –1.7) for strong short-acting opioids, and 7.8% annually (95% CI, –7.9 to –7.7) for weak short-acting opioids. By contrast, the mean days-supply per prescription rose modestly across all opioid types.

FIG 3.

2007-2017 changes in the number of opioid prescriptions filled per poor prognosis cancer decedent near EOL, and the mean days-supply and mean daily dose per prescription. (A) The first two columns show the distribution of 25,006 opioid prescriptions filled by 22,003 patients near the EOL in 2007; the last two columns show the distribution of 22,974 opioid prescriptions filled by 27,345 patients near the EOL in 2017. ^aThe x-axis represents the average number of opioid prescriptions filled per decedent (number of prescriptions filled by patients with poor prognosis cancers in the last 30 days, divided by the number of decedents with poor prognosis cancers in that year). (B) Blue bars represent the unadjusted annual change in rate in the number of opioid prescriptions filled per decedent; orange bars represent the unadjusted annual growth rate in the mean days-supply per prescription; gray bars represent the unadjusted annual change in rate in the mean daily dose per prescription, all calculated from 2007 to 2017. Error bars represent 95% CIs derived from linear regression models. EOL, end-of-life; ER, extended release; LA, long-acting; SA, short-acting; TD, transdermal.

Sensitivity analyses demonstrated that between 2007 and 2017, there were also meaningful declines in opioid utilization in the 60 and 90 days before death or hospice enrollment (Data Supplement). Suggesting that our main findings were not attributable to secular trends in hospice utilization, stratified analyses demonstrated declines in EOL opioid utilization among poor prognosis cancer decedents who enrolled in hospice, and those who did not (Data Supplement). Moreover, when the EOL period was defined as the 30 days before death without censoring the hospice period, declines in EOL opioid utilization were similar to our primary analyses (Data Supplement).

Rates of pain-related ED visits were explored as a potential consequence of undertreated pain. As shown in Figure 4 and the Data Supplement, between 2007 and 2017, the proportion of patients with ≥ 1 pain-related ED visit near EOL increased 50.8% (relative percent difference [RPD]), from 13.2% (95% CI, 12.7 to 13.6) to 19.9% (95% CI, 19.4 to 20.4); the proportion with ≥ 1 ED visit with a code for malignancy-associated pain doubled, from 1.2% (95% CI, 1.1 to 1.3) to 2.4% (95% CI, 2.2 to 2.5). By contrast, the proportion of patients with ≥ 1 ED visit for nausea or vomiting did not change statistically over the study period (P_trend = .168), and the proportion with any ED visit near EOL increased 16% (RPD), from 55.6% (95% CI, 54.9 to 56.2) to 64.5% (95% CI, 63.9 to 65.0).

FIG 4.

Annual trends in the proportion of patients with poor prognosis cancers receiving care in an ED near the EOL overall, and for pain. The blue line represents annual trends in the proportion of patients having ≥ 1 ED visit near EOL; the red line represents trends in the proportion of patients having ≥ 1 ED visit for pain near EOL using the CMS OP-35 definition; the green line represents trends in the proportion of patients having ≥ 1 ED visit with an International Classification of Diseases Ninth Revision or Tenth Revision code for malignancy associated pain near EOL; the purple line represents trends in the proportion of patients having ≥ 1 ED visit for nausea or vomiting near EOL using the CMS OP-35 definition. Outcomes were examined in the last 30 days before death or hospice enrollment. CMS, Centers for Medicare & Medicaid Services; ED, emergency department; EOL, end-of-life.

DISCUSSION

In this large representative cohort of Medicare decedents with poor prognosis cancers, we found that access to opioids near EOL decreased substantially between 2007 and 2017. The total amount of opioids prescribed per decedent fell by nearly 40% in relative terms. Moreover, the proportion of patients receiving any opioid near EOL decreased by 15.5% (RPD), and the proportion receiving long-acting opioids decreased by 36.5% (RPD). Declines in EOL opioid access were accompanied by a 50% (RPD) rise in pain-related ED visits, suggesting that pain management may be worsening for patients dying of cancer.

This study provides the most direct evidence to date that patients with advanced cancer have experienced reduced access to prescription opioids in the wake of the opioid crisis. Advocacy organizations have lobbied strongly to protect patients with cancer from heightened opioid regulations³⁴ based largely upon concerns of experts,¹³ non–peer-reviewed opinion surveys,^35,36 and anecdotal evidence that regulations were becoming obstacles to care.¹⁵ Two recent analyses of 2013-2017 Medicare prescriber data found that oncologists' opioid prescribing fell by approximately 21%, similar to that observed among generalists.^25,26 These studies were unable to determine whether these reductions affected patients with advanced-stage cancer, or patients with early-stage cancers or survivors—for whom a shift away from opioid analgesics might be appropriate.^26,37 Our study clarifies these findings by demonstrating that patients dying of cancer have experienced notable reductions in opioid access near EOL. Our study also demonstrates that opioid prescribing has fallen in numerous ways, including: the number of prescriptions, use of long-acting opioids, and the potency of prescriptions.

Interestingly, the trends in opioid access observed here do not entirely mirror those described in the general population. Per-capita opioid prescribing in the United States rose until 2010, and only in 2012 did it decline consistently.^4,12,38 By contrast, EOL opioid utilization among cancer decedents was slowly declining from the beginning of the study period and accelerated after 2012. These trends may point to differing factors driving opioid utilization in the general population versus patients dying of cancer. It is thought that the increase in population-based opioid prescribing in the early 2000s was driven both by the rising incidence of new opioid prescriptions and by the rising prevalence of people on chronic, long-term opioid therapy—many of whom required escalating doses over time.^4,39,40 By contrast, EOL opioid utilization is by definition time-limited and should be less affected by long-term opioid use. EOL opioid use among cancer decedents may therefore have been more sensitive to regulatory pressures and declined earlier than the general population.

The specific mechanisms for reduced EOL opioid access are less certain and likely multifactorial. State- and insurance-based opioid regulations expanded rapidly over the study period,^6-8,41,42 which may have disincentivized prescribing or prevented patients from filling prescriptions. A notable example was the expansion of electronic PDMPs that began in the early 2000s.⁴³ Electronic PDMPs have now been implemented in every state but Missouri,⁸ and have been shown to reduce prescribing of Schedule II opioids¹⁰—even among oncologists.⁴⁴ Simultaneously, Medicare Part D plans increasingly adopted opioid coverage restrictions,⁹ which reduce long-acting opioid prescribing, in particular.⁴⁵ Although coverage restrictions can usually be over-ridden by a cancer diagnosis, patients may be left without pain medication or must pay out-of-pocket while prior authorizations are processed. More recently, there has been a proliferation of state- and pharmacy-mandated limits on the duration and doses of opioid prescriptions.^7,46,47 The impact of this evolving regulatory landscape on patients with cancer requires monitoring. Nonpolicy factors may also have contributed to opioid declines. Clinicians may have become more reluctant to prescribe opioids as their risks were increasingly recognized and prescribing became more onerous.⁴⁸ Moreover, patients may have become more reluctant to accept opioids as these analgesics became increasingly stigmatized.^49,50 Further research is required to identify the main drivers of declining EOL opioid utilization and to identify practical policy solutions.

The most substantial reductions in opioid prescribing observed were for long-acting medications, particularly extended-release oxycodone and transdermal fentanyl. Long-acting opioids play a critical role in managing severe or persistent pain related to advanced malignancies because they prevent severe pain that occurs when short-acting opioids are used only on demand. Yet, long-acting opioids have long been recognized for their abuse potential⁵¹ and have therefore been more tightly regulated and more highly stigmatized than other opioids.^5,9,45 This may have led to earlier and steeper declines in prescribing of long-acting versus short-acting opioids. Strong, short-acting opioid prescribing was relatively stable during the first half of the study, and then declined modestly beginning in 2012—driven primarily by downtrends in morphine and hydrocodone use (Data Supplement). We observed a more precipitous decline in hydrocodone prescribing beginning in 2014 when the Federal Drug Enforcement Agency rescheduled it from Schedule III to the more restrictive Schedule II.⁵² The proportion of patients receiving weak short-acting opioids declined during the half of the study, and then stabilized after 2011. This early decline was largely attributable to the withdrawal of propoxyphene-containing products from the US market in response to a 2010 US Food and Drug Administration warning for cardiotoxicity.⁵³ Weak opioids hold a controversial place in cancer pain management and have been proven inferior to low-dose morphine for treating moderate cancer pain.^54,55 It is therefore problematic to observe weak opioid use persist, while prescribing of strong short-acting opioids and long-acting opioids continue to decline.

We were unable to determine whether the declines in EOL opioid prescribing directly harmed patients; however, the observed rise in pain-related ED visits raises this troubling possibility. Alternatively, these trends in pain-related ED visits could reflect secular shifts in providers' coding practices. Unfortunately, we were unable to test these hypotheses because Medicare claims do not provide a valid way to ascertain patients' pain levels. Nevertheless, it seems likely that reduced opioid access could exacerbate the problem of cancer pain undertreatment²¹ and threaten decades of progress in EOL cancer care.⁵⁶

This study has several limitations. First, it did not examine opioid use among patients receiving hospice services, although sensitivity analyses suggest that this did not bias the primary findings. Second, it could not determine whether patients used the opioid prescriptions filled; however, having opioids available is arguably just as relevant. Third, claims may not accurately characterize whether an ED visit was truly precipitated by pain and our assessment likely underestimates the true prevalence of pain among patients receiving care in the ED. Finally, the study focused on older Medicare beneficiaries and may represent a conservative estimate of the reductions in opioid access near EOL. Future studies should examine opioid access in other populations.

In summary, during the years spanning heightened opioid regulations, there have been striking reductions in opioid access among older patients dying of cancer. Future research is needed to understand the mechanisms for these declines, populations that may have been disproportionately affected (ie, racial minorities), and how opioid prescribing may have changed across other phases of cancer care and for patients with cancer with commercial or Medicaid insurance. Finally, policy solutions are needed to mitigate the burden of opioid regulations on patients with terminal cancer.

APPENDIX

TABLE A1.

ICD-9 and ICD-10 Codes Used to Identify Emergency Department Visits Related to Pain, Nausea, or Vomiting

AUTHOR CONTRIBUTIONS

Conception and design: Andrea C. Enzinger, Nancy L. Keating, David M. Cutler, Mary Beth Landrum, Alexi A. Wright

Financial support: David M. Cutler, Mary Beth Landrum

Collection and assembly of data: All authors

Data analysis and interpretation: All authors

Manuscript writing: All authors

Final approval of manuscript: All authors

Accountable for all aspects of the work: All authors

AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST

US Trends in Opioid Access Among Patients With Poor Prognosis Cancer Near the End-of-Life

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