Intrathecal Drug Delivery Systems for Cancer Pain: A Health Technology Assessment.

Background: Pain is a common and very distressing symptom for adults and children with cancer. Compared with other routes of delivery, infusing pain medication directly into the intrathecal space around the spinal cord may reduce the incidence of systemic side effects and allow for more rapid and effective pain relief. We conducted a health technology assessment of intrathecal drug delivery systems (IDDSs) for adults and children with cancer pain, which included an evaluation of effectiveness, safety, cost-effectiveness, the budget impact of publicly funding IDDSs, patient preferences and values, and ethical considerations. Methods: We performed a systematic literature search of the clinical evidence to retrieve systematic reviews, and we selected and reported results from 2 recent reviews that were relevant to our research questions. We complemented the chosen systematic reviews with a literature search to identify primary studies published after December 2020. We used the Risk of Bias in Systematic Reviews (ROBIS) tool to assess the risk of bias of each included systematic review. We assessed the quality of the body of evidence according to the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) Working Group criteria. We performed a systematic economic literature search and conducted a cost-effectiveness analysis comparing IDDSs with standard care (i.e., non-IDDS methods of pain management) from a public payer perspective. We also analyzed the budget impact of publicly funding IDDSs in Ontario. To contextualize the potential value of IDDSs, we spoke with patients with cancer pain and with caregivers of patients with cancer pain. We explored ethical considerations from a review of published literature on the use of IDDSs for the management of cancer pain in adults and children as well as a review of the other components of this health technology assessment to identify ethical considerations relevant to the Ontario context. Results: We included 2 systematic reviews (1 on adults and 1 on children) in the clinical evidence review. In adults with cancer pain who have a life expectancy greater than 6 months, intrathecal drug delivery was associated with a significant reduction in pain intensity compared with before implantation up to a 1-year follow-up (GRADE: Moderate to Low). Improved pain management appeared to be maintained beyond a 4-week follow-up. IDDSs likely decrease the use of systemic opioids (GRADE: Moderate to Low). They may also improve health-related quality of life (GRADE: Low), functional outcomes (GRADE: Low), and survival (GRADE: Low to Very low). In children with cancer pain, IDDSs may reduce pain intensity, improve functional outcomes, and improve survival, but the evidence is very uncertain (all GRADEs: Very low). IDDS implantation carries certain rare risks related to mechanical errors, drug-related side effects, and surgical complications. There are inherent limitations in conducting research in patients with refractory cancer pain; therefore, it is unlikely that higher-quality evidence will emerge in the next few years. Our primary economic evaluation found that IDDSs are more effective and more costly than standard care. The incremental cost-effectiveness ratio of IDDSs compared with standard care is $57,314 per quality-adjusted life-year (QALY) gained. The probability of IDDSs being cost-effective versus standard care is 43.46% at a willingness-to-pay of $50,000 per QALY gained and 72.54% at a willingness-to-pay of $100,000 per QALY gained. Publicly funding IDDSs in Ontario would cost an additional $0.27 million per year, for a total of $1.34 million over the next 5 years. The patients with cancer pain and caregivers with whom we spoke described the debilitating nature of cancer pain and the difficulty of finding effective pain management options. Patients with experience of an IDDS spoke of its effectiveness and its positive impact on their quality of life and mental health. Implementing IDDSs for patients with cancer pain raises several ethical and equity considerations related to the experiences and management of cancer pain, how limitations in evidence may entail uncertainties in clinical and health system decision-making, as well as clinical, geographic, and health system access barriers. Conclusions: Intrathecal drug delivery likely reduces pain intensity and decreases the use of systemic opioids in adults with cancer pain who have a life expectancy greater than 6 months. It may also improve health-related quality of life, functional outcomes, and survival, although the evidence for survival is very uncertain. The clinical evidence in children with cancer pain is very uncertain. IDDS implantation is reasonably safe. Intrathecal drug delivery is more effective and more costly than standard care. We estimate that funding IDDSs in Ontario will result in additional costs of $0.27 million per year, for a total of $1.34 million over the next 5 years. Considerations related to funding and implementing IDDSs for patients with cancer pain in Ontario will require explicit and focused attention to considerations of equity and access in the diagnosis and management of cancer pain and in the use, clinical uptake, and delivery of IDDS pain management.

Toward reducing racialized pain care disparities: Approaching cannabis research and access through the lens of equity and inclusion.

There is growing interest in cannabis use for cancer pain. This commentary aims to discuss the evidence surrounding cannabis use for cancer pain in the context of the long-racialized landscape of cannabis policies and the disparity in pain control among cancer patients holding minoritized racial identities. Much evidence surrounding both the benefits and harms of cannabis use in cancer patients, and all patients in general, is lacking. Although drawing on the research in cancer that is available, it is also important to illustrate the broader context about how cannabis' deep roots in medical, political, and social history impact patient use and health care policies. There are lessons we can learn from the racialized disparities in opioid risk mitigation strategies, so they are not replicated in the settings of cannabis for cancer symptom management. Additionally, the authors intentionally use the term "cannabis" here rather than "marijuana.: In the early 1900s, the lay press and government popularized the use of the word "marijuana" instead of the more common "cannabis" to tie the drug to anti-Mexican prejudice.

Cost-effectiveness analysis of epidural morphine/ropivacaine treatment in patients with cancer pain.

BACKGROUND: Cancer pain is one of the main causes of human suffering, which can generate disabilities and compromise quality of life, giving rise to several psychosocial and economic consequences. AIMS: This quantitative study sought to perform a cost-effectiveness pharmacoeconomic analysis to assess the impact of implanting epidural morphine associated with ropivacaine treatment in gastrointestinal cancer patients with pain that is difficult clinical control, compared with conventional oral treatment. MATERIALS AND METHODS: The study population consisted of 24 patients with gastrointestinal neoplasia who underwent treatment for cancer pain that was difficult to clinically control. 12 patients each were recruited into the control and intervention groups, respectively. While patients in the control group were administered drug treatment orally, patients in the intervention group underwent a surgical procedure for subcutaneous implantation of a catheter that allowed epidural administration of morphine and ropivacaine. For pain assessment, the Visual Analogue Scale was applied. Data analysis had a descriptive character of costs, taking into account the costs for the year 2021. The study perspective was the Brazilian public healthcare provider, referred to as the Unified Health System (Sistema Único de-SUS in Portuguese). Costs were computed over the time horizon corresponding to the duration of treatment, from the first medical consultation (when the treatment was defined) to the end (end of treatment, disease progression, or death). Treatment duration was divided into three phases (first 60 days, support with palliative care, and end-of-life care). To assess the robustness of the economic analysis, sensitivity analyses were performed, considering the effectiveness of pain reduction on the Visual Analogue Scale, and a comparison of results using the median prices of pharmaceutical components used in the study. RESULTS: The mean age of patients was 59.3 years. The results from the cost-effectiveness analysis showed the epidural morphine/ropivacaine treatment to be more effective with regard to pain reduction on the pain scale, particularly for end-of-life care, when compared to the conventional oral treatment, however, at a significantly higher cost. DISCUSSION: From the accomplishment of this research, it was observed that the application of the pain assessment scale is a way to better interpret and understand the patient's pain, facilitating care planning and decision-making by health professionals, as well as monitoring the effectiveness of the proposed new treatment. CONCLUSION: To present a better cost-effectiveness ratio, a reduction in the cost of the new epidural technology or an increase in the value of the existing oral intervention would be required. However, the latter is not feasible and unlikely to occur. A value judgement to decide whether the incremental benefit associated with the use of the new intervention is worth the extra cost will have to be made by the healthcare provider. Interventions that can relieve cancer pain symptoms should be investigated continuously, in search of evidence to support clinical practice and promote better quality of life for patients.

Opioid consumption by cancer patients in an Israeli Health Maintenance Organization from 2007-2018.

PURPOSE: Opioids are the cornerstone of therapy for cancer patients with moderate to severe pain. The objective was to characterize opioid purchases by cancer patients in Clalit Health Services (CHS), the largest Health Maintenance Organization in Israel, over the years 2007-2018. METHODS: Data for all CHS cancer patients aged 18 years old and above who purchased an opioid at least once during the 12-year study period were obtained from computerized databases. The amount of opioids was converted into oral morphine equivalents (OME). RESULTS: 108,543 cancer patients who purchased opioids at least once were enrolled. They comprised 30.5% of the CHS purchasers of opioids in the study period. The total number of cancer patients who purchased an opioid at least once increased gradually from 13,057 in 2007 to 20,675 (58% increase) in 2018, while the annual number of CHS cancer patients increased by only 39%. The annual OME per capita increased from 753 mg in 2007 to 1,432 mg in 2018 (91% increase). In 2007 8.1% of the cancer patients purchased opioids and 9.2% in 2018. Two thirds of all cancer patients purchased opioids for three months or less, 11.9% continued for more than one year, and 5.8% for more than two years. CONCLUSIONS: There is a clinically non-significant increase in the rate of cancer patients purchasing opioids. About two thirds of the cancer patients purchased opioids for only three months, and 94% for up to two years. Under-treatment of cancer pain should still be of concern. While patients are prescribed higher doses, under-prescription may still be a problem..

Ziconotide for the Management of Cancer Pain: A Budget Impact Analysis.

OBJECTIVES: Recent recommendations on starting dose, smaller dose increments, and longer intervals between dose increase have the potential to increase the safety of ziconotide administration in addition to improving its value for money. Ziconotide is not routinely commissioned in England, with one of the concerns being whether it represents the best use of resources. The aim of this project is to conduct a budget impact analysis to estimate the costs or savings associated with the changes in ziconotide dosage in addition to its use in combination with morphine for the management of cancer pain. MATERIALS AND METHODS: An open, Markov-like cohort decision analytic model was developed to estimate the budget impact of ziconotide in combination with morphine (ziconotide combination therapy) vs morphine monotherapy through intrathecal drug delivery (ITDD) for the management of cancer pain. The perspective adopted was that of the UK National Health Service, with a five-year time horizon. Sensitivity analyses were conducted to evaluate different scenarios. RESULTS: Ziconotide combination therapy was more expensive than treatment with morphine monotherapy. The total costs of ziconotide combination therapy and morphine monotherapy for the first year were £395,748 and £136,628 respectively. The estimated five-year cumulative budget impact of treatment with ziconotide combination therapy for the five-year time horizon was £2,487,539, whereas that of morphine monotherapy was £913,804. The additional costs in any of the first five years are below the resource impact significance level of £1 million for medical technologies in England. CONCLUSIONS: The results of this budget impact analysis suggest that although a combination of intrathecal ziconotide in combination with morphine is associated with higher costs to the health care system in England, the incremental costs are not significant. Routine commissioning of ziconotide alone or in combination with morphine would provide an alternative for a population with limited ITDD treatment options.

"Give My Daughter the Shot!": A Content Analysis of the Depiction of Patients with Cancer Pain and Their Management in Hollywood Films.

INTRODUCTION: Cinemeducation, the pedagogical use of films, has been used in a variety of clinical disciplines. To date, no studies have looked at the use of film depictions of cancer pain and its management in clinical education. We investigated how patients with cancer pain and their management are depicted in Hollywood films to determine whether there is content that would be amenable to use for cancer pain assessment and management education. METHODS: A qualitative content analysis was performed. Films that contained characters with or references to cancer pain were searched for using the International Movie Database, the Literature Arts Medicine Database, the History of Medicine and Medical Humanities Database, and Medicine on Screen. After review, 4 films were identified for review and analysis. RESULTS: Themes that emerged from the analysis concerned the films' depictions of characters with pain, their healthcare providers, the therapies used for pain management, and the setting in which pain management was provided. CONCLUSIONS: This study demonstrates that patients with cancer pain are depicted in a compassionate manner. Pain management focused on the use of opioids. The settings in which patients received pain management was depicted as not being amenable to providing holistic care. This variety of topics related to pain management covered in the films make them amenable to use in cinemeducation. This study therefore forms the basis for future work developing film-based cancer education modules.

Trends in opioid and non-opioid treatment for chronic non-cancer pain and cancer pain among privately insured adults in the United States, 2012-2019.

Recent clinical guidelines have emphasized non-opioid treatments in lieu of prescription opioids for chronic non-cancer pain, exempting cancer patients from these recommendations. In this study, we determine trends in opioid and non-opioid treatment among privately insured adults with chronic non-cancer pain (CNCP) or cancer. Using administrative claims data from IBM MarketScan Research Databases, we identified privately-insured adults who were continuously enrolled in insurance for at least one calendar year from 2012 to 2019. We identified individuals with CNCP diagnosis, defined as a diagnosis of arthritis, headache, low back pain, and/or neuropathic pain, and a individuals with cancer diagnosis in a calendar year. Outcomes included receipt of any opioid, non-opioid medication, or non-pharmacologic CNCP therapy and opioid prescribing volume, MME-per-day, and days' supply. Estimates were regression-adjusted for age, sex, and region. Between 2012 and 2019, the proportion of patients who received any opioid decreased across both groups (CNCP: 49.7 to 30.5%, p<0.01; cancer: 86.0 to 78.7%, p<0.01). Non-opioid pain medication receipt remained steady for individuals with CNCP (66.7 to 66.4%, p<0.01) and increased for individuals with cancer (74.4 to 78.8%, p<0.01), while non-pharmacologic therapy use rose among individuals with CNCP (62.4 to 66.1%, p<0.01). Among those prescribed opioids, there was a decrease in the receipt of at least one prescription with >90 MME/day (CNCP: 13.9% in 2012 to 4.9% in 2019, p<0.01; Cancer: 26.2% to 7.6%, p<0.01); >7 days of supply (CNCP: 56.3% to 30.7%, p <0.01; Cancer: 47.5% to 22.7%, p<0.01), the mean number of opioid prescriptions (CNCP: 5.2 to 3.9, p<0.01; Cancer: 4.0 to 2.7, p<0.01) and mean MME/day (CNCP: 49.9 to 38.0, p<0.01; Cancer: 62.4 to 44.7, p<0.01). Overall, from 2012-2019, opioid prescribing declined for CNCP and cancer, with larger reductions for patients with CNCP. For both groups, reductions in prescribed opioids outpaced increases in non-opioid alternatives.

Medicare Part D Coverage Restrictions and Patient Cost-Sharing for Opioids Commonly Used for Cancer Pain, 2015-2021.

PURPOSE: Nation-wide rapid declines in prescription opioid dispensing gave rise to concerns regarding restricted access to effective pain management for patients with cancer-related pain. One important mechanism for such restrictions could be through more restrictive insurance coverage for opioids. This study aims to assess recent changes in Medicare Part D formulary designs for opioids commonly used for cancer-related pain. METHODS: We used data from the 2015-2021 Medicare Prescription Drug Plan (PDP) Formulary Files to assess formulary changes for six opioid-dose combinations commonly used for cancer-related pain. We estimated % of PDPs adopting prior authorization, quantity limits (and limits adopted), and a higher cost-sharing tier for each opioid-dose combination. We further estimated median and mean out-of-pocket (OOP) costs across all PDPs for a 30-day supply of the drug. Trends in proportions were tested using the Cochrane-Armitage test; trends in continuous measures were tested using the Jonckheere-Terpstra test. RESULTS: Proportion of PDPs adopting prior authorization increased from close to 0% to about 50% for two long-acting opioids (P < .001). Distribution of quantity limits across PDPs shifted over time to being more restrictive for all opioids considered (P < .001). For four of the six opioids, the proportion of PDPs adopting tier 3 or above increased from below or about 50% to well over 70% (P < .001). For the same four opioids, median OOP costs doubled to quadrupled (P < .001). CONCLUSION: Medicare PDP coverage has become increasingly restrictive for opioids commonly used for cancer-related pain, with multifold increases in patient OOP costs over the past 7 years. These changes pose concerns for patients with cancer needing opioid therapies for pain control and call for strategies to effectively exempt cancer-related pain from insurance and pharmacy rules intended to apply to opioids for noncancer chronic pain.

A Survey of Knowledge and Barriers of Healthcare Professionals toward Opioid Analgesics in Cancer Pain Management.

Purpose: Pain is among the most frequent and troubling symptoms in cancer patients. Despite the availability of updated treatment guidelines and effective pharmacological therapies, undertreatment of cancer pain remains a global problem. Opioids are the mainstay analgesics to treat moderate-to-severe cancer pain. The goal of this study was to assess the knowledge and barriers towards opioid analgesics for cancer pain management among healthcare professionals in Oncology Units in Jordan. Methods: A structured questionnaire was administered to healthcare professionals (consultant doctors, resident doctors, pharmacists, and nurses) at three Oncology Units in a cross-sectional study design. Results: A total of 201 healthcare professionals completed the questionnaire. The average age was 34.8 ± 8.1 years (range 23-58) and 49.3% of respondents were nurses. The mean score for the knowledge of opioids was 12.5 ± 3.2 out of 24 points (range 2-20). An acceptable level of knowledge was observed in 50.7% of participants, while 49.3% had poor knowledge. Knowledge items mostly answered incorrectly were related to opioid administration, pharmacology, dosing, adverse events, rotation, and toxicity. Knowledge scores were significantly higher for consultant doctors compared to pharmacists and nurses (p=0.016 and p < 0.001, respectively). Healthcare professionals who handled opioid analgesics had significantly higher mean knowledge scores than those who did not (p=0.012). Linear regression analysis revealed that being a consultant physician has an independent, statistically significant association with higher knowledge scores. Among perceived barriers to using opioids, fear of addiction by patients was the most frequently reported barrier by respondents (79.6%). Other highly recognized barriers were fear of adverse effects by patients (67.2%) and lack of training programs on opioid dosing and monitoring (63.7%). Conclusions: This study revealed major gaps in the knowledge of opioids and pain management among healthcare professionals. There is an urgent need for developing innovative interventions to improve the knowledge of opioid analgesics and the understanding of pain management guidelines among healthcare professionals in Jordan.

Opioid prescribing attitudes of palliative care physicians versus other specialists: a questionnaire-based survey.

PURPOSE OF THE STUDY: While opioid overuse is a public health crisis in the USA, opioid analgesics are used suboptimally in Central and Eastern Europe, causing many pain cases to remain untreated or undertreated. STUDY DESIGN: This questionnaire study aimed to identify the prevalent prescribing patterns and attitudes and the possible internal impediments to optimal opioid use among palliative care physicians and other specialists in Poland. RESULTS: Tramadol was the most commonly preferred opioid. While palliative care physicians (n=81) used various strong opioids, other physicians (n=87) prescribed mostly buprenorphine, accessible with standard prescription forms. Neither internal prejudices and beliefs nor administrative regulations impede prescribing opioids by palliative care physicians, unlike specialists other than palliative medicine. Special prescription forms for psychoactive medications, fear of drug addiction of their patients and penalties for possible errors on prescriptions affect the latter's optimal prescribing. They also revealed significant gaps in the knowledge of prescribing opioids and would take part in additional training. Palliative care physicians appeared optimally prepared for cancer pain management and report fewer internal barriers than other specialists. CONCLUSIONS: Continuous medical education on cancer pain treatment should be provided to all specialists to ensure optimal opioid pharmacotherapy and avoid overprescribing or underprescribing opioids. Administrative restrictions are the main barrier to optimal pain treatment.

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.

Exemptions to state laws regulating opioid prescribing for patients with cancer-related pain: A summary.

BACKGROUND: Cancer-related pain is highly prevalent and is commonly treated with prescription opioids. The Centers for Disease Control and Prevention (CDC) now encourages conservative opioid prescribing in recognition of potential opioid-related risks. However, CDC guidelines have been misapplied to patients with cancer. Recent laws at the state level reflect the CDC's guidance by limiting opioid prescribing. It is unclear whether states exempt cancer-related pain, which may affect cancer pain management. Thus, the objective of this study was to summarize current state-level opioid prescribing laws and exemptions for patients with cancer. METHODS: Two study authors reviewed publicly available state records to identify the most recent opioid prescribing laws and cancer-related exemptions. Documents were required to have the force of law and be enacted at the time of the search (November 2020). RESULTS: Results indicated that 36 states had enacted formal legislation limiting the duration and/or dosage of opioid prescriptions, and this was largely focused on acute pain and/or initial prescriptions. Of these states, 32 (89%) explicitly exempted patients with cancer-related pain from opioid prescribing laws. Exemptions were broadly applied, with few states providing specific guidance for cancer-related pain prescribing. CONCLUSIONS: The results of this study indicate that most states recognize the importance of prescription opioids in cancer-related pain management. However, drafting nuanced and clinically relevant opioid legislation is challenging for a heterogenous population. Additionally, current attempts to regulate opioid prescribing by state law may unintentionally undermine patient-centered approaches to pain management. Additional resources are needed to facilitate clarity at the intersection of opioid-related legislation and clinical management for cancer-related pain. LAY SUMMARY: In this review of state-level legislation, current limitations on opioid prescribing are summarized and detailed information is provided on exemptions for patients with cancer. The majority of states have enacted specific dosage and/or duration limitations on opioid prescribing while including broad exemptions for cancer-related pain. Cancer-related pain exemptions are important to include, as is consistent with national and professional guidelines (eg, the Centers for Disease Control and Prevention). However, these exemptions may also unintentionally undermine patient-centered approaches to pain management. Additional resources, including specific guidance for patients with cancer, are needed to facilitate clarity at the intersection of opioid-related legislation and clinical pain management. ​.

Evaluation of pharmacists' interventions on drug-related problems and drug costs in patients with cancer pain.

BACKGROUND: Drug-related problems (DRPs) prevent patients from fully benefiting from drug treatment. Unrelieved pain in patients with cancer is still widespread. Pharmacists can play a role in closely monitoring cancer patients, pain control maintenance, and patient consultation. OBJECTIVE: To evaluate the clinical effects and changes in drug costs of pharmacists' interventions on patients with DRPs related to cancer pain. SETTING: An academic teaching hospital in Shanghai, China. METHODS: Patients with cancer pain admitted to Shanghai Tongren Hospital from October 2018 to February 2019 were randomized into the intervention and control groups. The Pharmaceutical Care Network Europe classification V8.02 was used to categorize DRPs treated with analgesics. Patients' pain relief, the occurrence of adverse drug reactions, and drug cost-saving through the resolution of DRPs were evaluated. MAIN OUTCOME MEASURE: Problems and causes of drug-related problems, interventions proposed, and outcome of pharmacy recommendations. RESULTS: A total of 172 patients were enrolled and randomized into the intervention group (n = 86) and the control group (n = 86). The pharmacist detected 66 DRPs in 48 patients (55.8%) of the intervention group, an average of 0.8 DRPs per patient. A total of 149 interventions were proposed by the pharmacist. Compared to the control group, the drug intervention produced more pain relief on the third day of analgesic treatment. In the intervention group, a total of 33 DRP interventions resulted in cost changes, saving a drug cost of $489.90, averaging $11.94 per intervention. CONCLUSION: Our study suggests that pharmacy service in patients with cancer pain can resolve drug-related problems and reduce drug costs.

Opioid use by cancer status and time since diagnosis among older adults enrolled in the Prostate, Lung, Colorectal, and Ovarian screening trial in the United States.

BACKGROUND: Dosing limits in opioid clinical practice guidelines in the United States are likely misapplied to cancer patients, however, opioid use may be difficult to ascertain as they are largely excluded from opioid use studies. METHODS: The primary objective was to determine whether cancer patients were more likely to be chronic opioid users after diagnosis. We described prescription opioid use among U.S. older adult cancer patients during two time periods, within 2 years of diagnosis (short-term) and at least 2 years beyond diagnosis (long-term), compared to those without cancer (controls). Among participants in the Prostate, Lung, Colorectal, and Ovarian (PLCO) screening trial with linkages to Medicare Part D data during 2011-2015, we used multivariable logistic regression to estimate the association between cancer diagnosis and opioid use outcomes controlling for demographics. The primary outcome of opioid use was measured with the following metrics: Any opioid use, chronic use (90 consecutive days supply of opioid use while allowing for a 7-day gap between refills), high use (average daily morphine equivalent (MME) ≥120 mg for any 90-day period), and total MME dose above 2,000 mg (MME2000 ). RESULTS: The short-term cohort included 1,491 cancer patients and 24,930 controls. Any use in the 2-year post-diagnosis period was higher among cancer patients OR 3.3 (95% CI: 3.0-3.7). Chronic use rates were similar by cancer status (4.6% vs. 3.8% for cases and controls, respectively). The long-term cohort included 4,377 cancer patients and 27,545 controls. Rates of any use were similar among cancer patients and controls (63% vs. 59%). CONCLUSIONS: Any opioid use was similar among long-term cancer survivors compared to controls, but differed among short-term survivors for any opioid use and marginally for chronic opioid use.

Regional and temporal variation in receipt of long-term opioid therapy among older breast, colorectal, lung, and prostate cancer survivors in the United States.

BACKGROUND: Older cancer survivors have high rates of long-term opioid therapy (≥90 days/year). However, the geographical and temporal variation in long-term opioid therapy rates for older cancer survivors is not known. METHODS: A retrospective cohort study was conducted using SEER-Medicare data. Persons aged ≥66 years, diagnosed with breast, colorectal, lung, or prostate cancer from 1991 to 2011, and alive ≥5 years after diagnosis were included. Persons were followed from 1/1/2008 until 12/31/2016. Persons were assigned to a census region in their state of residence each year. Individuals who were covered by an opioid prescription for at least 90 days in a calendar year were classified as having received long-term opioid therapy. Multivariable analysis was conducted using generalized estimating equations. RESULTS: Temporal trends significantly varied by region (p < 0.0001) and opioid-naïve status (p < 0.0001). Compared to 2013, opioid-naïve cancer survivors in the south and non-naïve survivors in the south and west experienced significant declines in long-term opioid therapy in 2015 and 2016. Significant declines were observed in 2016 for opioid-naïve and non-naïve cancer survivors residing in the northeast and among opioid-naïve cancer survivors living in the Midwest. CONCLUSION: The annual trends in the receipt of long-term opioid therapy significantly varied by region among older cancer survivors. Variation in a clinical practice suggests the need for more research and interventions to improve efficiency, process, cost, and quality of care.

Validation of an oncology-specific opioid risk calculator in cancer survivors.

BACKGROUND: Clinical guidelines recommend that providers risk-stratify patients with cancer before prescribing opioids. Prior research has demonstrated that a simple cancer opioid risk score might help identify to patients with cancer at the time of diagnosis with a high likelihood of long-term posttreatment opioid use. This current project validates this cancer opioid risk score in a generalizable, population-based cohort of elderly cancer survivors. METHODS: This study identified 44,932 Medicare beneficiaries with cancer who had received local therapy. Longitudinal opioid use was ascertained from Medicare Part D data. A risk score was calculated for each patient, and patients were categorized into low-, moderate-, and high-risk groups on the basis of the predicted probability of persistent opioid use. Model discrimination was assessed with receiver operating characteristic curves. RESULTS: In the study cohort, 5.2% of the patients were chronic opioid users 1 to 2 years after the initiation of cancer treatment. The majority of the patients (64%) were at low risk and had a 1.2% probability of long-term opioid use. Moderate-risk patients (33% of the cohort) had a 5.6% probability of long-term opioid use. High-risk patients (3.5% of the cohort) had a 75% probability of long-term opioid use. The opioid risk score had an area under the receiver operating characteristic curve of 0.869. CONCLUSIONS: This study found that a cancer opioid risk score could accurately identify individuals with a high likelihood of long-term opioid use in a large, generalizable cohort of cancer survivors. Future research should focus on the implementation of these scores into clinical practice and how this could affect prescriber behavior and patient outcomes. LAY SUMMARY: A novel 5-question clinical decision tool allows physicians treating patients with cancer to accurately predict which patients will persistently be using opioid medications after completing therapy.

The role of fentanyl in the treatment of breakthrough cancer pain: Different biotechnologies, different results and different drug costs.

The aim of this paper was to assess the drug costs of the different biotechnologies (intranasal fentanyl spray (INFS), oral transmucosal fentanyl citrate (OTFC) and fentanyl buccal tablet (FBT)) in the treatment of breakthrough cancer pain (BTCP). We have calculated the mean drug costs (expressed in euros (€)) for patients treated for BTCP. INFS resulted the less expensive towards OTFC and FBT, with 697 440 €versus (vs.) 809 552 €vs. 779 662 €every 100 patients treated for BTCP, respectively. In conclusion, combining drug costs of different biotechnologies (INFS, OTFC and FBT) with the measure of efficacy represented by the reduction of BTCP avoided (incremental cost-effectiveness ratio, ICER), INFS resulted in better cost-effectiveness.

Evaluation of knowledge and comfort with opioid prescribing among pediatric hematology/oncology fellows.

BACKGROUND: Deficits in knowledge and comfort related to pain management have been demonstrated in adult hematology/oncology fellows. No such evaluation has been undertaken in pediatric hematology/oncology (PHO) trainees. PROCEDURE: An IRB-approved survey was administered to PHO fellows throughout the United States (US) to assess comfort with opioid dosing, attitudes related to the use of opioids, and knowledge of basic concepts including weight-based dosing, incomplete cross-tolerance, and management of side effects. RESULTS: Email addresses were obtained for 132 fellows from 37 programs. Seventy-eight (59%) fellows participated. No significant difference was demonstrated between training level and comfort with dosing opioids in an opioid-naive patient, though a smaller proportion of first-year fellows (65%) reported comfort compared to more senior fellows (85.2% of second-year fellows, 80.6% of third- and fourth-year fellows). First-year fellows correctly answered a mean of 5.05 ± 0.43 out of 10 objective knowledge questions; second-year fellows answered 5.74 ± 0.35 correctly, and third- and fourth-year fellows 5.58 ± 0.30. The majority of respondents chose an appropriate dose of intravenous morphine based on weight (92%), and identified a low-dose naloxone drip as an appropriate intervention for opioid-induced pruritis (91%). However, the remainder of the questions had a correct response rate of 15-68%. CONCLUSION: This study characterizes PHO fellows' knowledge and comfort with prescribing opioids. Despite high levels of reported comfort, PHO fellows in all levels of training demonstrated knowledge gaps. PHO fellows may benefit from further education in pain management.

The Unmet Need for Intrathecal Drug Delivery Pumps for the Treatment of Cancer Pain in England: An Assessment of the Hospital Episode Statistics Database.

OBJECTIVES: Intrathecal drug delivery (ITDD) devices have been shown to be a clinically effective and cost-effective option for the management of cancer pain and recommended for use in England. The aim of this study is to assess the impact of the 2015 NHS England Clinical Commissioning Policy on the uptake of ITDD pumps for the management of cancer pain or if there is an ongoing unmet need for this intervention in England. MATERIALS AND METHODS: Hospital Episode Statistics (HES) were obtained for all patients undergoing ITDD for the management of cancer pain between 2014 and January 2020. In addition, HES were utilized to estimate the number of patients with cancer potentially eligible for ITDD pump during the same period. RESULTS: The number of patients with cancer and those potentially suitable to receive an ITDD for the management of cancer pain have increased year on year since 2014. This increase has not been matched by an uptake in the provision of ITDD. Conservative estimates suggest that at least 8000 people with cancer pain would be eligible for ITDD; 458 patients received an intervention for pain management between April 2018 and March 2019 and only 30 ITDD pumps were implanted in that same period. CONCLUSIONS: We observed a substantial gap between the need and provision of ITDD for patients with refractory cancer pain in England despite the recommendation for the use of ITDD for this patient population. In addition, we present suggestions for improvement of access to and provision of ITDD in England.

Assessment of the anti-allodynic efficacy of a glycine transporter 2 inhibitor relative to pregabalin and duloxetine in a rat model of prostate cancer-induced bone pain.

BACKGROUND: The pathobiology of prostate cancer-induced bone pain (PCIBP) is underpinned by both inflammatory and neuropathic components. Here, we used a rat model of PCIBP to assess the analgesic efficacy of a glycine transporter 2 (GlyT2) inhibitor (N-(6-((1,3-dihydroxypropan-2-yl)amino)-2-(dimethylamino)pyridin-3-yl)-3,5-dimethoxy-4-(4-(trifluoromethyl)phenoxy) benzamide) relative to two clinically available adjuvant drugs that are recommended for the relief of neuropathic pain, viz, pregabalin and duloxetine. METHODS: PCIBP was induced in male Wistar Han rats following intra-tibial injection (ITI) of rat prostate cancer (AT3B) cells into the left tibia. Sham-rats received an ITI of heat-killed AT3B cells. PCIBP rats with fully developed mechanical allodynia in the ipsilateral hindpaws as assessed using von Frey filaments, received single oral (p.o.) bolus doses of the GlyT2 inhibitor (3-30 mg/kg), pregabalin (3-100 mg/kg), duloxetine (3-100 mg/kg), or vehicle. Baseline paw withdrawal thresholds (PWTs) were determined in the ipsilateral (injured side) and contralateral hindpaws immediately prior to dosing and at scheduled times for 3 h post dosing in individual animals. RESULTS: Single oral bolus doses of the GlyT2 inhibitor (3-30 mg/kg) evoked partial pain relief at the doses tested in the ipsilateral hindpaws of PCIBP rats without any discernible behavioural side effects. By contrast, single oral bolus doses of pregabalin at 10-100 mg/kg evoked dose-dependent and complete alleviation of mechanical allodynia. By comparison, single oral bolus doses of duloxetine at doses up to 100 mg/kg lacked efficacy. CONCLUSION: Oral administration of this GlyT2 inhibitor evoked partial pain relief in PCIBP rats and did not evoke central nervous system side effects in contrast to GlyT2 inhibitors reported by others.