Assessment of Health Care Utilization and Cost of Targeted Drug Delivery and Conventional Medical Management vs Conventional Medical Management Alone for Patients With Cancer-Related Pain.

Importance: Targeted drug delivery (TDD) has potential for cost savings compared with conventional medical management (CMM). Despite positive clinical and economic evidence, TDD remains underused to treat cancer pain. Objective: To assess the cost of TDD and CMM in treating cancer-related pain. Design, Setting, and Participants: This retrospective economic evaluation using propensity score-matched analysis was conducted using MarketScan commercial claims data on beneficiaries receiving TDD and CMM or CMM only for cancer pain from January 1, 2009, to September 30, 2015. Participants were matched on age, sex, cancer type, comorbidity score, and pre-enrollment characteristics. Data analysis was performed from June 1 to September 30, 2017. Main Outcomes and Measures: Total 2-, 6-, and 12-month costs, number of health care encounters, length of hospital stay, additional components of cost, and health care utilization. Results: A total of 376 TDD and CMM patients (mean [SD] age, 51.88 [9.98] years; 216 [57.5%] female) and 4839 CMM only patients (mean [SD] age, 51.52 [11.16] years; 3005 [62.1%] female) were identified for study inclusion. After matching, 536 patients were included in the study: 268 patients in the TDD and CMM group and 268 in the CMM only group. Compared with CMM only, TDD and CMM was associated with mean total cost savings of $15 142 (95% CI, $3690 to $26 594; P = .01) at 2 months and $63 498 (95% CI, $4620 to $122 376; P = .03) at 12 months; cost savings at 6 months were not statistically different ($19 577; 95% CI, -$12 831 to $51 984; P = .24). The TDD and CMM group had fewer inpatient visits (2-month mean difference [MD], 1.0; 95% CI, 0.8-1.2; P < .001; 6-month MD, 1.3; 95% CI, 0.8-1.7; P < .001; 12-month MD, 2.3; 95% CI, 1.2-3.4; P < .001) and shorter hospital stays (2-month MD, 6.8 days; 95% CI, 5.0-8.7 days; P < .001; 6-month MD, 6.8 days; 95% CI, 3.1-10.5 days; P < .001; 12-month MD, 10.6 days; 95% CI, 2.9-18.3 days; P = .007). Use of CMM only was associated with greater opioid use at 12 months (MD, 3.2; 95% CI, 0.4-6.0; P = .03). Conclusions and Relevance: Compared with CMM alone, TDD and CMM together were associated with significantly lower cost and health care utilization. The findings suggest that TDD is a cost-saving therapy that should be considered in patients with cancer for whom oral opioids are inadequate or produce intolerable adverse effects and should be expanded as health care systems transition to value-based models.

The Polyanalgesic Consensus Conference (PACC): Recommendations on Intrathecal Drug Infusion Systems Best Practices and Guidelines.

INTRODUCTION: Pain treatment is best performed when a patient-centric, safety-based philosophy is used to determine an algorithmic process to guide care. Since 2007, the International Neuromodulation Society has organized a group of experts to evaluate evidence and create a Polyanalgesic Consensus Conference (PACC) to guide practice. METHODS: The current PACC update was designed to address the deficiencies and innovations emerging since the previous PACC publication of 2012. An extensive literature search identified publications between January 15, 2007 and November 22, 2015 and authors contributed additional relevant sources. After reviewing the literature, the panel convened to determine evidence levels and degrees of recommendations for intrathecal therapy. This meeting served as the basis for consensus development, which was ranked as strong, moderate or weak. Algorithms were developed for intrathecal medication choices to treat nociceptive and neuropathic pain for patients with cancer, terminal illness, and noncancer pain, with either localized or diffuse pain. RESULTS: The PACC has developed an algorithmic process for several aspects of intrathecal drug delivery to promote safe and efficacious evidence-based care. Consensus opinion, based on expertise, was used to fill gaps in evidence. Thirty-one consensus points emerged from the panel considerations. CONCLUSION: New algorithms and guidance have been established to improve care with the use of intrathecal drug delivery.

Health Services Utilization and Payments in Patients With Cancer Pain: A Comparison of Intrathecal Drug Delivery vs. Conventional Medical Management.

INTRODUCTION: To compare health services utilization and payments for cancer patients who received an implantable intrathecal drug delivery (IDD) system, consisting of a pump and catheter, vs. conventional medical management (CMM) for the treatment of cancer-related pain. METHODS: This retrospective claims-data analysis compared health services utilization and payments in a population of patients receiving either IDD or CMM for treatment of cancer pain. Patients were propensity score-matched 1:1 based on characteristics including, but not limited to, age, gender, cancer type, comorbid conditions, and health care utilization and payments. RESULTS: From a sample of 142 IDD patients and 3188 CMM patients who met all inclusion/exclusion criteria, 73 matched pairs were obtained. In the year following implant, IDD patients had a consistent trend of lower medical utilization, and total payments that were $3195 lower compared to CMM. CONCLUSIONS: Despite the high initial cost of IDD, this analysis suggests that patients with IDD incur lower medical utilization and payments over the first year post-implant. Further analysis comprised of a larger, longitudinal sample would contribute to health economics and outcomes research, and assist with future practice guideline development.

Subcutaneous peripheral nerve stimulation with inter-lead stimulation for axial neck and low back pain: case series and review of the literature.

OBJECTIVES: While pain in the extremities often responds to treatment using spinal cord stimulation (SCS), axial pain is notoriously refractory to SCS. Interest in subcutaneous peripheral nerve stimulation (SQ PNS) as an alternative to SCS has emerged, but the most appropriate electrode locations and neurostimulator programming techniques are not yet clear. METHODS: A retrospective review was conducted of consecutive patients evaluated from August 2009 to December 2010 who had undergone trial of SQ PNS with inter-lead stimulation for axial spine pain. Patients proceeding to implant were followed postoperatively with routine clinical visits and a survey form at last follow-up. Ultrasound was used intraoperatively to ensure placement of electrodes at the appropriate depth in patients with larger body mass index. Primary outcome was patient-reported pain relief at last follow-up. Literature review was conducted by searching MEDLINE (1948-present) and through an unstructured review by the authors. RESULTS: Ten patients underwent trial of SQ PNS and six proceeded to permanent implantation. Fifty percent (3/6) of implanted patients preferred neurostimulation programming that included inter-lead stimulation ("cross-talk"). Average duration of postoperative follow-up was 4.5 months (range 2-9 months). Average patient-reported pain relief at last follow-up was 45% (range 20-80%). One patient required re-operation for migration. Patients not proceeding to implant had paresthesia coverage but no analgesia. CONCLUSION: SQ PNS is a promising therapy for axial neck and back pain based on a small cohort of patients. Ultrasound was useful to assist with electrode placement at the most appropriate depth beneath the skin. While inter-lead stimulation has been preferred by patients in published reports, we did not find it clearly influenced pain relief. Future investigations should include a randomized, controlled study design, as well as defined implantation technique and neurostimulator programming algorithms.

Medical practice perspective: identification and mitigation of risk factors for mortality associated with intrathecal opioids for non-cancer pain.

OBJECTIVE: The authors recently determined that early and longer term mortality after initiation or reinitiation of intrathecal opioid therapy is higher than previously appreciated: 0.088% within 3 days, 0.39% at 1 month, and 3.89% at 1 year. These rates were 7.5 (confidence interval, 5.7-9.8), 3.4 (confidence interval, 2.9-3.8), and 2.7 (confidence interval, 2.6-2.8) times higher, respectively, at each interval than expected based on the age- and gender-matched general U.S. population. A substantial portion of this excess mortality is probably therapy related and cannot be entirely accounted for by underlying demographic or patient-related factors, or by device malfunctions. We also analyzed multiple complementary internal, governmental, and insurance databases to quantify mortality and to identify medical practice patterns that appear to be associated with patient mortality risks, and to suggest measures for physicians and health care facilities to consider in order to reduce those risks. Both of those objectives involve judgments, which may be controversial and are subject to practical limitations. RESULTS: Multiple clinical and patient- or therapy-related factors appear to increase the risk for early post-implant mortality. Specific risk mitigation measures associated with each factor include: close attention to the starting intrathecal opioid dose (or restarting dose after therapy interruption); avoidance of outpatient implant or other device procedures that involve less than 24-hour monitoring for respiratory depression; supervision of concomitant opioid, respiratory depressant, or other central nervous system active drug intake early post-implant and chronically in the outpatient setting; and careful programming or dosage calculations and decisions in order to avoid the unintentional administration of high intrathecal opioid drug doses. CONCLUSIONS: Mortality after initiation of or device interventions in intrathecal drug delivery patients appears to occur as a result of multiple factors that present possible mitigation opportunities for physicians and health care facilities.

Mortality associated with implantation and management of intrathecal opioid drug infusion systems to treat noncancer pain.

BACKGROUND: In 2006, the authors observed a cluster of three deaths, which circumstances suggested were opioid-related, within 1 day after placement of intrathecal opioid pumps for noncancer pain. Further investigation suggested that mortality among such patients was higher than previously appreciated. The authors performed investigations to quantify that mortality and compare the results to control populations, including spinal cord stimulation and low back surgery. METHODS: After analyzing nine index cases--three sentinel cases and six identified by a prospective strategy--the authors used epidemiological methods to investigate whether mortality rates reflected patient- or therapy-related differences. Mortality rates after intrathecal opioid therapy and spinal cord stimulation were derived by correlating Medtronic device registration data with de-identified data from the Social Security Death Master File. Aggregate demographic and comorbidity data were obtained from Medicare and United Healthcare population databases to examine the influence of demographics and comorbidities on mortality. RESULTS: Device registration and Social Security analyses revealed an intrathecal opioid therapy mortality rate of 0.088% at 3 days after implantation, 0.39% at 1 month, and 3.89% at 1 yr-a higher mortality than after spinal cord stimulation implants or after lumbar diskectomy in community hospitals. Demographic, illness profile, and mortality analyses of large databases suggest, despite limitations, that excess mortality was related to intrathecal opioid therapy, and could not be fully explained by other factors. These findings were consistent with the nine index cases that revealed that respiratory arrest caused or contributed to death in all patients. No device malfunctions associated with overinfusion were identified among cases where data were available. CONCLUSIONS: Patients with noncancer pain treated with intrathecal opioid therapy experience increased mortality compared to similar patients treated by using other therapies. Respiratory depression as a consequence of intrathecal drug overdosage or mixed intrathecal and systemic drug interactions is one plausible, but hypothetical mechanism. The exact causes for patient deaths and the proportion of those deaths attributable to intrathecal opioid therapy remain to be determined. These findings, although based on incomplete information, suggest that it may be possible to reduce mortality in noncancer intrathecal opioid therapy patients.

Randomized clinical trial of an implantable drug delivery system compared with comprehensive medical management for refractory cancer pain: impact on pain, drug-related toxicity, and survival.

PURPOSE: Implantable intrathecal drug delivery systems (IDDSs) have been used to manage refractory cancer pain, but there are no randomized clinical trial (RCT) data comparing them with comprehensive medical management (CMM). PATIENTS AND METHODS: We enrolled 202 patients on an RCT of CMM versus IDDS plus CMM. Entry criteria included unrelieved pain (visual analog scale [VAS] pain scores >/= 5 on a 0 to 10 scale). Clinical success was defined as >/= 20% reduction in VAS scores, or equal scores with >/= 20% reduction in toxicity. The main outcome measure was pain control combined with change of toxicity, as measured by the National Cancer Institute Common Toxicity Criteria, 4 weeks after randomization. RESULTS: Sixty of 71 IDDS patients (84.5%) achieved clinical success compared with 51 of 72 CMM patients (70.8%, P =.05). IDDS patients more often achieved >/= 20% reduction in both pain VAS and toxicity (57.7% [41 of 71] v 37.5% [27 of 72], P =.02). The mean CMM VAS score fell from 7.81 to 4.76 (39% reduction); for the IDDS group, the scores fell from 7.57 to 3.67 (52% reduction, P =.055). The mean CMM toxicity scores fell from 6.36 to 5.27 (17% reduction); for the IDDS group, the toxicity scores fell from 7.22 to 3.59 (50% reduction, P =.004). The IDDS group had significant reductions in fatigue and depressed level of consciousness (P <.05). IDDS patients had improved survival, with 53.9% alive at 6 months compared with 37.2% of the CMM group (P =.06). CONCLUSION: IDDSs improved clinical success in pain control, reduced pain, significantly relieved common drug toxicities, and improved survival in patients with refractory cancer pain.