Physician perspective on the implementation of risk mitigation strategies when prescribing opioid medications: a qualitative analysis.

OBJECTIVE: To understand the physician perspective on the barriers and facilitators of implementing nine different opioid risk mitigation strategies (RMS) when prescribing opioid medications. METHODS: We created and dispersed a cross-sectional online survey through the Qualtrics© data collection platform among a nationwide sample of physicians licensed to practice medicine in the United States who have prescribed an opioid medication within the past year. The responses were analyzed using a deductive thematic analysis approach based on the Consolidated Framework for Implementation Research (CFIR) to ensure a holistic approach to identifying the barriers and facilitators for each RMS assessed. In concordance with this method, the themes and codes for the thematic analysis were defined prior to the analysis. The five domains within the CFIR were used as themes and the 39 nested constructs were treated as the codes. Two members of the research team independently coded the transcripts and discussed points of disagreement until consensus was reached. All analyses were conducted in ATLAS.ti© V7. RESULTS: The completion rate for this survey was 85.1% with 273 participant responses eligible for analysis. Intercoder reliability was calculated to be 82%. Deductive thematic analysis yielded 2,077 descriptions of factors affecting implementation of the nine RMS. The most salient code across all RMS was Knowledge and Beliefs about the Intervention, which refers to individuals' attitudes towards and value placed on the intervention. Patient Needs and Resources, a code referring to the extent to which patient needs are known and prioritized by the organization, also emerged as a salient code. The physicians agreed that the patient perspective on the issue is vital to the uptake of each of the RMS. CONCLUSIONS: This deductive thematic analysis identified key points for actionable intervention across the nine RMS assessed and established the importance of patient concordance with physicians when deciding on a course of treatment.

Association of cash payment with intensity of opioid prescriptions.

BACKGROUND: It is difficult to track use and outcomes in patients who pay cash for their prescriptions at the pharmacy. In Texas, 14% of all opioid prescriptions are paid with cash, often by uninsured patients and pharmacy shoppers. OBJECTIVE: To evaluate the association of cash payment with intensity of opioid prescriptions. METHODS: Using a prescription drug monitoring program and the U.S. Census data for the 2019 calendar year, this cross-sectional descriptive study analyzed more than 4 million opioid prescriptions in Texas residents aged 18-64 years. The payment type was coded as insurance if the prescription was paid in whole or in part by a health plan and as cash otherwise. Daily morphine milligram equivalent (MME) dose was used to compare the intensity of opioid prescriptions. The association of uninsured rates with mean daily MME and the number of opioid prescriptions paid with cash per 100,000 persons were assessed at a county level. RESULTS: Cash payment was associated with 30% higher mean daily MME (59 vs. 45; P < 0.001) than insurance payment. This difference was driven by the prescriptions for patients aged 25-34 years and from the highest decile of prescribers based on the percentage of opioid prescriptions paid by cash. For instance, cash payment was associated with 82% higher mean daily MME (91 vs. 50; P < 0.001) when patients aged 25-34 years obtained their prescriptions from the highest decile of prescribers. At a county level, uninsured rates were not associated with mean daily MMEs or the number of opioid prescriptions paid with cash. CONCLUSION: Cash payment was associated with a higher intensity of opioid prescriptions, mirroring the rates of drug overdose deaths across the patient age groups. Further research and policy actions need to address unmet pain management needs in uninsured patients and potential pharmacy shopping with cash payment and fraudulent identifications.

Switching pharmacies leads to gaps in medication possession in individuals treated with buprenorphine.

BACKGROUND: Not all pharmacies stock and dispense buprenorphine, potentially complicating continuous access to care for patients with opioid use disorder (OUD). This may become problematic if a patient's primary pharmacy can no longer provide buprenorphine, and the patient cannot locate a new pharmacy. OBJECTIVES: To identify how often patients treated with buprenorphine for OUD switch pharmacies and to estimate the association between switching pharmacies and a clinically significant gap in therapy of 7 days or longer. METHODS: A retrospective repeated measures longitudinal cohort design was used. Patients initiating treatment with a buprenorphine product indicated for OUD were identified from the 2016-2018 Texas Prescription Monitoring Program. The predictor of interest-switching pharmacies-was defined by comparing the dispensaries used between subsequent prescriptions. The outcome of interest was defined as a gap in medication possession of 7 days or longer on the basis of the National Quality Forum's definition of continuity of pharmacotherapy for OUD. A generalized estimating equation approach was used to estimate a repeated measures logistic regression measuring the association between switching pharmacies and a gap in therapy. RESULTS: Of 13,375 eligible patients, 29.6% switched pharmacies at least once during treatment, and 51.6% of these did so more than once. The median time to initial switch was 30 days (interquartile range: 13-66 days). When patients switched pharmacies, they were significantly more likely to have a gap in therapy of between 7 and 29 days (adjusted odds ratio 1.67 [95% CI 1.57-1.78]). CONCLUSION: Patients receiving buprenorphine switch pharmacies early and frequently in treatment, which leads to clinically significant gaps in therapy. Although qualitative explanatory work is needed to understand why patients switch pharmacies so often, pharmacists and prescribers must ensure that patients have reliable access to a convenient source of buprenorphine to prevent gaps in therapy.

Association of wound healing with quality and continuity of care and sociodemographic characteristics.

OBJECTIVES: To evaluate the association between clinics' wound healing performance and clinic-level measures of care continuity, clinical quality, and sociodemographic characteristics of the population in their catchment areas. STUDY DESIGN: In this cross-sectional analysis, we analyzed electronic health records for 180,336 chronic wounds from 480 wound care clinics during the 2018 calendar year. METHODS: We measured healing performance using a clinic's observed to expected (O/E) ratio, which is based on the rate at which chronic wounds were predicted to heal within 12 weeks given its case mix and the actual healing rate. We compared the top and bottom quintiles, in terms of the O/E ratio, of clinics. Multivariable regression was used to estimate the effect of the clinic-level measures on the O/E ratio. RESULTS: Clinics in the top quintile had higher rates of care continuity and quality measures, as well as a lower proportion of disadvantaged populations in their catchment areas. In the regression model, 10% increases in a clinic's rate of weekly provider visits, nurse visits, and debridement were associated with 2.5%, 3.0% and 0.7% increases, respectively, in the O/E ratio. The weekly provider visit rate had a greater marginal effect when the proportion of African American residents in the clinic's catchment area was larger. CONCLUSIONS: Clinic-level measures of care continuity, clinical quality, and sociodemographic composition of their catchment areas' population explain a meaningful part of differences in clinics' wound healing performance. Better care continuity appears to have a greater beneficial effect in disadvantaged populations.

Outpatient Wound Clinics During COVID-19 Maintained Quality but Served Fewer Patients.

OBJECTIVE: To evaluate the impact of COVID-19-related disruptions on care continuity and outcomes of chronic wounds. DESIGN: Retrospective cohort study. SETTING AND PARTICIPANTS: Electronic medical records for 152,225 chronic wounds from a network of 488 wound care clinics in 45 US states and the District of Columbia. METHODS: Wound and patient characteristics, the number of chronic wounds newly seen at the clinics, and 12-week healing rates were compared between the first 2 quarters of 2019 and 2020. Multivariable regression models were constructed to evaluate whether the pandemic was associated with a statistically significant change in the probability of 12-week wound healing after risk adjustment. RESULTS: During the pandemic, wound and patient characteristics did not change compared to the previous year. Case volume dropped as much as 40% in April 2020 but returned to the previous year's level by June. No systematic changes in measures of care continuity were observed. Unadjusted 12-week healing rates remained stable at 0.502 in 2019 and 0.503 in 2020. Likewise, risk-adjusted 12-week healing rates were 0.504 and 0.505 in 2019 and 2020, respectively, but the difference was not statistically significant. States with stricter lockdowns saw a greater decline in case volume. However, the pandemic was not associated with a statistically significant change in the probability of 12-week wound healing in most states. The percentage of wounds with 1 or more telehealth visits increased from 0.14% in 2019 to 1.04% in 2020. CONCLUSIONS AND IMPLICATIONS: Despite COVID-19-related disruptions, our results suggest that wound care clinics maintained standards of care and outcomes for patients who sought care. This positive result should not detract from the problem that the number of new wounds seen at the clinics dropped sharply. Further research should evaluate outcomes in patients with unattended chronic wounds.

Value-Based Analysis of Therapies in Refractory Metastatic Colorectal Cancer in US.

BACKGROUND: Recent phase 2 trials have provided data supporting regorafenib dose optimization (ReDO) and trifluridine/tipiracil (TAS-102) with bevacizumab (TAS-BEV) as treatment options in refractory metastatic colorectal cancer (mCRC). Historically, regorafenib standard dose (RSD) and TAS-102 have been utilized as third-line options in mCRC. Given the incorporation of ReDO and TAS-BEV as treatment options, we sought to evaluate relative cost-effectiveness of ReDO vs. RSD, TAS-102, and TAS-BEV for mCRC from a payer perspective. METHODS: A Markov model was constructed to estimate total costs and quality-adjusted life-years (QALYs) for ReDO, RSD, TAS-102, and TAS-BEV. Clinical parameters were obtained from phase 2 and 3 trials for comparators. Health state utility values were from the RSD phase 3 clinical trial. Incremental cost-effectiveness ratios (ICERs) were utilized to compare treatments. Model robustness was checked with one-way and probabilistic sensitivity analyses. RESULTS: In the base case, ReDO was dominant over TAS-BEV (ie provided a higher QALY at a lower cost). ReDO produced an ICER of $104,308 per QALY relative to RSD and $37,966 relative to TAS-102. In one-way sensitivity analyses, monthly drug cost of TAS-BEV was the most influential parameter determining relative cost-effectiveness between TAS-BEV and ReDO. When TAS-102 and RSD were independently compared to ReDO, the most influential parameters were related to duration of OS and PFS and costs of managing AEs. CONCLUSIONS: The optimum dosing strategy for regorafenib has improved its benefit-to-toxicity ratio and relative cost-effectiveness compared to RSD, TAS-102, and TAS-BEV.

Projection of budgetary savings to US state Medicaid programs from reduced nursing home use due to an Alzheimer's disease treatment.

INTRODUCTION: The approval of a disease-modifying Alzheimer's disease (AD) treatment could provide relief to US state budgets that were hit hard by the COVID-19 pandemic, as mostly Medicare would cover treatment cost, whereas Medicaid would see savings from reduced nursing home use. METHODS: We project savings from 2021 to 2040 with a simulation model from the perspective of state Medicaid programs. RESULTS: Assuming a 40% and 22% relative reduction of disease progression rates with treatment, Medicaid would avoid payments of $186.2 and $93.5 billion for around 1.11 and 0.57 million nursing home patient-years, respectively. The savings correspond to a 5.06% and 2.49%, respectively, relative reduction of Medicaid spending on nursing home care. Higher per capita savings were projected for older states, those with higher Medicaid payment rates, those with more nursing home residents covered by Medicaid, and those with a lower federal contribution. DISCUSSION: States stand to realize substantial savings from a potential AD treatment. A state's health system preparedness to handle the large number of patients will influence the actual magnitude of the savings and how fast they will accrue.

Is Korea Prepared for an Alzheimer's Disease-Modifying Therapy? Assessing the Korean Healthcare System Infrastructure and the Effect of Blood-Based Biomarker Tests.

BACKGROUND: With the rapid demographic change in Korea, Alzheimer's disease has become a primary concern. Recent developments in disease-modifying therapies provide hope that therapy may become available soon. The high disease prevalence and complex evaluation process will create challenges for the healthcare system already burdened by the current pandemic. This study examined the preparedness of the South Korean healthcare system to identify and treat patients when such a therapy becomes available. METHODS: We used a Markov model to simulate a stylized patient's journey. Based on national data and expert input, we presented projections of the diagnosis and treatment wait times and respective queues of patients under treatment and no-treatment scenarios and further simulated the possible option of adopting a blood-based biomarker test. RESULTS: Under the current system, we estimated a peak waiting time of 14 months when a treatment became available, largely because of the limited number of dementia specialists. Adopting a blood-based biomarker test dramatically reduced the initial wait times by more than half. A disease-modifying therapy was estimated to avert 575,000 incident cases in the first 10 years after the treatment entered the market, and a blood-based test further avoided 86,000 additional cases. CONCLUSION: South Korea's healthcare infrastructure requires more preparation for the introduction of a disease-modifying therapy, with the primary capacity limitation being the low number of dementia specialists. The utilization of a blood-based test for Alzheimer's disease biomarkers may be an effective solution.

Blood-based biomarkers for Alzheimer's pathology and the diagnostic process for a disease-modifying treatment: Projecting the impact on the cost and wait times.

INTRODUCTION: Concerns have been raised about the limited health system capacity for identification of patients who are eligible for a disease-modifying Alzheimer's treatment (DMT). Blood-based biomarker (BBBM) tests are a promising tool to improve triaging at the primary care level. We projected their impact on cost of and wait times during the diagnostic process. METHODS: We compare four scenarios for triaging patients at the primary care level from the perspective of the U.S. health care system: (1) cognitive test only (Mini Mental State Examination [MMSE]), (2) BBBM test only, (3) MMSE followed by BBBM if positive, and (4) BBBM followed by MMSE if positive. RESULTS: Referring patients to dementa specialists based on MMSE or BBBM results alone would continuously require more specialist appointments than projected to be available until 2050. Combining MMSE and BBBM would eliminate wait lists after the first 3 years and reduce average annual cost by $400 to 700 million, while increasing correctly identified cases by about 120,000 per year. DISCUSSION: The combination BBBM with MMSE is projected to increase the efficiency and value of the triage process for DMT eligibility.

Development of a Model to Predict Healing of Chronic Wounds Within 12 Weeks.

Objective: Chronic wounds represent a highly prevalent but little recognized condition with substantial implications for patients and payers. While better wound care products and treatment modalities are known to improve healing rates, they are inconsistently used in real-world practice. Predicting healing rates of chronic wounds and comparing to actual rates could be used to detect and reward better quality of care. We developed a prediction model for chronic wound healing. Approach: We analyzed electronic medical records (EMRs) for 620,356 chronic wounds of various etiologies in 261,398 patients from 532 wound care clinics in the United States. Patient-level and wound-level parameters influencing wound healing were identified from prior research and clinician input. Logistic regression and classification tree models to predict the probability of wound healing within 12 weeks were developed using a random sample of 70% of the wounds and validated in the remaining data. Results: A total of 365,659 (58.9%) wounds were healed by week 12. The logistic and classification tree models predicted healing with an area under the curve of 0.712 and 0.717, respectively. Wound-level characteristics, such as location, area, depth, and etiology, were more powerful predictors than patient demographics and comorbidities. Innovation: The probability of wound healing can be predicted with reasonable accuracy in real-world data from EMRs. Conclusion: The resulting severity adjustment model can become the basis for applications like quality measure development, research into clinical practice and performance-based payment.

Budget Impact of 12-Month Fixed Treatment Duration Venetoclax in Combination with Obinutuzumab in Previously Untreated Chronic Lymphocytic Leukemia Patients in the United States.

OBJECTIVES: This study aimed to assess the total cost of care (TCC) and budget impact of introducing 12-month fixed duration venetoclax + obinutuzumab (VEN+G) as first-line treatment for chronic lymphocytic leukemia (CLL) from the perspective of a US health plan with 1,000,000 (1M) members. METHODS: The 3-year model included the following comparators: fludarabine + cyclophosphamide + rituximab (FCR), bendamustine + rituximab (BR), obinutuzumab + chlorambucil (GClb), ibrutinib (Ibr), and Ibr+Rituximab/obinutuzumab [Ibr+R/Ibr+G]). TCC included US-specific costs associated with treatment (i.e., drug, administration, and wastage), adverse events, routine care, and monitoring. Dosing and safety data were drawn from clinical trials and US package inserts. Budget impact outcomes were presented on an absolute and per-member per-month (PMPM) basis. Sensitivity analyses explored uncertainty in influential parameters, including scenarios testing the duration of treat-to-progression agents. RESULTS: Over the 3-year time horizon, introducing VEN+G in a 1M-member health plan resulted in total cost savings of $1,550,663 (PMPM - $0.04), compared to a scenario without VEN+G. The fixed 12-month duration of VEN+G contributed to this cost saving by reducing cumulative treatment costs compared with Ibr-based regimens. By year 3, the cumulative difference in TCC of VEN+G compared with Ibr, Ibr+G, and Ibr+R amounted to - $300,942, - $367,001, and - $369,784, respectively. Extensive sensitivity analyses supported the base case findings. CONCLUSIONS: Introducing VEN+G among first-line CLL treatments to a US health plan resulted in cost savings compared to a plan with chemoimmunotherapies and Ibr-based therapies only. Economic benefits of VEN+G, a novel agent with fixed treatment duration, coupled with proven clinical benefits should help inform formulary adoption decisions and treatment recommendations.

Complications and hospital costs during hematopoietic stem cell transplantation for non-Hodgkin lymphoma in the United States.

While the initial hospitalization accounts for 75% of total healthcare costs during the first 100 days following hematopoietic stem cell transplantation (HSCT), there is a lack of studies evaluating the considerable variation in cost estimates. Using the National Inpatient Sample (NIS) database from 2012-2014, we identified 1832 adult non-Hodgkin lymphoma (NHL) patients who received autologous or allogeneic HSCT and examined complications as predictors of hospital cost. Complications occurred in >70% of patients, and the presence of one or more complications was associated with an increase in mean hospital costs of 46% in autologous HSCT and 81% in allogeneic HSCT. The most common complications (∼40%) were mucositis, febrile neutropenia, and infection. Acute organ failure, acute graft-versus-host disease, and death were less frequent (∼10%) but had a greater impact on increasing hospital costs and length of stays. Despite recent advances in supportive care and pre-conditioning regimens, complications are common and costly during HSCT.

Cost-effectiveness Analysis of Regorafenib and TAS-102 in Refractory Metastatic Colorectal Cancer in the United States.

BACKGROUND: Regorafenib and TAS-102 are standard treatment options in refractory metastatic colorectal cancer based on improvement in overall survival by 6 and 8 weeks, respectively, when compared with best supportive care alone (BSC). Given the small incremental clinical benefit, we evaluated their cost-effectiveness from a United States payer's perspective. MATERIALS AND METHODS: A Markov model was constructed to compare costs and effectiveness of regorafenib, TAS-102, and BSC. Model inputs for clinical efficacy and adverse events were from the CORRECT trial (Regorafenib monotherapy for previously treated metastatic colorectal cancer: an international, multicentre, randomised, placebo-controlled, phase 3 trial) for regorafenib and the RECOURSE trial (Randomized, Double Blind, Phase 3 Study of TAS-102 plus Best Supportive Care [BSC] versus Placebo plus BSC in Patients with Metastatic Colorectal Cancer Refractory to Standard Chemotherapies) for TAS-102. The incremental cost-effectiveness ratios (ICERs) were reported to compare treatments. Model robustness was checked with univariate and probabilistic sensitivity analyses as well as a scenario analysis using the CONCUR trial data for regorafenib. RESULTS: In our base case, regorafenib and TAS-102 had the ICERs of $395,223 per quality-adjusted life year (QALY) and $399,740 per QALY versus BSC, respectively. Compared with regorafenib, TAS-102 provided an additional 0.041 QALY at the cost of $16,608 or $406,104 per QALY, but the differences were not robust in sensitivity analyses. The most influential parameters on the ICERs were efficacy and health state utility parameters as well as the cost of treating neutropenia. In probabilistic sensitivity analysis using cost-effectiveness acceptability curves, BSC was more cost-effective than both regorafenib and TAS-102 in 50% of repetitions at the willingness-to-pay threshold of $330,000 per QALY. CONCLUSION: Neither TAS-102 nor regorafenib are cost-effective at standard willingness-to-pay thresholds (ie, $150,000 per QALY) relative to BSC. There is no clear evidence that either treatment has better relative value.