The Influence of US Drug Price Dynamics on Cost-Effectiveness Analyses of Biologics.

OBJECTIVES: This study aimed to evaluate the influence of drug price dynamics in cost-effectiveness analyses. METHODS: We evaluated scenarios involving typical US drug price increases during the exclusivity period and price decreases after the loss of exclusivity (LOE). Worked examples are presented using the Institute for Clinical and Economic Review's assessments of tezepelumab for the treatment of severe asthma and targeted immune modulators for rheumatoid arthritis. RESULTS: Tezepelumab case: yearly 2% price increases during the period of exclusivity and a post-LOE price decrease of 25% yielded an incremental cost per quality-adjusted life-year (QALY) gained that increased over the base case from $430 300 to $444 600 (+3.2%). Yearly 2% price increases followed by a steeper post-LOE price reduction of 40% resulted in a cost per QALY gained of $401 400 (6.8% reduction vs the base case). Rheumatoid arthritis case: incorporating post-LOE price reductions for etanercept (intervention) and adalimumab (comparator) ranging from 25% to 40% yielded an incremental cost per QALY of $121 000 and $122 300, respectively (< 3% increase from the base case of $119 200/QALY). Including a 2% yearly price increase during the projected exclusivity periods of both intervention and comparator increased the cost per QALY gained by > 60%. CONCLUSION: Two biologic treatment cases incorporating price dynamics in cost-effectiveness analyses had varied impacts on the cost-effectiveness ratio depending on the magnitude of pre-LOE price increase and post-LOE price decrease and whether the LOE also affected the comparator. Yearly price increase magnitude during the period of exclusivity, among other factors, may counterbalance the effects of lower post-LOE intervention prices.

Benzodiazepine Dose Intensity among Patients Concurrently Prescribed Buprenorphine in Rhode Island.

Background: The concomitant use of buprenorphine and benzodiazepines has been linked to patient fatalities, with greater risk occurring with higher doses of benzodiazepines. We assessed benzodiazepine dose intensity among patients who were concurrently prescribed buprenorphine, as compared with patients prescribed benzodiazepines who were not receiving buprenorphine. Methods: We conducted a cross-sectional analysis of adult patients who received at least a 30-day supply of benzodiazepines during 2018, using data from the Rhode Island (RI) Prescription Drug Monitoring Program. Mean daily diazepam milligram equivalents (DME) were calculated overall and according to patient sex, age group, payment type, and RI county. Multivariable logistic regression analyses were conducted to assess the odds of higher-dose benzodiazepine utilization among patients with concurrent use of buprenorphine, as compared with patients not prescribed buprenorphine, adjusting for patient demographics. Results: Compared to patients prescribed benzodiazepines who were not receiving buprenorphine, those with concurrent buprenorphine utilization had a significantly higher mean DME/day (19.22, 95% CI: 18.70-19.74; vs 10.94, 95% CI: 10.93-10.95; p < 0.001). Patients who were prescribed benzodiazepines with concurrent utilization of buprenorphine also had a comparatively higher odds of a DME/day ≥15 (aOR: 2.86, 95% CI: 2.63-3.10), ≥20 DME/day (aOR: 2.98, 95% CI: 2.75-3.24), and ≥25 DME/day (aOR: 2.99, 95% CI: 2.65-3.18). Conclusion: Compared to patients prescribed benzodiazepines for at least 30 days who were not receiving buprenorphine, patients concurrently utilizing benzodiazepines and buprenorphine had more than twice the odds of higher dose benzodiazepine utilization. Future studies are needed to assess the relationship between benzodiazepine dose intensity, overdose outcomes, and treatment retention among patients receiving buprenorphine.

Addressing Posttreatment Selection Bias in Comparative Effectiveness Research, Using Real-World Data and Simulation.

To examine methodologies that address imbalanced treatment switching and censoring, 6 different analytical approaches were evaluated under a comparative effectiveness framework: intention-to-treat, as-treated, intention-to-treat with censor-weighting, as-treated with censor-weighting, time-varying exposure, and time-varying exposure with censor-weighting. Marginal structural models were employed to address time-varying exposure, confounding, and possibly informative censoring in an administrative data set of adult patients who were hospitalized with acute coronary syndrome and treated with either clopidogrel or ticagrelor. The effectiveness endpoint included first occurrence of death, myocardial infarction, or stroke. These methodologies were then applied across simulated data sets with varying frequencies of treatment switching and censoring to compare the effect estimate of each analysis. The findings suggest that implementing different analytical approaches has an impact on the point estimate and interpretation of analyses, especially when censoring is highly unbalanced.

Toward evaluation of disseminated effects of medications for opioid use disorder within provider-based clusters using routinely-collected health data.

Routinely-collected health data can be employed to emulate a target trial when randomized trial data are not available. Patients within provider-based clusters likely exert and share influence on each other's treatment preferences and subsequent health outcomes and this is known as dissemination or spillover. Extending a framework to replicate an idealized two-stage randomized trial using routinely-collected health data, an evaluation of disseminated effects within provider-based clusters is possible. In this article, we propose a novel application of causal inference methods for dissemination to retrospective cohort studies in administrative claims data and evaluate the impact of the normality of the random effects distribution for the cluster-level propensity score on estimation of the causal parameters. An extensive simulation study was conducted to study the robustness of the methods under different distributions of the random effects. We applied these methods to evaluate baseline prescription for medications for opioid use disorder among a cohort of patients diagnosed with opioid use disorder and adjust for baseline confounders using information obtained from an administrative claims database. We discuss future research directions in this setting to better address unmeasured confounding in the presence of disseminated effects.

Early buprenorphine-naloxone initiation for opioid use disorder reduces opioid overdose, emergency room visits, and healthcare cost compared to late initiation.

Background: Although the effectiveness of buprenorphine-naloxone (BUP-NX) has been established, real-world evidence on the benefits of early treatment initiation is limited.Objective: To evaluate the association between early BUP-NX initiation and health-related outcomes among insured adults with opioid use disorder (OUD).Methods: We conducted a cross-sectional analysis using the Optum's de-identified Clinformatics® Data Mart Database from 2010 to 2018. Patients who initiated BUP-NX within 30 days of OUD diagnosis were classified as early initiators. Patients who initiated BUP-NX later, but within the one-year follow-up, were defined as late initiators. Outcomes included opioid overdose, opioid overdose-related emergency department (ED) visits, and all-cause healthcare cost during the year after OUD diagnosis. We employed generalized linear models to compare outcomes between early and late initiators, adjusting for baseline covariates and accounting for missing information for covariates using multiple imputation.Results: A total of 8,388 patients with OUD were identified; mean age was 39.9 years; 36% were female; and 67.6% were early initiators. Early initiators had an estimated 42% lower rate of opioid overdose (adjusted rate ratio (aRR) = 0.58; 95% confidence interval (CI): 0.52, 0.64); 51% lower rate of opioid overdose-related ED visits (aRR = 0.49; 95% CI: 0.44, 0.55); and 31% lower total healthcare cost (adjusted cost ratio = 0.69; 95% CI: 0.66, 0.72), compared to late initiators.Conclusion: Compared to late BUP-NX initiation, early initiation was associated with a lower risk of opioid overdose and opioid overdose-related ED visits, and reduced total healthcare cost among insured adult patients with OUD.

Most Influential Physicochemical and In Vitro Assay Descriptors for Hepatotoxicity and Nephrotoxicity Prediction.

Drug-induced organ injury is a major reason for drug candidate attrition in preclinical and clinical drug development. The liver, kidneys, and heart have been recognized as the most common organ systems affected in safety-related attrition or the subject of black box warnings and postmarket drug withdrawals. In silico physicochemical property calculations and in vitro assays have been utilized separately in the early stages of the drug discovery and development process to predict drug safety. In this study, we combined physicochemical properties and in vitro cytotoxicity assays including mitochondrial dysfunction to build organ-specific univariate and multivariable logistic regression models to achieve odds ratios for the prediction of clinical hepatotoxicity, nephrotoxicity, and cardiotoxicity using 215 marketed drugs. The multivariable hepatotoxic predictive model showed an odds ratio of 6.2 (95% confidence interval (CI) 1.7-22.8) or 7.5 (95% CI 3.2-17.8) for mitochondrial inhibition or drug plasma Cmax >1 µM for drugs associated with liver injury, respectively. The multivariable nephrotoxicity predictive model showed an odds ratio of 5.8 (95% CI 2.0-16.9), 6.4 (95% CI 1.1-39.3), or 15.9 (95% CI 2.8-89.0) for drug plasma Cmax >1 µM, mitochondrial inhibition, or hydrogen-bond-acceptor atoms >7 for drugs associated with kidney injury, respectively. Conversely, drugs with a total polar surface area ≥75 Å were 79% (odds ratio 0.21, 95% CI 0.061-0.74) less likely to be associated with kidney injury. Drugs belonging to the extended clearance classification system (ECCS) class 4, where renal secretion is the primary clearance mechanism (low permeability drugs that are bases/neutrals), were 4 (95% CI 1.8-9.5) times more likely to to be associated with kidney injury with this data set. Alternatively, ECCS class 2 drugs, where hepatic metabolism is the primary clearance (high permeability drugs that are bases/neutrals) were 77% less likely (odds ratio 0.23 95% CI 0.095-0.54) to to be associated with kidney injury. A cardiotoxicity model was poorly defined using any of these drug physicochemical attributes. Combining in silico physicochemical properties descriptors along with in vitro toxicity assays can be used to build predictive toxicity models to select small molecule therapeutics with less potential to cause liver and kidney organ toxicity.

Guideline-Concordant Treatment Among Elderly Women With HER2-Positive Metastatic Breast Cancer in the United States.

BACKGROUND: It is crucial to identify whether women with HER2-positive (HER2+) metastatic breast cancer (MBC) are treated according to treatment guidelines and whether treatment disparities exist. This study examined guideline-concordant treatment among women with HER2+ MBC and determined the magnitude of differences in treatment between those with positive and negative hormone receptor (HR) status using a nonlinear decomposition technique. METHODS: A retrospective observational cohort study was conducted using the SEER-Medicare linked database. The study cohort consisted of women aged ≥66 years diagnosed with HER2+ MBC in 2010 through 2013 (n=241). Guideline-concordant initial treatment after cancer diagnosis was defined based on the NCCN Clinical Practice Guidelines in Oncology for Breast Cancer. A multivariable logistic regression was performed to identify significant predictors of guideline-concordant treatment. A postregression decomposition was conducted to identify the magnitude of disparities in treatment by HR status. RESULTS: Of 241 women included in the study, a total of 76.8% received guideline-concordant treatment. These women were significantly more likely to have positive HR status (P=.0298), have good performance status (P=.0009), and more oncology visits (P<.0001). With 1-year increments in age at cancer diagnosis, the likelihood of receiving guideline-concordant treatment reduced by 5% (P=.0356). The decomposition analysis revealed that 19.0% of the disparity in guideline-concordant treatment between women with positive and negative HR status was explained by differences in their characteristics. Enabling characteristics (marital status, income, and education) explained the highest (22.8%) proportion of the disparity. CONCLUSIONS: Nearly one-quarter of the study cohort did not receive guideline-concordant treatment. Our findings suggest opportunities to improve cancer care for elderly women with negative HR status who are unpartnered or have lower socioeconomic status. The high unexplained portion of the disparity by HR status can be due to patient treatment preferences, propensity to seek care, and organizational and physician-level characteristics that were not included in the study.

Chronic opioid use in women following hysterectomy: Patterns and predictors.

BACKGROUND: Most women are prescribed an opioid after hysterectomy. The goal of this study was to determine the association between initial opioid prescribing characteristics and chronic opioid use after hysterectomy. METHODS: This study included women enrolled in a commercial health plan who had a hysterectomy between 1 July 2010 and 31 March 2015. We used trajectory models to define chronic opioid use as patients with the highest probability of having an opioid prescription filled during the 6 months post-surgery. A multivariable logistic regression was applied to examine the association between initial opioid dispensing (amount prescribed and duration of treatment) and chronic opioid use after adjusting for potential confounders. RESULTS: A total of 693 of 50 127 (1.38%) opioid-naïve women met the criteria for chronic opioid use following hysterectomy. The baseline variables and initial opioid prescription characteristics predicted the pattern of long-term opioid use with moderate discrimination (c statistic = 0.70). Significant predictors of chronic opioid use included initial opioid daily dose (≥60 MME vs <40 MME, aOR: 1.43, 95% CI: 1.14-1.79) and days' supply (4-7 days vs 1-3 days, aOR: 1.28, 95% CI: 1.06-1.54; ≥8 days vs 1-3 days, aOR: 1.41, 95% CI: 1.05-1.89). Other significant baseline predictors included older age, abdominal or laparoscopic/robotic hysterectomy, tobacco use, psychiatric medication use, back pain, and headache. CONCLUSION: Initial opioid prescribing characteristics are associated with the risk of chronic opioid use after hysterectomy. Prescribing lower daily doses and shorter days' supply of opioids to women after hysterectomy may result in lower risk of chronic opioid use.

Outcomes in human immunodeficiency virus-infected recipients of heart transplants.

BACKGROUND: With the advent of combined antiretroviral therapy (cART), growing evidence has shown human immunodeficiency virus (HIV) may no longer be an absolute contraindication for solid organ transplantation. This study compares outcomes of heart transplantations between HIV-positive and HIV-negative recipients using SRTR transplant registry data. METHODS: Patient survival, overall graft survival and death-censored graft survival were compared between HIV-positive and HIV-negative recipients. Multivariate Cox regression and Cox regression with a disease risk score (DRS) methodology were used to estimate the adjusted hazard ratios among heart transplant recipients (HTRs). RESULTS: In total, 35 HTRs with HIV+ status were identified. No significant differences were found in patient survival (88% vs 77%; P = 0.1493), overall graft survival (85% vs 76%; P = 0.2758), and death-censored graft survival (91% vs 91%; P = 0.9871) between HIV-positive and HIV-negative HTRs in 5-year follow-up. No significant differences were found after adjusting for confounders. CONCLUSIONS: This study supports the use of heart transplant procedures in selected HIV-positive patients. This study suggests that HIV-positive status is not a contraindication for life-saving heart transplant as there were no differences in graft, patient survival.

Stevens-Johnson syndrome and toxic epidermal necrolysis with antiepileptic drugs: An analysis of the US Food and Drug Administration Adverse Event Reporting System.

OBJECTIVE: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare and potentially fatal adverse skin reactions that are most commonly triggered by certain medications. One class of medications that has been highly associated with SJS/TEN reactions is antiepileptic drugs (AEDs). We sought to quantify the risk of SJS/TEN associated with AEDs as a class, as well as individual AEDs, in the United States. METHODS: An analysis was performed of the US Food and Drug Administration Adverse Event Reporting System (FAERS) from July 2014 through December 2017. Rates of SJS/TEN were calculated for each AED compared with all other non-AEDs. Reporting odds ratios (RORs), proportional reporting ratios (PRRs), and 95% confidence intervals (CIs) were calculated using OpenEpi. RESULTS: With 198 reports, AEDs had more reports of SJS/TEN than any other medication class. AEDs as a class had an ROR of 8.7 (95% CI 7.5-10.2) and a PRR of 8.7 (95% CI 7.5-10.2) compared with all other non-AEDs. The AEDs with the highest risk estimates were zonisamide (ROR 70.2, 95% CI 33.1-148.7; PRR 68.7, 95% CI 32.9-143.5), rufinamide (ROR 60.0, 95% CI 8.3-433.5; PRR 58.9, 95% CI 8.4-411.5), clorazepate (ROR 56.0, 95% CI 7.8-404.1; PRR 55.1, 95% CI 7.8-385.0), lamotrigine (ROR 53.0, 95% CI 43.2-64.9; PRR 52.2, 95% CI 42.7-63.7), phenytoin (ROR 26.3, 95% CI 15.5-44.7; PRR 26.1, 95% CI 15.4-44.2), and carbamazepine (ROR 24.5, 95% CI 16.0-37.5; PRR 24.3, 95% CI 16.0-37.1). SIGNIFICANCE: Although AEDs as a class were associated with 9 times the risk of SJS/TEN compared with non-AEDs, there were 6 AEDs with risk estimates greater than 20. Increased awareness of this risk among both prescribers and patients, particularly variations in risk among different AEDs, along with education on early recognition of SJS/TEN signs/symptoms, may help mitigate the number and severity of these adverse events.

A primer on quality measurement and reporting in pharmacy benefit plans.

Pharmacy benefit plans in the United States are evaluated on quality measures and other requirements of the government and accrediting organizations. This primer describes the roles of key organizations involved in measuring and reporting quality in pharmacy benefit plans and explains the methods that pharmacy benefit plans use to promote quality of medication use.

Association between adherence with oral anticancer medications and short-term health care resource utilization: A 2010-2018 claims-based analysis.

BACKGROUND: There is limited evidence on the effect of adherence to oral anticancer medications on health care resource utilization (HRU) among patients with cancer. OBJECTIVE: To determine the association between adherence to oral anticancer medication and subsequent HRU. METHODS: A retrospective cohort study was conducted using Optum Clinformatics® Data Mart commercial claims database. Patients who initiated an oral anticancer medication between 2010 and 2017 were included. Proportion of days covered was used to calculate medication adherence in the first 6 months after oral anticancer medication initiation. All-cause HRU in the following 6 months was assessed. Multivariable negative binomial regressions were used to determine the association between oral anticancer medication adherence and HRU, after controlling for confounders. RESULTS: Of 37,938 patients, 51.9% were adherent to oral anticancer medications. Adherence with oral anticancer medication was significantly associated with more frequent physician office and outpatient visits for several cancer types with the strongest association among those with liver cancer (adjusted incidence rate ratio [aIRR] = 1.34; 95% CI = 1.18-1.52 and aIRR = 1.32; 95% CI = 1.13-1.55, respectively). Oral anticancer medication adherence was associated with more emergency department visits only among patients with lung cancer (aIRR = 1.22; 95% CI = 1.01-1.48). Oral anticancer medication adherence was significantly associated with a higher rate of inpatient hospitalizations and longer stays among patients with liver cancer (aIRRs were 1.45 [95% CI = 1.02-2.05] and 2.15 [95% CI = 1.21-3.81], respectively), whereas hospitalizations were fewer and length of stay was shorter among patients with colorectal cancer who were adherent with oral anticancer medication (aIRRs were 0.77 [95% CI = 0.68-0.86] and 0.77 [95% CI = -0.66 to 0.90], respectively). Other measures did not reveal statistically significant differences in HRU among adherent and nonadherent patients for the cancer types included in the study. CONCLUSIONS: HRU following the initial phase of oral anticancer medication therapy was generally similar among adherent and nonadherent patients. We observed a slightly higher rate of office and outpatient visits among adherent patients, which may reflect ongoing monitoring among patients continuing oral anticancer medication. Further studies are needed to determine how oral anticancer medication adherence may affect HRU over a longer time period.

Use of electronic personal health records to identify patients at risk for aspirin-induced gastrointestinal bleeding.

OBJECTIVE(S): The aim of this paper is to describe the utility of electronic personal health records (ePHRs) to identify patients with potential risk factors for aspirin-induced upper gastrointestinal bleeding (UGIB). SETTING: ER-Card, LLC. a for-profit ePHR company located in Rhode Island from October 2008 to May 2010. PRACTICE DESCRIPTION: Clinical pharmacists reviewed the records of 615 patients enrolled in an ePHR service. Records included patient self-report of all known medical conditions, current prescription medications, and self-care therapies utilized. PRACTICE INNOVATION: Pharmacists reviewed ePHR profiles for actual or potential medication-related problems. Patients taking low-dose aspirin (81 mg-325 mg daily) were screened for known additional risk factors for aspirin-induced UGIB. Patients identified were notified to contact their provider for information and/or providers were contacted directly by pharmacists with therapy recommendations. MAIN OUTCOME MEASURE(S): Number of patients at increased risk for aspirin-induced UGIB as a result of concomitant medications. RESULTS: Ninety-seven patients (16% of total records screened) with an average age of 72.1 years had risk factors for aspirin induced UGIB. In addition to daily aspirin therapy patients reported regular use of nonsteroidal anti-inflammatory drugs or cyclooxygenase-2 inhibitors (38%), other antiplatelet agents (22%), anticoagulants (24%), corticosteroids (4%), or a combination of these medications (12%). None of the patients included in this analysis reported use of prescribed or overthe-counter gastroprotective therapy (such as proton-pump inhibitors or histamine-2 receptor antagonists). CONCLUSION: Pharmacist screening of patient self-reported health information as part of an ePHR service can result in the detection of a significant number of patients at increased risk for aspirin-induced UGIB.

Rhode Island Has the Highest Rate of Medicare Part D Claims for Benzodiazepines Among New England States.

BACKGROUND: Benzodiazepine use among older adults is discouraged. METHODS: We analyzed the Medicare Part D Prescribers by Provider and Drug dataset to determine the number of benzodiazepine claims per 100 Medicare enrollees for each NE state between 2016-2020, and to determine the percentage of benzodiazepine claims by provider type. RESULTS: Rhode Island led all NE states the with highest annual rates of Part D benzodiazepine claims for all years from 2016 to 2020. Benzodiazepine claims decreased in all NE states over the 5-year period. Internal medicine and family practice providers were associated with the highest percentage of benzodiazepine claims. CONCLUSION: While Part D benzodiazepine claims declined between 2016-2020, the overall volume of dispensings suggests that these medications remain overprescribed among older adults. Our findings underscore the need for intensified efforts to reduce benzo- diazepine use among Medicare beneficiaries in RI.

PHARMACY DEDUCTIBLES CAN COMPLICATE THE RELATIONSHIP BETWEEN MEASURES OF PATIENT COST SHARING AND MEDICATION ADHERENCE.

DISCLOSURES: This letter pertains to our recent publication in JMCP, which describes a study that was jointly funded by the Pharmacy Quality Alliance and the National Pharmaceutical Council.

Evaluation of the association between health insurance status and healthcare utilization and expenditures among adult cancer survivors in the United States.

BACKGROUND: Health care expenditures for cancer care has increased significantly over the past decade and is further projected to rise. This study examined the associations between health insurance status and total direct health care expenditures and health care utilization among cancer survivors living in the United States. METHODS: A cross-sectional study of cancer survivors aged ≥18 years, identified from the Medical Expenditures Panel Survey (MEPS) during 2017 using International Classification of Diseases, Tenth Revision codes specific for cancer. Health insurance was categorized into Private, Medicare, Medicaid, and uninsured. Multivariable ordinary least squares regression was used to examine the association between log expenditures and health insurance. Negative binomial regression with log link was used to obtain adjusted incident rate ratios (AIRR) for health care utilization. Survey weights were used to produce nationally representative estimates of the US population. RESULTS: A total of 1140 (weighted = 13.9 million) cancer survivors were identified. Compared to the adjusted mean annual health care expenditures for the private group ($14,265; 95% confidence interval (CI): $12,645 to $16,092), the adjusted mean annual health care expenditures for the Medicare group were higher ($15,112; 95%CI: $13,361 to $17,092). As compared to the private group, the average annual expenditures for uninsured cancer survivors ($2315; 95%CI:1038 to $3501) was significantly lower and so was their health care utilization. Adjusted rates of ER visits for Medicaid were twice (AIRR:2.04; SE:0.28; p = 0.001) as compared to privately insured. CONCLUSIONS: A difference in the average total direct expenditures between uninsured and privately insured patients was found. Uninsured had the lowest health care utilization while Medicaid reported significantly higher number of ER visits. Despite differences in program structures, health care expenditures across insurance types were similar. Lower utilization of health care services among uninsured suggests cost maybe a barrier to accessing care.

Tramadol utilization among patients with higher risk of adverse drug events: A claims analysis of commercially insured and Medicare Advantage members.

OBJECTIVE: To assess prescribing of tramadol among patients with contraindications and higher risks of adverse events in a large population of commercially insured and Medicare Advantage members. DESIGN: We performed a cross-sectional analysis evaluating tramadol utilization in patients with higher risk of adverse outcomes. SETTING: This study utilized 2016-2017 data from the Optum Clinformatics Data Mart. PATIENTS AND PARTICIPANTS: Patients with at least one tramadol prescription without a cancer or sickle cell diagnosis during the study period. MAIN OUTCOME MEASURES: We first determined if tramadol was prescribed among patients with contraindications or risk factors for adverse outcomes. We then determined if patient demographic or clinical factors were associated with the use of tramadol in these higher-risk scenarios using multivariable logistic regression models. RESULTS: Among patients with at least one prescription for tramadol, 19.66 percent (99 percent CI: 19.57-19.75) concurrently received an interacting cytochrome P450 isoenzyme medication, 19.24 percent (99 percent CI: 19.15-19.33) concurrently received a serotonergic medication, and 7.93 percent (99 percent CI: 7.88-8.00) concurrently received a benzodiazepine. Additionally, 1.59 percent (99 percent CI: 1.56-1.61) of patients who received tramadol also had a seizure disorder, while 0.55 percent (99 percent CI: 0.53-0.56) of patients were under the age of 18. Overall, nearly one in three patients (31.17 percent) received tramadol in the presence of at least one of these risks (99 percent CI: 31.06-31.27). CONCLUSION: Almost one in three patients prescribed tramadol had a clinically significant drug interaction or contraindication for use, suggesting that prescribers often disregard these concerns. Real-world studies are needed to better understand the likelihood of harms associated with the use of tramadol in these contexts.

Researcher Views of Barriers to Clinical and Translational Research in a Statewide Program.

The Tracking and Evaluation Core of Rhode Island Advance-CTR conducted an online needs assessment survey at the program's inception in 2016 and again in 2021. Now dealing with well-established support systems provided by the grant, we were particularly interested in how the perceived needs of the research community in Rhode Island might have changed over five years. Specifically, what barriers have been reduced or eliminated and which have persisted or increased? How do those barriers vary by demographic status and what implications do those differences have for the CTR? An online survey was completed by 199 researchers, who reported the extent to which they perceived the lack of access to a range of research supports as a barrier to conducting research at their institution. Overall, researchers indicated statistically significant changes from 2016 to 2021 such that a lack of pilot project funding and proposal development support had decreased as barriers, while space for research, and advice on commercial development, had increased. Statistically significant differences in the salience of particular barriers by some demographic variables were also noted and the results of this study suggest Centers for Clinical and Translational Research can have salutary effects on the research paradigm within their partnering institutions in a relatively short time.

Concomitant use of triptan, and SSRI or SNRI after the US Food and Drug Administration alert on serotonin syndrome.

OBJECTIVE: The present study was designed to discern the prevalence of concomitant use of a 5-hydroxytryptamine receptor agonist (triptan), and a selective serotonin reuptake inhibitor (SSRI) or a selective serotonin/norepinephrine reuptake inhibitor (SNRI) after the US Food and Drug Administration issued an alert regarding serotonin syndrome in 2006 and to contrast findings with data published prior to the federal warning. BACKGROUND: In July 2006, the US Food and Drug Administration warned patients and health-care professionals to be aware that use of a triptan in combination with an SSRI or SNRI may result in a potentially life-threatening problem known as serotonin syndrome. In 2010, the American Headache Society published a position paper noting that there existed conflicting and insufficient information to discern the risk of serotonin syndrome with the use of triptan, and SSRI or SNRI, and that said Class IV data were not to be used as the basis for limiting the prescribing of triptan with SSRI or SNRI (Level U). Clinicians were cautioned as to the seriousness of serotonin toxicity and that monitoring was warranted. METHODS: We used weighted data from the US National Ambulatory Medical Care Survey for years 2007 and 2008 to derive national estimates of the number of office-based physician-patient encounters (visits), documenting the concomitant use of triptan, and SSRI or SNRI. Results are compared with previously published findings for the years 2003 and 2004. RESULTS: During the time-frame 2007-2008, an annualized mean of 5,256,958 patients were prescribed a triptan (vs 3,874,367 in 2003-2004, a 35.7% increase), and 68,603,600 patients were prescribed an SSRI or SNRI (vs 50,402,149 in 2003-2004, a 36.1% increase). An annualized mean of 1,319,763 patients were simultaneously prescribed or continued use of triptan, along with SSRI or SNRI (vs 694,276 in 2003-2004, a 90.1% increase). CONCLUSION: Our study documents that 1.8% (1,319,763/73,860,558) of patients in 2007-2008 were prescribed triptan, and SSRI or SNRI (vs 1.3% in 2003-04, an increase of 38.5%). While this is a small fraction overall, the actual number of patients on a nationwide basis is substantial. What remains missing from the literature is documentation as to the number of cases of serotonin syndrome and resulting consequences (clinical and economic) because of the concomitant use of triptan, and SSRI or SNRI in the time-frame 2007-2008. Absent in these data, it remains difficult to assess the risk benefit associated with the use of triptan, and SSRI or SNRI.

Network-based Analysis of Prescription Opioids Dispensing Using Exponential Random Graph Models (ERGMs).

The United States has been experiencing an unprecedented level of opioid overdose-related mortality due in part to excessive use of prescription opioids. Peer-driven network interventions may be beneficial. A key assumption of social network interventions is that of some members of the network act as key players and can influence the behavior of others in the network. We used opioid prescription records to create a social network of patients who use prescription opioid in the state of Rhode Island. The study population was restricted to patients on stable opioid regimens who used one source of payment and received the same opioid medication from ≥ 3 prescribers and pharmacies. An exponential random graph model (ERGM) was employed to examine the relationship between patient attributes and the likelihood of tie formation and modularity was used to assess for homophily (the tendency of individuals to associate with similar people). We used multivariable logistic regression to assess predictors of high betweenness centrality, a measure of influence within the network. 372 patients were included in the analysis; average age was 51 years; 53% were female; 57% were prescribed oxycodone, 34% were prescribed hydrocodone and 9% were prescribed buprenorphine/naloxone. After controlling for the main effects in the ERGM model, homophily was associated with age group, method of payment, number and type of opioid prescriptions filled, mean daily dose, and number of providers seen. Type of opioid and number of prescribers were identified as significant predictors of high betweenness centrality. We conclude that patients who use multiple prescribers or have a diagnosis of opioid use disorder may help promote positive health behaviors or disrupt harmful behaviors in an opioid prescription network.