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Papers by Carl Roland

This is supplemental data for this manuscript: Supplemental Methods – This is a descrip... more This is supplemental data for this manuscript: Supplemental Methods – This is a description of the additional inclusion and exclusion criteria and the adverse events of special interest. Supplemental Table S1 – This dataset describes the incidence and severity of all-causality treatment-emergent adverse events. Supplemental Table S2 – This dataset describes the treatment-related adverse events stratified according to whether subjects had two consecutive increases in IGF-1 SDS >2 Supplemental Table S3 – This dataset shows the values for glucose metabolism for subjects throughout the study. Supplemental Figure S1 – This dataset shows the height velocities for all the individual subjects. Supplemental Figure S2 – This dataset shows the instances of injection site pain for subjects throughout the study.

Epilepsia, Sep 20, 2013

A diazepam auto-injector (AI) has been developed for intramuscular administration to treat acute ... more A diazepam auto-injector (AI) has been developed for intramuscular administration to treat acute repetitive seizures (ARS). The objective of this study was to evaluate the efficacy and safety of the diazepam AI when administered by caregivers to control an episode of ARS. In this phase III, randomized, double-blind, parallel-group, placebo-controlled, multicenter study, subjects with epilepsy on a stable antiepileptic drug regimen who required intermittent medical intervention to control ARS were randomized 1:1 to the placebo AI or the diazepam AI group. Subjects were stratified according to age (2-5, 6-11, ≥12 years). Dose (5, 10, 15, or 20 mg) was based on age and weight. A single dose of study medication was dispensed to be administered by caregivers in an outpatient setting when required. The primary end point was time to next seizure or rescue from 15 min to 12 h postdose. Secondary end points included rescue medication use, number of seizures postdose, caregiver and physician treatment assessments, and safety measures. Of 234 subjects randomized, 81/110 in the placebo AI group and 82/124 in the diazepam AI group were included in the intent-to-treat analysis. Baseline characteristics were similar for both groups. Time to next seizure or rescue was significantly longer in the diazepam AI group compared with the placebo AI group, with a hazard ratio of 0.55 (95% confidence interval (CI) 0.34-0.88; p = 0.012) for diazepam AI versus placebo AI, adjusted for age group. The 25th percentile for time to the next seizure or rescue was 1.18 h (95% CI 0.38-2.03) for placebo AI and 2.70 h (95% CI 0.48-11.42) for diazepam AI; the median was 5.9 h for placebo AI and was inestimable for diazepam AI due to the low number of events experienced by subjects in that group. The proportion of subjects using rescue medication postdose was 30% (24/81) placebo AI versus 17% (14/82) diazepam AI (p = 0.066). An event (seizure or rescue) occurred in 55.6% of subjects in the placebo AI group and 35.4% in the diazepam AI group. The number of seizures experienced during the 12-h postdose period was significantly lower for diazepam AI (median 0.0) compared with placebo AI (median 1.0; p = 0.010). Treatment-emergent adverse events (TEAEs) were reported in 44% (35/79) of subjects in the placebo AI group and 42% (34/81) in the diazepam AI group. The most common TEAEs reported were injection site pain (15% placebo AI, 17% diazepam AI) and injection site hemorrhage (6% placebo AI, 5% diazepam AI). The diazepam AI was significantly more effective than placebo AI at delaying the next seizure or rescue. Secondary efficacy end points were generally supportive of the primary outcome. Diazepam AI administered by trained caregivers was effective for the treatment of ARS and was well-tolerated, with a safety profile similar to placebo.

Drug and Alcohol Dependence, 2014

Aims: Despite the growing problem of prescription opioid misuse, abuse, and diversion (MAD) in so... more Aims: Despite the growing problem of prescription opioid misuse, abuse, and diversion (MAD) in society, the prevalence of MAD in the pain patient population is not clear. Since there are no instruments that measure MAD in this patient population, a novel, self-report MAD Instrument has been developed. This instrument assesses tampering methods, overconsumption use by unintended routes of administration, and diversion. The instrument queries the motives behind these behaviors in order to classify them as either misuse or abuse. The MAD Instrument consists of several questions with multiple-choice options, and several questions where patients rate their concerns regarding prescription opioids on an 11-point (0 = not at all to 10 = extremely worried) numeric rating scale. This study assessed the content validity and patient interpretation of the MAD Instrument. Methods: Patients with chronic pain, who were at low risk for prescription opioid abuse and were currently taking opioids for optimal analgesia (≥30 days) have undergone 2 rounds of 1:1 cognitive interviews (round 1, n = 9; round 2, n = 11). Participants also completed sociodemographic and Brief Pain Inventory questionnaires. Results: Patient age ranged from 25 to 76 years, 60% were female, and 80% white. Overall, 17 (85%) patients reported feeling comfortable answering the questions honestly. Five (25%) patients stated concerns regarding confidentiality and legal consequences when completing the questionnaire via internet and 3 did not have internet access. Six (30%) did not understand the term "opioid"; the use of "strong pain medication" was clearer. Participants understood the meaning of each question and were not offended. Participants were able to answer questions with the given response options. For reasons of misuse/abuse, obtaining pain relief quicker or better were suggested as reasons to include. Conclusions: Overall, the patients understood the MAD Instrument and could answer its questions. Financial support: This study was sponsored by Pfizer Inc.

The Journal of Pain, 2013

The Journal of Clinical Endocrinology & Metabolism

Context Somatrogon is a long-acting recombinant human growth hormone (rhGH) in development for on... more Context Somatrogon is a long-acting recombinant human growth hormone (rhGH) in development for once-weekly treatment of children with growth hormone deficiency (GHD). Objective We aimed to compare the efficacy and safety of once-weekly somatrogon with once-daily somatropin in prepubertal children with GHD. Methods In this 12-month, open-label, randomized, active-controlled, parallel-group, phase 3 study, participants were randomized 1:1 to receive once-weekly somatrogon (0.66 mg/kg/week) or once-daily somatropin (0.24 mg/kg/week) for 12 months. A total of 228 prepubertal children (boys aged 3-11 years, girls aged 3-10 years) with GHD, impaired height and height velocity (HV), and no prior rhGH treatment were randomized and 224 received ≥1 dose of study treatment (somatrogon: 109; somatropin: 115). The primary endpoint was annualized HV at month 12. Results HV at month 12 was 10.10 cm/year for somatrogon-treated subjects and 9.78 cm/year for somatropin-treated subjects, with a treatm...

Journal of the Endocrine Society, 2021

Objectives: Somatrogon (hGH-CTP) is a long acting recombinant human growth hormone, consisting of... more Objectives: Somatrogon (hGH-CTP) is a long acting recombinant human growth hormone, consisting of the amino acid sequence of hGH and three copies of the carboxy-terminal peptide (CTP) of human chorionic gonadotropin (hCG) being developed as a once weekly treatment for children with pGHD. This report summarizes data from the first year of the optional open-label extension (OLE) of the pivotal phase 3 global trial (ClinicalTrials. gov: NCT02968004), comparing the efficacy and safety of children switched from Genotropin (rhGH; somatropin) to somatrogon (Geno/Soma) and children maintained on somatrogon (Soma/Soma). Methods: During the main study, 224 children were randomized to receive either once weekly somatrogon (0.66 mg/kg, n=109) or once daily Genotropin (0.24 mg/kg/wk, n=115) for 12 months. Of these, 222 completed the 12-month main study, and 212 chose to enter the OLE study. By Sept 30, 2020, 161 children (including 76 Geno/Soma) had complete auxological data at month 12 of the O...

Journal of Medical Economics, 2019

Objectives: To extend a previously published manuscript on a model for estimating potential avoid... more Objectives: To extend a previously published manuscript on a model for estimating potential avoided medical events and cost savings in the US associated with the introduction of extended-release abusedeterrent opioids and incorporate new methods of evaluating abuse deterrence using human abuse potential studies. Methods: A model was developed to estimate reductions in abuse-related events and annual savings in the US. Model inputs included: opioid abuse prevalence, abuse-deterrent opioid cost and effectiveness at deterring abuse, and opioid abuse-related events and costs. Direct (medical and drug) and indirect (work loss) cost savings (2017 US$) and abuse-related events were estimated assuming the replacement of the entire extended-release opioid market (brand and generic) by brand abuse-deterrent opioids. Results: Replacing the extended-release opioid market with abuse-deterrent opioids is estimated to lower annual abuse-related medical events by 13-31% (e.g. 78,000-186,000 emergency department visits) and lower annual medical costs by 640M−640 M-640M−1,538 M, depending on the abuse-deterrent technology (physical/chemical barrier or agonist/antagonist). Replacement of extended-release oxycodone with extended-release abuse-deterrent oxycodone is associated with the largest amount of cost savings and highest number of avoided medical events, followed by replacing extended-release morphine with an extended-release abuse-deterrent opioid. Replacement of transdermal fentanyl is associated with the smallest amount of cost savings and lowest number of avoided medical events. Conclusion: Agonist/antagonist abuse-deterrent opioid technology is associated with higher annual medical cost savings and more avoided events than physical/chemical barrier technology. Total net savings are dependent upon the abuse-deterrent opioid price relative to non-abuse-deterrent opioids.

Journal of Managed Care & Specialty Pharmacy, 2019

BACKGROUND: Reliance on prescription opioids to manage pain has been associated with increases in... more BACKGROUND: Reliance on prescription opioids to manage pain has been associated with increases in diversion, overdose, and addiction. Prevalence of misuse and abuse has been shown to be higher among governmentinsured populations than commercially insured populations. However, the prevalence and costs of misuse/abuse among the Medicare fee-for-service (FFS) population has not been studied. OBJECTIVES: To (a) determine the prevalence and costs of prescription opioid misuse/abuse and (b) evaluate the prevalence and costs associated with those identified as at risk for opioid misuse/abuse in Medicare FFS beneficiaries. METHODS: This retrospective case-control study used Medicare claims data for the calendar years of 2010 and 2011 and included Medicare beneficiaries aged at least 18 years. The index date was the date of first diagnosed misuse/abuse or at risk for abuse and had to occur between July 1, 2010, and June 30, 2011, and beneficiaries had to have at least 6 months continuous eligibility before and after the index date. Matching (1:1) was used for comparing opioid misusers/abusers with nonabuser controls, as well as comparing patients at risk for opioid abuse with controls not at risk for abuse. Controls were matched to cases by gender, age, disability, and geographic region. The index date of the control patient was set equal to the index date of the matched case. RESULTS: Prevalence of misuse/abuse in the Medicare FFS population was 13.1 per 1,000 persons, with the majority among patients receiving Medicare based on disability (76.2%). The prevalence of at risk for misuse/ abuse was 117.4 per 1,000 persons. Approximately half of the Medicare FFS patients used an opioid.

Journal of pain & palliative care pharmacotherapy

Prescription opioids are among the most effective analgesics to treat moderate to severe pain; ho... more Prescription opioids are among the most effective analgesics to treat moderate to severe pain; however, little is known about the use of prescription opioids in children, particularly those receiving an extended-release formulation for the treatment of chronic pain. In this retrospective study, the authors determined the prevalence of prescription opioid use among 7-17-year-old children and associated comorbid health conditions from 2010 to 2013 using Truven Health MarketScan (MarketScan) and Optum Clinformatics DataMart (Optum). The primary end points were prevalence of using any prescription opioids, using only prescription short-acting opioids (SAOs), and at least one prescription of a long-acting opioid (LAO). The prevalence of prescription opioid use among children is non-negligible and has been trending downwards: 6.90% in 2010 and 5.93% in 2013 using MarketScan and a similar trend using Optum: 5.47% in 2010 and 4.51% in 2013. Very few children had claims for LAOs, with only 0...

Value in Health, 2016

A243 MarketScan® Commercial Claims data (2003-2004). Patients prescribed orilistat, sibutramine o... more A243 MarketScan® Commercial Claims data (2003-2004). Patients prescribed orilistat, sibutramine or phentermine were included. Propensity-score matching was used to balance the baseline characteristics between the group of patients on orlistat and the group prescribed sibutramine or phentermine. A COX proportional hazard regression was estimated to compute risks for acute liver injury. Results: A total of 13,792 patients on antiobesity medication were identified. Overall, 145 patients (2.10%) in the orlistat group had at least one acute liver injury event, and 99 patients (1.44%) in the sibutramine/phentermine group experienced one. After propensityscore matching, orlistat patients were found to be significantly more likely to experience acute liver injury than patients in the sibutramine/phentermine group (Hazard Ratio (HR), 1.364; 95% CI: 1.055-1.763; p-value= 0.0177). In addition, elderly patients (HR, 1.021; 95% CI: 1.006-1.036; p-value= 0.0054), patients with type 2 diabetes (HR, 1.534; 95% CI: 1.155-2.038; p-value= 0.0032), patients with hyperlipidemia (HR, 1.476; 95% CI: 1.126-1.934; p-value= 0.0048), and patients who took hepatotoxic drugs in the washout period or up to 3 months before the liver event (HR, 1.840; 95% CI: 1.426-2.374; p-value< 0.0001) had an increased risk of injury. ConClusions: Orlistat is associated with an increased risk of acute liver injury. Future research is needed to guide clinical decision making.

Drug and Alcohol Dependence, 2015

Aims: Aberrant behaviors related to prescription drug use in the patient population remains to be... more Aims: Aberrant behaviors related to prescription drug use in the patient population remains to be an understudied phenomenon. Whilst there are several tools that may help to predict risk or estimate a patient's predisposition to drug abuse, limited tools are available that can assess and quantify events related to prescription abuse, misuse, and diversion that occur in the patient setting. Some studies suggest that up to 80.5% of the patient population evaluated may have exhibited one or more aberrant behaviors related to prescription drugs such as opioids (Fleming, 2008; Passik, 2011, 2014; Setnik, 2013). Since prescription drugs are primarily intended for the patient, assessing and understanding the complexity of this issue in this vulnerable population is critical. Various newer methods and findings from clinical and database studies that have assessed aberrant behaviors in the patient population will be reviewed and summarized. Clinical perspectives from high risk patients with substance use disorder will be discussed and methodological approaches will be covered. Also, the regulatory perspective will be provided with relevant updates from a recent study in progress assessing prescription opioid abuse, misuse, overdose, and addiction, in a population of pain patients receiving long-acting opioids (http://www.fda.gov/Drugs/NewsEvents/ ucm384489.htm). Results: Based on review of available data, aberrant prescription opioid drug taking behaviors related to abuse and misuse are prevalent in the patient population. Furthermore, this population is infrequently studied for such risks. It is integral to refine methodologies and tools to better assess the prevalence of presence of abuse and misuse in the patient population and to mitigate such risks. Conclusions: Based on review of available data. Financial support: Submission fee supported by INC Research.

Journal of managed care pharmacy : JMCP, 2009

Prescription opioid abuse and its associated costs are a problem in the United States, with signi... more Prescription opioid abuse and its associated costs are a problem in the United States, with significant epidemiologic and economic consequences. The breadth and depth of these consequences are not fully understood at present. To summarize published, English-language biomedical evidence pertaining to the epidemiology and costs of prescription opioid analgesic misuse and abuse and to describe efforts to reduce the burden of these problems. Published English-language articles on the epidemiology and economics of abuse, misuse, or diversion of prescribed opioid analgesics in the United States were identified by searching PubMed, Web of Science, the Cumulative Index to Nursing and Allied Health Literature database (CINAHL), EconLit, and PsycInfo, using (economics OR epidemiology) AND (misuse OR abuse) AND opioid as search terms or Medical Subject Heading (MeSH) terms. Article bibliographies were also searched manually for applicable papers. The search was limited to articles published fr...

Value in Health, 2012

Pso diagnoses (ICD-9 codes: 696.1). One Pso-free patient (i.e., without Pso or psoriatic arthriti... more Pso diagnoses (ICD-9 codes: 696.1). One Pso-free patient (i.e., without Pso or psoriatic arthritis diagnosis) was randomly selected to match each Pso patient by age and gender. Patient demographic characteristics and comorbidity profile information, including the Charlson comorbidity index (CCI) score, the prevalence of autoimmune diseases, and an exhaustive list of other comorbidities were compared between Pso and Pso-free patients using Wilcoxon signed rank tests or McNemar tests. RESULTS: Among the 106,128 selected matched pairs, 52% were female and the mean age was 52 years (SDϭ15 years). In the Pso population, 77% had mild Pso (i.e., patients who did not use any systemic therapies) and 23% had moderate-tosevere Pso (i.e., patients receiving phototherapy, conventional systemic therapies, or biologics). Pso patients had a higher mean CCI score compared to Pso-free patients (1.06 vs. 0.74; pϽ.01). Compared to Pso-free patients, Pso patients had a significantly higher prevalence of autoimmune diseases, including psoriatic arthritis (10.2% vs. 0.0%), rheumatoid arthritis (5.4% vs.1.4%), ankylosing spondylitis (1.5% vs. 0.8%), ulcerative colitis (1.0 vs. 0.5%), and Crohn's disease (0.8% vs. 0.4%) (all pϽ.01). As shown in other studies, Pso patients also had higher prevalence of other comorbidities, including hypertension (41.8% vs. 34.5%), chronic pulmonary diseases (17.7% vs. 12.6%), diabetes (16.4% vs. 12.6%), hypothyroidism (12.0% vs. 9.0%), deficiency anemias (9.3% vs. 6.7%), valvular diseases (7.8% vs. 5.6%), solid tumor without metastases (7.2% vs. 5.8%), psychoses (6.5% vs. 4.2%), and peripheral vascular disease (6.4% vs. 4.3%) when compared to Pso-free patients (all pϽ.01). CONCLUSIONS: Psoriasis was associated with a substantial comorbidity burden, including a significantly higher prevalence of autoimmune diseases and other physical and mental comorbidities.

Postgraduate Medicine, 2019

Objective: Opioids with abuse-deterrent properties may reduce widespread abuse, misuse, and diver... more Objective: Opioids with abuse-deterrent properties may reduce widespread abuse, misuse, and diversion of these products. This study aimed to quantify misuse, abuse, dependence, and health resource use of extended-release morphine sulfate with sequestered naltrexone hydrochloride (ER-MSN; EMBEDA®), compared with non-abuse-deterrent extended-release morphine (ERM) products in Medicaid non-cancer patients. Methods: Administrative medical and pharmacy claims data were analyzed for 10 Medicaid states from 1 January 2015, to 30 June 2016. Patients were included if they received a prescription for ER-MSN or any oral, non-abuse-deterrent ERM. Index date was the date of first prescription for an ER-MSN or ERM. Abuse/dependence, non-fatal overdose, emergency department (ED) visits, and ED/inpatient readmissions were determined for each participant. An overall measure of misuse and abuse was also calculated. To account for differences in follow-up, all counts are expressed per 100 patient-years. Results: There were 4,857 patients who received ER-MSN and 10,357 who received an ERM. The average age in the two cohorts was approximately 45 years old. From pre-index to follow-up, the number of patients per 100 patient-years with a diagnosis code indicating abuse or dependence increased by 0.91 (95% confidence interval [CI]: 0.85, 0.97) in the ER-MSN cohort and 2.23 (95% CI: 2.14, 2.32) in the ERM cohort. The number of patients per 100 patient-years with an opioid-related non-fatal overdose increased by 0.05 (95% CI: 0.04, 0.06) in the ER-MSN cohort compared with 0.11 (95% CI: 0.09, 0.13) in the ERM cohort. The opioid abuse overall composite score increased by 1.36 (95% CI: 1.24, 1.48) in the post-index period in the ER-MSN cohort compared to 3.21 (95% CI: 3.10, 3.32) in the ERM cohort. Conclusion: Misuse, abuse, and dependence events were numerically lower in patients receiving ER-MSN compared with those receiving ERM products.

Pain Medicine, 2011

Objectives. The objective of this study was to estimate the societal costs of prescription opioid... more Objectives. The objective of this study was to estimate the societal costs of prescription opioid abuse, dependence, and misuse in the United States. Methods. Costs were grouped into three categories: health care, workplace, and criminal justice. Costs were estimated by 1) quantity method, which multiplies the number of opioid abuse patients by cost per opioid abuse patient; and 2) apportionment method, which begins with overall costs of drug abuse per component and apportions the share associated with prescription opioid abuse based on relative prevalence of prescription opioid to overall drug abuse. Excess health care costs per patient were based on claims data analysis of privately insured and Medicaid beneficiaries. Other data/ information were derived from publicly available survey and other secondary sources. Results. Total US societal costs of prescription opioid abuse were estimated at $55.7 billion in 2007

Journal of Pain Research, 2011

The Journal of Pain, 2011