Cost-effectiveness analysis of intravenous levetiracetam versus intravenous phenytoin for early onset seizure prophylaxis after neurosurgery and traumatic brain injury

Rashid Kazerooni1, Mark Bounthavong1,21Pharmacoeconomics/Formulary Management, Veterans Affairs San Diego Healthcare System, San Diego, CA, USA; 2UCSD Skaggs School of Pharmacy and Pharmaceutical Sciences, San Diego, CA, USAObjective: There has been growing interest in newer anti-epileptic drugs (AEDs) for seizure prophylaxis in the intensive care setting because of safety and monitoring issues associated with conventional AEDs like phenytoin. This analysis assessed the cost-effectiveness of levetiracetam versus phenytoin for early onset seizure prophylaxis after neurosurgery and traumatic brain injury (TBI).Methods: A cost-effectiveness analysis was conducted from the US hospital perspective using a decision analysis model. Probabilities of the model were taken from three studies comparing levetiracetam and phenytoin in post neurosurgery or TBI patients. The outcome measure was successful seizure prophylaxis regimen (SSPR) within 7 days, which was defined as patients who did not seize or require discontinuation of the AED due to adverse drug reactions (ADRs). One-way sensitivity analyses and probabilistic sensitivity analysis were conducted to test robustness of the base-case results.Results: The total direct costs for seizure prophylaxis were $8,784.63 and$8,743.78 for levetiracetam and phenytoin, respectively. The cost-effectiveness ratio of levetiracetam was $10,044.91 per SSPR compared to$11,525.63 per SSPR with phenytoin. The effectiveness probability (patients with no seizures and no ADR requiring change in therapy) was higher in the levetiracetam group (87.5%) versus the phenytoin group (75.9%). The incremental cost effectiveness ratio for levetiracetam versus phenytoin was 360.82 per additional SSPR gained.Conclusions: Levetiracetam has the potential to be more cost-effective than phenytoin for early onset seizure prophylaxis after neurosurgery if the payer’s willingness-to-pay is greater than 360.82 per additional SSPR gained.Keywords: phenytoin, levetiracetam, seizure prophylaxis, cost-effectiveness, traumatic brain injury (TBI), and neurosurger

Program Evaluation of Academic Detailing on Naloxone Prescriptions Prescribed in the U.S. Department of Veterans Affairs

Thesis (Ph.D.)--University of Washington, 2018Background The rising incident of opioid overdose mortality has become a national epidemic in the U.S., especially among veterans whose mortality risk is twice that of the general population. The U.S. Department of Veterans Affairs (VA) implemented the Opioid Overdose Education and Naloxone Distribution (OEND) Program to provide education and training to providers and patients on opioid overdose prevention, recognition, response, and proper use of naloxone to reverse opioid-related overdose events. Penetration into the provider section required a partnership with the VA Pharmacy Benefits Management National Academic Detailing Service that delivers educational outreach to providers to align their naloxone prescribing to veterans at risk of an opioid overdose with evidence-based practice. This study focused on the impact of academic detailing on naloxone prescribing by evaluating the impact of the intervention as well as providers’ perception of the program and naloxone use to reverse opioid overdose events. In Aim 1, I evaluated the implementation strength of academic detailing at the VA from October 2014 to December 2017. This was complemented by Aim 2, which explored the providers’ perception of academic detailing and captured facilitators and barriers to naloxone prescribing. Methods In Aim 1, a repeated measures, retrospective cohort design with a fixed effects negative binomial model was used to evaluate the impact of implementation strength (proportion of providers exposed to exposed to academic detailing) on total number of naloxone prescriptions prescribed for each VA station from October 2014 to December 2017. Setting was in the VA system, which consists of 130 stations comprised of VA Medical Centers and their surrounding clinics. I evaluated a closed cohort of primary care providers who wrote a prescription for an opioid. In Aim 2, a mixed methods design was used to explore providers’ perception of academic detailing and naloxone prescribing using a survey and identify barriers and facilitators using semi-structured phone interviews. Online survey was developed based on a conceptual framework using existing theories (Theory of Planned Behavior, Social Marketing Theory, and the Framework for effective implementation), tested for face validity, and deployed to providers using who recently received an OEND-specific academic detailing visit within 2 to 4 weeks across the VA. Semi-structured phone interviews were conducted with providers who finished the survey and agreed to continue their participation. Results In Aim 1, there was a total of 5,452 providers who wrote for an opioid prescription. Increasing the proportion of providers exposed to academic detailing at each VA station from 0% to 100% was associated with a of 5.51 times higher incidence (95% CI: 1.86, 16.27) in the monthly number of naloxone prescriptions prescribed. Alternatively, this was a 9.13 increase in the monthly number of naloxone prescriptions. In Aim 2, 137 (12.2%) providers completed the survey. The average domain score for responders was highest for Satisfaction (6.28) followed by Attitude (6.02), Knowledge (5.96), Social norms (5.64), and Perceived barriers (4.86). Knowledge, Social norms, and Satisfaction domains were similar across the different provider types. However, pain specialists had a higher Attitude score (+0.56, P=0.011) and Perceived barriers score (+0.82, P=0.009) than primary care providers. A total of 11 responders participated in phone interviews. Participants identified limited time, poor data integration, social stigma, and lack of homeless support as barriers to prescribing naloxone. A patient list generated by academic detailers was identified as a facilitator to prescribing naloxone. Conclusions By combining the findings from these different approaches, I was able to develop a deeper understanding of academic detailing’s effectiveness to increase naloxone prescriptions prescribed as its phenomena for augmenting providers’ naloxone prescribing behavior

Decision analysis model evaluating the cost-effectiveness of risperidone, olanzapine and haloperidol in the treatment of schizophrenia

Purpose: To evaluate the cost-effectiveness of three antipsychotic medications (olanzapine, risperidone and haloperidol) in the treatment of schizophrenia using the Positive and Negative Symptom Scale. Study design and methods: A decision analysis model was created to evaluate the cost-effectiveness of two atypical antipsychotics (risperidone and olanzapine) and haloperidol. Outcome probabilities were determined from published clinical trials. The main dependent variable of interest was to compare the incremental cost-effectiveness ratios (ICER) of the atypical antipsychotic with haloperidol, and also to compare the ICER of olanzapine and risperidone. Sensitivity analyses were conducted for olanzapine and risperidone to determine the effects of altering drug cost, efficacy and re-hospitalization rate on total costs. Results: Risperidone and olanzapine were dominant strategies compared with haloperidol (less costly and more effective). Risperidone was also dominant when compared with olanzapine. A one-way sensitivity analysis for efficacy indicated that the efficacy of risperidone would need to decrease by approximately 3% from the base-case in order for olanzapine and risperidone to have equal total costs. In a two-way sensitivity analysis varying both the cost of olanzapine and risperidone, the difference in drug costs between them would have to increase from $2.12 per day to$4.12 per day in order to have equal total costs. In terms of varying re-hospitalization rates, the re-hospitalization rate for risperidone would have to increase from 3% to 33% greater than the re-hospitalization rate for olanzapine in order to have equal total direct costs. Conclusion: Based on this decision model, atypical antipsychotics were a dominant strategy over haloperidol primarily because of increased efficacy and lower re-hospitalizations. The ICER indicated that risperidone was dominant over olanzapine because of lower drug costs and increased number of responders, which leads to decreased total costs. © 2007 The Authors

Retrospective cohort study of anti-tumor necrosis factor agent use in a veteran population.

Introduction. Anti-tumor necrosis factor (TNF) agents are effective for several immunologic conditions (rheumatoid arthritis (RA), Crohn's disease (CD), and psoriasis). The purpose of this study was to evaluate the efficacy and safety of anti-TNF agents via chart review. Methods. Single-site, retrospective cohort study that evaluated the efficacy and safety of anti-TNF agents in veterans initiated between 2010 and 2011. Primary aim evaluated response at 12 months post-index date. Secondary aims evaluated initial response prior to 12 months post-index date and infection events. Results. A majority of patients were prescribed anti-TNF agents for CD (27%) and RA (24%). Patients were initiated on etanercept (41%), adalimumab (40%), and infliximab (18%) between 2010 and 2011. No differences in patient demographics were reported. Response rates were high overall. Sixty-five percent of etanercept patients, 82% of adalimumab patients, and 59% of infliximab patients were either partial or full responders, respectively. Approximately 16%, 11%, and 12% of etanercept, adalimumab, and infliximab were non-responders, respectively. Infections between the groups were non-significant. Etanercept and adalimumab patients had higher but non-significant odds of being a responder relative to infliximab. Conclusions. Most patients initiated with anti-TNF agent were responders at 12 months follow-up for all indications in a veteran population

Association of copayment with likelihood and level of adherence in new users of statins: a retrospective cohort study.

BackgroundStatins remain a fundamental component of pharmacologic therapy for hyperlipidemia. Health benefits of statin therapy are jeopardized when adherence is reduced.ObjectivesTo (a) assess the association between copayment and copayment type on statin adherence using 2 different thresholds of adherence and (b) identify the incremental change in statin adherence associated with presence of copayment and copayment type.MethodsWe executed a retrospective cohort study of new users of statins with dyslipidemia from the Veterans Health Administration (VHA) within the Veterans Integrated Service Network 22 who initiated a statin between November 30, 2006, and December 2, 2007. We used exposure categories of Any Copayment versus No Copayment, indicating a patient had a copayment or had no copayment in order to obtain medications, respectively. As a separate analysis, we varied the exposures to the standard VHA copayment categories: (a) Service-Connected (SC) Copayment (patients with service-related injury), (b) Non-Service-Connected (NSC) Copayment (patients without a service-related injury), and (c) No Copayment. Using each set of exposures, we conducted separate multiple logistic regression analyses using 2 different adherence outcomes based on medication possession ratio (MPR) threshold: (1) adherence defined as MPR ≥ 0.8 and (2) adherence defined as MPR ≥ 0.9. We then proceeded with multiple linear regression models to determine the incremental change in MPR associated with the 2 sets of exposures. Subjects were required to be enrolled in VHA services for at least 2 years prior to index date and throughout the 1-year study period.ResultsA total of 4,886 subjects were identified for analysis based on the inclusion and exclusion criteria. Patients who did not pay a copayment for their statin medications were more likely to have adherence rates of ≥ 0.8 MPR and ≥ 0.9 MPR relative to the No Copayment Group with odds ratios (OR) of 1.19 (95% CI = 1.03-1.37) and 1.28 (95% CI = 1.11-1.48), respectively. The second analysis applied the VHA exposure categories of SC Copayment, NSC Copayment, and No Copayment. Using the 0.8 MPR or greater adherence threshold, the No Copayment group was associated with an increased likelihood of adherence versus the SC Copayment category as reference group with an OR of 1.31 (95% CI = 1.10-1.58). The NSC Copayment was associated with a nonsignificant increase in odds of adherence at the 0.8 MPR level or greater with OR of 1.12 (95% CI = 0.98-1.39). Using the 0.9 MPR level or greater, adherence threshold findings were similar. The No Copayment group produced an OR of 1.42 (95% CI = 1.17-1.71) compared with the SC Copayment group. The NSC Copayment group was associated with a nonsignificant increase in odds of adherence at the 0.9 MPR level or greater with an OR of 1.12 (95% CI = 0.97-1.38).The No Copayment group was associated with an increase in MPR of 0.02 (95% CI = 0.002-0.035) versus the Any Copayment category. Using the VHA copayment categories, we observed an increase in MPR for the No Copayment group versus the SC Copayment group of 0.03 (95% CI = 0.01-0.05). The NSC Copayment group was associated with a nonsignificant increase in MPR versus the SC Copayment group of 0.02 (95% CI = -0.003-0.036).ConclusionsPatients without out-of-pocket payments for their statins were more likely to adhere to therapy. Patients who pay a copayment for their statin medications were also compared with each other based on whether they (a) received any of their nonstatin prescriptions without a copayment or (b) paid a copayment on all of their prescriptions including statins. Our findings suggest that, among those that pay for their statins, patients are less adherent to their statins if other medications they are prescribed are copayment free. Thus, patient consumption behavior may be influenced by the relative cost of medications in patient prescription lists. Additional counseling on the necessity of adherence should be given to patients paying a copayment for their statin prescriptions

Association of copayment with likelihood and level of adherence in new users of statins: a retrospective cohort study.

BackgroundStatins remain a fundamental component of pharmacologic therapy for hyperlipidemia. Health benefits of statin therapy are jeopardized when adherence is reduced.ObjectivesTo (a) assess the association between copayment and copayment type on statin adherence using 2 different thresholds of adherence and (b) identify the incremental change in statin adherence associated with presence of copayment and copayment type.MethodsWe executed a retrospective cohort study of new users of statins with dyslipidemia from the Veterans Health Administration (VHA) within the Veterans Integrated Service Network 22 who initiated a statin between November 30, 2006, and December 2, 2007. We used exposure categories of Any Copayment versus No Copayment, indicating a patient had a copayment or had no copayment in order to obtain medications, respectively. As a separate analysis, we varied the exposures to the standard VHA copayment categories: (a) Service-Connected (SC) Copayment (patients with service-related injury), (b) Non-Service-Connected (NSC) Copayment (patients without a service-related injury), and (c) No Copayment. Using each set of exposures, we conducted separate multiple logistic regression analyses using 2 different adherence outcomes based on medication possession ratio (MPR) threshold: (1) adherence defined as MPR ≥ 0.8 and (2) adherence defined as MPR ≥ 0.9. We then proceeded with multiple linear regression models to determine the incremental change in MPR associated with the 2 sets of exposures. Subjects were required to be enrolled in VHA services for at least 2 years prior to index date and throughout the 1-year study period.ResultsA total of 4,886 subjects were identified for analysis based on the inclusion and exclusion criteria. Patients who did not pay a copayment for their statin medications were more likely to have adherence rates of ≥ 0.8 MPR and ≥ 0.9 MPR relative to the No Copayment Group with odds ratios (OR) of 1.19 (95% CI = 1.03-1.37) and 1.28 (95% CI = 1.11-1.48), respectively. The second analysis applied the VHA exposure categories of SC Copayment, NSC Copayment, and No Copayment. Using the 0.8 MPR or greater adherence threshold, the No Copayment group was associated with an increased likelihood of adherence versus the SC Copayment category as reference group with an OR of 1.31 (95% CI = 1.10-1.58). The NSC Copayment was associated with a nonsignificant increase in odds of adherence at the 0.8 MPR level or greater with OR of 1.12 (95% CI = 0.98-1.39). Using the 0.9 MPR level or greater, adherence threshold findings were similar. The No Copayment group produced an OR of 1.42 (95% CI = 1.17-1.71) compared with the SC Copayment group. The NSC Copayment group was associated with a nonsignificant increase in odds of adherence at the 0.9 MPR level or greater with an OR of 1.12 (95% CI = 0.97-1.38).The No Copayment group was associated with an increase in MPR of 0.02 (95% CI = 0.002-0.035) versus the Any Copayment category. Using the VHA copayment categories, we observed an increase in MPR for the No Copayment group versus the SC Copayment group of 0.03 (95% CI = 0.01-0.05). The NSC Copayment group was associated with a nonsignificant increase in MPR versus the SC Copayment group of 0.02 (95% CI = -0.003-0.036).ConclusionsPatients without out-of-pocket payments for their statins were more likely to adhere to therapy. Patients who pay a copayment for their statin medications were also compared with each other based on whether they (a) received any of their nonstatin prescriptions without a copayment or (b) paid a copayment on all of their prescriptions including statins. Our findings suggest that, among those that pay for their statins, patients are less adherent to their statins if other medications they are prescribed are copayment free. Thus, patient consumption behavior may be influenced by the relative cost of medications in patient prescription lists. Additional counseling on the necessity of adherence should be given to patients paying a copayment for their statin prescriptions