Pharmacoeconomic Implications Research Articles

Role of polypill in cardiovascular prevention and treatment.

Cardiovascular diseases (CVD) remain the leading cause of mortality globally and require innovative strategies for effective prevention and treatment. The polypill concept, which integrates multiple cardioprotective agents into a single dosage form, has emerged as a promising approach to improve adherence and simplify the management of cardiovascular risk factors. We review clinical trials and observational studies evaluating the impact of the polypill on reducing the incidence of major cardiovascular events (MACEs), its influence on medication adherence, and its potential to fill treatment gaps in diverse populations. Also of note are the pharmacoeconomic implications of the widespread use of the polypill, particularly in low- and middle-income countries where the burden of cardiovascular disease is increasing. Although the polypill demonstrates a favorable profile in improving therapeutic compliance and reducing cardiovascular risk factors, debates persist regarding its efficacy compared to individualized treatment regimens. This review summarizes the current evidence on the efficacy, safety, and cost-effectiveness of the polypill in CVD primary and secondary prevention. Furthermore, potential challenges in implementing the polypill strategy include tailoring the components to patient-specific risk profiles and the need for robust evidence from large-scale randomized controlled trials to substantiate its long-term benefits.

Oral Bacterial Lysate OM-85: Advances in Pharmacology and Therapeutics.

Bacterial lysates are known for having immunomodulatory properties and have been used mainly for the prevention and treatment of respiratory tract infections (RTIs). However, rigorous studies are needed to confirm the clinical efficacy of bacterial lysates with various bacterial antigen components, preparation methods, administration routes and course of treatment. OM-85, an oral standardized lysate prepared by alkaline lysis of 21 strains from 8 species of common respiratory tract pathogens, is indicated as immunotherapy for prevention of recurrent RTIs and acute infectious exacerbations of chronic bronchitis. OM-85 acts on multiple innate and adaptive immune targets and can restore type 1helper T (Th1)/Th2 balance. Sporadic studies have shown advances in pharmacology and therapeutics of OM-85, and thus an update review is necessary. Literature was retrieved by searching PubMed, Web of science, Embase, CNKI, and Full Text Database of Chinese Medical Journals. New roles of OM-85 were discovered in prevention and treatment of lung cancer, pulmonary tuberculosis, SARS-CoV-2 infection, allergic rhinitis, pulmonary fibrosis, atopic dermatitis, and nephrotic syndrome. Pharmacoeconomic values of OM-85 were demonstrated in prophylaxis and treatment of RTIs, chronic obstructive pulmonary disease, asthma, chronic bronchitis, rhinosinusitis and allergic rhinitis. Two consecutive courses of OM-85 (6 or 12 months apart) could prevent recurrent RTIs in children. Maternal OM-85 treatment could offer benefits for offspring. Product-specific response was observed. The efficacy of OM-85 may be associated with patient's characteristics (eg, severity of the disease, age, immune response pattern, malignancy risk stratification). OM-85 can improve effectiveness of standard care for some primary diseases, and carry significant pharmacoeconomic implications. The benefits shown by OM-85 in vitro and in vivo, when extrapolated to humans, are exciting but also require caution. Individualized treatment may need to be considered. It is necessary to compare the efficacy and safety of various bacterial lysate preparations.

Not All Antihistamines Are Created Equal: Alimemazine As A Cause Of Drug Induced Parkinsonism

Abstract Background A 67year old female presented to a Movement Disorder Service for assessment of tremor. She had a history of presbycusis, dermatitis herpetiformis, bronchiectasis, osteoporosis and stage A chronic lymphocytic leukaemia. History elucidated hypophonia, somniloquy, REM-sleep behaviour disorder, bruxism, presence hallucinosis, insidious bradykinesia and of titubation of increasing prevalence and amplitude over 20years. Examination demonstrated cognitive impairment (Montreal Cognitive Assessment 12+1/30) in the domains of visuospatial function, executive thinking, naming, attention, language, abstraction and anterograde recall. Luria test was 0/6. Also found was: micrographia, left exotropia, reduced left arm and leg swing, kinetic tremor asymmetry, decrement of amplitude and frequency of rapid repetitive movements asymmetrically, mandibular and lingual tremor, positive Kinnier-Wilson test and orthostatic deterioration in yes-yes titubation. Drg history identified use of Alimemazine 10mg for insomnia for approximately 20years. Methods Modified Simpson Angus Scale score was 6 indicating a clinically significant degree of extrapyramidal side effects. Unified Parkinson’s Disease Rating Scale part III was 17. Results Functional dopamine uptake imaging did not indicate a parkinsonian syndrome. Drg induced parkinsonism was diagnosed. 0.0097% of the Northern Ireland population were prescribed Alimemazine in 2022 for non-dermatological reasons, representing 73.49% of all dispensed preparations. In the first financial quarter of 2024 in Northern Ireland, all dispensed prescriptions cost £218,395. Conclusion Not all antihistamines are created equal. Alimemazine is an older phenothiazine derivative antihistamine with central sedative effects equivalent to Chlorpromazine but without anti-adrenaline action. It is rarely prescribed and easily overlooked as “just another antihistamine”. It is commonly prescribed by dermatologists for urticaria. It has substantial pharmacoeconomic implications given its cost disparity with other antihistamines. Extrapyramidal features of tremor, akinesia and hypertonicity are more common in older people; usually developing within weeks or months of commencement. Stopping the drug is the first-line intervention. Resolution of symptoms is not guaranteed.

Pharmacoeconomic implications of preference toward reference- versus generic-brand antidepressants in primary care.

The prevalence of depression is gradually increasing worldwide with an increasing utilization of antidepressants. Nevertheless, despite their lower costs, generic-brand antidepressants were reported to be less prescribed. We aimed to examine the costs of reference- versus generic-brand antidepressant prescriptions in primary care practice. This cross-sectional study included electronic prescriptions for adult patients that contained antidepressants (World Health Organization's Anatomical Therapeutic Chemical (ATC)code: N06A), which were generated by a systematically selected sample of primary care doctors (n = 1431) in Istanbul in 2016. We examined the drug groups preferred, the reference- versus generic-brand status, and pharmacotherapy costs. The majority of the prescriptions were prescribed for women (71.8%), and the average age of the patients was 53.6 ± 16.2 years. In prescriptions with a depression-related indication (n = 40 497), the mean number and cost of drugs were 1.5 ± 1.0 and 22.7 ± 26.4 United States Dollar ($) per prescription, respectively. In these prescriptions, the mean number and cost of antidepressants per encounter were 1.1 ± 0.2 and $17.0 ± 13.2, respectively. Reference-brand antidepressants were preferred in 58.2% of depression-related prescriptions, where the mean cost per prescription was $18.3 ± 12.4. The mean cost per prescription of the generics, which constituted 41.8% of the antidepressants in prescriptions, was $15.1 ± 11.4. We found that if the generic version with the lowest cost was prescribed instead of the reference-brand, the mean cost per prescription would be $12.9 ± 11.2. Our study highlighted the substantial pharmacoeconomic impact of generic-brand antidepressant prescribing, whose preference over reference-brands could reduce the cost of antidepressant medication treatment by 17.5% in primary care, which could be approximately doubled if the cheapest generic antidepressant had been prescribed.

Treatment of Inflammatory Bowel Disease with Biologics in Japan: A Single-Center, Retrospective Pharmacoeconomic Study.

Biologics are essential for treating inflammatory bowel disease (IBD); however, only a few studies have validated cost-effective treatment options and patient factors for biologic use using real-world data from Japanese patients with IBD. Here, we aimed to provide pharmacoeconomic evidence to support clinical decisions for IBD treatment using biologics. We assessed 183 cases (127 patients) of IBD treated with biologics between November 2004 and September 2021. Data on patient background, treatment other than biologics, treatment-related medical costs, and effectiveness index (ratio of the C-reactive protein-negative period to drug survival time) were analyzed using univariate and multivariate logistic regression analyses. Drug survival was determined using Kaplan-Meier survival curve analysis. The outcomes were to validate a novel assessment index and elucidate the following aspects using this index: the effectiveness-cost relationship of long-term biologic use in IBD and cost-effectiveness-associated patient factors. Body mass index ≥25 kg/m2 and duration of hypoalbuminemia during drug survival correlated significantly with the therapeutic effectiveness of biologics. There were no significant differences in surgical, granulocyte apheresis, or adverse-event costs per drug survival time. Biologic costs were significantly higher in the group showing lower effectiveness than in the group showing higher effectiveness. These findings hold major pharmacoeconomic implications for not only improving therapeutic outcomes through the amelioration of low albumin levels and obesity but also potentially reducing healthcare expenditure related to the use of biotherapeutics. To our knowledge, this is the first pharmacoeconomic study based on real-world data from Japanese patients with IBD receiving long-term biologic therapy.

P099 - Low dose abiraterone in prostate cancer - safety, efficacy and pharmacoeconomic implications

P099 - Low dose abiraterone in prostate cancer - safety, efficacy and pharmacoeconomic implications

Monitoring Depth of Neuromuscular Blockade and Adequacy of Reversal: Clinical and Pharmacoeconomic Implications

Monitoring Depth of Neuromuscular Blockade and Adequacy of Reversal: Clinical and Pharmacoeconomic Implications

Abstract A083: Low dose abiraterone in prostate cancer - Safety, efficacy and pharmacoeconomic implications

Abstract Background and aim: Survival has improved in metastatic castration-resistant prostate cancer (mCRPC) because of the development of effective drugs such as abiraterone acetate, but universal accessibility to treatment is not always possible because of cost constraints in lower- and middle-income countries. Abiraterone in fasting state is the standard of care in mCRPC. Despite a large food effect, it was administered under fasting conditions in its pivotal trials. Recently, the National Comprehensive Cancer Network (NCCN) has included low-dose abiraterone (250 mg/day) with food as an alternative treatment option to full-dose abiraterone (1,000 mg/day) fasting. This translates to 75% cost reduction. This study aims to find safety, efficacy and pharmacoeconomic implications of low dose abiraterone in mCRPC. Materials and Methods: In this cohort study mCRPC Patients with progression were offered low dose abiraterone with low fat meal along with prednisone 5 mg twice daily. Prostate-specific antigen (PSA) was assessed monthly and toxicity assessment was made every week. Final PSA response (≥ 50% reduction) and toxicity assessment were done at 12 weeks. In case of grade IV toxicity (Anemia, Hypertension, Hypokalemia, Hypocalcemia – CTC AE V5.0) because of higher drug bioavailability, patient would be offered full dose abiraterone. 10 patients were offered low dose abiraterone in 2022. Results: 6 out of 10 patients achieved desired PSA response at 12 weeks which is a bit on higher side compared to standard dose abiraterone (recent literature). Fortunately, none of the patient developed grade IV toxicity. This finding was assuring, and no patient shifted to standard dosing. Conclusions: Low dose abiraterone (with low-fat breakfast) is noninferior to full dose abiraterone with respect to PSA metrics. Toxicity is the major thing to look at and given the pharmacoeconomic implications it’s imperative to adopt this strategy in places where affordability is the issue. Let the patients have something rather than nothing! Citation Format: Suryakanta Acharya. Low dose abiraterone in prostate cancer - Safety, efficacy and pharmacoeconomic implications [abstract]. In: Proceedings of the AACR Special Conference: Advances in Prostate Cancer Research; 2023 Mar 15-18; Denver, Colorado. Philadelphia (PA): AACR; Cancer Res 2023;83(11 Suppl):Abstract nr A083.

Impact of ferric carboxymaltose for iron deficiency at discharge after heart failure hospitalization: a European multinational economic evaluation.

Iron deficiency (ID) is comorbid in up to 50% patients with heart failure (HF) and exacerbates disease burden. Ferric carboxymaltose (FCM) reduced HF hospitalizations and improved quality of life when used to treat ID at discharge in patients hospitalized for acute HF with left ventricular ejection fraction <50% in the AFFIRM-AHF trial. We quantified the effect of FCM on burden of disease and the wider pharmacoeconomic implications in France, Germany, Poland, Spain and Sweden. The per country eligible population was calculated, aligning with the 2021 European Society of Cardiology (ESC) HF guidelines and the AFFIRM-AHF trial. Changes in burden of disease with FCM versus standard of care (SoC) were represented by disability-adjusted life years (DALYs), hospitalization episodes and bed days, using AFFIRM-AHF data. A Markov model was adapted to each country to estimate cost-effectiveness and combined with epidemiology data to calculate the impact on healthcare budgets. Between 335 (Sweden) and 13 237 (Germany) DALYs were predicted to be avoided with FCM use annually. Fewer hospitalizations and shorter lengths of stay associated with FCM compared to SoC were projected to result in substantial annual savings in bed days, from 5215 in Sweden to 205 630 in Germany. In all countries, FCM was predicted to be dominant (cost saving with gains in quality-adjusted life years), resulting in net savings to healthcare budgets within 1 year. This comprehensive evaluation of FCM therapy highlights the potential benefits that could be realized through implementation of the ESC HF guideline recommendations regarding ID treatment.

170P Safety, efficacy and pharmacoeconomic implications of low dose abiraterone in prostate cancer

1.4 million new prostate cancer cases were detected in 2020. Survival has improved in metastatic castration-resistant prostate cancer (mCRPC) because of the development of effective drugs such as abiraterone acetate, but universal accessibility to treatment is not always possible because of cost constraints in lower- and middle-income countries. Abiraterone in fasting state is the standard of care in mCRPC. Despite a large food effect, it was administered under fasting conditions in its pivotal trials.

Assessing Use of a Standardized Allergy History Questionnaire for Patients with Reported Allergy to Penicillin

Inappropriate allergy labelling is associated with significant clinical and pharmacoeconomic implications. Detailed antimicrobial allergy assessments represent a key component of antimicrobial stewardship and aid in identifying true type I (immediate hypersensitivity) reactions. The allergy history form currently used at the University Hospital of Northern British Columbia (UHNBC), in Prince George, relies on the assessor's ability to ask appropriate prompting questions to obtain a thorough history, but it may not be sufficient to accurately identify true allergies. To compare a standardized allergy history questionnaire and the current allergy history form in terms of the quality and quantity of documentation gathered. This prospective observational study involved patients who were admitted to medical and surgical services at UHNBC from November 2018 to January 2019 with a penicillin-class allergy reported on their electronic medical record (EMR). A list of patients with EMR-reported allergies was generated by the hospital's health information software system, and these patients were interviewed using the standardized allergy history questionnaire. A total of 48 patients were assessed during the study period. Nineteen (40%) of the patients had an inappropriate allergy label on their EMR. Only 36 (75%) had an allergic reaction described on their EMR. Furthermore, only 36 (75%) of the 48 patients had the same allergy recorded on the EMR and on the allergy history form contained in their paper chart, of whom 22 had a documented reaction. The mean time to complete the standardized allergy history questionnaire was 2 minutes. At the study institution, documentation of allergy histories was often incomplete. Detailed allergy assessments are the first step in identifying true immunoglobulin E-mediated hypersensitivity reactions. Utilization of a standardized allergy history questionnaire is feasible and may serve to improve documentation and overall antimicrobial stewardship.

Pharmacoeconomic savings associated with alternate dosing strategy of nivolumab and ipilimumab combination therapy.

79 Background: Nivolumab (NIVO) plus ipilimumab (IPI) is a commonly used therapy for advanced melanoma. Original weight-based dosing of NIVO 1 mg/kg plus IPI 3 mg/kg (NIVO1+IPI3) was approved in 2017. Recently, the CHECKMATE 511 trial demonstrated improved tolerability of NIVO 3 mg/kg plus IPI 1 mg/kg (NIVO3 + IPI1) compared to the original dosing regimen without observed differences in efficacy.Objective: To determine the pharmacoeconomic implications of NIVO1+IPI3 and NIVO3+IPI1 with a dose banding strategy applied. Methods: Patients with advanced melanoma (N = 21) who received IPI and NIVO in combination between 4/2019 – 7/2019 were evaluated via a single-center retrospective chart review. A total of 118 checkpoint inhibitor doses (59 NIVO, 59 IPI) were analyzed.Weapplied a dose banding strategy to both NIVO1+IPI3 and NIVO3+IPI1 regimens to examine pharmaceutical expenditures using the two dosing regimens, whichincluded our organization 10% dose-vial rounding policy. Pharmaceutical expenditure using average wholesale price (AWP), which was $32.42 per mg of NIVO and $180.03 per mg of IPI, was calculated for each dosing strategy (NIVO1+IPI3 and NIVO3+IPI1). Results: The anticipated cost savings of patients receiving NIVO3+IPI1 combination therapy compared to NIVO1+IPI3, (both with dose rounding strategy applied), was $1,459,473 or &gt;$70,000 per patient, representing a 47.2% savings from the original NIVO1 +IPI3 regimen (Table). Conclusions: In addition to improved tolerability and comparable efficacy for NIVO3+IPI1 vs NIVO1+IPI3, our study shows that adoption of the NIVO3+IPI1 regimen results in significant savings in drug costs. Considerations should be made in future combination trials to compare NIVO3+IPI1 as a treatment arm to NIVO1+IPI3 to see if comparable clinical results can be obtained with less toxicity and decreased pharmaceutical spending. [Table: see text]

Peripheral nerve block versus systemic analgesia in dogs undergoing tibial plateau levelling osteotomy: Analgesic efficacy and pharmacoeconomics comparison

ObjectiveTo compare the perioperative effects and pharmacoeconomics of peripheral nerve blocks (PNBs) versus fentanyl target-controlled infusion (fTCI) in dogs undergoing tibial plateau levelling osteotomy (TPLO). Study designRandomized clinical study. AnimalsA total of 39 dogs undergoing unilateral TPLO. MethodsAfter acepromazine and methadone, anaesthesia was induced with propofol and maintained with isoflurane. Dogs were allocated to group fTCI [target plasma concentration (TPC) 1 ng mL–1] or group PNB (nerve stimulator-guided femoral-sciatic block using 0.2 and 0.1 mL kg–1 of levobupivacaine 0.5%, respectively). If nociceptive response occurred, isoflurane was increased by 0.1%, and TPC was increased by 0.5 ng mL–1 in group fTCI; a fentanyl bolus (1 μg kg–1) was administered in group PNB. During the first 24 postoperative hours, methadone (0.2 mg kg–1) was administered intramuscularly according to the Short Form Glasgow Composite Pain Scale, or if pain was equal to 5/24 or 4/20 for two consecutive assessments, or if the dog was non-weight bearing. The area under the curve (AUC) of pain scores, cumulative postoperative methadone requirement, food intake and pharmacoeconomic implications were calculated. ResultsIncidence of bradycardia (p = 0.025), nociceptive response to surgery (p = 0.041) and AUC of pain scores (p < 0.0001) were greater in group fTCI. Postoperatively, 16/19 (84.2%) and eight/20 (40%) dogs in groups fTCI and PNB, respectively, were given at least one dose of methadone (p = 0.0079). Food intake was greater in group PNB (p = 0.049). Although total cost was not different (p = 0.083), PNB was more cost-effective in dogs weighing >15 kg. Conclusions and clinical relevanceCompared with group fTCI, incidence of bradycardia, nociceptive response to surgery, postoperative pain scores, cumulative methadone requirement were lower, and food intake was greater in group PNB, with an economic advantage in dogs weighing >15 kg.

Stratified medicine in schizophrenia: how accurate would a test of drug response need to be to achieve cost-effective improvements in quality of life?

ObjectiveStratified medicine refers to the use of tests that predict treatment response to drive treatment decisions for individual patient. The pharmacoeconomic implications of this approach in schizophrenia are unknown. We aimed to assess the cost-effectiveness of a hypothetical stratified medicine algorithm (SMA) compared with treatment as usual (TAU), for patients with schizophrenia who failed a first-line antipsychotic.MethodsA decision analytic model with embedded Markov process was constructed, which simulated the health and cost outcomes for patients followed SMA or TAU over a lifetime horizon, from healthcare and social care perspective. In the base-case analysis, sensitivity and specificity of the stratifier were both set as 60%. Extensive sensitivity analyses were conducted to test the impact of uncertainty around the value of important parameters. The primary outcome was the incremental cost per quality-adjusted life year (QALY) gained.ResultsWhen both sensitivity and specificity of the stratified test were set at 60%, SMA appeared to be the optimal strategy as it produces more QALYs and incurs lower costs than TAU. This is robust to all scenarios tested. At a willingness-to-pay threshold of £20,000 per QALY, the probability for SMA to be the optimal strategy is 82.4%.ConclusionsOur results suggest that use of any stratifier with a sensitivity and specificity over 60% is very likely to be cost-effective comparing to TAU, for psychotic patients who failed a first-line antipsychotic. This finding, however, should be interpreted with caution due to lack of evidence for clozapine as a second-line antipsychotic.

Stratified Medicine in Schizophrenia - How Accurate Would a Test of Drug Response Need to Be to Achieve Cost-Effective Improvements in Quality of Life?

Background: Stratified medicine refers to the use of tests that predict treatment response to drive treatment decisions for individual patient. The pharmacoeconomic implications of this approach in schizophrenia is unknown. We aimed to assess the cost-effectiveness of a hypothetical stratified medicine algorithm (SMA) compared with treatment as usual (TAU), for patients with schizophrenia who failed a first-line antipsychotic. Methods: A decision analytic model with embedded Markov process was constructed based on the best available evidence. This model simulated the health and cost outcomes for patients followed SMA or TAU over a lifetime horizon, from healthcare and social care perspective. In the base-case analysis, sensitivity and specificity of the stratifier were both set as 60%. Extensive sensitivity analyses were conducted to test the impact of uncertainty around the value of all important parameters, including but not limited to sensitivity and specificity of the stratifier. The primary outcome was the incremental cost per quality-adjusted life year (QALY) gained. Outcomes: When both sensitivity and specificity of the stratified test were set at 60%, SMA appeared to be the optimal strategy as it produces more QALYs and incurs less costs than TAU. This is robust to all scenarios tested. At a willingness-to-pay threshold of £20,000 per QALY, the probability for SMA to be the optimal strategy is 82.4%.. Interpretation: Our results suggest that SMA is very likely to be cost-effective comparing to TAU, even with the relatively modest specificity and sensitivity in recently reported pharmacogenetic studies. Funding Statement: Medical Research Council, UK (grant number MR/L011794/1), and the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London. Declaration of Interests: The authors declare no competing interests.

Cost-Effectiveness of Nivolumab-Ipilimumab Combination Therapy Compared with Monotherapy for First-Line Treatment of Metastatic Melanoma in the United States.

The approval of new immunotherapies has dramatically changed the treatment landscape of metastatic melanoma. These survival gains come with trade-offs in side effects and costs, as well as important considerations for third-party payer systems, physicians, and patients. To develop a Markov model to determine the cost-effectiveness of nivolumab, ipilimumab, and nivolumab-ipilimumab combination as firstline therapy in metastatic melanoma, while accounting for differential effectiveness in programmed death-ligand 1 (PD-L1) positive and negative patients. A 3-state Markov model (PD-L1 positive stable disease, PD-L1 negative stable disease, and progression and/or death) was developed using a U.S. societal perspective with a lifetime time horizon of 14.5 years. Transition probabilities were calculated from progression-free (PF) survival data reported in the CheckMate-067 trial. Costs were expressed in 2015 U.S. dollars and were determined using national sources. Adverse event (AE) management was determined using immune-related AE (irAE) data from CheckMate-067, irAE management guides for nivolumab and ipilimumab, and treatment guidelines. Utilities were obtained from published literature, using melanoma-specific studies when available, and were weighted based on incidence and duration of irAEs. Base case, one-way sensitivity, and probabilistic sensitivity analyses were conducted. Nivolumab-ipilimumab combination therapy was not the cost-effective choice ($454,092 per PF quality-adjusted life-year [QALY]) compared with nivolumab monotherapy in a base case analysis at a willingness-to-pay threshold of $100,000 per PFQALY. Combination therapy and nivolumab monotherapy were cost-effective choices compared with ipilimumab monotherapy. PD-L1 positive status, utility of nivolumab and combination therapy, and medication costs contributed the most uncertainty to the model. In a population of 100% PD-L1 negative patients, nivolumab was still the optimal treatment, but combination therapy had an improved incremental cost-effectiveness ratio (ICER) of $295,903 per PFQALY. Combination therapy became dominated by nivolumab, when 68% of the sample was PD-L1 positive. In addition, the cost of ipilimumab would have to decrease to < $21,555 per dose for combination therapy to have an ICER < $100,000 per PFQALY and to < $19,151 (a 42% reduction) to be more cost-effective than nivolumab monotherapy. Nivolumab-ipilimumab combination therapy was not cost-effective compared with nivolumab monotherapy, which was the most cost-effective option. Professionals in managed care settings should consider the pharmacoeconomic implications of these new immunotherapies as they make value-based formulary decisions, and future cost-effectiveness studies are completed. No funding supported this study. Merino was a contractor with EMD Serono at the time of this study but does not have any conflicts of interest and did not receive any funding related to this study. All other authors have no financial disclosures and no conflicts of interest. All the authors contributed to the study concept and design. Tran, McDowell, and Barcelon took the lead in data collection, along with Oh, Keyvani, and Merino. All authors except Merino contributed to data interpretation. The manuscript was written by Oh, Tran, McDowell, and Wilson and revised by Oh, Tran, McDowell, Wilson, and Keyvani. This analysis was presented at Academy of Managed Care Pharmacy Managed Care & Specialty Pharmacy Annual Meeting 2016, April 19-22, 2016, in San Francisco, California, and at the International Society for Pharmacoeconomics and Outcomes Research Annual International Meeting, May 21-25, 2016, in Washington DC.

A prospective international randomized phase II study evaluating the food effect on the pharmacokinetics (PK) and pharmacodynamics (PD) of abiraterone acetate (AA) in men with castration-resistant prostate cancer (CRPC).

176 Background: AA is a standard of care for the treatment of metastatic CRPC, with an approximate retail cost of $8000/month. Despite a large food effect (~17-fold increase in CMax with a high-fat meal), AA was administered under fasting conditions in its pivotal trials. There are no randomized continuous dosing studies examining prandial state dosing on AA PK/PD. We sought to test the hypothesis that LOW (250mg w/food) would have similar PK/PD and safety to standard (STD, 1000mg fasting) in patients with progressive CRPC. Methods: Patients (n = 72) with progressive CRPC from seven institutions in the US and Singapore were randomized to treatment with STD or LOW (with low-fat breakfast). Both arms received prednisone 5mg twice daily. PSA was assessed monthly, and testosterone, DHEA/DHEAS were assessed every 12 weeks along with standard disease burden assessments. PK samples were collected at day 1, 8 and months 2, 3, 4. Log change in PSA response rate from baseline to week 12 was examined as the primary endpoint, with a non-inferiority design based on a non-inferiority margin of 15%. This margin corresponds to a 0.51 standard deviation (SD) difference in the mean log changes between the groups. Results: Accrual was completed with n = 36 on STD and n = 36 on LOW. Median (range) age was 74 (52-89) and baseline PSA was 39.2(range 0.6-1789). Mean log-change in PSA at 12 weeks was nominally greater in the LOW arm (-1.59 vs. -1.19). The 95% confidence for the difference (STD-LOW) ranged from -0.40 to 1.19, with lower limit corresponding to -0.24SD. Thus, non-inferiority of LOW was established. Median time to PSA progression was ~14 month in both arms (p = 0.53). Preliminary analysis of PK showed no difference in CMaxbeyond the first cycle with lower PK variability in the LOW arm. Conclusions: Low-dose (250mg/day) abiraterone acetate with a low-fat breakfast is non-inferior to standard dosing in a fasted state with respect to PSA and PK metrics. Although PSA response and progression are not clinically validated surrogates, given the pharmacoeconomic implications, these data warrant consideration by prescribers and payors. Clinical trial information: NCT01543776.

Ipilimumab in melanoma

ABSTRACTIntroduction: The treatment of melanoma is evolving rapidly over the past few years. Patients with BRAFv600 mutations can be treated with a combination of a BRAF-inhibitor and an MEK-inhibitor. Patients with BRAF wild-type tumors and BRAFv600 mutated tumors can be treated with immunotherapy i.e. check point inhibitors.Areas covered: We conducted a comprehensive review of the literature on the efficacy and predictive markers, safety, and pharmacoeconomics of ipilimumab in melanomaExpert commentary: Ipilimumab was the first check point inhibitor reaching the clinic, gaining FDA and EMA approval for metastatic melanoma in 2011. Ipilimumab was also approved by FDA in the adjuvant setting for patients with high risk, stage III melanoma. The anti-PD1 directed antibodies pembrolizumab and nivolumab are superior to single agent ipilimumab, which is no longer considered the standard first line treatment in metastatic melanoma.The addition ipilimumab to nivolumab is associated with a higher response rate and a better PFS, particularly in patients with PD-L1 negative tumors, albeit at the cost of a steep increase in grade 3–4 adverse event rate. Definitive survival data on this combination are pending and the selection of patients potentially requiring the combination and its pharmacoeconomic implications are to be elucidated.

FOLFOX4 or sorafenib as the first-line treatments for advanced hepatocellular carcinoma: A cost-effectiveness analysis

BackgroundThis study aimed to investigate the pharmaco-economic implications of FOLFOX4 or sorafenib for advanced hepatocellular carcinoma in China. MethodsTo conduct the analysis, we performed a Markov model to simulate the process of advanced HCC treated with sorafenib or FOLFOX4. Clinical data were obtained from the ORIENTAL trial and the EACH trial. Incremental cost-effectiveness ratio was regarded as the primary outcome in the analysis. One-way sensitivity analysis as well as probabilistic sensitivity analysis was performed to explore the impact of essential variables on the results of the analysis. ResultsTreatment with sorafenib provided an effectiveness gain of 0.3935 quality-adjusted life year at an average cost of $18,748.00, whereas chemotherapy of FOLFOX4 brought 0.3808 quality-adjusted life year at a cost of $6876.02. The incremental cost-effectiveness ratio of FOLFOX4 versus sorafenib was $934,801.57/QALY. In a probabilistic sensitivity analysis based on a Monte Carlo simulation of 1000 items, the probabilities of FOLFOX4 and sorafenib being cost-effective were 100% and 0% using a willingness-to-pay threshold of $20,301.00 per quality-adjusted life year. ConclusionsFOLFOX4 chemotherapy is likely to be a cost-effective option compared with sorafenib in the treatment of advanced hepatocellular carcinoma in China.

Oral Chemotherapy in Patients with Hematological Malignancies-Care Process, Pharmacoeconomic and Policy Implications.

Patients with hematologic malignancies are increasing being prescribed oral anticancer medications (OAMs) and/or biologics. These newer targeted OAMs are associated with a host of practical and pharmacoeconomic implications for patients and healthcare providers. Issues such as safety, procurement challenges, and the need for proactive involvement of all stakeholders to optimize adherence for successful use of these agents are increasingly being recognized. The current reactive model is negatively impacting the patient experience through delays in care, financial toxicity, and decreased safety. It also impacts the healthcare providers in the form of lost revenue and staff burnout due to labor-intensive procurement and patient financial assistance burdens. In this review, we describe some of the issues identified and discuss potential strategies to improve patient access, minimize healthcare burden, and review current policy initiatives and patient advocacy efforts to reduce financial toxicity.