Assessment of the treatment effectiveness of men with mild and medium degree of erectile dysfunction.

OBJECTIVE: . Aim: To assess the effectiveness of monotherapy and complex treatment of patients with erectile dysfunction depending on its severity. PATIENTS AND METHODS: Materials and Methods: Men with moderate and mild erectile dysfunction took part in the study, who, in turn, were divided into groups, depending on the treatment, with the evaluation of the results of the International Index of Erectile Function (MIEF-15), the state of cavernous hemodynamics and the function of the vascular endothelium before and after treatment. RESULTS: Results: In patients with an average degree of severity, who received complex treatment including a course of low-energy shock wave therapy, against the background of taking sildenafil and L-arginine, the best results were obtained in the quality of erection and increased cavernous blood flow, which positively affected satisfaction with sexual intercourse and overall satisfaction. It has also been proven that the function of the endothelium was improved in patients receiving L-arginine, due to which there was a probable decrease in endothelin-1. A probable improvement of erectile function was obtained in the group of patients with a mild degree who received L-arginine, and there was no statistical difference from the indicators in the group who received sildenafil, which was confirmed by the data of dopplerography. CONCLUSION: Conclusions: Patients with an average degree of erectile dysfunction require comprehensive treatment. The use of L-arginine can be an alternative to phosphodiesterase type 5 inhibitors in the treatment of mild erectile dysfunction.

Cost-effectiveness and budget impact of dolutegravir/lamivudine for treatment of human immunodeficiency virus (HIV-1) infection in the United States.

BACKGROUND: Dolutegravir(DTG)/lamivudine(3TC) is the first 2-drug regimen recommended as an initial treatment for people living with HIV (PLHIV). OBJECTIVE: To assess the cost-effectiveness and potential budget impact of DTG/3TC in the US healthcare setting. METHODS: A previously published hybrid decision-tree and Markov cohort state transition model was adapted to estimate the incremental costs and health outcome benefits over a patients' lifetime. DTG/3TC was compared with current standard of care in treatment naive and treatment experienced virologically suppressed PLHIV. Health states included in the model were based upon virologic response and CD4 cell count, with death as an absorbing state. Clinical data was informed by the Phase III GEMINI 1 and 2 clinical trials, a published network meta-analysis (NMA) in treatment-naive patients and the Phase III TANGO clinical trial in treatment experienced patients. Costs and utilities were informed by published data and discounted annually at a rate of 3%. A separate 5-year budget impact analysis was conducted assuming 5%-15% uptake in eligible treatment naive and 10%-30% uptake in eligible treatment experienced patients. RESULTS: In the treatment naive analyses based on GEMINI 1 and 2, DTG/3TC dominated, i.e., was less costly and more effective, than all comparators. DTG/3TC resulted in 0.083 incremental quality-adjusted life-years (QALYs) at a cost saving of $199,166 compared with the DTG + tenofovir disoproxil(TDF)/emtricitabine(FTC) comparator arm. The incremental QALY and cost savings for DTG/3TC compared with DTG/abacavir(ABC)/3TC, cobicistat-boosted darunavir(DRV/c)/tenofovir alafenamide(TAF)/FTC, and bictegravir (BIC)/TAF/FTC, based on NMA results were 0.465, 0.142, and 0.698, and $42,948, $122,846, and $44,962, respectively. In the analyses of treatment-experienced virologically suppressed patients based on TANGO, DTG/3TC offered slightly lower QALYs (-0.037) with an estimated savings of $78,730 when compared with continuation of TAF-based regimen (TBR). Sensitivity analyses demonstrated that these conclusions were relatively insensitive to alternative parameter estimates. The budget impact analysis estimated that by 5th year a total of 70,240 treatment naive patients and 1,340,480 treatment experienced patients could be eligible to be prescribed DTG/3TC. The estimated budget savings over 5 years ranged from $1.12b to $3.35b (corresponding to 27,512 to 82,536 on DTG/3TC by year 5) in the lowest and highest uptake scenarios, respectively. CONCLUSION: In conclusion, DTG/3TC with its comparable efficacy and lower drug acquisition costs, has the potential to offer significant cost savings to US healthcare payers for the initial treatment of treatment naive patients and as a treatment switching option for virologically suppressed patients. DISCLOSURES: This study was funded in full by ViiV healthcare, Brentford, UK. Medical writing to support this study was also funded in full by ViiV Healthcare, Brentford, UK. Butler, Hayward, and Jacob are employees of HEOR Ltd, the company performing this study funded by ViiV Healthcare. Anderson is an employee of GlaxoSmithKline and owns shares in the company. Punekar, Evitt, and Oglesby are employees of ViiV Healthcare and own stocks in GlaxoSmithKline.

The Potential Teratogenicity Alert for Women Conceiving on Dolutegravir-Based Regimens: An Assessment of Risk Communication by an Urban HIV Clinic in Uganda and Choices made by Women.

INTRODUCTION AND OBJECTIVE: In May 2018, the World Health Organization and other regulatory authorities released a safety alert for dolutegravir related to a risk of neural tube defects among women exposed to dolutegravir at the time of conception. Models of how drug safety information can be shared effectively in the shortest time are necessary to prevent interruptions of public health programs. We sought to describe an implementation process to inform and support women already on dolutegravir-based regimens at the time of conception to make informed choices following the safety alert of a potential teratogenicity risk. We describe the choices made by women, as well as determine the factors associated with women's choices to switch off dolutegravir. METHODS: A clinic response plan was developed in the first week following the alert and clinic staff were trained on safety guidance. All women aged < 55 years taking dolutegravir were identified from the clinic database and contacted by phone for earlier appointments. Non-menopausal and non-surgically sterilized women were referred for urine pregnancy testing and evaluation of pregnancy intentions in the following 12 months and effective family planning was offered. We describe the coverage of women who received the communication as well as the fidelity to the outlined plan from 21 May to 12 September, 2018. We used modified a Poisson regression analysis to determine factors associated with switching off dolutegravir. RESULTS: Of all active patients in the clinic, 9% (690/7963) were identified as female aged < 55 years taking dolutegravir. Ninety-five percent (656/690) were reviewed by September 2018 and informed of the safety alert, implying a high level of uptake. Fidelity to standard operating procedures was also high at 72%. Twenty-two percent (146/656) of patients were menopausal or surgically sterilized. Five hundred and ten women were of reproductive potential with a median age (interquartile range) of 37 years (30-42 years). Five percent (23/510) were human chorionic gonadotrophin positive and all initial ultrasound reports revealed no deformities. Twenty-one percent (108/510) had intentions to conceive and opted to stop taking dolutegravir with 90% (97/108) switching to efavirenz. Seventy-nine percent (402/510) opted to remain taking dolutegravir. However, only 40% (160/402) chose effective contraceptive methods and 60% (242/402) opted for condoms only/no contraceptive method. CONCLUSIONS: A rapid well-coordinated response ensured prompt communication of the dolutegravir safety warning. The process developed by the clinic can act as a model for response during drug safety alerts. Women made informed decisions with most opting to remain taking dolutegravir; however, effective contraception uptake was low.

Cost-effectiveness of olaparib as a maintenance treatment for women with newly diagnosed advanced ovarian cancer and BRCA1/2 mutations in the United States.

OBJECTIVE: This study evaluated the cost-effectiveness of olaparib monotherapy in the first-line maintenance setting vs. surveillance in women with newly diagnosed advanced ovarian cancer and a BRCA1/2 mutation from a US third-party payer perspective. METHODS: A three-state (progression free, progressed disease, and death) partitioned survival model over a 50-year lifetime horizon was developed. Piecewise models were applied to data from the phase III trial SOLO1 to extrapolate survival outcomes. Health state utilities and adverse event disutilities were obtained from literature and SOLO1. Treatment costs, adverse event costs, and medical costs associated with health states were obtained from publicly available databases, SOLO1, and real-world data. Time on treatment was estimated using the data from SOLO1. Incremental costs per quality-adjusted life year (QALY) and life year (LY) gained were estimated. One-way deterministic and probabilistic sensitivity analyses were conducted. RESULTS: Over a lifetime horizon, olaparib was associated with an additional 3.63 LYs and 2.93 QALYs, and an incremental total cost of $152,545 vs. surveillance. Incremental cost per LY gained and per QALY gained for olaparib were $42,032 and $51,986, respectively. The incremental cost-effectiveness ratios remained below $100,000 across a range of inputs and scenarios. In the PSA, the probability of olaparib being cost-effective at a $100,000 per QALY threshold was 99%. CONCLUSIONS: Compared to surveillance, olaparib increases both the LYs and QALYs of women with newly diagnosed advanced ovarian cancer and with a germline or somatic BRCA mutation. Olaparib offers a cost-effective maintenance option for these women from a US third-party payer perspective.

Real world experience of poly (ADP-ribose) polymerase inhibitor use in a community oncology practice.

OBJECTIVE: This study aims to describe the real-world experience, including the clinical and financial burden, associated with PARP inhibitors in a large community oncology practice. METHODS: Retrospective chart review identified patients prescribed olaparib, niraparib or rucaparib for maintenance therapy or treatment of recurrent ovarian, primary peritoneal or fallopian tube cancer across twelve gynecologic oncologists between December 2016 and November 2018. Demographic, financial and clinical data were extracted. One PARP cycle was defined as a single 28-day period. For patients treated with more than one PARPi, each course was described separately. RESULTS: A total of 47 patients and 506 PARP cycles were identified (122 olaparib, 24%; 89 rucaparib, 18%; 294 niraparib, 58%). Incidence of grade ≥ 3 adverse events were similar to previously reported. Toxicity resulted in dose interruption, reduction and discontinuation in 69%, 63% and 29% respectively. Dose interruptions were most frequent for niraparib but resulted in fewer discontinuations (p-value 0.01). Mean duration of use was 7.46 cycles (olaparib 10.52, rucaparib 4.68, niraparib 7.34). Average cost of PARPi therapy was $8018 per cycle. A total of 711 phone calls were documented (call rate 1.4 calls/cycle) with the highest call volume required for care coordination, lab results and toxicity management. CONCLUSIONS: Although the toxicity profile was similar to randomized clinical trials, this real-world experience demonstrated more dose modifications and discontinuations for toxicity management than previously reported. Furthermore, the clinical and financial burden of PARP inhibitors may be significant and future studies should assess the impact on patient outcomes.

Movement of Poly-ADP Ribose (PARP) Inhibition into Frontline Treatment of Ovarian Cancer.

The use of poly (ADP-ribose) polymerase (PARP) inhibitors in the front-line management of advanced ovarian cancer has recently emerged as an exciting strategy with the potential to improve outcomes for patients with advanced ovarian cancer. In this article, we review the results of four recently published Phase III randomised controlled trials evaluating the use of PARP inhibitors in the primary treatment of ovarian cancer (SOLO1, PRIMA, PAOLA-1, and VELIA). Collectively, the studies suggest that PARP maintenance in the upfront setting is most beneficial among patients with BRCA-associated ovarian cancers (hazard ratios range from 0.31 to 0.44), followed by patients with tumours that harbour homologous recombination deficiencies (hazard ratios range from 0.33 to 0.57). All three studies that included an all-comer population were able to demonstrate benefit of PARP inhibitors, regardless of biomarker status. The FDA has approved olaparib for front-line maintenance therapy among patients with BRCA-associated ovarian cancers, and niraparib for all patients, regardless of biomarker status. In determining which patients should be offered front-line maintenance PARP inhibitors, and which agent to use, there are multiple factors to consider, including FDA indication, dosing preference, toxicity, risks versus benefits for each patient population, and cost. There are ongoing studies further exploring the front-line use of PARP inhibitors, including the potential downstream effects of PARP-inhibitor resistance in the recurrent setting, combining PARP-inhibitors with other anti-angiogenic drugs, immunotherapeutic agents, and inhibitors of pathways implicated in PARP inhibitor resistance.

Cost-effectiveness of niraparib, rucaparib, and olaparib for treatment of platinum-resistant, recurrent ovarian carcinoma.

BACKGROUND: Olaparib was approved on December 19, 2014 by the US FDA as 4th-line therapy (and beyond) for patients with germline BRCA1/2 mutations; rucaparib was approved on December 19, 2016 as 3rd-line therapy (and beyond) for germline or somatic BRCA1/2-mutated recurrent disease. On October 23, 2019, niraparib was approved for treatment of women with damaging mutations in BRCA1/2 or other homologous recombination repair genes who had been treated with three or more prior regimens. We compared the cost-effectiveness of PARPi(s) with intravenous regimens for platinum-resistant disease. METHODS: Median progression-free survival (PFS) and toxicity data from regulatory trials were incorporated in a model which transitioned patients through response, hematologic complications, non-hematologic complications, progression, and death. Using TreeAge Pro 2017, each PARPi(s) was compared separately to non­platinum-based and bevacizumab-containing regimens. Costs of IV drugs, managing toxicities, infusions, and supportive care were estimated using 2017 Medicare data. Incremental cost-effectiveness ratios (ICERs) were calculated and PFS was reported in quality adjusted life months for platinum-resistant populations. RESULTS: Non­platinum-based intravenous chemotherapy was most cost effective ($6,412/PFS-month) compared with bevacizumab-containing regimens ($12,187/PFS-month), niraparib ($18,970/PFS-month), olaparib ($16,327/PFS-month), and rucaparib ($16,637/PFS-month). ICERs for PARPi(s) were 3-3.5× times greater than intravenous non­platinum-based regimens. CONCLUSION: High costs of orally administered PARPi(s) were not mitigated or balanced by costs of infusion and managing toxicities of intravenous regimens typically associated with lower response and shorter median PFS. Balancing modest clinical benefit with costs of novel therapies remains problematic and could widen disparities among those with limited access to care.

Bioequivalence and Food Effect Assessment of 2 Fixed-Dose Combination Formulations of Dolutegravir and Lamivudine.

This single-dose study evaluated the bioequivalence, food effect, and safety of 2 experimental, 2-drug, fixed-dose formulations of 50 mg dolutegravir and 300 mg lamivudine (formulation AH and formulation AK) as compared with coadministration of single-entity tablets of 50 mg dolutegravir and 300 mg lamivudine (reference). In fasted subjects, formulation AH lamivudine exposure was similar to the reference; however, dolutegravir exposure was consistently higher in formulation AH, with area under the concentration-time curve (AUC) and maximum concentration (Cmax ) approximately 27% to 28% greater than reference. Formulation AK met bioequivalence standards to the reference for dolutegravir (AUC0-∞ and Cmax ) and lamivudine (AUC0-∞ and AUC0-t ) exposure; however, dolutegravir AUC0-t and lamivudine Cmax were approximately 16% and 32% higher than the reference, respectively. A high-fat meal increased dolutegravir AUC and Cmax by up to 33% and 21%, respectively, and decreased lamivudine Cmax by approximately 30%. Both test and reference formulations were well tolerated. The results support further development of formulation AK as a novel, 2-drug, fixed-dose combination tablet treatment for patients with HIV.

Cost-effectiveness and safety of palbociclib and everolimus for treating advanced and recurrent breast cancer.

This retrospective study compares the economic superiority of palbociclib versus everolimus for advanced and recurrent breast cancer. Furthermore, we investigated the safety and treatment continuity of palbociclib and everolimus regimens. Expected costs were calculated based on data from patients with advanced and recurrent breast cancer who were treated with palbociclib and everolimus. The progression-free survival (PFS) from the PALOMA-3 clinical trial and BOLERO-2 clinical trial was used to evaluate the therapeutic efficacy of the regimens. The cost-effectiveness ratio of each chemotherapy agent was calculated by dividing the expected cost by the progression-free survival (PFS). The cost-effectiveness ratio per month was JPY 391,551.3/PFS for palbociclib and JPY 488,690.5/PFS for everolimus (p=0.627). The incremental cost-effectiveness ratio per month of everolimus to palbociclib was JPY 100,133.7/PFS. For patients receiving everolimus, adverse drug reactions included stomatitis (77.3%), rash (59.1%) and leukopenia (59.1%). For patients receiving palbociclib, neutropenia (69.2%), leukopenia (69.2%) and anemia (30.8%) occurred. In terms of discontinuation owing to adverse events (AEs), pneumonitis, thrombocytopenia, edema, fatigue, and neutropenia were experienced in the everolimus group. The cost-effectiveness of everolimus and palbociclib are equivalent, but since the prevalence of AEs is high in patients receiving everolimus, its AE management is important.

Budget impact analysis of niraparib and olaparib for maintenance treatment of platinum-sensitive, recurrent ovarian cancer in the US.

AIMS: This study aimed to evaluate the budget impact of niraparib and olaparib in patients with platinum-sensitive, recurrent ovarian cancer from a US third party payer perspective. MATERIALS AND METHODS: A budget impact model was constructed to assess the additional per member per month (PMPM) costs associated with the introduction of niraparib and olaparib, two poly ADP-ribose polymerase ribose polymerase (PARP) inhibitors recently approved to be used in platinum-sensitive, recurrent ovarian cancer patients with and without a gBRCA mutation. The model assessed both pharmacy costs and medical costs. Pharmacy costs included adjusted drug costs, coinsurance, and dispensing fees. Medical costs included costs associated with disease monitoring and management of adverse events from the treatment. Epidemiological data from the literature were used to estimate the target population size. The analysis used 1-year time frame, and patients were assumed on treatment until disease progression or death. All costs were computed in 2017 USD. One-way sensitivity analyses were conducted to evaluate the model robustness. RESULTS: In a hypothetical plan of 1,000,000 members, 206 patients were estimated to be potential candidates for niraparib or olaparib maintenance treatment after applying all epidemiological parameters. At listed 30-day supply WAC prices of $14,750 for niraparib and $13,482 for olaparib, budget impacts of these two drugs were $0.169 PMPM and $0.156 PMPM, respectively, most of which were contributed by pharmacy costs. Sensitivity analyses suggested that assumptions around market share, platinum-sensitive rate after first treatment, and WAC prices affected results the most. LIMITATIONS: In this model, it was assumed that adopting niraparib and olaparib would not affect utilization of existing medications. Also, the estimated clinical parameters from clinical trials could differ from real-world data.

Economic impact of olaparib on maintenance treatment of patients with BRCA-mutation positive, platinum-sensitive relapsing high-grade serous epithelial ovarian cancer in Spain.

OBJECTIVE: To estimate the economic impact of the introduction of olaparib in  the Spanish National Health System as maintenance monotherapy in patients  with BRCA-mutation positive high-grade serous ovarian cancer. METHOD: A budget impact model was developed from the Spanish NHS perspective and a time horizon of 5 years for four treatment lines. The model included prevalent and incident patients estimated according to Spanish epidemiological data. Patients moved between treatment lines according to the progression-free survival and overall survival curves  obtained from the respective clinical trials. Only direct costs (€ 2017) were considered: pharmacological, administration, adverse effects and genetic tests. The robustness of the model was verified by a univariate  sensitivity analysis. RESULTS: The use of olaparib meant that, after 5 years, 6% fewer patients progressed to later lines compared to scenario without olaparib,  remaining longer in the second line and delaying the initiation of subsequent lines. The total estimated budgetary impact ranged between € 1.6  and € 5.4 million (1-5 years). The economic impact associated to the  introduction of olaparib is partially offset by the lower cost of chemotherapy, related adverse events, and palliative care in patients with  olaparib than in patients without it. CONCLUSIONS: Olaparib as maintenance treatment in patients with BRCA-mutation positive high-grade serous ovarian cancer increases progression-free  survival and delays the use of subsequent chemotherapy, with an budgetary  impact for the Spanish National Health System of 5.4 million euros after 5 years.

Objetivo: Estimar el impacto económico de la introducción de olaparib en el  Sistema Nacional de Salud como monoterapia de mantenimiento en pacientes  con cáncer de ovario seroso de alto grado y mutación BRCA.Método: Se desarrolló un modelo de impacto presupuestario desde la  perspectiva del Sistema Nacional de Salud y un horizonte temporal de cinco años a lo largo de cuatro líneas de tratamiento. El modelo incluye pacientes  prevalentes e incidentes estimadas a partir de datos epidemiológicos españoles.  Las pacientes se mueven entre las líneas de tratamiento en función de las curvas de supervivencia libre de progresión y supervivencia global obtenidas de los  respectivos ensayos clínicos. Solo se consideraron costes directos (€ 2017):  farmacológicos, de administración, efectos adversos y test genéticos. La  robustez del modelo se ha comprobado a través de un análisis de sensibilidad  univariante.Resultados: El uso de olaparib conllevó que, tras cinco años, un 6% menos de  pacientes progresaran a líneas posteriores, en comparación al escenario sin  olaparib, permaneciendo más tiempo en segunda línea y retrasando el inicio de  líneas subsiguientes. El impacto presupuestario total estimado osciló entre 1,6 y  5,4 millones de euros (1-5 años). Este impacto económico se ve parcialmente  compensado por los costes de la quimioterapia, el manejo de sus efectos  adversos y los cuidados paliativos, los cuales producen ahorros para el Sistema  Nacional de Salud.Conclusiones: Olaparib como tratamiento de mantenimiento en pacientes con  cáncer de ovario seroso de alto grado y mutación del gen BRCA aumenta la  supervivencia libre de progresión y retrasa la utilización de quimioterapia  posteriores, con un impacto presupuestario para el Sistema Nacional de Salud de  5,4 millones de euros tras 5 año.

Budget impact analysis of long-acting injectable aripiprazole once-monthly 400 mg in bipolar I disorder in the USA.

AIM: To estimate the budget impact (BI) of introducing aripiprazole once-monthly 400 mg/300 mg (AOM 400) in the maintenance monotherapy treatment of bipolar I disorder versus long-acting injectables, oral antipsychotics and best supportive care. METHODS: A BI model was developed from a US-payer perspective using treatment-related, hospitalization and adverse event management cost estimates for a hypothetical 1,000,000-member health plan over a 5-year period. RESULTS: Market share of AOM 400 was predicted to increase from 0.6% in Year 1 (current scenario) to 1.3% in Year 5 (predicted scenario), with predicted increases for paliperidone palmitate, asenapine and cariprazine. Treatment-related costs explained the BI increase, while adverse event and hospitalization costs were reduced. The per member per month incremental cost ranged from US$0.06 to US$0.26 in Years 1-5. The largest increases were predicted for paliperidone palmitate. CONCLUSION: As market shares of atypical antipsychotics are predicted to increase, payers may wish to re-evaluate their use.

Cost-effectiveness of long-acting injectable aripiprazole once-monthly 400 mg in bipolar I disorder in the USA.

AIM: To evaluate the cost-effectiveness of aripiprazole once-monthly 400/300 mg (AOM 400) in maintenance monotherapy treatment of bipolar I disorder (BP-I). METHODS: A de novo lifetime Markov model was developed for BP-I using available data for AOM 400 and relevant comparators. Base-case analysis considered costs and outcomes from the US payer perspective. RESULTS: The cost per quality-adjusted life year gained with AOM 400 versus comparators ranged from US$2007 versus oral asenapine to dominance (i.e., lower cost with quality-adjusted life gain) versus long-acting injectable risperidone, paliperidone palmitate, oral cariprazine and best supportive care. Patients treated with AOM 400 were estimated to have fewer mood episodes and hospitalizations per patient (5.37) than comparators (6.33, asenapine or cariprazine; 6.54, risperidone long-acting injectable; 7.64, paliperidone palmitate; and 8.93, best supportive care). Sensitivity analyses showed results were robust to parameter uncertainty. CONCLUSION: AOM 400 may be considered cost effective in the maintenance monotherapy treatment of BP-I in adults.

Palbociclib in hormone receptor positive advanced breast cancer: A cost-utility analysis.

INTRODUCTION: The addition of palbociclib to letrozole improves progression-free survival in the first-line treatment of hormone receptor positive advanced breast cancer (ABC). This study assesses the cost-utility of palbociclib from the Canadian healthcare payer perspective. METHODS: A probabilistic discrete event simulation (DES) model was developed and parameterised with data from the PALOMA 1 and 2 trials and other sources. The incremental cost per quality-adjusted life-month (QALM) gained for palbociclib was calculated. A time horizon of 15 years was used in the base case with costs and effectiveness discounted at 5% annually. Time-to- progression and time-to-death were derived from a Weibull and exponential distribution. Expected costs were based on Ontario fees and other sources. Probabilistic sensitivity analyses were conducted to account for parameter uncertainty. RESULTS: Compared to letrozole, the addition of palbociclib provided an additional 14.7 QALM at an incremental cost of $161,508. The resulting incremental cost-effectiveness ratio was $10,999/QALM gained. Assuming a willingness-to-pay (WTP) of $4167/QALM, the probability of palbociclib to be cost-effective was 0%. Cost-effectiveness acceptability curves derived from a probabilistic sensitivity analysis showed that at a WTP of $11,000/QALM gained, the probability of palbociclib to be cost-effective was 50%. CONCLUSION: The addition of palbociclib to letrozole is unlikely to be cost-effective for the treatment of ABC from a Canadian healthcare perspective with its current price. While ABC patients derive a meaningful clinical benefit from palbociclib, considerations should be given to increase the WTP threshold and reduce the drug pricing, to render this strategy more affordable.

The French addictovigilance network clinical assessment: Z-drugs, true false twins.

INTRODUCTION: In France, an addictovigilance network is responsible for evaluating drug dependence, by drawing on pharmacoepidemiological studies, clinical studies and by assessing healthcare professionals' reports on problematic consumption. METHODS: The aim of this study was to determine whether zolpidem and zopiclone have different dependence profiles, based on healthcare professionals' reports, and to identify various consumer dependence profiles among zolpidem users and among zopiclone users. Dependence in reports was assessed using the EGAP scale; a scale developed using the DSM diagnostic dependence criteria. RESULTS: The comparison of dependence profiles for zolpidem and zopiclone showed differences both in total EGAP score and EGAP item positivity. The descriptive analysis showed that EGAP scores were higher for zolpidem than for zopiclone, suggesting more severe problematic consumption with zolpidem. For zolpidem 2 subpopulations of consumers were identified, with one subpopulation's consumption being more severe than the other, with a significantly higher total EGAP score and more harmful consequences. No subpopulation was highlighted for zopiclone. CONCLUSION: These results were in favour of a higher prevalence of physical and compulsive signs of dependence and of harmful consequences of dependence, with zolpidem than with zopiclone.

Efficacy and Safety of Naftopidil in the Medical Expulsion Therapy for Distal Ureteral Stone: A Systematic Review and Meta-Analysis.

PURPOSE: The selective α-adrenoceptor blocker is widely used as a cost-effective treatment option for medical expulsive therapy (MET) of ureteral stones. In this review, we aimed to assess the efficacy and safety of naftopidil for MET compared with control or tamsulosin. METHODS: A systematic literature search was performed in PubMed, Cochrane Library, Embase, and Google Scholar to identify randomized controlled trials that compared naftopidil with either control or tamsulosin for the management of distal ureteral stones. RESULTS: We included 7 publications with 553 patients. Naftopidil was not only effective for distal ureteral calculi but also was comparable to tamsulosin in efficacy. The expulsion rate (risk ratio [RR] 2.00, 95% confidence interval [CI] 1.41, 2.83; P < 0.0001) and expulsion time (days) of distal ureteral stones (mean difference [MD] -1.72, 95% CI -3.27, -0.18, P = 0.03) indicated that naftopidil was more effective than control. Based on the expulsion rate (RR 1.05, 95% CI 0.74, 1.48; P = 0.80), expulsion time (days) (MD 0.18, 95% CI -0.49, 0.85; P = 0.59), and number of pain episodes (P = 0.87), naftopidil was comparable to tamsulosin. A little lower adverse effect rate was observed with naftopidil compared with tamsulosin (RR 0.47, 95% CI 0.23, 0.94; P = 0.03). CONCLUSIONS: In terms of efficacy for distal ureteral calculi, naftopidil would be superior to control and comparable to tamsulosin; moreover, the safety profile of naftopidil might be superior to that of tamsulosin. We conclude that naftopidil might be a powerful candidate in MET for distal ureteral stones.

Olaparib for Maintenance Treatment of BRCA 1 or 2 Mutated, Relapsed, Platinum-Sensitive Ovarian, Fallopian Tube and Peritoneal Cancer in People Whose Relapsed Disease has Responded to Platinum-Based Chemotherapy: An Evidence Review Group Perspective of a NICE Single Technology Appraisal.

As part of its Single Technology Appraisal process, the National Institute for Health and Care Excellence (NICE) invited the manufacturer of olaparib (AstraZeneca) to submit evidence on the clinical and cost effectiveness of olaparib for the maintenance treatment of BRCA1/2 mutated (BRCAm), platinum-sensitive relapsed (PSR) ovarian, fallopian tube and peritoneal cancer in people whose relapsed disease has responded to platinum-based chemotherapy. The Evidence Review Group (ERG) produced a critical review of the evidence contained within the company's submission (CS) to NICE. The clinical evidence related to one phase II, double-blind randomised controlled trial that recruited 265 patients with PSR serous ovarian cancer (OC) regardless of BRCAm status. Patients received olaparib 400 mg twice daily (b.i.d.) or matched placebo. In the whole population, the primary endpoint of progression-free survival (PFS) was met (hazard ratio [HR] 0.35; 95 % confidence interval [CI] 0.25-0.49, p < 0.01) for olaparib versus placebo. The BRCAm subgroup analysis (added after the study commenced but 1 month before the primary analysis was undertaken) reported an HR for PFS of 0.18 (95 % CI 0.10-0.31, p < 0.0001) for olaparib versus placebo, though interaction tests appeared inconclusive. Overall survival was not statistically significant in the whole group (HR 0.88; 95 % CI 0.64-1.21; p = 0.44) or the BRCAm subgroup (0.73; 95 % CI 0.45-1.17; p = 0.19), though treatment switching may have confounded results. The exclusion of data from sites allowing crossover resulted in an HR for overall survival (OS) of 0.52 (95 % CI 0.28-0.97, p = 0.039) in the BRCAm group. Health-related quality-of-life measures were not significantly different between groups. All post hoc exploratory outcomes (time to treatment discontinuation/death, time to first subsequent therapy/death, and time to second subsequent therapy/death) were statistically significantly better in the olaparib arm in the whole population and the BRCAm subgroup analyses. Adverse events were more frequent for olaparib but were largely minor or manageable. The company's semi-Markov model assessed the cost effectiveness of olaparib versus routine surveillance in patients with BRCAm PSR OC from a National Health Service (NHS) and Personal Social Services (PSS) perspective over a lifetime horizon. The model suggests that the incremental cost-effectiveness ratio (ICER) for olaparib versus routine surveillance is expected to be approximately £49,146 per quality-adjusted life-year (QALY) gained. The ERG did not consider the company's cost-effectiveness estimates to be credible. Additional ERG analyses suggested that the ICER is likely to be more than £92,214 per QALY gained. Additional analyses provided by the company in patients who received three or more lines of chemotherapy suggested a more favourable cost-effectiveness profile for olaparib. The NICE Appraisal Committee recommended olaparib for this subgroup provided the cost of olaparib for people who continue to receive treatment after 15 months will be met by the company.

Palbociclib: A new hope in the treatment of breast cancer.

Breast cancer being one of the common cancers has high morbidity and mortality. Despite the conventional treatment, the burden of the disease increases year after year. There is a need for newer drugs that target the different mechanisms in the pathogenesis. The interaction of cyclins with cyclin dependent kinases (CDKs) plays a major role in the abnormal cell cycle in cancer and it is considered to be an important target. Palbociclib is a CDK inhibitor currently approved for the treatment of breast cancer. The preclinical studies with breast cancer lines were sensitive to palbociclib and the clinical trials phase I, phase II (PALOMA 1), and phase III (PALOMA 2, 3, PENTELOPE, PEARL) showed that the drug was efficacious when combined other conventional drugs for breast cancer. Palbociclib was also been tested in various other germ cell tumors, melanoma, multiple myeloma, glioblastoma multiforme etc., The major adverse effect of the drug includes hematological toxicity mainly neutropenia, gastrointestinal adverse effects.

Changing the cost of care for chronic myeloid leukemia: the availability of generic imatinib in the USA and the EU.

Imatinib is an oral tyrosine kinase inhibitor and considered to be the most successful targeted anti-cancer agent yet developed given its substantial efficacy in treating chronic myeloid leukemia (CML) and other malignant diseases. In the USA and the European Union (EU), Novartis' composition of matter patent on imatinib will expire in 2016. The potential impact on health system spending levels for CML after generic imatinib becomes available is the subject of significant interest among stakeholders. The extent of the potential savings largely depends on whether and to what extent prices decline and use stays the same or even increases. These are also empirical questions since the likely spending implications following generic imatinib's availability are predicated on multiple factors: physicians' willingness to prescribe generic imatinib, molecule characteristics, and health system priorities. This article discusses each of these issues in turn. We then review their implications for the development of country-specific cost-effectiveness models to predict the implications for cost and quality of care from generic imatinib.

Fluid retention associated with imatinib treatment in patients with gastrointestinal stromal tumor: quantitative radiologic assessment and implications for management.

OBJECTIVE: We aimed to describe radiologic signs and time-course of imatinib-associated fluid retention (FR) in patients with gastrointestinal stromal tumor (GIST), and its implications for management. MATERIALS AND METHODS: In this Institutional Review Board-approved, retrospective study of 403 patients with GIST treated with imatinib, 15 patients with imaging findings of FR were identified by screening radiology reports, followed by manual confirmation. Subcutaneous edema, ascites, pleural effusion, and pericardial effusion were graded on a four-point scale on CT scans; total score was the sum of these four scores. RESULTS: The most common radiologic sign of FR was subcutaneous edema (15/15, 100%), followed by ascites (12/15, 80%), pleural effusion (11/15, 73%), and pericardial effusion (6/15, 40%) at the time of maximum FR. Two distinct types of FR were observed: 1) acute/progressive FR, characterized by acute aggravation of FR and rapid improvement after management, 2) intermittent/steady FR, characterized by occasional or persistent mild FR. Acute/progressive FR always occurred early after drug initiation/dose escalation (median 1.9 month, range 0.3-4.0 months), while intermittent/steady FR occurred at any time. Compared to intermittent/steady FR, acute/progressive FR was severe (median score, 5 vs. 2.5, p = 0.002), and often required drug-cessation/dose-reduction. CONCLUSION: Two distinct types (acute/progressive and intermittent/steady FR) of imatinib-associated FR are observed and each type requires different management.