Clinical and Economic Implications of Hydroxyurea Intolerance in Polycythemia Vera in Routine Clinical Practice.

Background/Objectives: Polycythemia vera (PV) is a chronic hematologic neoplasm commonly treated with hydroxyurea (HU). We utilized the advanced digitalized database of Maccabi Healthcare Services to retrospectively investigate the clinical and economic implications of HU intolerance in the routine clinical care of PV patients in Israel. Methods: We collected data on demographics, physician visits, hospitalizations, laboratory results, medication purchases, cardiovascular and thrombotic events, mental health, economic outcomes, and mortality. Outcomes included cardiovascular and other thrombotic events, disease progression, mental health events, economic outcomes, and overall mortality. Results: Of the 830 patients studied, 3 (0.4%) were resistant to HU treatment, 318 (38.3%) were intolerant to HU treatment, and 509 (61.3%) were stable on HU treatment. The venous thrombosis rate was significantly higher among HU-intolerant compared to HU-stable patients (1.58 vs. 0.47 per 100 person-years [PY], respectively; p < 0.001). The rate of progression to myelofibrosis was 6 vs. 0.9 per 100 PY in HU-intolerant patients vs. HU-stable patients, respectively (p < 0.001), and the rate of progression to acute myeloid leukemia (AML) was 1.16 vs. 0.2 per 100 PY in HU-intolerant patients vs. HU-stable patients, respectively (p < 0.001). The phlebotomy requirement, mortality rate, and total hospitalization days among HU-intolerant patients were significantly higher than in HU-stable patients (p = 0.049, p < 0.001, p < 0.001, respectively). More mental health-related events were noted in HU-intolerant patients vs. HU-stable patients (p = 0.007), and the total healthcare cost ratio was 2.65 for the HU-intolerant patients compared with HU-stable patients. Conclusions: This study suggests that HU-intolerant patients are more likely to have worse outcomes than HU-stable patients, highlighting the need for the close monitoring of these patients for disease-related complications or progression.

Economic evaluation of universal prenatal HIV screening compared with current 'at risk' policy in a very low prevalence country.

OBJECTIVES: Our objective was to economically evaluate universal HIV prenatal screening in Israel, a very low prevalence country (0.1%), compared with the current policy of testing only women belonging to high-risk (HR) groups. DESIGN: A cost-effectiveness analytical model was constructed. Life expectancies, direct medical costs and utility weights of an HIV-positive newborn and a healthy newborn were derived from the literature. Screening was assessed using fourth-generation combo tests. Structural uncertainties were discussed with leading Israeli HIV experts. Univariate and multivariate sensitivity analyses were conducted to account for uncertainty of the model's parameters. RESULTS: Under the current policy, about 2700 women are tested annually identifying 27 HIV-positive women. With the universal screening, 171 000 women would be tested yearly identifying 37 as HIV positive. The analysis included the increased life expectancy of vertically infected children based on current standards of care. Over the lifetime expectancy, universal screening is projected to grant 15 additional quality-adjusted life years and save $177 521 when compared with the current HR only policy. CONCLUSIONS: Universal prenatal HIV screening is projected to be cost saving in Israel, despite a very low HIV prevalence in the general population.

Does drug price-regulation affect healthcare expenditures?

BACKGROUND: Increasing health costs in developed countries are a major concern for decision makers. A variety of cost containment tools are used to control this trend, including maximum price regulation and reimbursement methods for health technologies. Information regarding expenditure-related outcomes of these tools is not available. OBJECTIVE: To evaluate the association between different cost-regulating mechanisms and national health expenditures in selected countries. METHODS: Price-regulating and reimbursement mechanisms for prescription drugs among OECD countries were reviewed. National health expenditure indices for 2008-2012 were extracted from OECD statistical sources. Possible associations between characteristics of different systems for regulation of drug prices and reimbursement and health expenditures were examined. RESULTS: In most countries, reimbursement mechanisms are part of publicly financed plans. Maximum price regulation is composed of reference-pricing, either of the same drug in other countries, or of therapeutic alternatives within the country, as well as value-based pricing (VBP). No association was found between price regulation or reimbursement mechanisms and healthcare costs. However, VBP may present a more effective mechanism, leading to reduced costs in the long term. CONCLUSIONS: Maximum price and reimbursement mechanism regulations were not found to be associated with cost containment of national health expenditures. VBP may have the potential to do so over the long term.

Burden of human papillomavirus infection and related diseases in Israel.

This manuscript provides the available data on the burden of human papillomavirus (HPV) infections and HPV-related diseases in Israel. The incidence of cervical intraepithelial neoplasia grade 3 (CIN3) among Jewish women was 17.4 per 100,000 in 2007, showing an increase since 1997. The incidence of cervical cancer was 5.3 per 100,000 Israeli Jewish women and 2.3 per 100,000 Israeli non-Jewish women in 2007. This rate is relatively low compared to other developed countries, and could be explained by cultural and religious factors such as male circumcision or sexual behavior. Mortality rates were around 1.5 per 100,000 Israeli women in 2007. Incidences of other anogenital, oral cavity, and pharynx cancers are very low, below 1.0 per 100.000 Israeli women and men. Information is scarce on HPV prevalence and HPV type distribution among women with cervical cancer. HPV types 16 and 18 were the two most common types in both preneoplastic lesions and cervical cancer, representing 60% of total invasive cases. Data on genital warts show an incidence rate of 239 per 100,000 men and 185 per 100,000 women, similar to that found in other Western countries. Despite these low incidences, it is important to improve the information on the overall burden of HPV-related morbidity and on the HPV prevalence to evaluate an organized cervical cancer screening program and the introduction of the HPV vaccine in the national school-based vaccine program. This article forms part of a regional report entitled "Comprehensive Control of HPV Infections and Related Diseases in Israel" Vaccine Volume 31, Supplement 8, 2013. Updates of the progress in the field are presented in a separate monograph entitled "Comprehensive Control of HPV Infections and Related Diseases" Vaccine Volume 30, Supplement 5, 2012.

A population based study of the epidemiology of Herpes Zoster and its complications.

OBJECTIVES: To assess the incidence of Herpes Zoster (HZ) and its complications in the Israeli general population and specifically in immune-compromised individuals, and to identify risk factors for developing HZ and post-herpetic neuralgia (PHN). METHODS: A retrospective database search for newly diagnosed cases of HZ and of PHN during 2006-2010 was conducted using the comprehensive longitudinal database of Maccabi Health Services. Cox-proportional hazards models were used to assess associations between risk factors and HZ and PHN. RESULTS: During 2006-2010 there were 28,977 newly diagnosed cases of HZ and 1508 newly diagnosed cases of PHN. Incidence density rate of HZ was 3.46 per 1000 person-years in the total population and 12.8 per 1000 person-years in immune-compromised patients. HZ and PHN incidence increased sharply with age. 12.4% and 3.1% of elderly HZ patients (≥ 65 years) developed PHN or ophthalmic complications, respectively. In multivariable analyses, HZ and PHN were associated with female sex, higher socioeconomic status, diabetes mellitus, cancer history, and HIV treatment. CONCLUSIONS: Extrapolating to the entire Israeli population, we estimate over 24,000 new cases of HZ and 1250 new cases of PHN each year. Cost-effectiveness analysis should be performed to determine the threshold age for vaccination against HZ.

Evaluating real-life clinical and economical burden of amphotericin-B deoxycholate adverse reactions.

BACKGROUND: Amphotericin-B (AMB) is associated with toxicity such as renal impairment, hypokalemia and infusion-related events (IRE). With the advent of AMB lipid formulations and newer antifungal drugs, presenting improved safety profiles, it was suggested that using the conventional deoxycholate (AMB-D) formulation should no longer be regarded acceptable. OBJECTIVES: Evaluation of real-life incidence of AMB-D-related adverse-drug effects (ADE) and associated costs. SETTING: Hadassah Hebrew University Medical Center, Jerusalem, Israel, a tertiary 1,100-bed teaching hospital. METHODS: A 1-year single-center prospective observational study following all patients administered AMB-D. Various parameters related to AMB-D administration were recorded. Main outcome measures Subsequent ADE-related events, discontinuations, switch to alternative antifungals and related resource-utilization were monitored. RESULTS: Among 119 patients (60 children, 59 adults) receiving AMB-D, serum creatinine doubling from baseline, hypokalemia and IRE occurred in 14.3 % (15 % in children, 13.6 % in adults), 16.8 % (16.6 % in children, 16.9 % in adults) and 10.9 % (10 % in children, 11.8 % in adults), respectively. AMB-D was discontinued due to an ADE in 12.6 % of patients (6.7 % in children, 18.6 % in adults). The total annual cost associated with AMB-D use was 58,600. CONCLUSION: The clinical as well as economic burden of AMB-D associated ADE, as observed in real-life settings, appears to be manageable. Considering the significant cost implications associated, as suggested by simulated evaluation of an overall theoretic replacement of AMB-D by an equivalent volume of alternative antifungals, total abandonment of AMB-D appears unjustified.

Evaluating the epidemiology and morbidity burden associated with human papillomavirus in Israel: accounting for CIN1 and genital warts in addition to CIN2/3 and cervical cancer.

BACKGROUND: Human papillomavirus (HPV) infection is mostly associated with cervical cancer (CC). However, it can cause other illnesses as well, all of which impact on people's wellbeing and consume healthcare resources. Measures for prevention or early detection of these conditions differ in their effectiveness and cost. An informative evaluation of the projected benefit of these measures depends on understanding the current unmet need, not only limited to CC. OBJECTIVE: To evaluate the burden of HPV-related conditions in Israel, including CC, cervical precancerous lesions and genital warts. METHODS: A retrospective database analysis was conducted for the second largest health management organization (HMO) in Israel, covering approximately 1.8 million people. Records were drawn following a search for key words indicative of related diagnoses, lab results, medications, or procedures for the time period of 2006-2008. Prevalence, incidence and resource utilization were analysed. Findings were extrapolated to the whole Israeli population using age and gender incidence rates. RESULTS: Incidence of CC was found to be 5 per 100,000 females. Incidences of cervical intraepithelial neoplasia (CIN) grades 1, 2 and 3 were 74, 27 and 36 per 100,000 females, respectively. Incidence of genital warts was 239 and 185 per 100,000 for men and women, respectively. The overall annual economic burden was calculated to be $US48,838,058 (year 2010 values). CONCLUSIONS: HPV poses a significant burden in terms of health (clinical and quality of life) and in monetary terms, even for conditions that are sometimes regarded as benign, such as CIN1 or genital warts. Current findings should be used for proper evaluation of measures to reduce HPV-related morbidity and mortality, such as regular screening and vaccination.

Utilization of health technologies-Do not look where there is a light; shine your light where there is a need to look! Relating national health goals with resource allocation decision-making; illustration through examining the Israeli healthcare system.

Innovative health technologies are often the focus of attention. However, in the allocation of public resources for improving health, the focus should be on the health needs of the population. It is the need that should be analyzed first, and decision makers should then evaluate the full range of interventions available, whether new or old, to meet this need. This is in contrast to analyzing the technology first and then characterizing the need it meets, which is the current practice in reimbursement decision-making in several countries. The identified health need should define national health goals, and these goals should be proactively assimilated into the reimbursement decision-making process. Differential reimbursement rates could reflect the relative contribution of the technology to the unmet health need.

It's time to choose the study design!: net benefit analysis of alternative study designs to acquire information for evaluation of health technologies.

Uncertainty in the decision-making process for reimbursement of health technologies could be reduced if additional information were available. Although methods to evaluate the monetary value of the uncertainty have been previously described, an economic evaluation of alternative methods to acquire additional information has not yet been thoroughly explored. Should resources be allocated to a retrospective study design or to a randomised controlled trial (RCT) when additional information is deemed justified? We propose an approach for cost-effectiveness analysis of designs of future studies that are required to evaluate health technologies for reimbursement. Biases inherent in study designs are the main factor that differentiates the ability of the studies to predict the technology's benefit. By quantifying this inherent-bias effect, the incremental effectiveness of future studies can be evaluated. Economic consequences of decisions regarding prioritization of the technologies, along with the expected costs incurred by the study's execution, account for the cost component of the equation. Deducting the result retrieved for the retrospective design from that of the RCT design gives the net information benefit.

Impact of smoking on asthma symptoms, healthcare resource use, and quality of life outcomes in adults with persistent asthma.

BACKGROUND: Smoking habits of asthmatics are similar to those of the general population. However, little attention has been paid to the associations between smoking and asthma-related outcomes. OBJECTIVE: To evaluate relationships between cigarette smoking, asthma symptoms, and asthma-related resource utilization in subjects with persistent asthma. METHOD: A stratified, random sample of adults from France, Germany, and the UK with persistent asthma were surveyed in 2001 through 2004. Statistical analyses compared asthma symptoms and healthcare resource utilization for cigarette smokers compared with those for non-smokers. RESULTS: Analyses included 1109 subjects with persistent asthma symptoms in 2001-2003 and 852 subjects with persistent asthma symptoms in 2004. Using multivariate analysis of data from eligible subjects in 2004 that did not have concomitant chronic obstructive pulmonary disease and adjusting for subjects' baseline and demographic characteristics, cigarette smokers were more likely to experience nighttime symptoms (OR 1.46, 95% CI 1.07, 1.97 P = 0.015) and were more likely to use healthcare resources than were non-smokers (P < or = 0.004). Findings were similar in a secondary analysis of subjects < or =55 years of age. CONCLUSIONS: Cigarette smoking appears to be associated with more asthma symptoms and more ED visits and hospitalizations in adults with persistent asthma.