Predictors of loss due to pharmaceutical fraud: evidence from the U.S.

BACKGROUND: Globally and in the U.S. in particular, pharmaceutical fraud account for a large number out of all crimes in health care, which result into severe costs to the society. The Academy of Managed Care Pharmacists (Fraud, waste, and abuse in prescription drug benefits. 2019. Posted May 20. https://www.amcp.org/policy-advocacy/policy-advocacy-focus-areas/where-we-stand-position-statements/fraud-waste-and-abuse-prescription-drug-benefits .) estimate that pharmacy fraud is 1% of costs, therefore estimating that pharmacy fraud costs at $3.5 billion, given that pharmacy costs are $358 billion (Statista. Prescription drug expenditure in the United States from 1960 to 2020. 2021. https://www.statista.com/statistics/184914/prescription-drug-expenditures-in-the-us-since-1960/ ). AIM: This exploratory study aims to demonstrate a fraudster's profile as well as to estimate average consequences in terms of costs and identify the loss predictors' hierarchy in the pharmaceutical industry in the U.S. MATERIALS AND METHODS: Data from the Corporate Prosecution Registry and mixed-effects models are utilized for this purpose. The dataset covers years 2001-2020 and 75 cases, falling into one of the following broad sub-categories: misbranding, counterfeit, off-label use of drugs/deceptive marketing; violation of the Food, Drug and Cosmetic Act. RESULTS: The main factors positively associated with loss due to pharmaceutical fraud are: (i) duration of , and (ii) the scheme and scheme being executed at a U.S. public company. Surprisingly, presence of collusion negatively and significantly effects the cost. Potential factors include: (a) principal perpetrator being a white American and/or male, and (b) number of employees at individual and organizational level respectively. CONCLUSION: This study empirically justifies considering loss, due to pharmaceutical fraud, from a multi-level perspective. Identified profiles of a typical fraudster helped to elaborate on specific practical recommendations aimed at pharmaceutical fraud prevention in the U.S.

Dynamics of Health Care Financing and Spending in Serbia in the XXI Century.

Serbia is an upper-middle income Eastern European economy. It has inherited system of health provision and financing, which is a mixture of Soviet Semashko and German Bismarck models. So far, literature evidence on long-term trends in health spending remains scarce on this region. Observational descriptive approach was utilized relying on nationwide aggregate data reported by the Republic Health Insurance Fund (RHIF) and the Government of Serbia to the WHO office. Consecutively, the WHO Global Health Expenditure Database was used. Long-term trends were extrapolated on existing data and underlying differences were analyzed and explained. The insight was provided across two distinctively different periods within 2000-2016. The first period lasted from 2000 till 2008 (the beginning of global recession triggered by Lehman Brothers' bankruptcy). This was a period of strong upward growth in ability to invest in health care. Spending grew significantly in terms of GDP share, national and per capita reported expenditures. During the second period (2009-2016), after the beginning of worldwide economic crisis, Serbia was affected in a way that its health expenditure growth in PPP terms slowed down effectively fluctuating around plateau values from 2014 to 2016. Serbia health spending showed promising signs of steady growth in its ability to invest in health care. Consolidation marked most of the past decade with certain growth rates in recent years (2017-2019), which were not captured in these official records. The future national strategy should be devised to take into account accelerated population aging as major driver of health spending.

Life expectancy and health expenditure evolution in Eastern Europe-DiD and DEA analysis.

BACKGROUND: Exploration of long-term health expenditure and longevity trends across three major sub-regions of Eastern Europe since 1989. METHODS: 24 countries were classified as EU 2004, CIS, or SEE. European Health for All Database (HFA-DB) 1989-2012 data were processed using difference-in-difference (DiD) and data envelopment analysis (DEA). RESULTS: The strongest expenditure growth was recorded in EU 2004 followed by SEE and the CIS. A surprisingly similar longevity increase was present in SEE and EU 2004. In 1989, countries that joined EU in 2004 were relatively inefficient in the number of life-years gained yet had a lower life expectancy than the SEE region and was only slightly higher than the CIS region (DEA). By 2012 the revenue spent was roughly linear to additional life-year expectancies. CONCLUSION: EU 2004 members were the best performers in terms of balanced longevity increase followed by health expenditure growth. The SEE economies' longevity gains were lagging slightly behind at a far lower cost. An extrapolated CIS expenditure to longevity increase ratio has the fastest-growing long-term promise.

Can didactic continuing education improve clinical decision making and reduce cost of quality? Evidence from a case study.

INTRODUCTION: Administration of human serum albumin (HSA) solutions for the resuscitation of critically ill patients remains controversial. The objective of this study was to assess the effect of continuing medical education (CME) on health care professionals' clinical decision making with regard to HSA administration and the costs of quality (COQ). A quasi-experimental study of time series association of CME intervention with COQ and use of HSA solution was conducted at the Surgery Department of the Hospital Valjevo, Serbia. The CME contained evidence-based criteria for HSA solution administration in surgical patients. The preintervention period was defined as January 2009 to May 2011. CME was provided in June 2011, with the postintervention period June 2011 to May 2012. METHODS: Total mortality rate, the rate of nonsurgical mortality, the rate of surgical mortality, the rate of sepsis patient mortality, index of irrational use of HSA solutions, and number of hospital days per hospitalized patient were collected for each month as quality indicators. Statistical analysis was performed by multivariate autoregressive integrated moving average (MARIMA) modeling. The specification of the COQ was performed according to a traditional COQ model. RESULTS: The CME intervention resulted in an average monthly reduction of the hospital days per hospitalized patient, the rate of sepsis patient mortality, index of irrational use of HSA solutions, and COQ for $593,890.77 per year. DISCUSSION: Didactic CME presenting evidence-based criteria for HSA administration was associated with improvements in clinical decisions and COQ. In addition, this study demonstrates that models combining MARIMA and traditional COQ models can be useful in the evaluation of CME interventions aimed at reducing COQ.

Evolution of the Serbian pharmaceutical market alongside socioeconomic transition.

INTRODUCTION: South-eastern European socioeconomic transition followed by extensive health systems reforms has completely changed the pharmaceuticals market landscape in the region. Serbia, as the largest Western Balkans market, may serve as an example of such changes. METHODS: Descriptive trend analysis of national-level dispensing of medicines in Serbia 2004-2012 was performed. RESULTS: Total public health expenditure in Serbia increased sharply in less than a decade (€1,175,158,679 to €1,847,971,776); public spending on pharmaceuticals doubled (€339,279,304 to €742,013,976). Market growth was primarily driven by statins, novel platelet aggregation inhibitors, monoclonal antibodies and combined preparations indicated in asthma and chronic obstructive pulmonary disease. CONCLUSION: The pharmaceutical market of Serbia has undergone thorough and complete transformation from within. Serious crisis of medicine supply sustainability is currently shaking Balkan health systems due to increasing public debt worsened by global recession. More responsible reimbursement policy rooted in cost-effectiveness principle is needed in years to come.

10th World IHEA and ECHE Joint Congress: health economics in the age of longevity.

The 10th consecutive World Health Economics conference was organized jointly by International Health Economics Association and European Conference on Health Economics Association and took place at The Trinity College, Dublin, Ireland in July 2014. It has attracted broad participation from the global professional community devoted to health economics teaching,research and policy applications. It has provided a forum for lively discussion on hot contemporary issues such as health expenditure projections, reimbursement regulations,health technology assessment, universal insurance coverage, demand and supply of hospital services, prosperity diseases, population aging and many others. The high-profile debate fostered by this meeting is likely to inspire further methodological advances worldwide and spreading of evidence-based policy practice from OECD towards emerging markets.

Contemporary generic market in Japan - key conditions to successful evolution.

The Japanese pharmaceutical market, the world's second largest, is traditionally renowned for the domination of patented drugs and the weakest generics share among major established economies. An in-depth observation of published evidence in Japanese/English language provided closer insight into current trends in Japanese domestic legislation and pharmaceutical market development. Recent governmental interventions have resulted in significant expansion of the generic medicines market size. Substantial savings due to generic substitution of patent-protected drugs have already been achieved and are likely to increase in future. Nationwide population aging threatening sustainable healthcare funding is contributing to the relevance of generic policy success. Serious long-term challenges to the modest Japanese generic manufacturing capacities will be posed by foreign pharmaceutical industries particularly the ones based in emerging BRIC economies.

Cross-sectional survey on complementary and alternative medicine awareness among health care professionals and students using CHBQ questionnaire in a Balkan country.

OBJECTIVE: To conduct a study on attitudes, knowledge, and use of complementary and alternative medicine (CAM) therapies in Serbia. Available data about CAM therapies in the region are scarce, opinions lacking from health sector. Balkan region countries had a delay in issuing national policies on CAM therapies. METHODS: The questionnaire used was based on previously validated CAM Health Belief Questionnaire (CHBQ), formulated as 5-item Likert type scale, adjusted for local environment. Health care students and professionals were evaluated. The questionnaire comprehended 10 closed questions on attitudes, knowledge and use of CAM therapies. This survey was conducted in eight cities of Serbia, January 2010-July 2011. A total of 797 participants was included. The second group of participants was 145 healthcare professionals (50 academic staff, 64 clinical staff, 19 pharmacists, 6 other clinical branch specialists and 6 nurses). Data were collected by an interview. Examinees could acquire maximum of 70 points, 35 representing neutral attitude. RESULTS: Students of dentistry (54.65±6.07) were better informed on CAM therapies than medicine students (50.26±7.92). Pharmacy students (51.16±7.10) accepted low-scientific CAM. Pharmacists scored better than university professors (55.12±6.55 vs. 50.29±9.50). Primary health care professionals had better awareness than pharmacists in dispensing pharmacies. Both groups of participants preferred use of vitamins over any other CAM therapy. CONCLUSION: These pioneering efforts in the region exposed weaknesses in CAM attitudes of current and future health care professionals. Nevertheless, awareness on alternative medicine treatment choices is growing among Balkan prescribers. Supportive legal framework would facilitate dissemination of CAM medical practices.

Resource allocation strategies in Southeastern European health policy.

The past 23 years of post-socialist restructuring of health system funding and management patterns has brought many changes to small Balkan markets, putting them under increasing pressure to keep pace with advancing globalization. Socioeconomic inequalities in healthcare access are still growing across the region. This uneven development is marked by the substantial difficulties encountered by local governments in delivering medical services to broad sectors of the population. This paper presents the results of a systematic review of the following evidence: published reports on health system reforms in the region commissioned by WHO, IMF, World Bank, OECD, European Commission; all available published evidence on health economics, funding, reimbursement in world/local languages since 1989 indexed at Medline, Excerpta Medica and Google Scholar; in depth analysis of official website data on medical care financing related legislation among key public institutions such as national Ministries of health, Health Insurance Funds, Professional Associations were applicable, in local languages; correspondence with key opinion leaders in the field in their respective communities. Contributors were asked to answer a particular set of questions related to the issue, thus enlightening fresh legislative developments and hidden patterns of policy maker's behavior. Cost awareness is slowly expanding in regional management, academic and industrial establishment. The study provides an exact and comprehensive description of its current extent and legislative framework. Western Balkans policy makers would profit substantially from health-economics-based decision-making to cope with increasing difficulties in funding and delivering medical care in emerging markets with a rapidly growing demand for health services.

[Pharmacokinetic modelling of valproate in epileptic patients].

INTRODUCTION: The aim of our study was to develop and use a population pharmacokinetic model for assessment of individual valproate clearance in children and young adults suffering from epilepsy. MATERIAL AND METHODS: The analysis was performed using 52 steady-state concentrations of valproate collected from 26 epileptic patients during the routine clinical practice in our hospital. The mean values of age and total body weight were 19.92 years and 57.12 kg, respectively. NONMEM software with ADVAN 1 subroutine was used for model building and assessing the influence of different covariates. A validation set of 20 epileptic patients (one blood sample per a patient) was used to estimate predicted performances of the pharmacokinetic model. RESULTS: The typical mean value of the clearance of valproate estimated by the base model in our population was 0.3 77 I/h. Out of five considered covariates (total body weight, age, total daily dose, gender and polytherapy) only the age of the patients was a significant determinant of the clearance of valproate. The final regression model for the clearance of valproate was as following: CL (l/h) = 0.223 + 0.00819 * AGE CONCLUSION: The derived pharmacokinetical model describes the clearance of valproate in relation to patient's age in the observed population. it will help to improve the seizure control in young patients with epilepsy in Serbian population.

A nonlinear mixed effects modelling analysis of topiramate pharmacokinetics in patients with epilepsy.

Topiramate pharmacokinetics is influenced by individual factors such as patient age, renal function and co-treatment. The aim of this study was to develop a population pharmacokinetic model of topiramate to assist dosage adjustments in individual patients. Steady-state topiramate plasma concentrations in patients with epilepsy were determined by HPLC using fluorescent labelling. Demographic, biochemical data and dosing history including concomitant drug therapy were collected from patients' charts. Nonlinear mixed effects modelling was used to fit a one-compartment pharmacokinetic model. The influence of patient weight and gender, body surface area, age, creatinine clearance, serum transaminases, topiramate daily dose and co-treatment with carbamazepine, valproic acid, benzodiazepines, and risperidone on topiramate pharmacokinetics was evaluated. Additionally, the relationship between topiramate plasma concentration and clinical response was investigated. Volume of distribution of topiramate was 0.518 l/kg. For a typical patient oral clearance was estimated at 1.47 l/h, with interindividual variability of 39.2%. Clearance was 70% higher in patients co-treated with carbamazepine and was found to increase with patient age. Somnolence was the most frequently observed adverse event. Incidence of headache was associated with topiramate plasma concentration. Somnolence, ataxia, tremor, speech disorders and fatigue were associated with adjunctive therapy with carbamazepine, valproic acid, benzodiazepines, risperidone, and clozapine. No association of topiramate plasma concentration with frequency of seizures or patient quality of life was observed. The developed model can be used for Bayesian estimation of pharmacokinetic parameters based on sparse plasma samples and for selection of optimum dosing in routine patient care.

Inverse correlation of valproic acid serum concentrations and quality of life in adolescents with epilepsy.

BACKGROUND: Correlation between steady-state serum concentrations of antiepileptic drugs and both seizure control and adverse drug reactions frequency (two major determinants of quality of life in patients with epilepsy) is still matter of controversy. OBJECTIVE: The aim of our study was to investigate whether a correlation exists between steady-state serum concentration of valproic acid and quality of life in adolescent patients with epilepsy. METHOD: Twenty-one adolescent patients with epilepsy, treated with valproic acid for more than 6 months entered the study. On two occasions, 3 months apart, both through and 2-h-after-the-dose serum concentrations of valproic acid were measured, as well as quality of life, using QOLIE-AD-48 for adolescents. Adverse drug reactions and seizure control were also recorded. RESULTS: Significant inverse correlation between through serum concentrations of valproic acid and total QOLIE-AD-48 scores was observed, together with correlation between through serum concentrations and adverse drug reactions frequency. The scores of memory/concentration and physical functioning QOLIEAD-48 domains were significantly and inversely correlated with through serum concentrations. CONCLUSION: Our study suggests that therapeutic monitoring of valproic acid serum concentrations could be useful predictor and marker of the most important epilepsy treatment outcome--quality of life.