Abstract ECONOMIC IMPACT OF WASTE IN PRESCRIBING, DISPENSING, AND MEDICATION CONSUMPTION IN THE UNITED STATES By Sarah A. Almanie, M.S. A thesis submitted in partial fulfillment of the requirements for the degree of Master of Science at Virginia Commonwealth University. Virginia Commonwealth University, 2015. Major Director: David A. Holdford, R.Ph., M.S., Ph.D., FAPhA Professor Department of Pharmacotherapy and Outcomes Science OBJECTIVES: This research examines waste associated with the medication use process which consists of unfilled prescriptions, abandoned prescriptions, or unused prescription medications. The aim of this study is to quantify the direct medical costs of medication waste in delivery of care in the United States. METHODS: A review of published literature and data from the 2012 Medical Expenditure Panel Survey was used to quantify the number of prescriptions wasted at different stages of the medication prescribing and use process and the associated costs were calculated. RESULTS: In 2012, more than 26 million prescriptions were either unfilled or abandoned, and more than 225 million resulted in dispensed medications that were not used. The total cost of this waste was estimated at $30.4 billion. CONCLUSIONS: Patients who do not fulfill their role in the medication use process cause significant, avoidable costs to the health care system beyond the health outcomes not achieved.

Introdução: As mucopolisaccaridoses tipo I (MPS I), tipo II (MPS II) e tipo VI (MPS VI) são doenças lisossômicas (DL) para as quais está disponível a terapia de reposição enzimática (TRE) com laronidase, idursulfase e galsufase, respectivamente. Objetivo Primário: Analisar a frequência anual de intervenções médicas (número de consultas, internações, cirurgias, exames solicitados, medicamentos prescritos, equipamentos de uso crônico e outras formas de terapia) em uma amostra de pacientes brasileiros com MPS I, II e VI e, desta forma, contribuir para o conhecimento dos aspectos farmacoeconômicos relacionados a essas doenças. Metodologia: Estudo exploratório, retrospectivo, de base hospitalar, baseado em revisão de prontuário, com amostragem por conveniência, e que foi realizado em duas etapas (etapas 1 e 2). Um instrumento específico para a coleta de dados de ambas as etapas foi construído pela equipe do estudo, que é multidisciplinar. Os desfechos de interesse foram as frequências anuais de intervenções médicas (consultas, exames, cirurgias, internações, medicamentos utilizados, outras formas de terapia). A etapa 1 consistiu em estudo pré-experimental, realizado no Serviço de Genética Médica do Hospital de Clínicas de Porto Alegre (SGM-HCPA), e que comparou as variáveis de interesse, para o mesmo grupo de pacientes, entre o período pré e pós-TRE. Os critérios de inclusão dessa etapa foram: ter diagnóstico confirmado de MPS I; estar em acompanhamento regular no SGM-HCPA desde o diagnóstico; estar em TRE por pelo menos um ano; e não ter participado de ensaio clínico envolvendo TRE ou ter realizado transplante de células-tronco hematopoiéticas. A etapa 2 foi transversal, multicêntrica (centros incluídos: SGMHCPA, Departamento de Genética Médica da Universidade Estadual de Campinas - UNICAMP, Pontifícia Universidade Católica de Campinas – PUC-Campinas, e Departamento de Pediatria da Universidade Estadual do Rio de Janeiro - UERJ), e comparou as variáveis de interesse entre grupos diferentes de pacientes (aqueles recebendo TRE e aqueles não recebendo TRE). Para essa etapa, foram considerados somente os dados relativos a 2010, sendo os seguintes os critérios de inclusão dos pacientes: ter diagnóstico confirmado de MPS I, II e VI; não estar participando de nenhum ensaio clínico envolvendo TRE ou ter realizado transplante de células-tronco hematopoiéticas; estar em TRE por pelo menos 12 meses antes do início da coleta, ou em acompanhamento por pelo 12 meses antes do início da coleta. Resultados: Etapa 1 - Nove pacientes (graves=3; atenuados=6) com MPS I foram incluídos no estudo, com mediana de idade de diagnóstico de 4,4 anos. Somente o número de cirurgias/ano/paciente foi dependente do tempo de doença (p=0,0004) e da gravidade do fenótipo (p=0,014). Com relação às comparações pré e pós-TRE, as variáveis que apresentaram diferença significativa (média do número/ano/paciente) foram: exames (pré-TRE=10,2+2,7; pós-TRE=22,5+2,1; p=0,005) e internações (pré-TRE=0,05+0,04; pós-TRE=0,30+0,11; p=0,013). Para as demais variáveis, não foi encontrada associação. Etapa 2 - Trinta e quatro pacientes com MPS I (n=12), II (n=17) e VI (n=5) foram incluídos no estudo. Desses, sete não utilizavam TRE (grupo “sem TRE") e 27 faziam uso de tratamento específico (grupo “com TRE"). Não foi encontrada correlação significativa entre tempo de doença e as variáveis estudadas. Considerando a amostra total, foi encontrada diferença entre o grupo “sem TRE” e o grupo “com TRE” em relação à mediana de internações hospitalares e de cirurgias realizadas [1(0-2) vs. 0 (0-1), p=0,015; e 0 (0-2) vs. 0 (0-0), p=0,040, respectivamente]. Para as crianças/adolescentes (<18 anos), não foi encontrada diferença estatística entre os grupos. Os pacientes com comprometimento cognitivo utilizavam mais medicamentos que os demais (p=0,024). Encontrou-se correlação negativa entre as variáveis duração da TRE e número anual de internações (r= -0,504; p=0,007). Discussão/ Conclusões: Este é um dos primeiros estudos a avaliar aspectos relacionados à farmaconomia da TRE para as MPS. De acordo com os resultados obtidos na etapa 2, verifica-se que, desconsiderando-se o custo associado às infusões, o custo do tratamento de pacientes com MPS parece ser menor para aqueles pacientes que utilizam a TRE do que para os pacientes que fazem somente tratamento sintomático. Entretanto, de acordo com a etapa 1 do estudo, a TRE parece não impedir a evolução da doença, pelo menos em relação à MPS I, e, assim, a cada ano de vida do paciente ocorreria um incremento do custo associado ao tratamento. Estudos adicionais, com maior tamanho amostral, deverão ser realizados para confirmar nossos achados. / Introduction: The mucopolysaccharidoses type I (MPS I), II (MPS II) and VI (MPS VI) are lysosomal disorders (LSD) for which enzyme replacement therapy (ERT) with laronidase, idursulfase and galsulfase, respectively, are available. Principal objective: To analyze the annual frequency of medical interventions (number of medical appointments, hospital admissions, surgical procedures, exams performed, medications prescribed, ancillary therapies and the use of medical devices) in a sample of Brazilian patients with MPS I, II and VI, and thus, contribute to the understanding of some pharmacoeconomic aspects related to these diseases. Methodology: Retrospective, exploratory, hospital-based study, based on medical records review, with convenience sampling, which was conducted in two steps (steps 1 and 2). A specific data collection instrument for both steps was designed by the study team, which is multidisciplinary. The chosen outcomes were: annual frequencies of medical interventions (medical appointments, exams, surgical procedures, hospital admissions, medications used and ancillary therapies). Step 1 was a pre-experimental study conducted at the Medical Genetics Service of Hospital de Clínicas de Porto Alegre (SGM-HCPA), and compared the variables of interest between the pre and post-ERT periods for the same group of patients. The patient inclusion criteria were: a biochemical diagnosis of MPS I and regular follow-up at SGM-HCPA since diagnosis; ERT for at least 1 year; no enrollment in any clinical trials involving ERT, and no history of hematopoietic stem cell transplantation. Step 2 was a cross-sectional and multicentric estudy (Centers included: SGM-HCPA), the Department of Medical Genetics of Universidade Estadual de Campinas - UNICAMP, Pontifícia Universidade Católica de Campinas - PUC-Campinas, and the Department of Pediatrics at Universidade Estadual do Rio de Janeiro – UERJ, which compared the variables of interest between different groups of patients (those receiving and those not receiving ERT). For this step only data from 2010 were considered. The inclusion patient criteria were: a biochemical diagnosis of MPS I, II or VI; no enrollment in any clinical trials involving ERT, and no history of hematopoietic stem cell transplantation, to be on ERT for at least 12 months before the start of data collection or to undergo regular follow-up for at least 12 months before the start of data collection. Results: Step 1 – Nine MPS I patients (severe=3; attenuated phenotype=6) were included in the study with median age at diagnosis was 4.4 years. Only the number/year/patient of surgeries was found to be dependent on length of disease (p=0.0004) and on severity of phenotype (p=0.014). Regarding pre- and post-ERT comparisons, the variables for which a significant difference was detected (mean number/year/patient) were exams (pre-ERT, 10.2±2.7; post-ERT, 22.5±2.1; p=0.005) and hospital admissions (pre-ERT, 0.05±0.04; post-ERT, 0.30±0.11; p=0.013). For the other variables, no association was found. Step 2: Thirty-four patients with MPS I, II and VI were included (I=12, II=17, VI=5). From them, 27 on ERT (“ERT group”) and 7 receiving supportive care only (“non-ERT group”). There were no significant correlation between length of disease and any of the variables of interest. There were significant between-group differences in the median number of hospital admissions and surgical procedures, both of which were higher in the non-ERT group [1(0-2) vs. 0 (0-1), p=0,015; e 0 (0-2) vs. 0 (0-0), p=0,040, respectively]. There were no significant between-group differences when only children and adolescents (<18 years) were taken into account. Patients with cognitive involvement used more medications than the others (p=0.024). A correlation was detected between time on ERT and the hospital admissions variable (r= -0.504; p=0.007). Discussion/conclusions: This was one of the first studies to evaluate aspects related to pharmacoeconomics of ERT for MPS. According to the results of step 2, and not acknowledging the costs associated with recombinant enzyme infusions, patients with MPS who undergo ERT generate less cost to SUS than patients on symptomatic treatment. On the other hand, according to the results of step 1, ERT seems not to stop the disease progress, at least in respect to MPS I, and thus, for each year of a patient life occurred an increase in cost associated with treatment. Additional studies with larger sample size are needed to confirm our findings.

Thesis (M. Pharm.)--North-West University, Potchefstroom Campus, 2008.

In South Africa, significant changes in health care have taken place since the first democratic elections in 1994. The change had lead to a position of integrated service delivery with specific reference to primary health care. Increasingly in developing countries, the private sector impacts significantly on the rights to education and the highest attainable standard of health. Inappropriate prescribing e.g. prescribing a drug without an acceptable indication, specifying an incorrect dosage, schedule or duration of treatment, duplicating therapeutic agents and prescribing drugs without adequate regard to potential interactions, can cause adverse outcomes, deplete health care resources, compromise the quality of care and possible increase in health costs. One approach monitoring prescribing practices is drug utilisation review. The general objective of this study was to review and interpret aspects of drug usage patterns in a private primary health care setting, with special reference to the top ten diagnoses made and the top twenty medicine items prescribed as well as the associated costs. A quantitative, retrospective drug utilisation review as well as certain aspects of managed and primary health care, pharmacoeconomics, pharmacoepidemiology, medicine formularies and standard treatment guidelines were reviewed in the literature as a base for the study. The results of the empirical study showed that 83648 patients consulted at the nine medicentres during the study period (1 January to 31 December 2001). A total number of 132591 patient visits (consultations) were made, 140723 medical conditions (diagnoses) performed and 516177 medicine items prescribed during the study period. Analysis of medicine usage patterns and associated costs of the top ten diagnoses made and top twenty medicine items prescribed in the study population, revealed the following: The top ten diagnoses determined accounted for 29.07% of the total number of diagnoses made, . a total medicine treatment cost accounting for 32.11% in the study population, . the top twenty medicine items determined accounted for 56.23% of the total medicine items prescribed and . a total medicine treatment cost accounting for 28.63% in the study population. The highest prevalence of diagnoses made and medicine items prescribed was found in age groups 4 and 5 (Le. patients between the ages of 19 to 40 years) and was also found to be more prevalent in the female than in the male population. In completion of the research, recommendations to review the medicentres medicine treatment protocols and on provision of primary health care education were made. Reference to the investigation of environmental factors is also made. / Thesis (M.Pharm.)--North-West University, Potchefstroom Campus, 2004.

Health is a fundamental human right. Access to health care, which includes providing a population with safe, effective, good quality drugs at the least possible cost, is a prerequisite to realising that right. Drugs or medicines play a fundamental role in the effectiveness, efficiency and responsiveness of health care systems. Drugs also constitute a major recurrent expense in both state-run and private sector health care. To ensure that health care workers prescribe the most cost-effective drugs through the essential drugs list, training, as well as evaluation and monitoring systems must be regarded as important elements of containing costs. Pharmaceutical benefit management programmes such as pharmacoeconomics, drug utilisation review (DUR), evidence-based medicine and disease management have emerged as tools to ensure cost-effective selection and use of drugs, particularly for chronic diseases. These managed care tools are often investigated to determine whether new technologies or interventions are appropriate and have "value". Affordable prices of medicines, on their own, however, do not ensure access to medicines. Also important are reliable procurement, distribution and storage systems, and appropriately trained personnel to manage these components of drug management. Poorly regulated drug supply systems can have serious consequences such as antibiotic resistance, problems with safety or quality and most importantly wastage, as it is believed that a significant proportion of drugs purchased by the state in South Africa find their way into the private sector market through a "grey market". The general objective of this study was to review and analyse the cost and medicine usage of the "top twenty" pharmaceutical products according to the monthly pharmaceutical purchasing reports of the Department of Health in the North West Province. The research can be classified as retrospective and quantitative. The data used for the analysis were obtained over a two-year study period (1 Apr 2000 - 28 Feb 2002) from the private provider operating the medical stores in the North West Province. The results of the empirical investigation, showed the total number of "top twenty" products appearing during the study period amounted to 460 different products having a total purchasing cost of R 66,263,674.51 representing 37.2% (n = R 178,163,061.50) of all pharmaceutical products purchased during the two-year period. Through analysis it was found, when classified according the Anatomical Therapeutic Chemical (ATC) therapeutic main group, antihypertensives had the highest quantity purchased for year one (20.69%; n = 134,515,640) with cough and cold preparations revealing the highest purchasing quantity for year two (40.55%; n = 103,567,031) of all "top twenty" pharmaceuticals during the study period. Antibacterials for systemic use presented with the highest cost percentages for both years, representing 20.68% (n = R35, 568,221.31) and 16.72% (n = R 31,370,435.51) respectively. Hydrochlorothiazide presented with the highest purchasing quantity for both years when classified according to chemical substance with, Methyldopa having the highest purchasing cost for year one followed by vaccine Hib-DTP 10 dose vial (Haemophilus influenzae type B vaccine-diphtheria, pertusis and tetanus vaccine) for year two. Furthermore it was also found that the majority of the "top twenty" products were in the oral dosage form. Finally it was concluded that drugs used in the treatment of hypertension and cardiac failure were the most utilised in comparison to other "top twenty" products during the study period. Possible misappropriation based on the defined daily dose of the "top twenty" products might have occurred. In completion of this study, recommendations for future research were made. / Thesis (M.Pharm.)--North-West University, Potchefstroom Campus, 2004.

Increasing health care costs is an international problem from which South Africa is not excluded. Prescription medication contributes most to these high health care costs, and methods to reduce their costs to society are implemented worldwide. In South Africa, such a method is a managed care reference medicine price list, as introduced by a PBM (pharmacy benefit management) company. This step had some cost implications in the private health sector in South Africa, and these implications were investigated in this study. Central nervous system (CNS) medicine items are among the top ten medicine items claimed and represent a substantial amount of the costs of all medicine items claimed during the study period. Antidepressants, a subdivision of the CNS agents, comprise the largest share of CNS agents claimed and CNS costs, and were therefore investigated more closely. The objective of this study was to analyse the usage patterns and costs of central nervous system medicine items, and more specifically, the antidepressants, against the background of the implementation of a managed care reference medicine price list in the private sector of South Africa. This study was conducted as a retrospective, non-experimental quantitative research project. The study population consisted of all medicine items claimed as observed on the database over the two-year study period of May 2001 to April 2002 (pre-MPL) and May 2002 to April 2003 (post-MPL). Data were provided by MedschemeTM/lnterpharm, and the Statistical Analysis System® SAS 8.2® was used to extract the data from the database. The central nervous system agents had a prevalence of 8.10% (N=49098736) and a total cost of R757576976.72 over the two-year study period. The cost per CNS item increased by 5.98% or R11.50 per CNS item in the year after MPL implementation, and the cost per prescription containing CNS medicine items increased by 4.09% or R9.07 per prescription. CNS agents are classified into ten sub-pharmacological groups, according to the MIMSC3 (Snyman, 2003:13a). One of these sub-pharmacological groups, antidepressants, comprised 33.97% of all CNS medicine items claimed (N=3978364) and 45.53% of all costs associated with CNS medicine items (N=R757576976.72) over the study period. The number one antidepressant claimed was amitriptyline, a tricyclic antidepressant. Of the antidepressants with generic substitutes, all with the exception of clomipramine, were prescribed at generic substitution rates of more than 50%. After the MPL implementation, generic antidepressant products were more frequently prescribed (16.48% increase, N=617190), although patient co-payments did not decrease immediately. Some innovator products had price reductions after the implementation of the MPL. This study indicates that cost minimisation analyses and retrospective drug utilisation reviews are valuable tools in the evaluation of managed care medicine price lists. / Thesis (M. Pharm. (Pharmacy Practice))--North-West University, Potchefstroom Campus, 2005.

The commonest prescribed group of drugs is antimicrobials. Various studies have shown that they are overused globally. Since Primary health care represents the first tier of the health care system, evaluation of antimicrobial use in primary health w e settings is a necessity to ensure rational and cost-effective use of these agents in the treatment of infectious diseases. It has been reported by Hooton and Levy (2001 : 1088) that 20% to 50% of antimicrobials are inappropriately used in developing countries. According to Rebana et al. (1998: 175) the increasing overuse of antimicrobials has resulted in an enormous escalation in the total costs of drugs contributing to 15% to 30 % of the total health budget. Hooton and Levy (2001: 1087) reported in a study that inappropriate use and overuse of antimicrobials are risk factors for the emergence of antibiotic resistant bacteria. There is a high incidence of infectious diseases in developing countries that are due to the rapid spread of resistant strains through over-crowding, poor sanitation and unsafe sexual practices (Liu et al., 1999: 540). The general objective of the study was the analysis and interpretation of the usage and related costs of antimicrobial prescriptions in a private primary health w e setting in South Africa. The study is a non-experimental, quantitative, retrospective drug utilisation review of antimicrobial usage in a private primary health care setting. Data were obtained from the central database of a private primary health care service provider. Data of nine randomly selected clinics, situated in different geographical areas of South Africa, were extracted for the period 1st January to 31st December 2001. The study population was made of the total patient population of patients using antimicrobials during this one year period. Antimicrobial usage was analysed according to: number of patients, age and gender distribution, diagnosis, pharmacological groups. The total number of patients who visited the nine clinics during the year was 83 655 of which 59.50% were females and 40.22% males. In 0.28% of the cases gender was not indicated. Patients in age groups 6 (20-40 years) and 7 (40-60 years) accounted for the highest number of patients (66.31%, n = 54 964). A total of 515 976 medicine items costing R1 716 318.90 were prescribed, of these, 18.69%, (N=96 423) were antimicrobials costing 60.89%, (R1 045 108.00). Of the total number of patients that visited the nine clinics, 65.34% (N=54 663) were prescribed antimicrobials. The total number of diagnoses (140 723) where antimicrobials were prescribed accounted for 68.52% (N46 42 1). The highest number of antimicrobial prescriptions according to pharmacological and age groups were: penicillins followed by sulphonamides and tetracyclines. The diagnoses with the highest number of antimicrobial prescriptions were the respiratory tract infections (viral influenza, acute bronchitis and upper respiratory tract infection) and pelvic inflammatory disease The prescribing of antimicrobials in respiratory tract infections could indicate overuse and inappropriate use of these drugs. Because most of these infections are caused by viruses or other non-bacterial agents, are self limiting. Therefore, the use of antibiotics courses is neither necessary nor appropriate in these conditions. The overuse and inappropriate use of such drugs have an effect on the health of the patients needing cure, and the general budget on health care service. It is recommended that further studies are conducted on antimicrobial prescribing and use. / Thesis (M. Pharm. (Pharmacy Practice))--North-West University, Potchefstroom Campus, 2005.

In South Africa, significant changes in health care have taken place since the first democratic elections in 1994. The change had lead to a position of integrated service delivery with specific reference to primary health care. Increasingly in developing countries, the private sector impacts significantly on the rights to education and the highest attainable standard of health. Inappropriate prescribing e.g. prescribing a drug without an acceptable indication, specifying an incorrect dosage, schedule or duration of treatment, duplicating therapeutic agents and prescribing drugs without adequate regard to potential interactions, can cause adverse outcomes, deplete health care resources, compromise the quality of care and possible increase in health costs. One approach monitoring prescribing practices is drug utilisation review. The general objective of this study was to review and interpret aspects of drug usage patterns in a private primary health care setting, with special reference to the top ten diagnoses made and the top twenty medicine items prescribed as well as the associated costs. A quantitative, retrospective drug utilisation review as well as certain aspects of managed and primary health care, pharmacoeconomics, pharmacoepidemiology, medicine formularies and standard treatment guidelines were reviewed in the literature as a base for the study. The results of the empirical study showed that 83648 patients consulted at the nine medicentres during the study period (1 January to 31 December 2001). A total number of 132591 patient visits (consultations) were made, 140723 medical conditions (diagnoses) performed and 516177 medicine items prescribed during the study period. Analysis of medicine usage patterns and associated costs of the top ten diagnoses made and top twenty medicine items prescribed in the study population, revealed the following: The top ten diagnoses determined accounted for 29.07% of the total number of diagnoses made, . a total medicine treatment cost accounting for 32.11% in the study population, . the top twenty medicine items determined accounted for 56.23% of the total medicine items prescribed and . a total medicine treatment cost accounting for 28.63% in the study population. The highest prevalence of diagnoses made and medicine items prescribed was found in age groups 4 and 5 (Le. patients between the ages of 19 to 40 years) and was also found to be more prevalent in the female than in the male population. In completion of the research, recommendations to review the medicentres medicine treatment protocols and on provision of primary health care education were made. Reference to the investigation of environmental factors is also made. / Thesis (M.Pharm.)--North-West University, Potchefstroom Campus, 2004.

Health is a fundamental human right. Access to health care, which includes providing a population with safe, effective, good quality drugs at the least possible cost, is a prerequisite to realising that right. Drugs or medicines play a fundamental role in the effectiveness, efficiency and responsiveness of health care systems. Drugs also constitute a major recurrent expense in both state-run and private sector health care. To ensure that health care workers prescribe the most cost-effective drugs through the essential drugs list, training, as well as evaluation and monitoring systems must be regarded as important elements of containing costs. Pharmaceutical benefit management programmes such as pharmacoeconomics, drug utilisation review (DUR), evidence-based medicine and disease management have emerged as tools to ensure cost-effective selection and use of drugs, particularly for chronic diseases. These managed care tools are often investigated to determine whether new technologies or interventions are appropriate and have "value". Affordable prices of medicines, on their own, however, do not ensure access to medicines. Also important are reliable procurement, distribution and storage systems, and appropriately trained personnel to manage these components of drug management. Poorly regulated drug supply systems can have serious consequences such as antibiotic resistance, problems with safety or quality and most importantly wastage, as it is believed that a significant proportion of drugs purchased by the state in South Africa find their way into the private sector market through a "grey market". The general objective of this study was to review and analyse the cost and medicine usage of the "top twenty" pharmaceutical products according to the monthly pharmaceutical purchasing reports of the Department of Health in the North West Province. The research can be classified as retrospective and quantitative. The data used for the analysis were obtained over a two-year study period (1 Apr 2000 - 28 Feb 2002) from the private provider operating the medical stores in the North West Province. The results of the empirical investigation, showed the total number of "top twenty" products appearing during the study period amounted to 460 different products having a total purchasing cost of R 66,263,674.51 representing 37.2% (n = R 178,163,061.50) of all pharmaceutical products purchased during the two-year period. Through analysis it was found, when classified according the Anatomical Therapeutic Chemical (ATC) therapeutic main group, antihypertensives had the highest quantity purchased for year one (20.69%; n = 134,515,640) with cough and cold preparations revealing the highest purchasing quantity for year two (40.55%; n = 103,567,031) of all "top twenty" pharmaceuticals during the study period. Antibacterials for systemic use presented with the highest cost percentages for both years, representing 20.68% (n = R35, 568,221.31) and 16.72% (n = R 31,370,435.51) respectively. Hydrochlorothiazide presented with the highest purchasing quantity for both years when classified according to chemical substance with, Methyldopa having the highest purchasing cost for year one followed by vaccine Hib-DTP 10 dose vial (Haemophilus influenzae type B vaccine-diphtheria, pertusis and tetanus vaccine) for year two. Furthermore it was also found that the majority of the "top twenty" products were in the oral dosage form. Finally it was concluded that drugs used in the treatment of hypertension and cardiac failure were the most utilised in comparison to other "top twenty" products during the study period. Possible misappropriation based on the defined daily dose of the "top twenty" products might have occurred. In completion of this study, recommendations for future research were made. / Thesis (M.Pharm.)--North-West University, Potchefstroom Campus, 2004.

Increasing health care costs is an international problem from which South Africa is not excluded. Prescription medication contributes most to these high health care costs, and methods to reduce their costs to society are implemented worldwide. In South Africa, such a method is a managed care reference medicine price list, as introduced by a PBM (pharmacy benefit management) company. This step had some cost implications in the private health sector in South Africa, and these implications were investigated in this study. Central nervous system (CNS) medicine items are among the top ten medicine items claimed and represent a substantial amount of the costs of all medicine items claimed during the study period. Antidepressants, a subdivision of the CNS agents, comprise the largest share of CNS agents claimed and CNS costs, and were therefore investigated more closely. The objective of this study was to analyse the usage patterns and costs of central nervous system medicine items, and more specifically, the antidepressants, against the background of the implementation of a managed care reference medicine price list in the private sector of South Africa. This study was conducted as a retrospective, non-experimental quantitative research project. The study population consisted of all medicine items claimed as observed on the database over the two-year study period of May 2001 to April 2002 (pre-MPL) and May 2002 to April 2003 (post-MPL). Data were provided by MedschemeTM/lnterpharm, and the Statistical Analysis System® SAS 8.2® was used to extract the data from the database. The central nervous system agents had a prevalence of 8.10% (N=49098736) and a total cost of R757576976.72 over the two-year study period. The cost per CNS item increased by 5.98% or R11.50 per CNS item in the year after MPL implementation, and the cost per prescription containing CNS medicine items increased by 4.09% or R9.07 per prescription. CNS agents are classified into ten sub-pharmacological groups, according to the MIMSC3 (Snyman, 2003:13a). One of these sub-pharmacological groups, antidepressants, comprised 33.97% of all CNS medicine items claimed (N=3978364) and 45.53% of all costs associated with CNS medicine items (N=R757576976.72) over the study period. The number one antidepressant claimed was amitriptyline, a tricyclic antidepressant. Of the antidepressants with generic substitutes, all with the exception of clomipramine, were prescribed at generic substitution rates of more than 50%. After the MPL implementation, generic antidepressant products were more frequently prescribed (16.48% increase, N=617190), although patient co-payments did not decrease immediately. Some innovator products had price reductions after the implementation of the MPL. This study indicates that cost minimisation analyses and retrospective drug utilisation reviews are valuable tools in the evaluation of managed care medicine price lists. / Thesis (M. Pharm. (Pharmacy Practice))--North-West University, Potchefstroom Campus, 2005.