Showing papers in "Disease Management & Health Outcomes in 2004"

The Costs of Non-Adherence to Oral Antihyperglycemic Medication in Individuals with Diabetes Mellitus and Concomitant Diabetes Mellitus and Cardiovascular Disease in a Managed Care Environment

Abstract: Objective: To assess the relationship between diabetic medication adherence, total healthcare costs, and utilization within patients with type 2 diabetes mellitus and concomitant diabetes and cardiovascular disease (CVD). Research design and methods: This study was a retrospective analysis of pharmacy and medical claims from 1 April 1998 through 31 March 2000 within a managed care organization’s database. Patients were identified who had received an oral antihyperglycemic medication or had a diagnosis of CVD, were continuously enrolled in the health plan, and were ≥30 years of age. The likelihood of an emergency room (ER) or hospital admission and total healthcare costs related to all causes, stratified by antihyperglycemic medication adherence cohort within the diabetes only and diabetes + CVD groups, were examined over 360 days from the date the patient was identified. Results: For diabetes patients with ≤75, >75 to ≤95, and >95% adherence, adjusted total healthcare costs (from April 1998 to March 2000) were $US5706, $US5314, and $US4835, respectively (p 75 to ≤95% adherence had a 31% and 19% greater chance of a hospital/ER admission than those in the >95% cohort, respectively. Adjusted healthcare costs (from April 1998 to March 2000) for those with ≤75, >75 to ≤95, and >95% adherence within the diabetes + CVD cohort was $US37 648, $US31 547, and $US25 354 (p 75 to ≤95% adherent had a 44% and 51% greater chance of a hospital/ER admission than those with >95% adherence, respectively. Conclusions: Higher adherence to oral antihyperglycemic agents is associated with lower healthcare resource utilization and costs for patients with diabetes only and patients with concomitant diabetes and CVD.

Overview of Disease Management Approaches Implications for Corporate-Sponsored Programs

Abstract: Corporations have engaged in sponsorship of health management programs and, more recently, disease management programs to facilitate healthy and productive work environments. The purpose of this review is to examine the health and financial outcomes from these corporate-sponsored disease management programs. This article focuses on seven diseases or chronic conditions (arthritis, asthma, cancer, depression, diabetes mellitus, heart disease, and migraine) that potentially impact employee productivity (both in time away from work and in loss of effectiveness at work) and health status including medical and pharmaceutical utilization and costs. Corporate-sponsored disease management programs typically focus on education and screening for selected diseases or chronic conditions. Partnerships have been formed with health plans and third-party program providers to reach employees with interventions and treatment. The typical outcome measures from these programs have primarily been clinical indicators and medical utilization. Measures of productivity need to be incorporated as important outcome measures for disease management programs. The estimated financial opportunity for the corporation is a reflection of the cost differential for a given disease and the prevalence of that disease within the employee population. Primary diseases, chronic conditions, and health risks contribute to increased medical utilization and decreased productivity within the corporation. Promoting programs that focus on the whole person, including health risks, chronic conditions, and diseases, will likely increase the possibility of success in helping the employee to better self-manage their health conditions and consequently provide gains for both the individual and the corporation.

Improving Treatment Regimen Adherence in Coronary Heart Disease by Targeting Patient Types

Abstract: Patient adherence to a treatment plan is central to the control of coronary heart disease (CHD) and in the prevention of complications; it is reported to be the single most important challenge in the management of CHD and related conditions. The following article provides an overview of adherence in CHD, with particular emphasis on two important theories of behavior change: the ‘Health Belief Model’ and the ‘Transtheoretical Model’. Three types of individuals are discussed in relation to these theories: (i) patients who are non-adherent (5–10% of the CHD population); (ii) patients who are partially adherent (30–40% of the CHD population); and (iii) patients who are near-optimally adherent (50–60% of the CHD population). Adherence predictor strategies and recommended interventions for each of these groups are provided in table format. Disease management tools and resources that assist in targeting interventions to the unique adherence needs of these three very different groups are also listed. It was our conclusion that regardless of the interventions that are utilized in CHD management programs, understanding the differences between partially adherent, non-adherent, and near-optimally adherent patients, and targeting interventions to these groups, can optimize the impact of CHD interventions.

Management of Mild to Moderate Alzheimer Disease

Abstract: Alzheimer disease is a common, progressive neurodegenerative disorder of the elderly, affecting approximately 3% of individuals 65–74 years of age, and up to half of those aged ≥85 years. Along with progressive loss of memory and cognitive function, other symptoms include depression and behavioral and motor disturbances. Some estimates of the cost of Alzheimer disease in the US exceed $US100 billion annually. While no drug clearly slows progression of Alzheimer disease, cholinesterase inhibitors have provided the greatest symptomatic benefit, particularly in improving or delaying the decline in cognitive function. As such, rivastigmine, donepezil, and galantamine are recommended as first-line treatment options for patients with mild to moderate Alzheimer disease. Rivastigmine has been evaluated in a number of clinical trials, including two large multicenter studies in patients with mild to moderate Alzheimer disease. In the observed-case analyses of these 26-week pivotal trials, rivastigmine 3–6mg twice daily was consistently associated with statistically significant benefits versus placebo in key measures of cognition, global function, and activities of daily living. Intent-to-treat analyses showed similar results, with most differences versus placebo achieving statistical significance. Follow-up data of up to 5 years’ total duration demonstrated long-term cognitive benefits with continued rivastigmine therapy. As with all cholinesterase inhibitors, gastrointestinal adverse effects including nausea, vomiting, diarrhea, and anorexia are relatively common with rivastigmine. Individualized dosage titration and administration with food are recommended to minimize these problems, which are generally of mild to moderate severity and limited duration. Pharmacoeconomic analyses of rivastigmine in mild to moderate Alzheimer disease indicate that the cost of the drug is essentially off-set by reductions in other costs after about 2 years of therapy, primarily by delaying institutionalization. Most were modeled analyses from the US, Canada, and the UK conducted from societal or provider perspectives. In conclusion, rivastigmine is one of a very limited number of first-line medications for the symptomatic treatment of mild to moderate dementia in Alzheimer disease. Along with improving or delaying the decline in cognitive function, rivastigmine also has beneficial effects on global function, activities of daily living, and behavioral problems. Rivastigmine is also a useful treatment option for patients not responding to therapy with other cholinesterase inhibitors. Potential advantages of rivastigmine include its low drug interaction potential and dual inhibitory effect on both acetyl- and butyrylcholinesterase. Large, randomized comparisons between rivastigmine, donepezil, and galantamine are needed to provide further insight into clinically significant differences between these cholinesterase inhibitors.

The Burden of Osteoporosis and the Case for Disease Management

Abstract: Currently, osteoporosis, defined as low bone mineral density (BMD), affects 30% of postmenopausal women and 8% of men >50 years old in Western society and these percentages are likely to increase as our elderly population expands. Osteoporosis-related fractures increase with age and reductions in BMD, with the greatest increase in hip, followed by vertebral, and then wrist fractures. Osteoporosis is associated with significant mortality and for each 1 SD decrease in BMD there is a 1.5-fold increase in mortality risk. Following a hip fracture, 25–30% of patients will die within 3–6 months and in some populations hip fractures account for 1.5% of all deaths. Osteoporosis and related fractures are associated with significant morbidity, with loss of independence, psychological effects, and an overall decreased quality of life. The current financial cost of osteoporosis in the US is $US14 billion and in the UK just over £1 billion, and these costs will increase 3- to 8-fold over the next 50 years. Treatments are available that have been shown to significantly increase BMD, decrease bone turnover, and as a result decrease fracture incidence. For reductions in both vertebral and fracture, the evidence is strongest for the use of the bisphosphonates alendronate and risedronate; while for vertebral fracture, effective treatments include raloxifene, etidronate, calcitonin, and calcium plus vitamin D. Recent data suggest that hormone replacement therapy (HRT) can prevent hip and vertebral fractures, but long-term use, or commencement in elderly women of some continuous combined preparations, is no longer recommended. It has been recognized that bone turnover and bone quality contribute to fracture risk and, therefore, biochemical assessment of bone resorption and formation may increase the clinical and cost effectiveness of treatment. Using a conservative estimate of fracture reduction (35%) over a 5-year period, an intervention costing $US500 (£333) per year is cost effective when targeted to women with osteoporosis who are ≥65 years of age. It has been calculated that the lower the intervention cost and the higher the effectiveness of treatment the lower the age at which the treatment would be cost effective. The increasing healthcare burden and effective treatments make osteoporosis an excellent candidate for disease management programs.

Improvements in Asthma Pharmacotherapy and Self-Management

Abstract: In day-to-day practice, asthma treatment and self-management often fall short of the objectives defined by clinical practice guidelines. The objective of this study was to determine whether a population-based asthma disease management program, using broad-based educational interventions, can have a favorable impact on physician and patient adherence to guidelines-based care. A longitudinal, before-and-after design was used to evaluate program impacts on pharmacotherapy and health status. Patients with asthma (n = 35 450) were enrolled in the program from September 2000 through to June 2001. Patients were identified for the study based on a 12-month retrospective analysis of pharmacy claims. Patients were members of prescription benefit plans managed by Medco Health and were aged 5 years and older. Patients in the intervention group received asthma education materials during the 12-month period following enrollment. The materials emphasized guidelines-based principles of asthma pharmacotherapy, self-management, trigger avoidance and patient-physician partnership. Physicians received guidelines-based flow sheets to facilitate therapy tracking, and pharmacotherapy review. Asthma drug utilization was measured during the 12-month period prior to enrollment and the 12-month period following enrollment. Utilization data on controller and reliever medications were derived from a pharmacy claims database. Drug utilization changes for the intervention group were compared with those for matched controls. A health survey was conducted on a random sample of program participants at enrollment and at 12-month follow-up. The health survey included questions on asthma-related quality of life (QOL), medical utilization, productivity, and self-management skills. The percentage of patients who started controller therapy during the study period was significantly higher for the intervention group than the control group (20.7% versus 18.1%, p < 0.001). The controller prescription fill rate increased significantly in the intervention group compared with controls (p < 0.0001); the increase was primarily driven by increased refill rates for patients already using controllers. Reliever prescription fill rates decreased for both the intervention group and controls. Program participants reported significant improvements in asthma-related QOL (p < 0.05) and self-management skills. Self-reported medical utilization decreased for office visits (p < 0.05) and emergency room visits (p < 0.01). A population-based asthma disease management program can improve controller prescribing rates (new therapy starts), controller adherence rates (refill persistency), and self-management skills. These changes in physician and patient behavior help close the gaps between guidelines and practice in asthma therapy.

Effectiveness, Quality of Life, and Cost of Caring for Children in France with Recurrent Acute Rhinopharyngitis Managed by Homeopathic or Non-Homeopathic General Practitioners

Abstract: In France, non-homeopathic general practitioners (GPs) often use antibacterials to treat children with recurrent acute viral rhinopharyngitis; whereas homeopathic GPs tend to use homeopathic medicines. We compared the effectiveness, the quality of life of the parents, and the direct and indirect costs associated with treatment from homeopathic and non-homeopathic GPs. We assessed the direct (consultations, medicines, further tests) and indirect (time off work) costs of the two types of treatment to society, the patient, and social security. We also assessed the effectiveness of the treatment received and the quality of life of the parents. Of the 499 children included, 231 were treated by 62 non-homeopathic GPs and 268 by 73 homeopathic GPs. The effectiveness (assessed as complications/patient, total number of adverse events, and quality of life) [mean overall Parents of children with Ear, Nose, and Throat infections Quality of Life questionnaire© scale score] was better in the homeopathic GP group than in the non-homeopathic GP group. No significant difference was found between the two groups for the total costs to social security (€98.55 for homeopathic GPs vs €96.17 for non-homeopathic GPs). Homeopathic GPs initiated preventive treatment in 82.2% of their patients and used antibacterials in 20.9% of their patients, while non-homeopathic GPs initiated preventive treatment in 43.3% of patients and prescribed antibacterials for 89.6% of patients. This study produced new findings that indicate that, in France, acute rhinopharyngitis is handled differently by homeopathic GPs and non-homeopathic GPs: homeopathic GPs prescribe fewer antibacterials than non-homeopathic GPs for the treatment of recurrent acute rhinopharyngitis in children aged between 18 months and 4 years. Moreover, homeopathic treatment gave better results in terms of pragmatic medical effectiveness (fewer episodes and fewer complications) and the parents’ quality of life, with similar total medical costs to social security. However, this study is potentially biased by the lack of homogeneity of the two patient-samples in terms of the ‘passive smoking’, ‘patient age’, ‘childcare’, and ‘type of occupation’ criteria because our study protocol did not provide for prior matching of the two patient-samples with respect to these criteria. The observations found in this study need to be confirmed by randomized clinical trials.

Impact of Three-Tier Pharmacy Benefit Structures on Consumer Attitudes, Pharmacy, Medical Utilization and Costs

Abstract: Three-tier pharmacy benefit plans are the dominant structure in prescription drug coverage today. In these plans three copayments exist. The lowest copayment is for generics, the middle copayment is for preferred brands and the highest copayment is for non-preferred brands. The premise of these plans is that by shifting the burden of cost onto the consumer, consumers will be more judicious in their prescription purchasing behavior. This review article outlines the empirical evidence regarding the utility of three-tier plans in changing consumer’s prescription purchasing behavior. The results from a few key studies appear to suggest that three-tier plans reduce prescription drug spending for health plans while significantly increasing the cost-sharing amount for consumers. While the increased cost sharing created higher levels of dissatisfaction among three-tier plan members, it appears that they modify their behavior in accordance with these plans by switching to lower cost formulary alternatives. The factors that appeared to affect these behaviors included provider opinion and the comparability of the formulary and non-formulary alternatives. However, there are a myriad of factors that could influence the decision to switch from one drug to another (one example is switching for purely clinical reasons), and thus a clear link between the implementation of three-tier plans and switching behavior is hard to establish. What still remains unanswered is the impact of three-tier plans on vulnerable populations such as the elderly, low-income individuals and individuals with chronic disease who may be most adversely affected by the implementation of such policies. These individuals may discontinue or reduce appropriate utilization of their medications that could lead to adverse outcomes. Adequate follow-up for these vulnerable populations who are enrolled in a three-tier plan needs to be conducted to ensure appropriate medication use.

Specialist and Generalist Care for Type 1 Diabetes Mellitus

Abstract: The incidence of diabetes mellitus (both type 1 and type 2) is growing to epidemic proportions, with an expected combined worldwide prevalence of 220 million by the year 2010. A subsequent increase in the incidence of diabetes complications is likely to follow if present trends continue, placing an increased burden on already troubled healthcare systems. While there are many identified biologic mechanisms for the development of diabetes complications, there has been little exploration of healthcare provider issues and their contribution to these outcomes. One area of research with few data is the influence of diabetes specialty care on outcomes in type 1 diabetic patients. Evidence demonstrates that both process delivery and outcomes are better in individuals with typel diabetes who are cared for by diabetes specialists compared with generalists. For example, those receiving care from diabetes specialists were more likely to receive diabetes education, to be treated with intensive insulin therapy (>2 injections/day), and to receive an eye examination compared with those receiving generalist care. Additionally, lower rates of proliferative retinopathy were observed in those receiving specialist care. Recent evidence also demonstrates that there are lower incidences of neuropathy, overt nephropathy, and coronary artery disease in those patients who spend a higher proportion of the duration of their diabetes in specialist care. Based on these observations, it is recommended that attempts be made to replicate the favorable characteristics of specialty care in the primary care setting. Healthcare systems should ensure the availability of access to diabetes specialists, as well as ancillary healthcare professionals including diabetes educators, with increased emphasis placed on coordinated care.

Employer-Based Disease Management Programs in Cancer

Abstract: The cancer disease management field took root in the early 1990s Health plans in the US seeking to aggressively manage cancer reached out to entrepreneurial start-ups that had infused the general principles of managed care into cancer programs More than two dozen health plans had adopted some form of cancer disease management by the end of the century However, employers, witnessing the managed care backlash and experiencing difficulty recruiting an adequate pool of skilled labor during flush economic times, have abstained from aggressive management of their workforces’ cancer treatment Employers, unlike health plans, pay for work loss associated with disability and absenteeism Hence, the per capita cost of cancer to employers greatly exceeds that of health plans As the US economy soured in 2000 and healthcare premiums grew at double-digit rates, employers began to abandon their previous reluctance in adopting disease-specific programs Some employer initiatives to date are not fully-fledged cancer disease management programs; rather, pieces of such programs have been introduced The return on investment achievable by implementing a comprehensive cancer disease management program, once known to employers and their consultants, will likely spur much greater adoption of such programs in the next 5 years This review highlights piecemeal efforts where employers have adopted a form of cancer disease management Attention is given to some of the employer costs associated with cancer, suggesting that greater awareness of the exposure and potential upside will likely result in more employers embracing fully-fledged cancer disease management

Short-Term Aggressive Disease Management Programs for Heart Failure

Abstract: Cardiovascular disease is the leading cause of death in developed countries. It is estimated that about 15 million people worldwide die every year from heart disease, with a substantial proportion of these deaths occurring in developing nations. Congestive heart failure (CHF) is a condition that develops as a late complication from a variety of heart disease states. CHF remains a devastating disease. It exacts a high toll in terms of mortality and morbidity and carries a high price burden. As the population ages and treatments for conditions such as acute coronary syndrome and hypertension improve, the prevalence of heart failure can be expected to increase, because survivors of hypertension and myocardial infarction live long enough to develop complications such as congestive heart failure. Recent advances have clearly shown that treatment strategies including ACE inhibitors, β-adrenoceptor antagonists, and aldosterone inhibitors improve morbidity and survival. However, even among patients treated with recommended therapy at recommended doses, mortality remains high. Opportunities exist for further improvement of prognosis beyond current guidelines for heart failure. As new evidence emerges, it is evident that survival can be further improved by using other strategies such as angiotensin receptor antagonists as alternative or add-on therapy and ventricular resynchronization for qualifying candidates. The management of heart failure patients in the community presents unique challenges. Patients who are managed in community hospitals are often elderly and/or very ill, with several comorbidities and clinical characteristics that may be different from patients who qualify for clinical trials. Furthermore, there appears to be a delay in incorporating scientific evidence into practice and studies continue to show that many heart failure patients do not receive recommended medications at adequate doses. Disease management programs have evolved as a way of improving heart failure care. Different models have been established and some institutions have published the results of their specific programs. The consistent findings include reductions in hospitalization rates, improvements in quality of life, and reductions in cost. However, to date, such studies have not compared different models and until large prospective trials are available, the true benefits of these programs will continue to be debated.

Economic Benefits of Including Environmental Issues as a Component of Comprehensive Asthma Care

Abstract: Asthma in the US is widespread, with incidence rates and morbidity increasing dramatically over the last 2 decades. The cost of asthma-related morbidity and mortality is large. There is substantial and convincing evidence that environmental factors are associated with asthma exacerbation, and more limited evidence that environmental factors play a role in the development of asthma. Educational interventions, which include an avoidance of ‘triggers’ or focus on reducing exposure to cigarette smoke, have been shown to be moderately effective. While various interventions have been shown to reduce environmental exposures, fewer studies have collected sufficient information on their effectiveness in reducing morbidity. Cost-effectiveness analyses on educational interventions suggest that reductions in direct costs are most prominently seen for severe asthma, with the interpretation of study findings impaired by a lack of methodological consistency. One analysis from a study that included physical interventions found that the incremental cost-effectiveness ratio was $US9.20 per symptom-free day (95% CI -$US12.56, $US55.29), with potential cost savings for more severe asthma. We point out that current practice in managed care organizations (MCOs), as well as in other settings, rarely conforms to the current clinical practice guidelines for asthma. Two reviews of the policies and actions of MCOs found that while some were integrating environmental controls into their asthma disease management plans, their commitment to these strategies was limited by lack of a strong evidence base. We recommend the following: (i) continuation of educational programs; (ii) continuation and expansion of case management, including home visits; (iii) full integration of smoking cessation programs into asthma disease management; (iv) development of policies around reimbursement for durable goods; (v) participation in the setting of a policy agenda for population-based approaches to controlling key environmental factors; (vi) development of exploratory programs to address occupational asthma; (vii) integration, analysis and dissemination of environmental data collected by MCOs; and (viii) widespread MCO participation in research on environmental prevention of asthma.

Optimizing Drug Prescribing in Managed Care Populations

Abstract: Managed care presents interesting opportunities to optimize clinical and economic outcomes related to drug prescribing. There are very few randomized controlled trials that have evaluated methods to educate or incentivize physicians, implement formulary management or guideline tools, profile physicians, and implement pharmacist interventions to ensure optimal drug prescribing. Single methods of optimizing medication outcomes have not been shown to be as effective as multifaceted approaches. Specific reinforcement of the message at the time of prescribing has been shown to improve antibiotic prescribing in patients with chronic bronchitis and improve adherence to treatment guidelines for the management of patients following myocardial infarction. Results from a randomized controlled trial showed that changes in pharmacy benefit design decreased costs and medication utilization. Much of the literature evaluating the effectiveness of utilization management techniques in optimizing drug therapy outcomes is retrospective in nature. However, pharmacist intervention has been shown to reduce polypharmacy in a randomized controlled trial in the elderly. Appropriate prescribing scores were improved and this improvement was sustained at 12 months post intervention. Clinical pharmacy services have been shown to reduce hospital admission and hospital days, decrease prescription and total health care costs, reduce the number of drugs per patient, and improve attainment of target low density lipoprotein cholesterol values. Recent analyses have shown that there is a higher likelihood of achieving improved outcomes of care when three or more of the following aspects of healthcare are impacted: patient self-management, clinical information availability, redesign of the way care is delivered, decision support strategies, the healthcare system, and the provider organization. In a review of interventions designed to improve the care of patients with chronic illnesses, process variables were improved when one or two of the aspects were improved. Outcome variables were improved when three or four of the aspects were impacted. There continues to be great focus on improving the quality of care in managed care environments. With the passing of the Medicare legislation in the US, by 2006 the vast majority of citizens will receive healthcare in managed care environments. Additional research designed to explore methods of optimizing drug therapy outcomes is needed to characterize the most efficient, transparent, and least costly ways to reduce misuse, overuse, and underuse of prescription drugs.

National Performance Measures for Diabetes Mellitus Care

Abstract: When considering the trends in disease management, the focus of healthcare in the US has shifted from communicable diseases, which can most often be managed successfully, to chronic diseases, which are currently not managed very well. Chronic diseases, such as diabetes mellitus, become a lifelong health problem for the individual, the family, and in the workplace. Currently, there is no vaccine to prevent diabetes and no cure for diabetes once acquired. In order to improve the quality of care for diabetes, national performance measures have been developed to provide a unified set of diabetes-specific performance and outcome measures.

Impact of a Migraine Disease Management Program

Abstract: Objective: To assess the impact of a comprehensive migraine disease management program, as measured by humanistic outcomes measures, conducted in a managed care setting. Design: A prospective comparative study comprised of an intervention and a control group to evaluate the impact of the disease management initiative. Setting: Independent Practice Association (IPA)-type managed care organization. Study participants and main outcomes measures: Study participants resided in adjacent regions (intervention region included Minneapolis, MN, USA and the usual care region included St Paul, MN, USA and adjacent areas in MN, USA) separated by natural geographic barriers. Eligible patients were identified through a review of the Medica plan’s administrative claims database and were asked to complete the Migraine Therapy Assessment Questionnaire (MTAQ), a tool to assess the presence of migraine management issues. Responders (patients completing the MTAQ) who reported ≥2 migraine care risk indicators in the intervention region received the disease management intervention, while all responders in the control region received usual care. Responders in both regions with ≥2 migraine care risk indicators were also asked to complete the Migraine Disability Assessment (MIDAS) questionnaire and the 12-item Short Form Health Survey (SF-12) at baseline. All participants were asked to complete the same instruments at the end of the program as they did at baseline. Interventions: Disease management intervention activities included patient and physician education, as well as a patient feedback report containing migraine care risk indicators, which was sent to the treating physicians. All patients were encouraged to contact their physicians if they reported two or more migraine management issues. Results: A total of 2232 patients with migraine were enrolled in the study (1373 from the intervention region and 859 in the control region). Compared with patients in the control region, patients in the intervention region reported, as measured by MTAQ, significant improvement in migraine symptom relief, more knowledge about potential migraine triggers, a decrease in economic burden, and more satisfaction with migraine treatment. In addition, the change in MIDAS scores from baseline showed a greater shift towards decreasing disability in the intervention group compared with the control group. However, no statistically significant improvement was detected in terms of health status as measured by SF-12. Of the participants in the intervention region who completed the program evaluation survey, 40% indicated that they called or visited their physicians regarding their migraine survey results if it was recommended. For those contacting their physicians, 76% had their medications changed and 75% noted an improvement in relief due to a change in medication. Conclusions: Considering the significant toll of migraine on patients, employers, and the healthcare system, healthcare plans should consider implementing migraine disease management programs to improve migraine care.

Management of Parkinson Disease

Abstract: Parkinson disease is a movement disorder caused by progressive dopaminergic neuron degeneration in the substantia nigra and characterized by four cardinal symptoms: resting tremor, bradykinesia, rigidity, and postural instability. Levodopa has been considered the first-choice intervention for Parkinson disease for more than three decades. However, up to 50–90% of levodopa-treated patients develop motor complications within 5–10 years of starting treatment. It is important, therefore, to delay the initiation and/or reduce the dosage requirements of levodopa. The non-ergoline dopamine agonist ropinirole (Requip®) is used as monotherapy or in combination with low-dose levodopa in patients with early disease, and as an adjunct to levodopa in patients with advanced Parkinson disease. As an adjunct to levodopa therapy in patients with more advanced disease, ropinirole is generally more effective than bromocriptine and more effective than placebo. Ropinirole (with or without levodopa) is more effective than placebo and at least as effective as bromocriptine when administered as therapy for early Parkinson disease. It reduces the risk of dyskinesia relative to levodopa and maintains long-term control of the underlying disease symptoms, factors that are associated with improved functional ability. Ropinirole reduced the loss of putamen dopamine storage capacity compared with levodopa in a functional imaging study. However, it was unclear whether this resulted from any neuroprotective activity of ropinirole; further research is required to identify any clinically important neuroprotective activity of dopamine agonists. Ropinirole has a tolerability profile generally similar to that of bromocriptine and levodopa when used as monotherapy. In common with all dopaminergic agents, ropinirole has been linked with sedation and unintended sleep episodes; however, these effects may also result from the underlying disease process in patients with Parkinson disease. Only limited data are available from pharmacoeconomic evaluations of ropinirole. Nevertheless, a cost-minimization analysis indicates that, from a societal viewpoint in Canada, ropinirole is cost saving relative to treatment with levodopa plus a dopa decarboxylase inhibitor in patients with early Parkinson disease. Further economic and quality-of-life assessments of ropinirole are required, particularly comparisons with other dopamine agonists and antiparkinsonian interventions. In conclusion, ropinirole is established as an adjunct to levodopa in advanced Parkinson disease, and as monotherapy or in combination with low-dose levodopa in early disease. It is in the setting of early Parkinson disease that ropinirole may see greatest expansion of its overall role in disease management programs.

Reducing the Incidence of Type 2 Diabetes Mellitus

Abstract: The evidence base derived from the research literature has clearly established that type 2 diabetes mellitus may be prevented or delayed through pharmacological interventions and, most efficaciously, through lifestyle interventions. Unfortunately, efforts to translate the research results into programs that may be applied to the clinical or healthcare system setting are lacking. The purpose of this article is 3-fold: (i) to briefly review the results of the major trials conducted in the area of type 2 diabetes; (ii) to outline an approach that may guide the design and development of type 2 diabetes prevention programs for clinical care; and (iii) to present a protocol that may support the process of implementation in the practice setting.

Prevention and Treatment of Osteoporosis in Postmenopausal Women

Abstract: Postmenopausal osteoporosis is characterized by an increased rate of bone turnover accompanied by a reduction in bone mineral density (BMD) that results in an increased risk of fracture, especially of the vertebrae, hip, or wrist. Alendronate (Fosamax®, Fosamax Once-Weekly®), an oral bisphosphonate that inhibits osteoclast-mediated bone resorption and modulates bone metabolism, is a first-line therapy for the management of postmenopausal women with, or at risk of developing, osteoporosis. Alendronate produces sustained increases in BMD and reductions in bone turnover from baseline, and reduces the risk of vertebral, hip, wrist, and other fractures in women with postmenopausal osteoporosis. It also prevents bone loss, and reduces the risk of radiographic or clinical vertebral fracture in postmenopausal osteopenia. Provided administration instructions are followed, alendronate is generally well tolerated. Adverse events are usually transient and are associated with the upper gastrointestinal tract (abdominal pain, nausea, acid regurgitation, dyspepsia); moreover, the incidence of these adverse events with alendronate was similar to those with placebo. More serious events (esophagitis, gastric or duodenal ulceration or bleeding) are uncommon. Once-weekly formulations are as effective and as well tolerated as once-daily alendronate in postmenopausal women. Pharmacoeconomic evaluations suggest that alendronate is a viable treatment option in postmenopausal osteoporosis. The reduction in fracture-related healthcare utilization seen with alendronate results in decreased direct costs, including inpatient or long-term care. Markov state-transition models suggest that this could at least partially offset costs incurred with alendronate therapy. Treatment of women with osteoporosis aged 65 years and older, and postmenopausal women with a previous osteoporotic fracture, are cost-effective strategies. Alendronate is also likely to increase quality-adjusted life-years in any postmenopausal women with osteoporosis. In conclusion, clinical and economic data support the use of alendronate in postmenopausal osteoporosis. It effectively reduces bone turnover, increases BMD, and reduces the risk of osteoporotic fracture in postmenopausal women with established osteoporosis, especially older women with a higher risk of fracture. Although its cost effectiveness in postmenopausal women with osteopenia is not clearly established, alendronate is clinically effective in these patients. In addition, it is generally well tolerated when taken as recommended. Consequently, alendronate should be considered a therapy of choice in the prevention and treatment of osteoporosis in postmenopausal women.

Atypical Antipsychotics as First-Line Treatments for Schizophrenia

Abstract: The poor efficacy and tolerability of conventional antipsychotic treatment in schizophrenia, together with discovery of the ‘atypical’ antipsychotic Clozapine, led to the development of several other atypical antipsychotic drugs. Those now available manifest clinically relevant differences in symptom efficacy and adverse effects, and most evidence supports their superior efficacy and tolerability compared with conventional treatment. Alongside these novel drugs have arrived concerns regarding new adverse effects, instead of the extrapyramidal phenomena which were one of the main drawbacks of conventional antipsychotics. These adverse effects comprise weight gain, diabetes mellitus and QTc interval prolongation. Overall, however, there is no evidence that atypical antipsychotics are more problematic than conventional antipsychotics, as there are marked differences between individual drugs in both classes. Current guidelines recommend the use of atypical antipsychotics as first-line treatments in a wide range of patients with schizophrenia, despite significant caveats regarding the quality of evidence to support use of these drugs in general. Advantages claimed over conventional antipsychotics are greater cost effectiveness, superior relapse prevention and possible benefits regarding quality of life and the natural course of schizophrenia. These advantages, if valid, will benefit stakeholders, whether they are consumers or providers of mental healthcare. However, major discrepancies remain between guidelines for first-line use and current practice. Poor take-up of atypical treatment and off-license use of both conventional and atypical drugs, particularly in primary care, are substantial problems that remain unaddressed. If guidance on first-line atypical therapy for schizophrenia is to be followed, processes such as audit must be applied widely to facilitate implementation of best-practice guidelines. Only then will the supposed benefits of first-line use be verified, or otherwise.

Pulmonary Rehabilitation Programs

Abstract: Pulmonary rehabilitation programs aim to improve the health of elderly patients disabled by lung disease. Despite the widespread application of these programs limited scientific data is available on the subject, except in chronic obstructive pulmonary disease (COPD). This review presents an overview on outcomes of pulmonary rehabilitation programs in elderly patients with COPD. Statistically significant improvements can be found for functional and maximal exercise capacity, as well as for health-related quality of life (HR-QOL). However, clinically relevant improvements are mainly found for functional exercise capacity and especially for HR-QOL. Rehabilitation programs including elderly patients with COPD also showed clinically relevant improvements in dyspnea and fatigue and an enhancement of the patient’s control over their condition. Therefore, rehabilitation is an important form of treatment and one of the main components of the management of COPD in elderly patients.

Caring for Hypertension on Initiation: Costs and Effectiveness (CHOICE)

Abstract: Success in treating hypertension is greater in clinical trials than in actual practice. To prospectively study real-world antihypertension treatment patterns, therefore, naturalistic studies are essential. The primary objective of the Caring for Hypertension on Initiation: Costs and Effectiveness (CHOICE) study was to evaluate the feasibility of performing a naturalistic study in patients with newly diagnosed hypertension in terms of enrollment, adequacy, and the timeliness of data collection and study procedures. The CHOICE study prospectively collected actual practice data from physicians, who were blind to the study purpose and hypotheses, treating newly diagnosed hypertensive patients. The initial therapy was randomly assigned to either Group 1 (diuretics or β-adrenoceptor antagonists) or Group 2 (calcium channel antagonists or ACE inhibitors). The protocol made no demands on usual medical care in scheduling visits and changing treatment during follow-up. Only a final visit at 5 ± 1 months was mandated. Direct involvement of the CHOICE study team was minimized using a remote study monitoring system to collect data and communicate with study sites. Within 30 weeks, a total of 55 physicians enrolled 512 patients with a mean age blood pressure of 158/99mm Hg. In all, 46 different antihypertensive medications were prescribed and 2554 office visits (range 1–16 visits per patient) were attended. Other medical resource use was low during the study period. A final, clean database was ready for analysis 30 days after the last patient visit. The results of this pilot study demonstrate that CHOICE is a feasible framework within which the real-world effectiveness and cost effectiveness of initial therapy for patients with newly diagnosed hypertension can be studied. Protocol flexibility and a novel electronic data entry system are core elements of this naturalistic design.

Management of Overactive Bladder

Abstract: Overactive bladder (OAB), a common condition affecting ≈16–17% of adult men and women in Europe and the US, is characterized by symptoms of urinary urgency, with or without urge urinary incontinence (UUI), usually with micturition frequency and nocturia. OAB is thought to result from abnormal, involuntary detrusor contractions during bladder filling. The symptoms of OAB have a considerable adverse effect on quality of life (QOL) in affected patients, and are associated with an increased risk of comorbidities, and increased direct and indirect costs. Management of OAB focuses on symptom improvement, and includes nonpharmacologic and pharmacologic therapy. Extended-release tolterodine (Detrusitol® XL, Detrol LA®, Detrusitol SR®, Detrusitol® Neo, Detrusitol® Retard, Unidet™) is an oral, once-daily, nonselective, competitive antimuscarinic drug. It acts on smooth muscle motor efferent pathways, including bladder detrusor muscle, and is a first-line therapy for OAB. Extended-release tolterodine is at least as effective as immediate-release tolterodine in improving UUI and other symptoms associated with OAB (including urinary frequency, urgency symptoms, voided volume/micturition), and in improving health-related QOL. It has similar efficacy to oral immediate- or extended-release oxybutynin, or transdermal oxybutynin. The likelihood of dry mouth, the most bothersome anticholinergic adverse effect associated with antimuscarinic drugs, is significantly reduced with extended-release tolterodine in patients with OAB compared with immediate-release tolterodine. Dry mouth also occurs significantly less frequently with extended-release tolterodine than with immediate- or extended-release oxybutynin. The incidence of dry mouth with extended-release tolterodine or transdermal oxybutynin is similar. In economic models, extended-release tolterodine is more cost effective in patients with OAB than no treatment, or treatment with immediate-release tolterodine or immediate-release oxybutynin, and is as cost effective as extended-release oxybutynin. In conclusion, clinical and economic data support the use of extended-release tolterodine as a first-line therapy in the management of adult patients with OAB. It is at least as effective as immediate-release tolterodine, but is associated with a lower incidence of dry mouth. Moreover, the convenient once-daily administration regimen offers the potential for good compliance. The favorable efficacy and tolerability profile of extended-release tolterodine has been demonstrated for up to 12 months. Extended-release tolterodine is as effective as oral immediate- or extended-release oxybutynin, but is better tolerated in terms of dry mouth. It has similar efficacy and tolerability (including dry mouth) to transdermal oxybutynin. Extended-release tolterodine is, therefore, a valuable first-line therapy in the treatment of OAB.

Management of Benign Prostatic Hyperplasia

Abstract: Lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH) are common among older men, and can reduce their quality of life considerably. The disease also has substantial economic implications for healthcare providers and society in general, particularly in view of the aging of populations in developed countries. The management of patients with LUTS associated with BPH can include watchful waiting, medical therapy, or surgery, and disease management programs may use shared care approaches that involve both primary and secondary providers. Patient preference is important when making treatment decisions, and many patients will prefer medical treatment over surgery. This form of treatment is often managed within the primary-care setting. Among medical therapies, the α1-adrenoceptor antagonists are the preferred option for patients requiring rapid symptom relief. The efficacy of these drugs is sustained over a number of years. Generally, α1-adrenoceptor antagonists provide better symptom relief than 5α1-reductase inhibitors, and although they do not reduce the long-term risk of acute urinary retention or need for prostatic surgery (in contrast to 5α1-reductase inhibitors), they do delay the time to acute urinary retention, and are likely to reduce referrals to secondary care. Although generally well tolerated, hypotension-related events are the most common adverse events for most α1-adrenoceptor antagonists. Compared with the other drugs in its class, tamsulosin appears to have a lower propensity to interfere with blood pressure regulation, particularly in the elderly. This may reduce the amount of monitoring by physicians required during the initial period of treatment, and also the risk of hypotension-related falls and associated secondary care. The increasing importance of pharmacologic interventions in the long-term management of BPH, together with the efficacy and tolerability profile of tamsulosin, suggest that the drug may be useful as part of a disease management program, although the long-term economic impact of tamsulosin remains to be determined.

Performance Measurement of Disease Management Programs

Abstract: After the establishment of an industry trade association and accreditation, standardizing performance measurement is the third critical milestone in the maturation of the disease management (DM) industry. The publication of Standard Outcome Metrics and Evaluation Methodology for Disease Management Programs by American Healthways, a leading DM vendor, in 2003 is the first credible effort at achieving this milestone. This report is the product of collaboration between American Healthways and Johns Hopkins Outcomes Verification Program, along with a conference of almost 150 physicians and other healthcare professionals. It proposes 64 measures across five disease states, seven financial and utilization measures and survey standards for member and provider satisfaction. This paper presents a framework for developing and evaluating performance measurement standards based on four components or aspects: purpose, perspective, process and products (‘four Ps’). Purpose refers to the reasons and uses for the measurement. Perspective refers to who will use the measures and what the unit of analysis is. Process is how the standards are developed and chosen and includes the use of explicit criteria for selecting measures and standards, representative participation by all constituencies, the use of subject matter experts as consultants, and transparency. Products are the measures and their descriptions and specifications. With respect to the ‘four Ps’ framework, the American Healthways and Johns Hopkins paper includes a stated purpose, but is unclear with respect to who the intended users would be. Its perspective is primarily of physicians with lesser consideration given to public, DM purchaser and DM program manager stakeholders. The process by which the measures were selected and defined is not described, nor are the roles of the conference participants. No criteria for selecting measures are provided. The product is a reasonably comprehensive set of process and outcome indicators for the five disease states. No rationales for selecting these measures are provided, however, and the methodologies are not always well defined. There are many models of performance measurement standards and measures available. The performance measurement standards established by the National Committee for Quality Assurance and the Joint Commission on Accreditation of Healthcare Organizations are used as reference programs. These programs have done better at fulfilling the attributes offered in the framework, recognizing that they have developed through well-funded efforts over many years. The American Healthways and Johns Hopkins paper is a significant accomplishment and an important step in the establishment of measurement standards for DM. Further work needs to be done to achieve standards that will be useful and acceptable across the industry and among all constituents. A broader-based and broader-funded effort with more formalized or well-documented measure selection is needed, as well as testing, validation and dissemination of measures not commonly used in DM settings.

Barrett's Esophagus Is Screening and Surveillance Justified?

Abstract: Barrett's esophagus is a condition that develops in approximately 10-15% of patients with chronic gas- Abstract troesophageal reflux disease and is the only known major risk factor for esophageal adenocarcinoma The incidence of esophageal adenocarcinoma has increased by 350% over the last 3 decades and the reasons for this dramatic increase are unclear At the time of cancer diagnosis up to 50% of patients will have advanced regional or distant metastatic disease, with little or no chance of cure The overall 5-year survival rate with advanced disease remains poor at <10% Several studies have demonstrated an early stage of diagnosis and a marked improvement in the survival of patients with esophageal cancer detected by routine endoscopic surveillance in patients known to have pre-existing Barrett's esophagus The aim of endoscopic surveillance in patients with Barrett's esophagus is the early diagnosis of esophageal cancer, when it is still potentially curable The desired outcome is to further decrease the mortality rate associated with esophageal adenocarcinoma and identify and screen populations at risk for the development of dysplasia arising from Barrett's esophagus This is the principle of the current screening and surveillance guidelines set out by several societies, including the American College of Gastroenterology, the American Society of Gastrointestinal Endoscopy, and the European Society of Gastrointestinal Endoscopy However, as most patients with Barrett's esophagus do not develop adenocarcino- ma, the cost effectiveness of endoscopic screening and surveillance strategies is questionable To date, no prospective, randomized trials have been performed to evaluate the effectiveness of surveillance, the survival benefit in patients undergoing surveillance or the subsequent impact on healthcare costs In this article, we focus on the basic principles and reasoning underlying the surveillance guidelines for Barrett's esophagus In particular, that the disease is clinically important and has a high prevalence; the transition to adenocarcinoma could have a high death and/or disability rate; early diagnosis of adenocarcinoma should reduce mortality; and the screening method should be easily applied, safe, relatively inexpensive, and applicable to a large number of patients We then review arguments for and against screening and surveillance as they apply to these principles and discuss the current literature that reviews the effectiveness of such surveillance strategies, including an outline of cost analysis

A Surveillance System for the Real-Time Reporting of Influenza Activity

Abstract: Background: Effective influenza surveillance and communication of influenza activity are crucial for the management of influenza outbreaks. The accuracy of clinical diagnoses can be enhanced if the influenza virus is known to be circulating in the community. Objective: To report on the development of a new influenza surveillance system in Germany (2001–2002) based on consultation rates and near patient test results using the Influenza A/B Rapid Test (IRT) and RealFlu™ Surveillance methodology. Methods: This is the first internationally standardized, rapid influenza surveillance system providing harmonized influenza-specific information. RealFlu™ Surveillance is unique in its approach by generating two baselines: one with morbidity rates and one with specific influenza activity based on near patient test results. The baselines are set independently for each participating country and its constituent regions, thereby allowing monitoring of national as well as regional influenza activity. The system is highly specific and sensitive to influenza and differentiates between three levels of the RealFlu™ Surveillance influenza activity: (i) no/sporadic activity; (ii) moderate activity; and (iii) high activity. Weekly activity is presented in graphs, maps, and data tables with daily updates and comments. In this report, data collected during the influenza season 2001–2002 in Germany are presented. Results: The RealFlu™ Surveillance system has been running for four consecutive influenza seasons since 1999. The first increase in influenza circulation was seen from week 2 (from year start) to week 4. In week 5, a steep increase in influenza positives was observed. A significant amount of excess morbidity was seen from week 7, peaking in week 11. The season started in western regions of Germany and ended in eastern regions of Germany. Regional outbreaks were detected also when the aggregated country data did not indicate any significant increase in influenza activity. Conclusion: By providing specific, real-time monitoring of regional and national influenza outbreaks, the RealFlu™ Surveillance system complements existing schemes and presents a practical surveillance methodology for countries where influenza surveillance does not exist.

Dosing Patterns of Anti-TNF Therapy in Patients with Rheumatoid Arthritis in a Managed Care Setting

Abstract: Objective: To characterize the dose administration patterns of tumor necrosis factor (TNF) inhibitors for the treatment of rheumatoid arthritis (RA) within a managed care organization (MCO). Methods: Patients with RA who received either infliximab or etanercept between 1 January 2001 and 31 May 2002 were identified using MCO pharmacy and medical claims. Prescribers were asked to send copies of the identified patients’ charts. TNF inhibitor dose administration information was abstracted from the charts. Results: 1869 patients were potentially eligible and 936 of these could be linked to prescribers. A total of 457 of 936 (49%) requested charts were obtained. Of the 369 eligible patients, 164 received infliximab (44%) and 205 received etanercept (56%). The mean first doses ordered of infliximab and etanercept were 3.5 ± 0.6 mg/kg and 27.9 ± 24.2mg, respectively. Subsequent doses ordered were 4.2 ± 1.4 mg/kg and 25.7 ± 13.9mg, respectively. Overall, 67% of infliximab infusions used less than or equal to the expected number of vials if administered at 3 mg/kg. The estimated mean annual medication cost per patient (2004 values) was determined to be $US13 936-$US 15 734 for infliximab and $US17 105 for etanercept; however, these costs do not consider the need for methotrexate administration with infliximab and costs associated with the route of administration (intravenous for infliximab and subcutaneous for etanercept). Conclusion: The majority of TNF inhibitor doses were within recommended ranges. Although infliximab can be administered at doses up to 10 mg/kg, the majority of infliximab infusions were administered at less than or equal to the number of vials expected for a 3 mg/kg dose (the minimum recommended dose). While these results indicate that a large-scale initiative to improve prescribing of TNF inhibitors may not be needed, a further understanding of the factors that lead to prescribing of high doses of TNF inhibitors might be warranted.

Long-Term Drug Treatment of GERD

Abstract: Gastroesophageal reflux disease (GERD) is one of the most common disorders of the gastrointestinal tract. Clinical presentation can vary from simple heartburn to erosive esophagitis. Some patients require long-term, possibly life-long, therapy. The cost of treatment is substantial, as patients with moderate to severe disease are high consumers of healthcare resources. The goal of therapy is to control symptoms, and to prevent complications, at a reasonable and manageable cost. Formulary decision making is more complex than simply choosing between proton pump inhibitors (PPIs) and histamine H2 receptor antagonists (H2RAs); more importantly, it involves choosing the most cost-effective treatment strategy for a patient population. Since there are no long-term prospective economic studies available on the management of GERD, modeling studies provide the primary source of data for decision makers. A critical review of selected studies found that conclusions can vary based on a number of factors. These include the severity of GERD in the population being modeled, effectiveness endpoints, costs (drug and nondrug), and the inclusion of anti-reflux surgery. Effectiveness variables used in these models are generally based on randomized control trials in which endoscopic findings are used to judge success. This differs from the management of symptoms, as is common in clinical practice. In addition, the selection of which randomized clinical trial is used to define effectiveness endpoints can have a significant effect on the outcome. Thus, generalizability of economic studies often limits their value to decision makers. Pharmaceutical manufacturers have funded most of the studies in this area. For formulary decision makers to apply long-term economic analysis to their clinical practice, a critical review of these analyses is essential. Economic analysis can be a supplement to rational clinical judgment and experience in formulary decision making.

Adalimumab for Rheumatoid Arthritis

Abstract: Third-party payors and national health systems require evidence that new medications for rheumatoid arthritis are cost effective. To determine cost effectiveness, one must consider the cost of a given therapy versus the long-term cost of the disease, with and without therapy. The direct and indirect costs of rheumatoid arthritis over the course of the disease, including the considerable costs related to hospitalization and disability, have been quantified. Resource utilization and treatment costs are high for patients with rheumatoid arthritis, and there is a strong link between functional disability and direct cost of care. Traditional disease-modifying antirheumatic drugs (DMARDs) [such as methotrexate and gold] have limited long-term effects in improving lives and avoiding costs for patients with rheumatoid arthritis. Tumor necrosis factor (TNF) antagonists, the newest class of rheumatoid arthritis drug therapies, significantly improve patient outcomes, including reducing the signs and symptoms of rheumatoid arthritis, improving physical function and health-related quality of life, and inhibiting radiographie damage. Failing to treat rheumatoid arthritis effectively is very costly; effective treatment includes early, aggressive therapy. As a result, the National Health Service in the UK, other societal decision-makers, and third-party payors have recommended the use of TNF antagonists, in many instances, for the treatment of rheumatoid arthritis. The TNF antagonists — infliximab, etanercept, and the most recently approved, adalimumab — address the limitations of traditional DMARDs, thus setting a new therapeutic standard for rheumatoid arthritis. Data from three key studies (Anti-TNF Research Program of the Monoclonal Antibody Adalimumab in Rheumatoid Arthritis, DE019 and DE011) indicate that adalimumab provides a rapid, sustainable, predictable, and significantly greater reduction in the signs and symptoms of rheumatoid arthritis than traditional DMARDs. Adalimumab yields significantly less structural joint damage as measured by the total Sharp scores and scores on its two major components: joint erosions and joint space narrowing. It also improves physical function (as measured by the Health Assessment Questionnaire Disability Index) and health utility (as measured by the Health Utilities Index Mark 3). In conclusion, rheumatoid arthritis and other musculoskeletal diseases are costly, but an upfront investment in highly effective therapies may provide long-term cost savings compared with traditional therapies. The immediate, out-of-pocket costs of TNF antagonists are greater than traditional DMARDs, but with the potential to significantly improve response rates, inhibit structural joint damage, and improve disability and health utility, TNF antagonists have the potential to be more cost effective over the long run. TNF antagonists can be valuable for patients in need and therefore appropriate for reimbursement by national health systems and third-party payors.