Cost-Effectiveness of Lovotibeglogene Autotemcel (Lovo-Cel) Gene Therapy for Patients with Sickle Cell Disease and Recurrent Vaso-Occlusive Events in the United States.

BACKGROUND AND OBJECTIVE: Gene therapies for sickle cell disease (SCD) may offer meaningful benefits for patients and society. This study evaluated the cost-effectiveness of lovotibeglogene autotemcel (lovo-cel), a one-time gene therapy administered via autologous hematopoietic stem cell transplantation, compared with common care for patients in the United States (US) with SCD aged ≥ 12 years with ≥ 4 vaso-occlusive events (VOEs) in the past 24 months. METHODS: We developed a patient-level simulation model accounting for lovo-cel and SCD-related events, complications, and mortality over a lifetime time horizon. The pivotal phase 1/2 HGB-206 clinical trial (NCT02140554) served as the basis for lovo-cel efficacy and safety. Cost, quality-of-life, and other clinical data were sourced from HGB-206 data and the literature. Analyses were conducted from US societal and third-party payer perspectives. Uncertainty was assessed through probabilistic sensitivity analysis and extensive scenario analyses. RESULTS: Patients treated with lovo-cel were predicted to survive 23.84 years longer on average (standard deviation [SD], 12.80) versus common care (life expectancy, 62.24 versus 38.40 years), with associated discounted patient quality-adjusted life-year (QALY) gains of 10.20 (SD, 4.10) and direct costs avoided of $1,329,201 (SD, $1,346,446) per patient. Predicted societal benefits included discounted caregiver QALY losses avoided of 1.19 (SD, 1.38) and indirect costs avoided of $540,416 (SD, $262,353) per patient. Including lovo-cel costs ($3,282,009 [SD, $29,690] per patient) resulted in incremental cost-effectiveness ratios of $191,519 and $124,051 per QALY gained from third-party payer and societal perspectives, respectively. In scenario analyses, the predicted cost-effectiveness of lovo-cel also was sensitive to baseline age and VOE frequency and to the proportion of patients achieving and maintaining complete resolution of VOEs. CONCLUSIONS: Our analysis of lovo-cel gene therapy compared with common care for patients in the US with SCD with recurrent VOEs estimated meaningful improvements in survival, quality of life, and other clinical outcomes accompanied by increased overall costs for the health care system and for broader society. The predicted economic value of lovo-cel gene therapy was influenced by uncertainty in long-term clinical effects and by positive spillover effects on patient productivity and caregiver burden.

Economic evaluation of betibeglogene autotemcel (Beti-cel) gene addition therapy in transfusion-dependent ß-thalassemia.

Background: Standard of care (SoC) for transfusion-dependent ß-thalassemia (TDT) requires lifelong, regular blood transfusions as well as chelation to reduce iron accumulation. Objective: This study investigates the cost-effectiveness of betibeglogene autotemcel ('beti-cel'; LentiGlobin for ß-thalassemia) one-time, gene addition therapy compared to lifelong SoC for TDT. Study design: Microsimulation model simulated the lifetime course of TDT based on a causal sequence in which transfusion requirements determine tissue iron levels, which in turn determine risk of iron overload complications that increase mortality. Clinical trial data informed beti-cel clinical parameters; effects of SoC on iron levels came from real-world studies; iron overload complication rates and mortality were based on published literature. Setting: USA; commercial payer perspective Participants: TDT patients age 2-50 Interventions: Beti-cel is compared to SoC. Main outcome measure: Incremental cost-effectiveness ratio (ICER) utilizing quality-adjusted life-years (QALYs) Results: The model predicts beti-cel adds 3.8 discounted life years (LYs) or 6.9 QALYs versus SoC. Discounted lifetime costs were $2.28 M for beti-cel ($572,107 if excluding beti-cel cost) and $2.04 M for SoC, with a resulting ICER of $34,833 per QALY gained. Conclusion: Beti-cel is cost-effective for TDT patients compared to SoC. This is due to longer survival and cost offset of lifelong SoC.

Routine management, healthcare resource use and patient and carer-reported outcomes of patients with transfusion-dependent ß-thalassaemia in the United Kingdom: A mixed methods observational study.

Objectives: We evaluated routine healthcare management, clinical status and patient- and carer-reported outcomes in UK paediatric and adult patients with transfusion-dependent ß-thalassaemia (TDT). Methods: A multi-centre, observational mixed-methodology study evaluated 165 patients (50% male; median age 24.1 [interquartile range (IQR)] 11.8-37.2] years) from nine UK centres. Results: Patients had a mean of 13.7 (standard deviation [SD] ±3.2) transfusion episodes/year (mean retrospective observation period 4.7 [±0.7] years). The median (IQR) for iron overload parameters at the last assessment during the observation period were: serum ferritin (n = 165) 1961.0 (1090.0-3003.0) µg/L (38% > 2500 µg/L); R2 liver iron (n = 119) 5.4 (2.9-11.6) mg/g (16% ≥15 mg/g); T2* cardiac iron (n = 132) 30.3 (22.0-37.1) ms (10% < 10 ms). All patients received ≥1 iron chelator during the observation period; 21% received combination therapy. Patients had a mean of 7.8 (±8.1) non-transfusion-related hospital attendances or admissions/year. Adult patients' mean EQ-5D utility score was 0.69 (±0.33; n = 94 [≥16 years]) and mean Transfusion-dependent quality of life score was 58.6 (±18.4; n = 94 [≥18 years]). For Work Productivity and Activity impairment, mean activity impairment for patients ≥18 years (n = 88) was 48% (±32%) and for carers (n = 29) was 28% (±23%). Conclusions: TDT presents significant burden on patients, carers and healthcare resources.

Patient- and Caregiver-Reported Burden of Transfusion-Dependent ß-Thalassemia Measured Using a Digital Application.

BACKGROUND AND OBJECTIVE: Transfusion-dependent ß-thalassemia (TDT) is a rare genetic disease characterized by a deficiency of functional ß-globin, ultimately leading to lifelong dependence on blood transfusions. There is little patient- and caregiver-reported data with which to understand the holistic and societal impact of TDT. The objective of this study was to evaluate the patient- and caregiver-reported disease-management, symptom, and quality-of-life burden of TDT. METHODS: We conducted a prospective, observational, real-world study of adults with TDT and caregivers of adolescents with TDT, in Italy, the UK, and the USA. Over 90 days, participants used a smartphone application to respond to surveys about their or their dependent's TDT, including bespoke background and disease-management surveys, the Brief Fatigue Inventory (BFI), the Transfusion-dependent Quality of life questionnaire (TranQol), and the Brief Pain Inventory Short Form (BPI-SF). RESULTS: Eighty-five individuals participated. Mean BFI and TranQol scores on enrollment were 5.0 (0-10 scale; 10 = worst symptoms) and 51 (0-100 scale; 100 = best quality of life), respectively. Mean transfusion frequency was every 3.2 weeks. Mean time spent on TDT management was 592 min on transfusion days and 91 min on non-transfusion days (11 h per week). Mean BFI and BPI-SF "worst fatigue" and "worst pain" scores were higher in the 5 days pre-transfusion than in the 5 days post-transfusion (fatigue 5.05 vs 4.29; pain 4.33 vs 3.85; 0-10 scale; 10 = worst symptoms). CONCLUSIONS: The patient- and caregiver-reported burden of TDT is high, influenced by disease-management time, fatigue, pain, and quality-of-life impairment.

Co-morbidities and mortality associated with transfusion-dependent beta-thalassaemia in patients in England: a 10-year retrospective cohort analysis.

A retrospective cohort analysis to explore 10-year mortality and prevalence of transfusion-dependent ß-thalassaemia (TDT)-associated co-morbidities in patients with TDT was undertaken using Hospital Episode Statistics (HES) data from the National Health Service (NHS) in England. A 10-year forward-looking cohort analysis for the period 2009-2018 was completed using HES admitted patient care (APC), outpatient data, and linked HES/Office of National Statistics mortality data for patients with ß-thalassaemia (ICD-10 diagnosis code D56.1). TDT-associated co-morbidity rates were high in the 612 patients with TDT, with 76% having at least one co-morbidity, 54% suffering from two of more, and 37% three or more. The three most common TDT-associated co-morbidities, occurring in more than one third of patients were: endocrine disorders (excluding diabetes) 40%, osteoporosis 40%, and diabetes 34%. Cardiac disease was observed in 18% of patients overall, with atrial fibrillation and heart failure being the most common with a prevalence of 11% and 9%, respectively. The crude 10-year mortality rate in the TDT cohort was 6·2% (38/612), significantly greater than the 1·2% age/sex-adjusted mortality rate of the general population (P < 0·001). These data support the notion that the unmet need in TDT remains significant, with high rates of co-morbidity and mortality.

Opioid Treatment Patterns Following Prescription of Immediate-Release Hydrocodone.

BACKGROUND: Immediate-release (IR) hydrocodone is the most widely prescribed opioid in the United States; however, little is known about the utilization patterns and duration of opioid use among patients prescribed IR hydrocodone. A better understanding of the use of IR hydrocodone would result in more appropriate prescribing patterns of extended-release opioids. OBJECTIVE: To assess downstream length of opioid therapy and utilization patterns of extended-release/long-acting (ER/LA) opioids among patients on IR hydrocodone to provide a better understanding of how IR and ER/LA opioids are used to manage pain. METHODS: Retrospective analysis using health care claims from the Truven MarketScan Commercial, Medicare Supplemental, and Medicaid databases was performed. Patients prescribed IR hydrocodone during the 6-month baseline period (July 2011-December 2011) and with continuous enrollment for a 12-month follow-up period (2012) post-index date (January 1, 2012) were selected. Downstream length of therapy, defined as number of days supplied with opioids, and downstream use of ER/LA opioids during follow-up were examined by average pills per month (≤ 60 vs. > 60 pills per month) and days supply (< 60 vs. ≥ 60 days supply) of IR hydrocodone during baseline to mimic intermittent and consistent IR users. RESULTS: At baseline, 1,743,933 commercial, 277,096 Medicare, and 157,922 Medicaid IR hydrocodone patients were identified. During follow-up, 1.7%, 2.9%, and 2.8% of patients initiated (i.e., converted to or newly started) ER/LA opioids for commercial, Medicare, and Medicaid groups, respectively. Approximately 90% of patients were prescribed IR hydrocodone for less than 2 months in the following year, while 10% were high utilizers, averaging nearly 8 months of prescribed opioid use during follow-up. Downstream initiation of ER/LA opioids was significantly higher among commercial patients prescribed IR hydrocodone for > 60 pills per month than with ≤ 60 pills per month (7.8% vs. 1.2%, respectively, P < 0.05) at baseline. For commercial patients initiating ER/LA opioids, length of ER/LA therapy during follow-up was significantly longer among patients with baseline IR hydrocodone > 60 pills per month than with ≤ 60 pills per month. All results were consistent when examined by levels of days supply. CONCLUSIONS: A majority of the population prescribed IR hydrocodone was not prescribed opioid therapy beyond 2 months on average in the 1-year follow-up period. Only a small subset of patients with increased pills per month or days supply of IR hydrocodone in the baseline period continued to be high utilizers in the following year, averaging nearly 8 months of prescribed opioid use. A limited proportion of patients prescribed IR hydrocodone converted to ER/LA opioids. This knowledge can assist policymakers and physicians, providing an opportunity to identify small subsets of patients to improve ER/LA opioid prescribing. DISCLOSURES: Funding and support for this study was provided by Purdue Pharma L.P. Consulting fees were paid to Evidera by Purdue Pharma L.P. for this study. Kansal, Chitnis, and Paramore are employees of Evidera and were paid consultants to Purdue Pharma for this research. Holly is an employee for Purdue Pharma, and Bell and Ben-Joseph were full-time employees of Purdue Pharma during the design, planning, and execution of the studies and during the preparation of this manuscript. Burgoyne and Brixner were consultants on this project. Study design was created by Ben-Joseph, Brixner, Paramore, and Burgoyne. Data were collected by Kansal, Chitnis, Bell, Ben-Joseph, and Holly and interpreted by Ben-Joseph, Bell, Kansal, and Holly, with assistance from Brixner, Paramore, Burgoyne, and Chitnis. The manuscript was written by Ben-Joseph, Bell, Paramore, Chitnis, and Holly, with assistance from Kansal, and revised by Bell and Holly, along with Ben-Joseph, Brixner, Kansal, Paramore, Burgoyne, and Chitnis.

Characterizing downstream healthcare resource utilization and costs based on prior utilization patterns of immediate-release hydrocodone.

OBJECTIVE: To assess downstream healthcare resource utilization (HRU) and costs among immediate release (IR) hydrocodone patients by days' supply and average doses/month in the prior 6 months. METHODS: Retrospective analysis using healthcare claims from Truven MarketScan commercial, Medicare supplemental, and Medicaid multistate databases was performed. Patients prescribed IR hydrocodone during the 6-month baseline (July-December 2011), and with continuous enrollment during baseline and the 12-month follow-up (2012) were selected. HRU and per-patient-per-month (PPPM) costs (2014 US dollars) were assessed at follow-up. Descriptive analyses and multivariate regressions were conducted to compare HRU and costs at follow-up by days' supply (<60 vs ≥60 days) and average doses per month (≤60 vs >60 doses/month) of IR hydrocodone at baseline. RESULTS: In total, 1,698,845 commercial, 264,038 Medicare, and 151,063 Medicaid IR hydrocodone patients were identified. During follow-up, commercial patients with prior ≥60 days' supply were more likely to have an inpatient admission (13.2% vs 7.5%), outpatient hospital visit (69.1% vs 57.0%), office visit (97.6% vs 91.0%), emergency room (ER) visit (28.1% vs 21.4%), and had higher PPPM total costs ($1494 vs $842) than the <60 days' supply sub-group (all p < 0.05). Among commercial patients the adjusted odds ratio for prior ≥60 days' supply of IR hydrocodone vs prior <60 days' supply was 1.62 (inpatient), 1.33 (outpatient), 2.58 (office visit) and 1.48 (ER) (all p-values <0.05). Adjusted all-cause total costs were higher ($1245 vs $851, p <0.05) among commercial patients with longer days' supply than those with shorter days' supply. Trends were similar with ≤60 vs >60 doses per month sub-groups and across all plan types. CONCLUSION: Increased days' supply and higher doses/month of IR hydrocodone in the prior 6 months may help to predict levels of HRU and costs in the following year, providing an opportunity to identify patients in order to implement interventions to improve their quality of care.

Systemic sclerosis prevalence and comorbidities in the US, 2001-2002.

OBJECTIVE: Large, population-based assessments of systemic sclerosis (SSc) prevalence and comorbidity in the United States (US) are rare. We explored autoimmune disease and other comorbidity patterns among SSc patients in the US from 2001 to 2002 and compared these with controls. RESEARCH DESIGN AND METHODS: Two US datasets with patient-level medical and drug claims were used to assess SSc prevalence and comorbidity: IMS Health Integrated Administrative Claims Database (IMS Health) and the MarketScan Commercial Claims and Encounters Database (MarketScan). SSc patients and comorbidities were identified by International Classification of Diseases (ICD), 9th revision diagnostic codes appearing on medical claims. Patients without SSc diagnostic codes (controls) were selected and matched 4:1 to SSc patients based on sex, age, Census Bureau region, and previous insurance coverage. The prevalence relative risk (RR) statistic compared comorbidity occurrence between SSc patients and controls, with 95% confidence intervals estimated using the Mantel-Haenszel method. Several sensitivity analyses tested methods used for identifying SSc cases and the prevalence of comorbidities. RESULTS: In both databases, SSc prevalence was 0.05% using the standard population model, 0.03% under sensitivity analysis. Among SSc patients the risks for inflammatory bowel disease (IBD) and multiple sclerosis (MS) were notably higher across datasets than for those without SSc: RR 3.2-6.6 for MS, RR 2.1-2.2 for IBD, in MarketScan and IMS Health, respectively (p < 0.05 for all). The chronic disease burden of SSc patients was much higher than that of controls, as confirmed by two chronicity measures (Chronic Disease Score, Elixhauser Comorbidity Index). The risks for cardiovascular, renal, liver and several neuropsychiatric diseases were higher for SSc patients across both datasets. Sensitivity analyses supported these findings. CONCLUSIONS: These data provide a population-based estimate of US prevalence of SSc and document the higher risk for certain other autoimmune diseases among SSc patients when compared to controls. Patients with SSc also had a higher chronic disease burden than those without SSc. These findings are limited by the unknown validity of ICD-9 codes for SSc case identification, unbalanced regional representation, and a likely 'healthy worker' effect in these databases.

Autoimmune disease concomitance among inflammatory bowel disease patients in the United States, 2001-2002.

BACKGROUND: Recent studies suggest that inflammatory bowel disease (IBD) may share an underlying pathogenesis with other autoimmune diseases. METHODS: Two United States data sets with patient-level medical and drug claims were used to explore the occurrence of autoimmune diseases in patients with IBD, particularly Crohn's disease (CD) and ulcerative colitis (UC), with that in controls. From 2001 to 2002 IBD patients were identified using International Classification of Diseases, 9th revision, diagnosis codes in the IMS Health Integrated Administration Claims Database and the Market Scan Commercial Claims and Encounters Database. Controls were selected by matching on sex, age, Census Bureau region, and length of previous medical insurance coverage. Odds ratios (ORs) evaluated the risk relationship between IBD patients and controls within an estimated Mantel-Haenszel 95% confidence interval. Sensitivity analysis tested the case identification method used to select IBD patients. RESULTS: The risk for ankylosing spondylitis (AS) was substantially increased across both data sets: OR (95% confidence interval [CI]) of 7.8 (5.6-10.8) in IMS Health and 5.8 (3.9-8.6) in MarketScan. The risk for rheumatoid arthritis (RA) was 2.7 (2.4-3.0) and 2.1 (1.8-2.3), respectively; for multiple sclerosis (MS); the ORs were 1.5 (1.2-1.9) and 1.6 (1.2-2.1), respectively. There was no increased risk for type 1 diabetes mellitus, and the results for psoriatic arthritis (PsA) were inconsistent. The sensitivity analysis supported these findings. CONCLUSIONS: A much higher risk for RA, AS, PsA, and MS was observed in IBD patients compared with controls. Prospective epidemiologic studies are needed to confirm these findings and explore the pathogenic mechanism of this relationship.

Assessing the direct costs of treating nonvalvular atrial fibrillation in the United States.

OBJECTIVE: To determine the health-care resource use and costs attributable to treating atrial fibrillation (AF) in the United States. METHODS: Retrospective analyses of three federally funded US databases (2001 data): 1) hospital inpatient stays (the Healthcare Cost and Utilization Project [HCUP]); 2) physician office visits (the National Ambulatory Medical Care Survey [NAMCS]); and 3) emergency department (ED) and hospital outpatient department visits (OPD) (the National Hospital Ambulatory Medical Care Survey [NHAMCS]). Identification of AF medical encounters was based on occurrence of AF-specific International Classification of Diseases (9th Edition)--Clinical Modification (ICD-9-CM) diagnosis code 427.31 (principal discharge diagnosis for inpatient setting; any diagnosis field for other settings). For the 10 most common principal discharge diagnoses in the inpatient setting, case-control comparison analyses were performed to estimate annual incremental costs of AF as a comorbid discharge diagnosis for hospital stays. Regression models were used to assess the impact of AF on hospitalization costs. Costs were estimated in year 2005 US dollars. RESULTS: Approximately 350,000 hospitalizations, 5.0 million office visits, 276,000 ED visits, and 234,000 OPD were attributable to AF annually within the United States. Total annual costs for treatment of AF were estimated at $6.65 billion, including $2.93 billion (44%) for hospitalizations with a principal discharge diagnosis of AF, $1.95 billion (29%) for the incremental inpatient cost of AF as a comorbid diagnosis, $1.53 billion (23%) for outpatient treatment of AF, and $235 million (4%) for prescription drugs. In all regressions, AF was a significant contributor to hospital cost. CONCLUSIONS: Treatment of AF represents a significant health-care burden with the costs of treating AF in the inpatient setting outweighing the costs of treating AF in the office, emergency room or hospital outpatient settings. Further research is needed to fully capture the costs of treating AF.

Cost of illness of hyponatremia in the United States.

BACKGROUND: Hyponatremia is a disorder of fluid and electrolyte balance characterized by a relative excess of body water relative to body sodium content. It is the most common electrolyte disorder encountered in clinical medicine and is associated with negative outcomes in many chronic diseases. However, there is limited information in the literature about health care resource use and costs attributable to the effects of the condition. The purpose of this analysis was to estimate the annual cost of illness of hyponatremia in the United States. METHODS: The study utilized a prevalence-based cost of illness framework that incorporated data from publicly available databases, published literature and a consensus panel of expert physicians. Panel members provided information on: classification of hyponatremia patients, treatment settings for hyponatremia (i.e., hospital, emergency room, doctor's office), and health care resource use associated with the diagnosis and treatment of hyponatremia. Low and high prevalence scenarios were estimated and utilized in a spreadsheet-based cost of illness model. Costs were assigned to units of resources and summarized across treatment settings. RESULTS: The prevalence estimate for hyponatremia ranged from 3.2 million to 6.1 million persons in the U.S. on an annual basis. Approximately 1% of patients were classified as having acute and symptomatic hyponatremia, 4% acute and asymptomatic, 15%-20% chronic and symptomatic, and 75-80% chronic and asymptomatic. Of patients treated for hyponatremia, 55%-63% are initially treated as inpatients, 25% are initially treated in the emergency room, and 13%-20% are treated solely in the office setting. The direct costs of treating hyponatremia in the U.S. on an annual basis were estimated to range between $1.6 billion and $3.6 billion. CONCLUSION: Treatment of hyponatremia represents a significant healthcare burden in the U.S. Newer therapies that may reduce the burden of hyponatremia in the inpatient setting could minimize the costs associated with this condition.

A review of the economic burden of ADHD.

Attention-deficit hyperactivity disorder (ADHD) is a common disorder that is associated with broad functional impairment among both children and adults. The purpose of this paper is to review and summarize available literature on the economic costs of ADHD, as well as potential economic benefits of treating this condition. A literature search was performed using MEDLINE to identify all published articles on the economic implications of ADHD, and authors were contacted to locate conference abstracts and articles in press that were not yet indexed. In total, 22 relevant items were located including published original studies, economic review articles, conference presentations, and reports available on the Internet. All costs were updated and presented in terms of year 2004 US dollars. A growing body of literature, primarily published in the United States, has demonstrated that ADHD places a substantial economic burden on patients, families, and third-party payers. Results of the medical cost studies consistently indicated that children with ADHD had higher annual medical costs than either matched controls (difference ranged from 503 dollars to 1,343 dollars) or non-matched controls (difference ranged from 207 dollars to 1,560 dollars) without ADHD. Two studies of adult samples found similar results, with significantly higher annual medical costs among adults with ADHD (ranging from 4,929 dollars to 5,651 dollars) than among matched controls (ranging from 1,473 dollars to 2,771 dollars). A limited number of studies have examined other economic implications of ADHD including costs to families; costs of criminality among individuals with ADHD; costs related to common psychiatric and medical comorbidities of ADHD; indirect costs associated with work loss among adults with ADHD; and costs of accidents among individuals with ADHD. Treatment cost-effectiveness studies have primarily focused on methylphenidate, which is a cost-effective treatment option with cost-effectiveness ratios ranging from 15,509 dollars to 27,766 dollars per quality-adjusted life year (QALY) gained. As new treatments are introduced it will be important to evaluate their cost-effectiveness to provide an indication of their potential value to clinicians, patients, families, and third-party payers.

Drug persistency patterns for patients treated with rivastigmine or donepezil in usual care settings.

OBJECTIVE: To compare levels of persistency with 2 cholinesterase (ChE) inhibitors--rivastigmine and donepezil--for the treatment of Alzheimer's disease (AD) through the use of administrative claims data. METHODS: This retrospective cohort study identified treatment-naive, community-based AD patients having an initial prescription (index event) for rivastigmine or donepezil between June and December 2000, in the United States, from pharmacy claims in a proprietary administrative claims database. Patients were excluded if they received either drug during the 180 days prior to their index prescription or if they did not have continuous plan enrollment during this period and for at least 90 days following the index date. The probability of treatment discontinuation within the first 60 days of treatment was estimated. Time to treatment discontinuation was analyzed for the cohort of patients that remained on therapy > or =60 days as well as for subgroups of the cohort reaching either approved or maximum recommended doses of donepezil or rivastigmine. Treatment discontinuation was defined as either a stop of therapy (no prescription refill within 60 days of estimated completion of prior prescription) or a switch to an alternative AD drug. Kaplan-Meier survival and proportional hazard model analyses were performed. Proportion of days covered (PDC) by an AD therapy was also evaluated in each quarter during the first year of follow-up. RESULTS: Of the newly treated AD study population, 30.4% (171/563) of rivastigmine patients and 31.2% (583/1,871) of donepezil patients discontinued treatment within 60 days of starting therapy (P = 0.72). For the cohort of patients that remained on therapy > or =60 days, the mean time to treatment discontinuation was 331 days (95% confidence interval [CI], 307-355) for rivastigmine patients (n = 392) versus 337 days (95% CI, 322-352) for donepezil patients (n = 1288). The proportion of patients with a PDC > or =80% after 12 months of follow-up was 23% for the donepezil group and 19% for the rivastigmine group (P = 0.34). For the cohort subgroup that reached an approved dose, the mean time to treatment discontinuation was 346 days (95% CI, 318-374) for rivastigmine patients (n = 282) versus 338 days (95% CI, 323-353) for donepezil patients (n = 1,283). For the cohort subgroup that reached the maximum recommended dose, the mean time to treatment discontinuation was 396 days (95% CI, 343-449) for rivastigmine patients (n = 61) versus 364 days (95% CI, 344-384) for donepezil patients (n = 712). CONCLUSION: Newly treated AD patients in a usual care setting who initiate therapy with either rivastigmine or donepezil have similar levels of persistency with treatment.

Incorporating pharmacoeconomic and health outcomes into randomized clinical trials.

Clinical trials represent the most scientifically valid study design for evaluating the safety and efficacy of new medical treatments. However, for pharmacoeconomic outcomes, the usual efficacy clinical trial may not always provide the appropriate vehicle for generating information on the cost-effectiveness of medical treatments. Pragmatic, or naturalistic, clinical trials may be more suited to understanding cost-effectiveness. There are several issues associated with designing clinical trials that include patient-reported outcomes or pharmacoeconomic outcomes. For patient-reported outcomes, it is important to match the domains and instruments with the objectives and characteristics of the target patient population, examine psychometric characteristics (i.e., reliability, validity and responsiveness) when selecting measures, and also consider practical issues related to data collection. Plans need to be put into place to minimize missing patient-reported outcome item level and form data. For pharmacoeconomic outcomes, it is necessary to collect healthcare resource data and to value these resources in some way. This may be challenging when multinational clinical trials are designed and conducted. There are challenges associated with the analysis of cost data and in conducting cost-effectiveness analyses. Design and reporting of prospective, pharmacoeconomic trials will help inform evidence-based medicine and hopefully improve the delivery and outcomes of medical care.