Persistence with osteoporosis medications among postmenopausal women in the UK General Practice Research Database.

OBJECTIVE: The aims of this study were to estimate persistence with osteoporosis therapies and to assess persistence by different users (stable and switching), type of osteoporosis drug, and calendar year of initiation among postmenopausal women. METHODS: This study was conducted using the data from the UK General Practice Research Database. We identified all women in the General Practice Research Database who had a first-ever recording of a prescription for an oral bisphosphonate, oral raloxifene, or oral strontium ranelate between January 1, 1995, and March 31, 2008, and who were 50 years or older or had a diagnosis to indicate menopause at an earlier age.Persistence was estimated as the proportion of women who continued therapy at 6 months and at 1, 3, and 5 years, using Kaplan-Meier methodology. Because women could have multiple episodes (of one or more therapies) over the follow-up period, persistence was evaluated for each individual episode. RESULTS: There were 66,116 eligible postmenopausal women who received at least one prescription for one of the osteoporosis therapy drugs in this study during the period 1995 to 2008. Overall, the women were continuing with osteoporosis therapy at 6 months after the index date in the full study population in 44% of episodes and in 32%, 16%, and 9% of episodes at 1, 3, and 5 years later, respectively. CONCLUSIONS: Persistence with osteoporosis therapies has improved over the study period, but persistence in the first 6 months remains below 50%, leaving a large unmet need to improve the management of postmenopausal women through novel adherence programs and therapies.

Adjusting for patient crossover in clinical trials using external data: a case study of lenalidomide for advanced multiple myeloma.

OBJECTIVES: In some trials, particularly in oncology, patients whose disease progresses under the comparator treatment are crossed over into the experimental arm. This unplanned crossover can introduce bias in analyses because patients who crossover likely have a different prognosis than those who do not cross over; for instance, sicker patients not responding to standard therapy or those expected to benefit the most may be selectively chosen to receive the experimental treatment. Standard statistical methods cannot adequately correct for this bias. We describe an approach designed to minimize the impact of crossover, and illustrate this by using data from two randomized trials in multiple myeloma (MM). METHODS: The MM-009/010 trials compared lenalidomide and high-dose dexamethasone (Len+Dex) with dexamethasone alone (Dex). Nearly half (47%) of the patients randomized to Dex crossed over to Len with or without Dex (Len+/-Dex) at disease progression or study unblinding. Data from these trials was used to predict survival in an economic model evaluating the cost-effectiveness of lenalidomide. To adjust for crossover, the prediction equations were calibrated to match survival with Dex or Dex-equivalent therapies in trials conducted by the Medical Research Council (MRC) in the United Kingdom. To adjust for differences between the MM and MRC trial populations, a prediction equation was developed from the MRC data and used to predict survival by setting predictors to mean values for patients in the MM-009/010 trials. The expected survival with Dex without crossover was then predicted from the calibrated MM-009/010 equation (i.e., adjusted to match survival predicted from the MRC equation). RESULTS: The adjusted median overall survival predicted by the MRC equation was 19.5 months (95%CI, 16.6-22.9) for patients with one prior therapy, and 11.6 months (95% CI, 9.5-14.2) for patients with >1 prior therapy. These estimates are considerably shorter than was observed in the clinical trials: 33.6 months (27.1-NE) and 27.3 months (95% CI, 23.3-33.3) as of December 2005. CONCLUSION: The calibration method described here is simple to implement, provided that suitable data are available; it can be implemented with other types of endpoints in any therapeutic area.

A predictive model of health state utilities for HIV patients in the modern era of highly active antiretroviral therapy.

OBJECTIVE: Existing estimates of human immunodeficiency virus (HIV)-related health state utilities are inadequate for comparing alternative treatments on the basis of regimen-specific attributes such as dosing requirements or tolerability. The objective of this study was to examine the marginal impact of dosing, adverse events (AEs), and other factors on patients' health state utilities. METHODS: Treatment naive and experienced HIV patients participating in five open-label trials of highly active antiretroviral therapy (HAART) completed the 36-Item Short Form Health Survey (SF-36) instrument at various time points. SF-36 responses were converted to utilities using a previously reported algorithm. Expected utilities were estimated as a function of patient demographics, regimen attributes, disease status, and AEs using a mixed-effects maximum likelihood model. Mean utilities for five HIV health states were derived from predicted patient utilities. RESULTS: Negative predictors of utility included greater age (-0.001), prior acquired immune deficiency syndrome-defining events (-0.036), female gender (-0.038), and injection drug use (-0.056; P < 0.01 for all). Utility also depended on CD4+ cell count (P < 0.01), but not the presence of undetectable viral load. Regimen attributes were marginally associated with changes in utility. Depression was associated with the largest decrease in utility (-0.054, P < 0.001) among the AEs examined. Using the model to generate predicted utilities from the sample provided mean estimates ranging from 0.742 (SD 0.058) to 0.798 (0.052) for CD4+ counts between 0 and 99 and > or =500 cells/mm(3), respectively. CONCLUSIONS: HIV patients' health-related quality of life may be substantially affected by clinically relevant patient-, disease-, and treatment-related factors, such as injection drug use, disease status, food/drink restrictions, and AEs.

Cost-effectiveness of rosiglitazone combination therapy for the treatment of type 2 diabetes mellitus in the UK.

INTRODUCTION: Recent clinical trial results have demonstrated that, in patients with type 2 diabetes, second-line treatment of rosiglitazone in combination with metformin can lead to significant improvements in the control of fasting plasma glucose/ glycosylated haemoglobin A1c (HbA1c) after the failure of metformin monotherapy. Our objective was to assess the cost-effectiveness of the use of rosiglitazone in combination with metformin in overweight and obese patients with type 2 diabetes in the UK, failing to maintain glycaemic control with metformin monotherapy compared with conventional care using metformin in combination with sulfonylurea. METHODS: The Diabetes Decision Analysis of Cost--type 2 (DiDACT) model, an established long-term economic model of type 2 diabetes, which projects the relationship between treatment and HbA1c over extended periods, was used to determine the health outcomes and economic impact for matched age and sex cohorts of 1000 patients with type 2 diabetes. The perspective was that of the UK National Health Service and all costs were in UK pounds sterling. RESULTS: Treatment with rosiglitazone in combination with metformin provides better glycaemic control over the remaining lifetime of patients than metformin and sulfonylurea combination therapy. Patients treated with rosiglitazone combination therapy were predicted to have a longer life expectancy, gaining 123 and 140 additional life years per 1000 patients in the obese and overweight cohorts, respectively. Improvements in morbidity and a delay in the start of insulin therapy resulted in a projected improvement in quality of life. These effects combine with projected improved survival to yield 131 and 209 additional quality-adjusted life-years (QALYs) per 1000 patients in the obese and overweight cohorts, respectively. Discounted incremental cost-effectiveness ratios were estimated at pounds 16,700 per QALY gained for the obese cohort and pounds 11,600 per QALY gained for the overweight cohort. CONCLUSION: The model predicts that rosiglitazone in combination with metformin is a cost-effective treatment in the UK for both obese and overweight patients failing on metformin monotherapy, compared with conventional therapy using metformin in combination with sulfonylurea.

Cost-effectiveness of rosiglitazone oral combination for the treatment of type 2 diabetes in Germany.

AIMS/HYPOTHESIS: To assess the cost-effectiveness of rosiglitazone in combination with other oral agents for the treatment of overweight and obese patients with type 2 diabetes in Germany. METHODS: The Diabetes Decision Analysis of Cost--type 2 model was adapted for clinical practice and healthcare financing rules in Germany. The model was calibrated using Cost of Diabetes in Europe Type 2 study data and national statistics. The perspective is that of the sickness funds, and includes all hospital inpatient, ambulatory, rehabilitation, and diabetes therapy, other medications, and sickness leave. The model simulates lifetime treatment histories and associated health outcomes and costs for age and sex-matched cohorts of 1000 overweight and obese patients. The measures of effectiveness used in the analysis were life-years and quality adjusted life-years (QALYs). RESULTS: The combination therapy of rosiglitazone with metformin or sulfonylurea produces better glycaemic control than conventional care of metformin with sulfonylurea and insulin in most patients, extends the viability of oral therapy before requiring insulin, and typically leads to lifetime cost increases across all treatment types. The improvements in glycaemic control lead to survival gains and reductions in morbidity, because of the reduced risk of developing or progressing to later stages of complications. Improvements in morbidity and mortality generate additional QALYs. Costs and health outcomes combine to yield favourable incremental cost-effectiveness ratios, which fall below international 'willingness-to-pay' thresholds in the medium term. CONCLUSION: The model predicts that rosiglitazone in combination with other oral agents is a cost-effective intervention for the treatment of normal weight, overweight and obese patients with type 2 diabetes when compared with conventional care in Germany.

Lifetime health consequences and cost-effectiveness of rosiglitazone in combination with metformin for the treatment of type 2 diabetes in Spain.

OBJECTIVE: To assess the lifetime diabetes health consequences and cost-effectiveness in Spain of rosiglitazone in combination with metformin for the treatment of type 2 diabetes in overweight and obese patients failing to maintain glycaemic control with metformin monotherapy compared with conventional care of metformin in combination with either sulfonylureas or bedtime insulin. RESEARCH DESIGN AND METHODS: The Diabetes Decision Analysis of Cost--Type 2 was adapted for clinical practice and healthcare funding in Spain, and was calibrated with Spanish epidemiological, healthcare resource use and cost data, taking the perspective of the Spanish National Health System. The model simulates lifetime treatment histories, complications and consequences of type 2 diabetes, and associated health outcomes and costs for age and sex-matched cohorts of 1000 overweight and obese patients. The primary health outcome measures compared are glycaemic control, time to insulin, incidence and prevalence of coronary heart disease, stroke, clinical nephropathy, ulceration and amputation, and severe visual loss, and incremental life-years and quality-adjusted life-years (QALYs). RESULTS: Rosiglitazone in combination with metformin produces better glycaemic control than conventional care of metformin in combination with either sulfonylureas or bedtime insulin in most patients, and extends the viability of combination therapy by between 6 and 13 years before requiring insulin. Rosiglitazone patients have a longer life expectancy, gaining between 106 and 175 additional life-years per 1000 patients, experience fewer episodes of coronary disease and clinical nephropathy, and live for longer periods free of complications. The improvements in morbidity and mortality are projected to yield between 134 and 238 additional QALY per 1000 patients over their lifetime. Discounted incremental cost-effectiveness ratios range from euro 9406 to euro 23,514 per QALY gained. CONCLUSION: The model predicts that rosiglitazone in combination with metformin is a cost-effective intervention for the treatment of both overweight and obese patients with type 2 diabetes when compared with conventional care in Spain.

The health care costs of diabetic nephropathy in the United States and the United Kingdom.

PROBLEM: Diabetic nephropathy (DN) is a common microvascular complication of diabetes and can result in end-stage renal disease (ESRD) necessitating long-term dialysis or kidney transplantation. The costs of these complications are relatively high. The aim of this study was to quantify and compare the rates and annual costs of DN in the USA and the UK. METHODS: A cost of illness model was used to estimate the numbers of people with DN (microalbuminuria, overt nephropathy, and ESRD) or a previous kidney transplant at a given point in time and the numbers of new kidney transplants during a year. All costs were estimated in 2001 currencies. A sensitivity analysis assessed the robustness of the national annual cost estimates. RESULTS: In the USA, the total annual medical costs incurred by all payers in managing DN were US dollars 1.9 billion for Type 1 diabetes (range: US dollars 1.0-2.8 billion), US dollars 15.0 billion for Type 2 diabetes (range: US dollars 7.6-22.4 billion), and US dollars 16.8 billion for all diabetes (range: US dollars 8.5-25.2 billion). In the UK, the total annual costs to the National Health Service (NHS) of managing DN were US dollars 231 million ( pound 152 million) for Type 1 diabetes (range: US dollars 190-350 million [ pound 125-230 million]), US dollars 933 million (pound 614 million) for Type 2 diabetes (range: US dollars 809 million-US dollars 1.4 billion [pound 532-927 million]), and US dollars 1.2 billion ( pound 765 million) for all diabetes (range: US dollars 999 million-US dollars 1.8 billion [pound 657 million- pound 1.2 billion]). CONCLUSIONS: The total annual cost of DN is 13 times greater in the USA than in the UK. Controlling for the substantially higher number of people at risk, the total cost per person with DN and/or a kidney transplant is 40% higher: US dollars 3735 in the USA and US dollars 2672 (pound 1758) in the UK.

Predicted costs and outcomes from reduced vibration detection in people with diabetes in the U.S.

OBJECTIVE: The ability to perceive vibration (vibration detection) has been shown to be a good predictor of the long-term complications of diabetic peripheral neuropathy (DPN). We aimed to estimate the predicted complications and costs for the U.S. health care system associated with reduced vibration detection (vibration perception threshold >or=25 V), estimated using a quantitative sensory testing device. RESEARCH DESIGN AND METHODS: A Markov model was constructed for a hypothetical cohort of people with DPN. The model was run over a 10-year period using Monte Carlo simulations to estimate disease progression, predicted costs, and complications according to vibration detection levels. RESULTS: The average individual with reduced vibration detection incurs approximately five times more direct medical costs for foot ulcer and amputations, yields 0.18 fewer quality-adjusted life-years, and lives for approximately 2 months less than an average individual with normal vibration detection. CONCLUSIONS: The treatment of foot ulceration and amputation is time-consuming and expensive. If individuals with reduced vibration detection could be identified, then preventative care could be concentrated on those patients, potentially saving valuable resources and improving health outcomes.

The health care costs of diabetic peripheral neuropathy in the US.

OBJECTIVE: Peripheral neuropathy is common among people with diabetes and can result in foot ulceration and amputation. The aim of this study was to quantify the annual medical costs of peripheral neuropathy and its complications among people with type 1 and type 2 diabetes in the U.S. RESEARCH DESIGN AND METHODS: A cost-of-illness model was used to estimate the numbers of diabetic individuals in the U.S. who have diabetic peripheral neuropathy (DPN) and/or neuropathic foot ulcers (both those with no deep infection and those accompanied by cellulitis or osteomyelitis) at a given point in time, and/or a toe, foot, or leg amputation during a year. Prevalence and incidence rates were estimated from published studies and applied to the general U.S. population. All costs were estimated in 2001 U.S. dollars. In a sensitivity analysis, we varied the rates of complications to assess the robustness of the cost estimates. RESULTS: The annual costs of DPN and its complications in the U.S. were 0.8 billion US dollars (type 1 diabetes), 10.1 billion US dollars (type 2 diabetes), and 10.9 billion US dollars (total). After allowing for uncertainty in the point estimates of complication rates, the range of costs were between 0.3 and 1.0 billion US dollars (type 1 diabetes), 4.3b and 12.7 billion US dollars (type 2 diabetes), and 4.6 and 13.7 billion US dollars (type 1 and type 2 diabetes). CONCLUSIONS: The total annual cost of DPN and its complications in the U.S. was estimated to be between 4.6 and 13.7 billion US dollars. Up to 27% of the direct medical cost of diabetes may be attributed to DPN.

Waiting times for hospital admissions: the impact of GP fundholding.

Waiting times for hospital care are a significant issue in the UK National Health Service (NHS). The reforms of the health service in 1990 gave a subset of family doctors (GP fundholders) both the ability to choose the hospital where their patients were treated and the means to pay for some services. One of the key factors influencing family doctors' choice of hospital was patient waiting time. However, without cash inducements, hospitals would get no direct reward from giving shorter waiting times to a subset of patients. Using a unique dataset, we investigate whether GP fundholders were able to secure shorter waiting times for their patients, whether they were able to do so in cases where they had no financial rewards to offer hospitals, and whether the impact of fundholding spilled over into shorter waiting times for all patients.