The cost of treating diabetic ketoacidosis in an adolescent population in the UK: a national survey of hospital resource use.

AIMS: Adolescents with Type 1 diabetes commonly experience episodes of ketoacidosis. In 2014, we conducted a nationwide survey on the management of diabetic ketoacidosis in young people. The survey reported how individual adolescents with diabetes were managed. However, the costs of treating diabetic ketoacidosis were not reported. METHODS: Using this mixed population sample of adolescents, we took a 'bottom-up' approach to cost analysis aiming to determine the total expense associated with treating diabetic ketoacidosis. The data were derived using the information from the national UK survey of 71 individuals, collected via questionnaires sent to specialist paediatric diabetes services in England and Wales. RESULTS: Several assumptions had to be made when analysing the data because the initial survey collection tool was not designed with a health economic model in mind. The mean time to resolution of diabetic ketoacidosis was 15.0 h [95% confidence interval (CI) 13.2, 16.8] and the mean total length of stay was 2.4 days (95% CI 1.9, 3.0). Based on data for individuals and using the British Society of Paediatric Endocrinology and Diabetes (BSPED) guidelines, the cost analysis shows that for this cohort, the average cost for an episode of diabetic ketoacidosis was £1387 (95% CI 1120, 1653). Regression analysis showed a significant cost saving of £762 (95% CI 140, 1574; P = 0.04) among those treated using BSPED guidelines. CONCLUSION: We have used a bottom-up approach to calculate the costs of an episode of diabetic ketoacidosis in adolescents. These data suggest that following treatment guidelines can significantly lower the costs for managing episodes of diabetic ketoacidosis.

The cost of treating diabetic ketoacidosis in the UK: a national survey of hospital resource use.

AIM: Diabetic ketoacidosis is a commonly encountered metabolic emergency. In 2014, a national survey was conducted looking at the management of diabetic ketoacidosis in adult patients across the UK. The survey reported the clinical management of individual patients as well as institutional factors that teams felt were important in helping to deliver that care. However, the costs of treating diabetic ketoacidosis were not reported. METHODS: We used a 'bottom up' approach to cost analysis to determine the total expense associated with treating diabetic ketoacidosis in a mixed population sample. The data were derived from the source data from the national UK survey of 283 individual patients collected via questionnaires sent to hospitals across the country. RESULTS: Because the initial survey collection tool was not designed with a health economic model in mind, several assumptions were made when analysing the data. The mean and median time in hospital was 5.6 and 2.7 days respectively. Based on the individual patient data and using the Joint British Diabetes Societies Inpatient Care Group guidelines, the cost analysis shows that for this cohort, the average cost for an episode of diabetic ketoacidosis was £2064 per patient (95% confidence intervals: 1800, 2563). CONCLUSION: Despite relatively short stays in hospital, costs for managing episodes of diabetic ketoacidosis in adults were relatively high. Assumptions made in the calculations did not consider prolonged hospital stay due to comorbidities or costs incurred as a loss of productivity. Therefore, the actual costs to the healthcare system and society in general are likely to be substantially higher.

The prioritization preferences of pan-Canadian Oncology Drug Review members and the Canadian public: a stated-preferences comparison.

The pan-Canadian Oncology Drug Review (pcodr) is responsible for making coverage recommendations to provincial and territorial drug plans about cancer drugs. Within the pcodr process, small groups of experts (including public representatives) consider the characteristics of each drug and make a funding recommendation. It is important to understand how the values and preferences of those decision-makers compare with the values and preferences of the citizens on whose behalf they are acting. In the present study, stated preference methods were used to elicit prioritization preferences from a representative sample of the Canadian public and a small convenience sample of pcodr committee members. The results suggested that neither group sought strictly to maximize quality-adjusted life year (qaly) gains and that they were willing to sacrifice some efficiency to prioritize particular patient characteristics. Both groups had a significant aversion to prioritizing older patients, patients in good pre-treatment health, and patients in poor post-treatment health. Those results are reassuring, in that they suggest that pcodr decision-maker preferences are consistent with those of the Canadian public, but they also imply that, like the larger public, decision-makers might value health gains to some patients more or less highly than the same gains to others. The implicit nature of pcodr decision criteria means that the acceptability or limits of such differential valuations are unclear. Likewise, there is no guidance as to which potential equity factors-for example, age, initial severity, and so on-are legitimate and which are not. More explicit guidance could improve the consistency and transparency of pcodr recommendations.

Cost-effectiveness of febrile neutropenia prevention with primary versus secondary G-CSF prophylaxis for adjuvant chemotherapy in breast cancer: a systematic review.

The adoption of primary (PP) versus secondary prophylaxis (SP) of febrile neutropenia (FN), with granulocyte colony-stimulating factors (G-CSF), for adjuvant chemotherapy (AC) regimens in breast cancer (BC) could be affected by its "value for money". This systematic review examined (i) cost-effectiveness of PP versus SP, (ii) FN threshold at which PP is cost-effective including the guidelines 20 % threshold and (iii) potential impact of G-CSF efficacy assumptions on outcomes. The systematic review identified all cost-effectiveness/cost-utility analyses (CEA/CUA) involving PP versus SP G-CSF for AC in BC that met predefined inclusion/exclusion criteria. Five relevant CEA/CUA were identified. These CEA/CUA examined different AC regimens (TAC = 2; FEC-D = 1; TC = 2) and G-CSF formulations (filgrastim "F" = 4; pegfilgrastim "P" = 4) with varying baseline FN-risk (range 22-32 %), mortality (range 1.4-6.0 %) and utility (range 0.33-0.47). The potential G-CSF benefit, including FN risk reduction with P versus F, varied among models. Overall, relative to SP, PP was not associated with good value for money, as per commonly utilized CE thresholds, at the baseline FN rates examined, including the consensus 20 % FN threshold, in most of these studies. The value for money associated with PP versus SP was primarily dependent on G-CSF benefit assumptions including reduced FN mortality and improved BC survival. PP G-CSF for FN prevention in BC patients undergoing AC may not be a cost-effective strategy at the guidelines 20 % FN threshold.

Cost-utility of adjuvant zoledronic acid in patients with breast cancer and low estrogen levels.

BACKGROUND: Adjuvant zoledronic acid (za) appears to improve disease-free survival (dfs) in women with early-stage breast cancer and low levels of estrogen (lle) because of induced or natural menopause. Characterizing the cost-utility (cu) of this therapy could help to determine its role in clinical practice. METHODS: Using the perspective of the Canadian health care system, we examined the cu of adjuvant endocrine therapy with or without za in women with early-stage endocrine-sensitive breast cancer and lle. A Markov model was used to compute the cumulative costs in Canadian dollars and the quality-adjusted life-years (qalys) gained from each adjuvant strategy, discounted at a rate of 5% annually. The model incorporated the dfs and fracture benefits of adjuvant za. Probabilistic and one-way sensitivity analyses were conducted to examine key model parameters. RESULTS: Compared with a no-za strategy, adjuvant za in the induced and natural menopause groups was associated with, respectively, $7,825 and $7,789 in incremental costs and 0.46 and 0.34 in qaly gains for cu ratios of $17,007 and $23,093 per qaly gained. In one-way sensitivity analyses, the results were most sensitive to changes in the za dfs benefit. Probabilistic sensitivity analysis suggested a 100% probability of adjuvant za being a cost-effective strategy at a threshold of $100,000 per qaly gained. CONCLUSIONS: Based on available data, adjuvant za appears to be a cost-effective strategy in women with endocrine-sensitive breast cancer and lle, having cu ratios well below accepted thresholds.

Identification of patients with systemic lupus erythematosus in administrative healthcare databases.

OBJECTIVE: Our aim was to validate and compare decision rules for the identification of patients with systemic lupus erythematosus (SLE) in administrative healthcare databases. METHODS: A retrospective cohort study was performed using administrative health care data from a population of 1 million people with access to universal healthcare. Information was available on hospital discharges and physician billings over a 10-year period. Each SLE case was matched 4:1 by age and gender to randomly selected controls. Seven case definitions were applied to identify SLE cases and their performance compared with the diagnosis by a rheumatologist. RESULTS: We identified 373 SLE cases and 1492 non-SLE controls, all of whom had been reviewed by a rheumatologist. The overall accuracy of the case definitions for SLE cases varied between 88.2-95.6% with a kappa statistic between 0.53-0.86. The sensitivity varied from 41.0-86.6% and the specificity between 92.4-99.9%. In a total reference population of 1 million the mean estimated annual incidence of SLE was between 29-255 and the mean estimated annual prevalence was between 172-920. CONCLUSION: The accuracy of case definitions for the identification of SLE patients in administrative healthcare databases is variable and this should be considered when comparing results across studies. This variability may also be used to advantage in different study designs depending on the relative importance of sensitivity and specificity for identifying the population of interest to the research question.

Is adjuvant trastuzumab a cost-effective therapy for HER-2/neu-positive T1bN0 breast cancer?

BACKGROUND: In light of clinical uncertainty and the high acquisition costs of trastuzumab, we examined the value for money associated with concurrent or sequential trastuzumab in women with HER-2/neu-positive breast cancer with small node-negative tumours (T1bN0). MATERIALS AND METHODS: A probabilistic economic model was developed to estimate the likelihood of adjuvant trastuzumab meeting a $100 000 per quality-adjusted life year gained threshold over a range of 10-year recurrence risks by age. The primary analysis took an incremental approach, comparing trastuzumab plus chemotherapy with chemotherapy alone. A secondary analysis took an 'all-or-nothing' approach, comparing trastuzumab plus chemotherapy with neither treatment. RESULTS: The primary analysis suggested that concurrent trastuzumab plus adjuvant chemotherapy was likely to meet the $100 000 threshold at recurrence risks of 29-35%. Sequential trastuzumab was less likely to meet such a threshold. The secondary analysis was more favourable for both trastuzumab strategies, but of limited relevance as clinical benefits were predominantly driven by chemotherapy without trastuzumab. CONCLUSIONS: Concurrent trastuzumab plus adjuvant chemotherapy appears to offer favourable value for money at the upper ranges of baseline recurrence risks reported to date, although more precise estimates of underlying risk are required to confirm the cost-effectiveness of adjuvant trastuzumab in T1bN0 breast cancer.

The cost-utility of adjuvant chemotherapy using docetaxel and cyclophosphamide compared with doxorubicin and cyclophosphamide in breast cancer.

PURPOSE: The adoption of a chemotherapeutic regimen in oncologic practice is a function of both its clinical and its economic impacts on cancer management. For breast cancer, U.S. Oncology trial 9735 reported significant improvements in disease-free and overall survival favoring adjuvant tc (docetaxel 75 mg/m(2) and cyclophosphamide 600 mg/m(2) every 3 weeks for 4 cycles) compared with ac (doxorubicin 60 mg/ m(2) and cyclophosphamide 600 mg/m(2) every 3 weeks for 4 cycles). We carried out an economic evaluation to examine the cost-utility of adjuvant tc relative to ac, in terms of cost per quality-adjusted life year (qaly) gained, given the improved breast cancer outcomes and higher costs associated with the tc regimen. METHODS: A Markov model was developed to calculate the cumulative costs and qalys gained over a 10-year horizon for hypothetical cohorts of women with breast cancer treated with ac or with tc. Event rates, costs, and utilities were derived from the literature and local resources. Efficacy and adverse events were based on results reported from U.S. Oncology trial 9735. The model takes a third-party direct payer perspective and reports its results in 2008 Canadian dollars. Costs and benefits were both discounted at 3%. RESULTS: At a 10-year horizon, tc was associated with $3,960 incremental costs and a 0.24 qaly gain compared with ac, for a favorable cost-utility of $16,753 per qaly gained. Results were robust to model assumptions and input parameters. CONCLUSIONS: Relative to ac, tc is a cost-effective adjuvant chemotherapy regimen, with a cost-effectiveness ratio well below commonly applied thresholds.

Cost-utility analysis of proton pump inhibitors and other gastro-protective agents for prevention of gastrointestinal complications in elderly patients taking nonselective nonsteroidal anti-inflammatory agents.

BACKGROUND: The use of proton pump inhibitors (PPIs) among elderly patients using nonselective nonsteroidal anti-inflammatory drugs (nsNSAIDs) has increased; the price of PPIs is higher than that of majority of alternative treatment strategies. AIM: To evaluate the cost-effectiveness of nsNSAIDS + PPIs relative to alternative gastroprotective regimens in the prevention of GI complications among elderly patients (aged > or = 65 years). METHODS: An incremental cost-utility analysis, comparing PPIs with alternative gastroprotective regimens was conducted using a decision analytical model. Clinical outcomes, costs and utilities were derived from recently published studies. Probabilistic and deterministic sensitivity analyses were performed to test the robustness of the results to variation in model inputs and assumptions. RESULTS: The incremental cost-utility ratio (ICUR) of PPIs, relative to nsNSAID alone, was $206,315 per QALY gained or were more costly and less effective. Other co-prescribed treatment options had higher costs per QALY gained. In patients with a history of a complicated or uncomplicated ulcer, PPIs had ICURs of $24,277 and $40,876, respectively. CONCLUSIONS: Use of PPIs in all elderly patients taking nsNSAIDs is unlikely to represent an efficient use of finite healthcare resources. Co-prescribing PPIs, however, to elderly patients taking nsNSAIDs who have a history of complicated or uncomplicated ulcers appears to be economically attractive.

The cost burden of trastuzumab and bevacizumab therapy for solid tumours in Canada.

OBJECTIVE: Monoclonal antibodies (MAbs) such as trastuzumab and bevacizumab have become important yet expensive components of systemic cancer therapy across a variety of disease sites. We assessed the potential cost implications of adopting trastuzumab and bevacizumab therapy in the context of their potential utilization in breast, lung, and colorectal cancers. DESIGN: We first estimated MAb costs per patient and treatment indication and then included the MAb acquisition cost and the costs of medical resource utilizations required for therapy delivery. Drug costs were based on 2005 average Canadian wholesale prices, assuming full drug delivery and uncomplicated cycles. A direct-payer perspective was undertaken, and results are reported in Canadian dollars. Potential lifetime costs were then derived according to constructed schema, which account for absolute numbers of target patients and systemic therapy utilization. We subsequently estimated costs of MAb therapy relative to total costs of conventional management without MAb therapy. RESULTS: Trastuzumab costs $49,915 and $28,350 per patient treated in the adjuvant and metastatic breast cancer settings, respectively; bevacizumab costs $48,490 and $39,614 per patient treated in the metastatic lung and colorectal cancer settings, respectively. Potential lifetime absolute costs to Canada's health care system were approximately $127 million and $299 million for trastuzumab and bevacizumab respectively, corresponding to an average increase in health care expenditure of approximately 19% for breast cancer and 21% for lung and colorectal cancer over conventional management without MAbs. CONCLUSIONS: Novel Mab-based therapies such as trastuzumab and bevacizumab will likely add a significant cost burden to Canada's publicly funded health care system.

How effective are disease-modifying drugs in delaying progression in relapsing-onset MS?

OBJECTIVE: Our objective was to estimate the effectiveness of disease-modifying drugs (DMDs) in delaying multiple sclerosis (MS) disability progression in relapsing-onset (R-onset) definite MS patients under "real-world" conditions. METHODS: Treatment effect size, for DMDs as a class, was estimated in absolute terms and relative to MS natural history. A basic model estimated annual Expanded Disability Status Scale (EDSS) change before and after treatment. An expanded model estimated annual EDSS change in pretreatment years, treatment years on first drug, treatment years after drugs were switched, and in years after treatment stopped. Models were populated with 1980 through 2004 clinical data, including 1988 through 2004 data for all Nova Scotians treated with DMDs. Estimates were made for relapsing-remitting MS (RRMS), secondary progressive MS (SPMS), and R-onset groups. RESULTS: Estimated pretreatment annual EDSS increases were approximately 0.10 of one EDSS point for the RRMS group, 0.31 for the SPMS group, and 0.16 for the R-onset group. Estimates of EDSS increase avoided per treatment year on the first drug were significant for the RRMS group (-0.103, 0.000), the SPMS group (-0.065, 0.011), and the R-onset group (-0.162, 0.000); relative effect size estimates were 112%, 21%, and 105%. Estimated EDSS progression was faster in years after drug switches and treatment stops. CONCLUSIONS: Our estimates of disease-modifying drug (DMD) relative treatment effect size, in the context of "real-world" clinical practice, are similar to DMD treatment efficacy estimates in pivotal trials, though our findings attained statistical significance. DMDs, as a class, are effective in delaying Expanded Disability Status Scale progression in patients with relapsing-onset definite multiple sclerosis (MS) (90%), although effectiveness is much better for relapsing-remitting MS than for secondary progressive MS groups.

Cost-utility of adjuvant hormone therapies with aromatase inhibitors in post-menopausal women with breast cancer: upfront anastrozole, sequential tamoxifen-exemestane and extended tamoxifen-letrozole.

This evaluation adapts a previous Canadian analysis of upfront and sequential adjuvant AI strategies in postmenopausal women with breast cancer to a Belgian perspective and includes an extended aromatase inhibitor (AI) strategy. A Markov model calculated monthly costs and outcomes in a hypothetical cohort of postmenopausal women with early-stage breast cancer. Baseline event rates and hazard ratios were derived from the Arimidex, Tamoxifen Alone or in Combination trial, International Exemestane Study and MA.17 trials. The analysis took a Belgian healthcare payer perspective with a 20-year time horizon. Costs and outcomes were discounted by 3%. Costs are in 2005 Euros. The cost-utility of all three strategies was favourable (<30,000 euros per QALY gained). Based on indirect comparisons using tamoxifen (TAM) alone as a common comparator, sequential TAM-AI was less costly and more effective than upfront or extended strategies. All three AI strategies were cost-effective alternatives to TAM alone, but sequential TAM-AI appears to be the economically preferred strategy.

Cost-utility of adjuvant hormone therapies for breast cancer in post-menopausal women: sequential tamoxifen-exemestane and upfront anastrozole.

BACKGROUND: Adjuvant Anastrozole (ANA) for 5 years and Tamoxifen followed by Exemestane (TAM-EXE) for 2.5 years each have become acceptable alternatives to 5 years of Tamoxifen (TAM) for post-menopausal women with breast cancer. As these newer options are associated with higher drug costs as well as improved outcomes, an economic evaluation was undertaken to compare the cost-utility of ANA and TAM-EXE relative to TAM alone and to each other in terms of cost per quality-adjusted life year (QALY) gained. METHODS: A Markov model was developed to calculate monthly costs and outcomes in a hypothetical cohort of post-menopausal women with early-stage breast cancer. Baseline rates of cancer recurrence and adverse effects with TAM, and hazard ratios associated with ANA and EXE, were derived from the ATAC and IES trials. Patients received hormonal therapy for 5 years and benefit was modeled to persist 5 years beyond treatment. The analysis took a direct payer perspective with a 20-year time horizon. Costs and outcomes were discounted by 3%. Costs are in 2005 Canadian dollars. RESULTS: ANA and TAM-EXE were associated with increased costs and QALYs, though the cost-utility of both relative to TAM alone was strongly favourable (<$50,000/QALY). Based on an indirect comparison of ANA and TAM-EXE, using TAM alone as a common comparator, the cost-utility of ANA relative to TAM-EXE appears unfavourable. CONCLUSIONS: Both upfront and sequential AI options were cost-effective alternatives to TAM alone, but TAM-EXE appears to be the economically preferred AI option based on its more favourable cost-utility versus ANA.

Modeling for cost-effective-adjuvant aromatase inhibitor strategies for postmenopausal women with breast cancer.

BACKGROUND: To determine cost-effective (CE) strategies comparing adjuvant upfront aromatase inhibitor (AI) with sequential tamoxifen (TAM) AI in postmenopausal (PM) women with breast cancer (BC). DESIGN: A Markov model was constructed to calculate cumulative costs and quality-adjusted life year (QALY) gains for upfront AI and TAM-AI in a hypothetical cohort of 60-year-old PM women with BC. Costs, utilities and probabilities were derived from the literature. The hazard ratios (HRs) of AI strategies were applied to a baseline cancer recurrence risk (RR) to determine CE strategies at the $50,000/QALY gain threshold. A direct payer perspective is utilized, and costs and benefits were discounted at 3%. RESULTS: Two-way sensitivity analyses are presented to determine CE strategies across a wide range of HRs and in different clinical scenarios including varying RRs (low, average, high and very high). TAM-AI is the preferred CE strategy at low and average RR, while upfront AI is CE at very high RR. The CE strategy in patients with high RR was dependent on the scenario examined. CONCLUSIONS: This model may help health care providers select CE-adjuvant AI strategies in PM women with BC, until further direct evidence is available from randomized clinical trials.

Cost-effectiveness of interferon beta-1b in slowing multiple sclerosis disability progression. First estimates.

OBJECTIVE: To estimate the cost-effectiveness (CE) of interferon beta-1b (IFN beta-1b) in slowing disability progression in persons with relapsing-remitting multiple sclerosis (RRMS). METHODS: Treatment program costs and health outcomes are modeled for cohorts of 1,000 females and 1,000 males followed 40 years from onset. Fifteen scenarios model MS natural history progression, treatment efficacy, direct treatment costs, and MS healthcare costs. A single randomized placebo-controlled trial of IFN beta-1b found reduced disease activity by MRI, reduced frequency and severity of exacerbations, and a tendency toward slower disability progression. Disability years avoided are modeled as the primary health outcome analyzed. A ministry of health (MOH) perspective is adopted, using Nova Scotia population-based data. Annual IFN beta-1b direct treatment costs (Can $16,685) are high relative to both MOH healthcare costs per person with MS (Can $2,000) and estimated MOH costs avoided. RESULTS: Given "reference case" assumptions for women with RRMS, treatment reduces lifetime disability years by 10%. Cost per disability year avoided before discounting is Can $189,230 (US $124,892), and Can $274,842 (US $181,395) after discounting at 5%. Estimates for alternative scenarios vary greatly, leaving main findings unchanged. CONCLUSIONS: Using the Expanded Disability Status Scale, cost per disability year avoided due to interferon beta-1b treatment in RRMS is quite high. Comparable CE estimates, using MS-specific or generic health-related quality-of-life outcome measures, are even higher. Further research is required to better measure treatment effects, modification of MS natural history, and net societal costs of IFN beta-1b in RRMS.

Hospital-based psychiatric service utilization and morbidity in multiple sclerosis.

BACKGROUND: Despite the common association of psychiatric morbidity and multiple sclerosis (MS), population-based prevalence estimates of these disorders are limited. Such estimates are of particular importance to those conducting trials of interventions for the treatment of MS. This study examined the prevalence of bipolar disorder, depression, and attempted suicide among hospital service utilizers in Nova Scotia and compared these measures for the MS and non-MS population. METHODS: Data regarding diagnosis and utilization were extracted from two linked databases which included all hospital separation records for Nova Scotia over a 3 year period (1992/93-1994/95). RESULTS: The prevalence of bipolar disorder in hospitalized MS patients was 1.97% and depression was 4.27%. These rates were significantly higher than the 0.92% and 2.04%, respectively, for the non-MS hospital utilizers. These diagnoses also accounted for more than half of the primary diagnostic codes for psychiatric service separations by MS patients. The proportion of total hospital utilization which was accounted for by psychiatric services did not differ between MS and non-MS utilizers. While suicide attempts were rare, the estimated frequency of suicide attempts in the total MS population was more than three times that of the general population. CONCLUSIONS: Bipolar disorder and depression were twice as prevalent in hospitalized MS patients as in the general population of hospital utilizers while the estimated frequency of suicide attempts was at least three times greater. These results illustrate that psychiatric morbidity and service utilization are important considerations in the care of MS patients.