Use and cost of hospital and community service provision for children with HIV infection at an English HIV referral centre

OBJECTIVE: To describe the use of hospital and community services for children infected with HIV and estimate the cost per patient-year by stage of HIV infection during the era of antiretroviral monotherapy. DESIGN: Data on the use of hospital services were collected from case notes; the use of statutory and nonstatutory community services was recorded through diaries and interviews. Total cost estimates were calculated from unit costs from relevant hospital departments and community organisations. SETTING: Children managed at St. Mary's Hospital (London, England) between 1 January 1986 and 31 December 1994, some of whom used statutory and nonstatutory community services in South East England between 1 November 1994 and 31 May 1996. PATIENTS AND PARTICIPANTS: 118 children with positive HIV antibody status. MAIN OUTCOME MEASURES AND RESULTS: Mean inpatient days, outpatient visits, tests and procedures performed, drugs prescribed, community services used, associated unit costs and average cost estimates per patient-year by stage of HIV infection (1995/1996 values), and lifetime costs. Service provision during the study period was predominantly hospital-based. The use of services increased for different stages of HIV infection and increased with increasing severity of HIV infection. A shift from an inpatient-based to an outpatient-based service was seen between the periods 1986 to 1991 and 1992 to 1994. As symptoms evolved, children used more hospital inpatient services, with an accompanying shift in the use of community services from general services, such as schooling, to increased use of nurses, social care and home help. The estimated total cost of hospital and community care was 18,600 Pounds per symptomatic non-AIDS patient per year and 46,600 Pounds per AIDS patient per year. Similar estimates for children with indeterminate HIV infection and asymptomatic infection amounted to 8300 Pounds and 4800 Pounds per patient-year, respectively. Nondiscounted lifetime costs for hospital care amounted to 152,400 Pounds (44,300 Pounds to 266,800 Pounds) compared with discounted lifetime costs of 122,700 Pounds (42,000 Pounds to 182,200 Pounds); nondiscounted lifetime costs for community care amounted to 24,300 Pounds (7900 Pounds to 41,600 Pounds) compared with discounted lifetime costs of 21,000 Pounds (6800 Pounds to 32,000 Pounds). CONCLUSIONS: The continued emphasis on the use of hospital services may be due to the small number of children infected with HIV, most of whom lived in the London metropolitan area where specialist care was concentrated in a few centres. A shift from an inpatient- to an outpatient-based service was observed over time; the advent of the use of combination antiretroviral therapy in this population may further facilitate a shift in service provision and promote shared care between specialist centres, local hospital and community-based services.     

Cost-effectiveness analysis of inhaled zanamivir in the treatment of influenza A and B in high-risk patients

OBJECTIVE: To evaluate the cost effectiveness of zanamivir 10 mg twice daily for 5 days in the treatment of influenza in high-risk patients. DESIGN: Bootstrap cost-effectiveness analysis incorporating within-trial analysis of pooled patient-level cost and effect data. SETTING: UK unit costs and utilities applied to high-risk patients drawn from 6 multinational clinical trials. PATIENTS: A total of 154 zanamivir and 167 placebo high-risk patients were included in the analysis. MAIN OUTCOME MEASURES: Cost per day of normal activities; cost per symptom-free day; cost per complication averted; cost per quality-adjusted life-year (QALY). RESULTS: The mean benefit was estimated to be 2.5 days [95% confidence interval (CI): 0.68 to 4.27] of normal activities gained; 2.0 (95% CI: 0.56 to 3.51) symptom-free days; and a 9% reduction in complications (95% CI: 0 to 18%). Excluding the effect of rare hospitalisation costs, the cost (1999 values) of gaining a day of normal activities was 9.50 Pounds (95% CI: 5 Pounds to 39 Pounds); cost per symptom-free day was 11.56 Pounds (95% CI: 6 Pounds to 43 Pounds); cost per complication averted was 262 Pounds (95% CI: 90 Pounds to 1574 Pounds). Influenza was estimated to reduce utility by 0.883 per day, demonstrating the debilitating effect of the disease. Extrapolating a day of normal activities to a standard utility measure resulted in a cost per QALY of 3900 Pounds excluding inpatient costs (7490 Pounds including inpatient costs). Cost-effectiveness acceptability curves demonstrated 90% certainty that zanamivir would be cost effective at 8000 Pounds per QALY. CONCLUSIONS: Significant health benefits can be obtained with zanamivir treatment in high-risk patients. The cost per QALY for zanamivir in these patients compares well with that of other commonly used pharmacological interventions.     

Modelling the cost effectiveness of lamivudine/zidovudine combination therapy in HIV infection

The use of combination antiretroviral therapy is supported by clinical evidence for its superiority over monotherapy. Lamivudine (3TC) has been studied in combination with zidovudine (ZDV) and is recommended for use specifically in combination therapy. With the associated increase in drug acquisition cost, the economics of combination therapy versus monotherapy warrant study. An economic evaluation was undertaken to compare 3TC/ZDV combination therapy with ZDV monotherapy, taking a UK public finance perspective. The cost effectiveness of each of the 2 treatments was estimated using a Markov model of progression through 3 HIV-positive disease states: (i) CD4 cells > 200 and < 500 cells/mm3; (ii) CD4 < 200 cells/mm3, non-AIDS; and (iii) AIDS to eventual death. Progression probabilities and life expectancy were derived from a cohort treated at Chelsea and Westminster Hospital in London, using data for 1987 to 1995, along with cost data for a ZDV intent-to-treat population for 1994 and 1995. The relative risk of progression for 3TC/ZDV compared with ZDV monotherapy was estimated from meta-analysis of 4 completed comparative trials. To predict the effect of 3TC/ZDV on life expectancy and lifetime costs, progression probabilities were adjusted by the relative risk statistic for the duration of treatment with 3TC/ZDV. On the basis of an estimated relative risk of progression of 0.509 (95% CI 0.365 to 0.710), treatment with 3TC/ZDV is predicted to yield an incremental cost-effectiveness ratio of Pounds 6276 (95% CI Pounds 5337 to Pounds 9075) per life year saved (discounted at 6% per year). Extensive sensitivity analyses were performed to test the effects of varying values of input parameters on the model results. Under reasonable assumptions, the predicted cost effectiveness of 3TC/ZDV combination therapy compares favourably with previously reported economic analyses of various HIV treatments.     

Costs associated with symptomatic systolic heart failure

OBJECTIVE: To investigate whether the extent of systolic dysfunction is a useful predictor of the costs of healthcare and social support for patients with heart failure. DESIGN: Cross-sectional study with collection of cost data attributed to management of heart failure in the previous year. SETTING: Four primary-care practices in Scotland. PATIENTS: Patients receiving long term therapy with loop diuretics for suspected heart failure. INTERVENTIONS: Two-dimensional and Doppler echocardiography. MAIN OUTCOME MEASURES AND RESULTS: Two hypotheses were tested: (i) the proportion of patients incurring costs is higher in patients with abnormal left ventricular (LV) function; and (ii) the median cost per patient that incurs costs is higher in patients with abnormal LV function. Of the 226 patients in the study, 67 (30%) had abnormal systolic function. In comparison with the remaining 159 patients, they had higher healthcare costs [560 Pounds vs 440 Pounds per patient year (1994/1995 values)], were more likely to incur hospital inpatient or outpatient costs [Odds ratio (OR): 2.02; 95% confidence interval (CI): 1.06 to 3.84] and had significantly higher primary-care costs (mean 292 Pounds vs 231 Pounds per patient year; p = 0.02, Mann Whitney test). In contrast, they were no more likely to incur social support costs (OR: 1.22; 95% CI: 0.52 to 2.86) and the mean cost of social support per patient year was lower (234 Pounds vs 373 Pounds). CONCLUSIONS: Patients with objectively measured systolic dysfunction incurred significantly higher healthcare costs in the year before diagnosis. This suggests that treatment that improves systolic function will reduce healthcare costs, even in a primary-care population with relatively mild congestive heart failure.     

The cost of HIV treatment and care. A global review

This review of published studies on the costs of HIV treatment and care describes some of the recent developments that have influenced these costs in industrialised and industrialising countries, especially within the context of changing drug treatments. Some of the different approaches to estimating the economic impact of HIV infection are briefly presented. The methods used to review the literature are described, particularly the criteria of a scoring system that was specifically developed to systematically screen some of the studies identified. The mean review score for studies dealing with direct hospital costs increased significantly (p = 0.003) over the 3 periods analysed (before 1987, 1987 to 1995, and 1996 and beyond), indicating that the overall 'quality' of studies increased over time. All cost estimates, other than those from non-industrialised regions, were converted to 1996 US dollars using country-specific total health expenditure inflaters and country-specific Gross Domestic Product Purchasing Power Parity converters. A summary of hospital cost estimates over time and by region demonstrated that the costs of treating asymptomatic individuals and people with symptomatic non-AIDS increased over the period, but that the costs of treating individuals with AIDS appears to have stabilised since the late 1980s. As fewer studies could be identified on the costs of community and informal care, indirect productivity costs and population cost estimates, and costs of care for children with HIV infection, all of these studies were reviewed without the use of the scoring system. Finally, the discussion explores the evidence on the global costs of HIV in non-industrialised economies and the affordability of HIV treatment and care. Some suggestions for the direction of future HIV costing studies are also presented. A need remains for good quality cost data. Adequate research effort should be directed to improving the scope and quality of information on costs of HIV service provision around the world.     

Cost of schizophrenia to UK Society. An incidence-based cost-of-illness model for the first 5 years following diagnosis.

OBJECTIVE: This study estimated the cost to UK society of an annual cohort of newly diagnosed patients with schizophrenia over the first 5 years following diagnosis, using an incidence-based cost-of-illness framework. DESIGN AND SETTING: A discrete event model of the course of schizophrenia was constructed, based on a literature review and interviews among a panel of healthcare professionals (n = 7). Seven discrete disease states were defined within the model. Patients' movements between these disease states enabled 10 disease courses to be identified. In each disease state, the model estimated resource use and corresponding costs borne by the National Health Service (NHS), Local Authorities, the Home Office and society as a result of lost productivity. PATIENTS AND PARTICIPANTS: The model simulated patients' movements between disease states over the first 5 years following diagnosis. Since there are 7500 new cases of schizophrenia per year in the UK, the model was run for 7500 patient simulations. MAIN OUTCOME MEASURES AND RESULTS: The total discounted cost to society attributable to an annual cohort of newly-diagnosed patients with schizophrenia over the first 5 years following diagnosis was estimated at 862 million Pounds (range: 788 million Pounds to 926 million Pounds in sensitivity analysis). The discounted mean 5-year cost was estimated to be approximately 115,000 Pounds (range: 105,000 Pounds to 124,000 Pounds) per patient or approximately 23,000 Pounds (range: 21,000 Pounds to 25,000 Pounds) per patient per year. The NHS accounted for 38% of the total cost, Local Authorities for 12% and the Home Office for 1%. Indirect costs due to lost productivity accounted for 49%. Of the NHS costs, hospital admissions accounted for 69% and hospital visits (outpatient, day ward and day centre attendances) for a further 26%. Drugs (antipsychotics and adjunctive medications) accounted for 2%. CONCLUSIONS: NHS expenditure and lost productivity costs predominated, irrespective of disease course. This indicates that treatments that reduce hospitalisation and potentially enable patients to return to active employment could significantly reduce the societal burden of schizophrenia.     

Cost-effectiveness model of cytomegalovirus management strategies in renal transplantation. Comparing valaciclovir prophylaxis with current practice

BACKGROUND: Cytomegalovirus (CMV) disease may occur following renal transplantation and has been shown to have health and cost consequences in this setting. OBJECTIVE: To compare the cost effectiveness of different CMV management strategies for renal transplant patients: prophylaxis with (i) oral valaciclovir or (ii) intravenous ganciclovir; viral testing for CMV followed by (iii) pre-emptive therapy with intravenous ganciclovir or (iv) adjustment of immunosuppression and intensive monitoring; or (v) waiting to treat when CMV disease develops. METHODS: A decision-tree model was constructed that included the different management strategies for the donor seropositive/recipient seronegative (D+R-) population. Clinical outcomes for the D+R- population came from clinical trials. Treatment algorithms and costs for CMV syndrome and tissue invasive disease were developed from published literature and UK physician interviews. One- and 2-way sensitivity analyses were performed. STUDY PERSPECTIVE: UK National Health Service. RESULTS: Prophylaxis with either oral valaciclovir or intravenous ganciclovir dominated (lower costs and fewer cases of CMV disease) the pre-emptive treatment and wait-and-treat strategies. The cost per patient was from 157 Pounds to 438 Pounds higher with oral valaciclovir prophylaxis compared with intravenous ganciclovir prophylaxis and the incremental cost per case of CMV disease avoided with valaciclovir prophylaxis ranged from 2243 Pounds to 8111 Pounds (1996 values). These results are sensitive to the efficacy of intravenous ganciclovir prophylaxis and CMV management costs. CONCLUSIONS: For D+R- renal transplant patients, prophylaxis is the dominant (more effective and less costly) management strategy compared with pre-emptive and wait-and-treat strategies. The cost per patient with oral valaciclovir prophylaxis compared with intravenous ganciclovir prophylaxis is slightly higher in our base case scenario, but may be lower under reasonable alternative assumptions.     

The economic impact of Parkinson's disease. An estimation based on a 3-month prospective analysis

OBJECTIVE: This study prospectively assesses the medical costs of Parkinson's disease (PD). DESIGN: Over a period of 3 months (from July to September 1995), patients with PD documented all items of healthcare provision. These data were then used to calculate medical costs for an individual patient as well as the costs of PD. PATIENTS AND SETTING: We included 20 outpatients with idiopathic PD from the neurological outpatient clinic, Klinikum Grosshadern, Munich, and 20 patients from two office-based neurologists in South-West Germany. MAIN RESULTS: The mean 3-month medical cost of PD in 1995 deutschmarks (DM) was 5210 ($US3390, 2240 Pounds) consisting of DM1410 ($US920, 610 Pounds) for care and nursing, DM1580 ($US1030, 680 Pounds) for drug therapy, DM1320 ($US860, 570 Pounds) for inpatient hospital care, DM40 ($US26, 17 Pounds) for outpatient care and DM860 for other expenses ($US560, 370 Pounds). The expenditure was related to the disease evolution. Patients complaining of one-sided symptoms [Hoehn and Yahr stage I; (HY I)] were less expensive to treat (DM1930, $US1250, 830 Pounds) than patients who were severely incapacitated (HY V) [DM9740, $US6330, 4200 Pounds; HY V]. After 3 to 5 years of levodopa treatment approximately 50% of patients start to experience fluctuations in motor ability and dyskinesias [Unified Parkinson's disease rating scale, part IV (UPDRS IV)]. This onset of motor complications parallels an increase in costs. For patients who experienced motor fluctuations, annual costs were DM6550 ($US4260, 2820 Pounds) compared with DM3030 ($US1960, 1300 Pounds) for patients lacking this problem. Indirect non-medical costs were not calculated due to the limited number of patients. The impact of the disease on work, however, is clearly apparent from the patients' history: 19 out of 34 patients who had already stopped working attributed this to the disease, and only 6 patients were still working at the time of the survey. CONCLUSION: PD poses a major financial impact to society which is expected to increase in future years as the age distribution shifts to older age groups. On the basis of a prevalence of PD of 183 per 100,000, we calculated an annual expenditure of DM3.0 billion for the direct medical costs of PD in Germany.     

Costs incurred by patients undergoing advanced colorectal cancer therapy. A comparison of raltitrexed and fluorouracil plus folinic acid

BACKGROUND: To assess the cost effectiveness of healthcare interventions from a societal perspective, it is necessary to include costs such as patients' travel costs and the opportunity cost of patients' time spent consuming healthcare. OBJECTIVE: To analyse patients' travel and time costs associated with 2 alternative drug therapies for advanced colorectal cancer: raltitrexed and fluorouracil plus folinic acid (leucovorin) [5FU + FA]. DESIGN AND SETTING: The analysis is based on a prospective substudy within a multinational randomised controlled trial of raltitrexed versus 5FU + FA. PATIENTS AND PARTICIPANTS: 495 patients with advanced colorectal cancer were enrolled in the trial, 270 of whom completed the questionnaire on costs. METHODS: Data were collected within the trial to estimate the numbers of journeys made to and from hospital by patients and the time lost from usual activities over the period of therapy. A subset of patients were asked to complete a questionnaire to provide the information necessary to value time and travel costs in monetary terms. These data, together with UK transport costs and forgone time values, were used to value the transport and opportunity costs of time of all patients in the trial. RESULTS: The total travel cost per patient was statistically significantly higher in the 5FU + FA group (p < 0.001; median of 31.50 Pounds with raltitrexed, 96.00 Pounds with 5FU + FA; 1997 prices). Overall time cost per patient was also higher in the 5FU + FA group (p = 0.005; median of 168.80 Pounds with raltitrexed, 224.04 Pounds with 5FU + FA). Adding the two gives a median total cost per patient of 206.08 Pounds [interquartile range (IQR) 108 Pounds to 482 Pounds] among patients randomised to raltitrexed and 342.25 Pounds (IQR 214 Pounds to 555 Pounds) for those in the 5FU + FA group (p < 0.001). The sensitivity analysis showed that, even under extreme assumptions, raltitrexed imposed fewer time and travel costs on patients. These cost differences are likely, in part, to reflect the longer treatment times for 5FU + FA patients (median 16.9 vs 12.7 weeks). CONCLUSIONS: Different chemotherapy regimens for advanced colorectal cancer can impose different travel and time costs on patients. Over the period of treatment in a randomised controlled trial of 495 patients, those randomised to 5FU + FA were found to have a median travel plus time cost 136 Pounds per patient higher than those randomised to raltitrexed.     

A model to compute the medical cost of patients in intensive care.

OBJECTIVE: Our objective was to identify, among the information routinely collected on patients in intensive care units (ICUs), data that determine the total cost for a given patient. DESIGN: We developed a model that could help physicians in medical ICUs to estimate the cost of care for their patients when no cost data were available at the individual patient level. SETTING: A Medical ICU. PATIENTS AND PARTICIPANTS: The model was developed using a random sample of 73 patients admitted to the medical ICU in 1996 and 1997, validated by another random sample of 29 patients admitted during the same period. INTERVENTIONS: The actual medical variable cost per patient was computed from data on the total resources used (excluding personnel and fixed costs), collected from the patients' records plus pharmacy, laboratory and blood bank logs. The explanatory variables tested were: length of stay, nursing workload, severity of condition, and procedures recorded by a score [omega (omega)] including 3 components related to the frequency of procedure use. The model was constructed in a stepwise fashion, assuming a linear relation. Equations were tested on the basis of the residual mean square; criteria for inclusion and elimination of variables were the level of its partial regression coefficient and medical criteria. The model was validated by analysis of variance of the regression on a second population of 29 patients using the F-test. MAIN OUTCOME MEASURES AND RESULTS: The median length of stay was 7 days (range: 3 to 22 days). Mortality rate was 25%. Median medical variable cost was 805 Pounds (mean medical variable cost was 1738 Pounds, total cost was 6279 Pounds). The variables selected in the multiple regression model as relevant predictors of medical costs were: procedures recorded only once during the ICU stay irrespective of their reiteration (omega 1), procedures recorded every time they are performed (omega 2), procedures recorded daily in the ICU (omega 3) and the presence or absence of an invasive procedure (Kc). The final equation, calibrated with r2 of 0.826 and p > 0.0001, was: medical cost (Pounds) = 23 omega 1 + 53 omega 2 + 8 omega 3 + 2352Kc + 96. The validation with the other sample of 29 patients compared actual to predicted costs. Analysis of variance of the regression from the model was r2 = 0.596 (p > 0.05). CONCLUSIONS: Our standardised cost model is a possible approach to allow comparison of medical costs within and between ICUs.     

Cost effectiveness of letrozole in the treatment of advanced breast cancer in postmenopausal women in the UK

OBJECTIVE: To simulate the treatment of postmenopausal women with advanced breast cancer from second-line hormone therapy to death, and to generate estimates of the cost and effectiveness of letrozole and megestrol in order to determine the incremental cost effectiveness of letrozole, expressed as cost per life-years gained. DESIGN: A decision-analytic model, using Markov process techniques, was designed to evaluate the lifetime clinical and economic consequences of treatment with letrozole compared with standard care with megestrol. The model was based on clinical trial results showing a clear advantage of letrozole in terms of time to progression and duration of response. SETTING: The setting of the study was that of the UK healthcare system in 1996. PATIENTS AND PARTICIPANTS: A hypothetical cohort of patients, identical to the patients recruited for the AR/BC2 clinical trial, who were postmenopausal women with advanced breast cancer who had previously failed to respond to first-line or adjuvant anti-estrogen therapy. INTERVENTIONS: The dosages of medications were 2.5 and 160 mg/day for letrozole and megestrol, respectively. The analysis covered the period from treatment initiation until death (lifetime model). Effectiveness was expressed as survival and time without progression, and the model also included all relevant economic measures. MAIN OUTCOME MEASURES AND RESULTS: Based on the model, the average survival time of the letrozole group was 2.1 years (25.3 months) versus 1.9 years (21.5 months) for the megestrol group, a gain in survival of 2.4 months (10.5%). The average time without progression, cumulatively calculated over the different treatment options, amounted to 20.2 months for letrozole and 17.8 months for megestrol, an increase of 13.7% for the former patients. The total average cost per patient for the treatment of advanced breast cancer starting from second-line hormone therapy until death was higher in the letrozole group at 7547 Pounds versus 6820 Pounds for the megestrol group (discounted at an annual rate of 5%), leading to an incremental cost-effectiveness ratio of 3588 Pounds per life-year gained (1996 values). CONCLUSIONS: Based on the assumptions used in this model, letrozole offers a suitable alternative to megestrol in the treatment of second-line hormone therapy.     

HIV prevalence and correlates of receptive needle sharing among injection drug users in the Mexican-U.s. border city of Tijuana

Injection drug use is a growing but understudied problem in Tijuana, a city situated on the northwestern Mexico-U.S border. The authors studied factors associated with receptive needle sharing in an effort to inform prevention activities. In 2003, street-recruited injection drug users (IDUs) in Tijuana underwent interviews on injection risk behaviors and rapid HIV antibody tests. Logistic regression was used to identify correlates of receptive needle sharing at the last injection episode. Of 402 IDUs, 87.6% were male; the median age was 34. HIV prevalence was 4.01% (95% CI: 2.29-6.51). One third reported receptive needle sharing at last injection. Factors independently associated with receptive needle sharing were years living in Tijuana (Adjusted Odds Ratio [AdjOR]= 0.97 per year, 95% CI: 0.96-0.99), being bisexual/homosexual (AdjOR=2.12; 95% CI: 1.30 - 3.44), unemployed (AdjOR=2.5; 95% CI: 1.52-4.10), never having an HIV test (AOR: 4.02; 95% CI: 2.44-6.60), having friends who placed importance on avoiding HIV (AdjOR: 0.36; 95% CI: 0.19-0.68) and last injecting in a shooting gallery (AdjOR=1.98; 95% CI: 1.21-3.24). These results underscore the need to increase access to voluntary HIV testing and counseling to IDUs and migrants in Tijuana, as well as expand access to sterile syringes in an effort to avert widespread HIV transmission.     

Economic analysis of long-term reversible contraceptives. Focus on Implanon

OBJECTIVE: To examine the economic impact of a new implantable contraceptive, Implanon, in comparison with other available contraceptive methods. DESIGN: This was a modelling study using cost data derived from national published sources and effectiveness data from either controlled clinical trials (Implanon) or reports in the literature (other contraceptives). In the baseline analysis, Implanon was compared with 2 long term reversible contraceptives, Norplant and Mirena. Further analyses were then carried out comparing Implanon with Depo-Provera and with combined oral contraceptives. SETTING: The study concentrated on the UK, but also made reference to several other European countries. MAIN OUTCOME MEASURES AND RESULTS: The baseline analysis showed that all 3 long term reversible contraceptives produce very good rates of return, with Implanon providing the best rate of return (both average and internal) of the 3 methods. The payback period for Implanon was calculated as 146 days, compared with 339 and 368 days for Norplant and Mirena, respectively. In terms of cost effectiveness, the cost per protected year for Implanon was 95 Pounds, compared with 146 Pounds and 168 Pounds for Norplant and Mirena, respectively. In comparison with Depo-Provera (an injectable contraceptive), Implanon was both less costly and more effective, the cost per protected year for Depo-Provera being 131 Pounds. The threshold beyond which Implanon delivers cost savings compared with combined oral contraceptives was at a failure rate of 4.9% for the combined pill. CONCLUSIONS: Reversible long term approaches to contraception provide an effective and efficient use of healthcare resources and generate an excellent return on public investment. Implanon produces better rates of return than both Norplant and Mirena, and is also more cost effective in terms of cost per pregnancy avoided and cost per protected year than Norplant, Mirena, Depo-Provera and oral contraceptives.     

Cost analysis of the treatment of schizophrenia in the UK. A simulation model comparing olanzapine, risperidone and haloperidol

OBJECTIVE: To compare the costs of 2 atypical drug therapies (olanzapine and risperidone) with one another and with a conventional antipsychotic (haloperidol) in the treatment of schizophrenia. DESIGN AND SETTING: The analysis is based on a simulation model with parameter values taken mainly from clinical trial data in patients with schizophrenia, and was conducted within a UK context. RESULTS: The 3 therapies are approximately cost neutral over a 5-year period (olanzapine 35,701 Pounds, risperidone 36,590 Pounds and haloperidol 36,653 Pounds). There is evidence of greater efficacy with the atypical drugs [average percentage of 5 years with Brief Psychiatric Rating Scale (BPRS) scores < 18: olanzapine 63.6%, risperidone 63.0% and haloperidol 52.2%]. The cost and efficacy differences between the 2 atypical drugs are too small to rank them in terms of cost effectiveness. Extensive sensitivity analysis does not change any of the main conclusions. CONCLUSIONS: Given evidence of efficacy gains to the atypical drugs, these represent cost-effective treatment options. Prospective data from nontrial treatment settings would help substantiate the model findings.     

Economics of the antithymocyte globulins Thymoglobulin and Atgam in the treatment of acute renal transplant rejection

OBJECTIVE: To evaluate the economic implications for transplant centres, Medicare and society of treatment of corticosteroid-resistant Banff Grades I, II and III acute kidney transplant rejection with the antithymocyte globulins Thymoglobulin or Atgam. DESIGN AND SETTING: This was a cost analysis of a randomised double-blind multicentre clinical trial comparing the safety and efficacy of Thymoglobulin and Atgam that was performed at 25 centres in the US in 1994 to 1996. PATIENTS AND PARTICIPANTS: The study enrolled 163 patients, 82 in the Thymoglobulin arm and 81 in the Atgam arm. METHODS: Estimates of the cost of care from the initiation of rejection therapy to 90 days post-therapy were derived from various publicly available sources and applied to patient-specific clinical events documented in the clinical trial. Patients received either intravenous Thymoglobulin (1.5 mg/kg/day) for an average of 10 days or intravenous Atgam (15 mg/kg/day) for an average of 9.7 days. RESULTS: On average, Thymoglobulin provided significant cost savings compared with Atgam from the perspective of society [$US5977 (1996 values); 95% confidence interval (CI) $US3719 to $US8254], Medicare ($US4967; 95% CI $US3256 to $US6678) and the transplant centre ($US3087; 95% CI $US1512 to $US4667). The overall advantage attributable to Thymoglobulin was primarily due to savings from fewer recurrent rejection treatments and less frequent return to dialysis. CONCLUSIONS: Treatment of acute renal transplant rejection with Thymoglobulin is a cost saving strategy when compared with treatment with Atgam.     

Economic impact of tibolone compared with continuous-combined hormone replacement therapy. In the management of postmenopausal women with climacteric symptoms in the UK

OBJECTIVE: To estimate the economic impact of using tibolone 2.5 mg compared with 17 beta-estradiol 2 mg/norethisterone acetate 1 mg (E2/NETA) in postmenopausal women with climacteric symptoms. DESIGN AND SETTING: This was a modelling study performed from the perspective of the UK's National Health Service (NHS). METHODS: The clinical outcomes from a previously reported trial were used as the clinical basis for the analysis, which showed that 48 weeks' treatment with tibolone and E2/NETA significantly alleviated the climacteric symptoms experienced by postmenopausal women. These data were combined with resource utilisation estimates derived from a panel of 10 GPs and 3 gynaecologists, enabling us to construct a Markov model depicting changes in the health status of postmenopausal women. The model was used to estimate the expected NHS costs and consequences after 48 weeks' treatment with tibolone and E2/NETA. MAIN OUTCOME MEASURES AND RESULTS: The mean expected direct healthcare cost of using tibolone and E2/NETA to manage postmenopausal women for 48 weeks was estimated to be 260 Pounds and 239 Pounds (1997/1998 prices) per patient, respectively. Starting hormone replacement therapy (HRT) with tibolone instead of E2/NETA was equally effective in alleviating climacteric symptoms (65.9 and 62.2%, respectively; p = 0.516) over 48 weeks and significantly reduced the incidence of vaginal bleeding by 36% (p < 0.0001) and breast tenderness by 57% (p < 0.0001) for a mean additional cost of 21 Pounds (ranging between -3 Pounds and 42 Pounds) per patient. The acquisition cost of HRT was the primary cost driver for tibolone-treated patients, whereas the cost of managing adverse events was the primary cost driver for E2/NETA-treated patients. CONCLUSIONS: The true cost of prescribing tibolone and E2/NETA is impacted on by a broad range of resources, not only drug acquisition costs. Although the acquisition cost of tibolone is higher than that of E2/NETA, the difference in the expected NHS cost of the first year of treatment between the 2 HRTs is negligible. This is because of the higher incidence of adverse events among E2/NETA-treated patients, which also results in a higher continuation rate among tibolone-treated patients. Factors such as patient preferences should also be taken into consideration so that treatment choices are not decided solely on the basis of acquisition costs.     

Cost effectiveness of human immunodeficiency virus postexposure prophylaxis for healthcare workers

OBJECTIVE: The United States Public Health Service (USPHS) published recommendations for human immunodeficiency virus (HIV) postexposure prophylaxis (PEP) of healthcare workers in May 1998. The aim of this study was to analyse the cost effectiveness of the USPHS PEP guidelines. DESIGN AND SETTING: This was a modelling study in the setting of the US healthcare system in 1989. The analysis was performed from the societal perspective; however, only HIV healthcare costs were considered and health-related losses of productivity were not included. METHODS: A decision tree incorporating a Markov model was created for 4 PEP strategies: the current USPHS recommendations, triple drug therapy, zidovudine monotherapy or no prophylaxis. A probabilistic sensitivity analysis using a Monte Carlo simulation was performed. Confidence intervals (CIs) around cost-effectiveness estimates were estimated by a bootstrapping method. RESULTS: The costs (in 1997 US dollars) per quality-adjusted life-year (QALY) save by each strategy were as follows: monotherapy $US688 (95% CI: $US624 to $US750); USPHS recommendations $US5211 (95% CI: $US5126 to $US5293); and triple drug therapy $US8827 (95% CI: $US8715 to $US8940). The marginal cost per year of life saved was: USPHS recommendations $US81 987 (95% CI: $US80 437 to $US83 689); triple drug therapy $US970 451 (95% CI: $US924 786 to $US 1 014 429). Sensitivity testing showed that estimates of the probability of seroconversion for each category of exposure were most influential, but did not change the order of strategies in the baseline analysis. With the prolonged HIV stage durations and increased costs associated with recent innovations in HIV therapy, the marginal cost effectiveness of the USPHS PEP strategy was decreased to $US62 497/QALY saved. All 3 intervention strategies were cost effective compared with no postexposure prophylaxis. CONCLUSIONS: Current USPHS PEP recommendations are marginally cost effective compared with monotherapy, but the additional efficacy of triple drug therapy for all risk categories is rewarded by only a small reduction in HIV infections at great expense. For the foreseeable future, assuming innovations in therapy that employ expensive drug combinations earlier in the HIV disease course to extend life expectancy and the increasing prevalence of HIV drug resistance, our model supports the use of the USPHS PEP guidelines.     

The cost of reaching National Cholesterol Education Program (NCEP) goals in hypercholesterolaemic patients. A comparison of atorvastatin, simvastatin, lovastatin and fluvastatin

OBJECTIVE: Recognising the importance of treating hyperlipidaemia, the National Cholesterol Education Program (NCEP) has established widely accepted treatment goals for low density lipoprotein cholesterol (LDL-C). Medications used most commonly to achieve these LDL-C goals are HMG-CoA reductase inhibitors. The relative resource utilisation and cost associated with the use of reductase inhibitors of different LDL-C lowering efficacy are unknown, but are major health and economic concerns. The objective of this study was to determine the mean total cost of care to reach NCEP goals with various reductase inhibitors. DESIGN: In a randomised, 54-week, 30-centre controlled trial we compared resources used and costs associated with treating patients to achieve NCEP goals using 4 reductase inhibitors: atorvastatin, simvastatin, lovastatin and fluvastatin. PATIENTS AND PARTICIPANTS: The trial studied 662 patients; 318 had known atherosclerotic disease. INTERVENTIONS: Reductase inhibitor therapy was initiated at recommended starting doses and increased according to NCEP guidelines and package insert information. For patients who did not reach the goal at the highest recommended dose of each reductase inhibitor, the resin colestipol was added. MAIN OUTCOME MEASURES AND RESULTS: Patients treated with atorvastatin, compared-with other reductase inhibitors, were more likely to reach NCEP goals during treatment (p < 0.05), required fewer office visits (p < 0.001) and less adjuvant colestipol therapy (p = 0.001). Consequently, the mean total cost of care (1996 values) to reach NCEP goals was lower with atorvastatin [$US1064; 95% confidence interval (CI): $US953 to $US1176] compared with simvastatin ($US1471, 95% CI: $US1304 to $US1648), lovastatin ($US1972; 95% CI: $US1758 to $US2186) and fluvastatin ($US1542; 95% CI: $US1384 to $US1710). Results were similar for patients with or without known atherosclerotic disease. CONCLUSIONS: In patients requiring drug therapy for hypercholesterolaemia, NCEP LDL-C goals are achieved significantly more often using fewer resources with atorvastatin compared with simvastatin, lovastatin or fluvastatin.