Costs of adverse events among patients with HIV infection treated with nonnucleoside reverse transcriptase inhibitors.

OBJECTIVES: The aim of the study was to assess the incidence and costs of adverse events (AEs) among patients with HIV infection treated with nonnucleoside reverse transcriptase inhibitors (NNRTIs) from the health care system perspective. METHODS: US medical and pharmacy claims during 2004-2009 were examined to select adult new NNRTI users with HIV infection. The incidence of selected AEs and time to occurrence were assessed during the first year. Episodes of care for each AE were identified using claims associated with AE management. For each AE, a propensity score model was used to match patients with an AE to those without (1:4) based on the propensity of having an AE. Mean total health care costs, AE-associated costs and incremental costs per episode, and annual total health care costs per patient were calculated. RESULTS: Of the 2548 NNRTI-treated patients, 29.3% experienced AEs. The incidence ranged from 0.4 episodes/1000 person-years for suicide/self-injury to 14.9 episodes/1000 person-years for dizziness, 49.8 episodes/1000 person-years for depression and 150.3 episodes/1000 person-years for lipid disorder. The mean AE-associated cost (duration) per episode ranged from $586 (88 days) for lipid disorder to $975 (33 days) for rash, $2760 (73 days) for sleep-related symptoms and $4434 (41 days) for nausea/vomiting. The mean incremental cost per episode ranged from $1580 for rash to $2032 for lipid disorder, $8307 for sleep-related symptoms and $12 833 for nausea/vomiting. During the 12 months following NNRTI initiation, the mean annual total health care cost was $27 299 (efavirenz: $26 185; other NNRTIs: $34 993) and AE-associated costs were $608 (efavirenz: $554; other NNRTIs: $979) among all NNRTI users. CONCLUSIONS: With treatment increasing patient survival, comparisons of therapeutic regimens should consider treatment-associated AEs. Findings from this study could be informative for clinicians and payers in managing HIV infection with NNRTIs.

Economic and health-related quality-of-life (HRQoL) comparison of lopinavir/ritonavir (LPV/r) and atazanavir plus ritonavir (ATV+RTV) based regimens for antiretroviral therapy (ART)-naïve and -experienced United Kingdom patients in 2011.

BACKGROUND: Using a United Kingdom (UK)-based National Health Services perspective for 2011 this study first estimated the cost-effectiveness and budget impact implications for lopinavir/ritonavir (LPV/r) vs atazanavir plus ritonavir (ATV+RTV) treatment of antiretroviral therapy (ART)-naïve patients and secondly examined the long-term health-related quality-of-life (HRQoL) and economic implications for LPV/r vs ATV+RTV treatment of ART-experienced patients. METHODS: A previously published Markov model that integrates epidemiological data of human immunodeficiency virus (HIV) with predictors of coronary heart disease (CHD) was modified under a clearly specified set of assumptions to reflect viral load (VL) suppression profiles and other differences for these two regimens, applying results from the CASTLE study in ART-naïve patients and using data from BMS-045 in ART-experienced patients. ART costs were referenced to current (2011) pricing guidelines in the UK. Medical care costs reflected UK treatment patterns and relevant drug pricing. Costs and outcomes were discounted at 3.5% per year. Costs are expressed in British pounds (£) and life expectancy in quality-adjusted life years (QALYs). RESULTS: In the ART-naïve subjects, the model predicted a marginal improved life expectancy of 0.031 QALYs (11 days) for the ATV+RTV regimen as a result of predicted CHD outcomes based on lower increases in cholesterol levels compared with the LPV/r regimen. The model demonstrated cost savings with the LPV/r regimen. The total lifetime cost savings was £4070 per patient for the LPV/r regimen. LPV/r saved £2133 and £3409 per patient at 5 and 10 years, respectively. Referenced to LPV/r, the incremental cost-effectiveness ratio (ICER) for ATV+RTV was £149,270/QALY. For ART-experienced patients VL suppression differences favored LPV/r, while CHD risk associated with elevated total cholesterol marginally favored ATV+RTV, resulting in a net improvement in life expectancy of 0.31 QALYs (106 days) for LPV/r. Five-year costs were £5538 per patient greater for ATV+RTV, with a discounted lifetime saving of £1445 per LPV/r patient. LPV/r was modestly dominant economically, producing better outcomes and cost savings. LIMITATIONS: The limitations of this study include uncertainty related to how well the model's assumptions capture current practice, as well as the validity of the model parameters used. This study was limited to using aggregated data in the public domain from the two clinical trials. Thus, some of the model parameters may reflect limitations due to trial design and data aggregation bias. This study has attempted to illuminate the effect of these limitations by presenting the results of the comprehensive sensitivity analysis. CONCLUSIONS: Based on 2011 costs of HIV in the UK and the published efficacy data from the CASTLE and BMS-045 studies, ATV+RTV-based regimens are not expected to be a cost-effective use of resources for ART-naïve patients similar to patients in the CASTLE study, nor for ART-experienced patients based on the only published comparison of ATV+RTV and LPV/r.

Economic decision analysis model of screening for lung cancer.

The objective of this study was to evaluate the potential clinical and economic implications of an annual lung cancer screening programme based on helical computed tomography (CT). A decision analysis model was created using combined data from the Surveillance, Epidemiology and End Results (SEER) registry public-use database and published results from the Early Lung Cancer Action Project (ELCAP). We found that under optimal conditions in a high risk cohort of patients between 60 and 74 years of age, annual lung cancer screening over a period of 5 years appears to be cost effective at approximately $19000 per life year saved. A sensitivity analysis of the model to account for a 1-year decrease in survival benefit and changes in assumptions for incidence rate and costs generated cost effectiveness estimates ranging from approximately $10800 to $62000 per life year saved. Based on the assumptions embedded in this model, annual screening of high risk elderly patients for lung cancer may be cost effective under optimal conditions, but longer term data are needed to confirm if this will be borne out in practice.

Potential cost-effectiveness of one-time screening for lung cancer (LC) in a high risk cohort.

The development of low-dose helical computed-tomography (CT) scanning to detect nodules as small as a few mm has sparked renewed interest in lung cancer (LC) screening. The objective of this study was to assess the potential health effects and cost-effectiveness of a one-time low-dose helical CT scan to screen for LC. We created a decision analysis model using baseline results from the Early Lung Cancer Action Project (ELCAP); Surveillance, Epidemiology and End Results (SEER) registry public-use database; screening program costs estimated from 1999 Medicare reimbursement rates; and annual costs of managing cancer and non-cancer patients from Riley et al. (1995) [Med Care 1995;33(8):828-841] and Taplin et al. (1995) [J Natl Cancer Inst 1995;87(6):417-26]. The main outcome measures included years of life, cost estimates of baseline diagnostic screening and follow up, and cost-effectiveness of screening. We found that in a very high-risk cohort (LC prevalence of 2.7%) of patients between 60 and 74 years of age, a one-time screen appears to be cost-effective at $5940 per life year saved. In a lower risk general population of smokers (LC prevalence of 0.7%), a one-time screen appears to be cost-effective at $23100 per life year. Even when a lead-time bias of 1 year is incorporated into the model for a low risk population, the cost-effectiveness is estimated at $58183 per life year. Based on the assumptions embedded in this model, one-time screening of elderly high-risk patients for LC appears to be cost-effective.

Effectiveness and economic impact of screening for colorectal cancer by mass fecal occult blood testing.

OBJECTIVES: Fecal occult blood testing has been shown to reduce mortality from colorectal cancer in large randomized, controlled trials conducted in the United States, Denmark, and the United Kingdom, and mathematical simulation modeling found it to be cost-effective relative to other health care services. Before making a concerted effort to implement mass fecal occult blood testing based on this evidence alone, however, we considered it prudent to critically re-evaluate the effectiveness and economic impact of screening in the US population as a whole. METHODS: To assess the effectiveness of screening, we projected published outcomes from each of the three large randomized controlled trials of fecal occult blood testing to the US population, as if each clinical trial had been done in the population as a whole. We then determined the resource costs of detection and treatment that would be associated with the outcomes predicted from each trial. RESULTS: More than 1 million colorectal cancers could be expected to arise over 10 yr in the cohort of US residents eligible to enter a screening program in 1997, and trial outcomes indicate that > or = 60% of these cancers would be fatal. If the 60-67% compliance rate of the population-based randomized controlled trials were achieved, a fecal occult blood testing program would detect 30% of known colorectal cancers and save 100,000 lives over 10 yr. Screening would incur total costs of $3-4 billion over 10 yr, or $2,500 per life-year saved. CONCLUSIONS: Mass fecal occult blood testing is cost-effective, and, although not inexpensive, many would consider the total cost acceptable. Even with a concerted effort to achieve compliance, however, the effectiveness of fecal occult blood testing would be limited to saving the lives of < or = 15% of those who otherwise would die from their cancer in the first 10 yr after beginning mass screening. The limitations of fecal occult blood testing suggest the need to further evaluate the role of endoscopy in screening, and to develop more effective, noninvasive screening tools.

Impact of zidovudine-based triple combination therapy on an AIDS drug assistance program.

A static deterministic model was used to estimate the effect of the shift to a triple combination therapeutic standard on the annual AIDS Drug Assistance Program (ADAP) budget, total medical care expenditures, and population health outcomes for New York (NY) state ADAP enrollees. The model used opportunistic disease incidence data from the Multicenter AIDS Cohort Study (MACS) and other studies. Costs of treating opportunistic infections (OIs) and other HIV complications with each type of therapy were derived from treatment algorithms and standard unit costs. CD4+ cell counts were used as an index of need for OI prophylaxis and for determining OI incidence. Treatment with zidovudine-based combination therapy has been shown to increase CD4+ cell counts and reduce OI incidence. The model estimated that a change from monotherapy to triple therapy would have increased NY ADAP budget expenditures per enrollee by 115%. However, total medical system costs per ADAP enrollee (including ADAP costs) would decrease by 0.4% in the base case as a result of reduction in OIs and other HIV sequelae and associated costs. Results are sensitive to the assumed percentage of people taking combination therapy as well as to the assumptions made about the impact of the combination therapy on CD4+ cell count. Total ADAP budget impacts will depend on the growth in ADAP enrollment as a result of the availability of more effective therapies. In conclusion, this model demonstrates how access to newer, more effective HIV drug treatments can reduce the costs of treating OIs and provide major health benefits for ADAP enrollees.

Measuring the effect of clinical guidelines on patient outcomes.

OBJECTIVES: To identify and examine the methodologic issues related to evaluating the effectiveness of treatment adherence to clinical guidelines. The example of antiretroviral therapy guidelines for human immunodeficiency virus (HIV) disease is used to illustrate the points. METHODS: Regression analysis was applied to observational HIV clinic data for patients with CD4+ cell counts less than 500 per microL and greater than 50 per microL at baseline (n = 704), using Cox proportional hazards time-varying covariates models controlling for baseline risk. The results are compared with simpler models (Cox model [without time-varying covariates] and logistic regression). In addition, the effect of including a measure of exposure to antiretroviral guidelines in the model is explored. RESULTS: This study has three implications for modeling clinical guideline effectiveness. To capture events that are time-sensitive, a duration model should be used, and covariates that are time-varying should be modeled as time-varying. Thirdly, incorporating a threshold measure of exposure to reflect the minimum period of time for guideline adherence required for a measurable effect on patient outcome should be considered. CONCLUSIONS: The methods proposed in this paper are important to consider if guidelines are to evolve from being a tool for summarizing and transferring the results of research from the literature to clinicians into a practical tool that influences clinical practice patterns. However, the methodology tested in this study needs to be validated using additional data on similar patients and using data on patients with other diseases.

Modeling the use of triple combination therapy in five countries: nevirapine, Zidovudine, and Didanosine.

OBJECTIVE: In this study, we modify previously published models to estimate the short- and long-term consequences of nevirapine triple combination therapy use in five developed countries. Current pharmacoeconomic practice requires the de novo model development for each new therapy comparison. This approach is lengthy and costly, and it may yield models with very different structures. Standardized, detailed disclosure of model assumptions and parameters makes it possible to recycle published models with minor structural modifications to examine the efficiency of therapies based on new trial data. METHODS: Two well-publicized models of HIV therapy are modified to fit new trial data comparing double and triple combination therapy with nevirapine; model parameters are adjusted to represent clinical practice and cost structure in five countries. A short-term model uses trial data from advanced-stage patients to estimate first-year costs and consequences. A long-term model uses data from antiretroviral-naïve patients to estimate long-term cost-effectiveness. RESULTS: During the first year, for each 100 individuals treated with nevirapine triple combination therapy, 2.7 deaths and 30.8-31.4 opportunistic disease events would be averted compared to employing dual therapy. Additionally, 61% to 142% of the first-year costs of nevirapine therapy would be offset by other medical care costs savings [FF19,749, DM3,778, 3334 (x1000) lire, 293 (x1000) ptas, and US $3,569]. Compared to dual combination therapy, nevirapine triple combination therapy is predicted to yield incremental cost-effectiveness ratios (discounted at 3%) of FF101,057, DM30,709, 28,066 (x1000) lire, 1294 (x1000) ptas, and US $14,338. CONCLUSION: Published, well-constructed, and documented cost-effectiveness models can be reused to estimate the economic impact of therapies for HIV disease. Such models can also be used to provide insight into the factors that affect efficiency across countries. Our use of clinical trial data on nevirapine, together with published HIV economic models, provides support for the hypothesis that nevirapine is cost-effective under the cost structures of five developed countries.

Idiopathic thrombocytopenia purpura: Treatment patterns and an analysis of cost associated with intravenous immunoglobulin and anti-D therapy.

A retrospective study was conducted to determine treatment patterns for idiopathic thrombocytopenia purpura (ITP) across the US and to determine the cost of its treatment with high-dose intravenous immunoglobulin (IVIg) and anti-D therapy. Information on the incidence, treatment patterns, hospital care, and costs for ITP was derived from three data bases and supplemented by in-depth case studies from five hospital centers in the US. Data collection forms were developed to collect data on treatment patterns and costs at the five hospital centers. Treatment patterns were analyzed and used to model the comparative costs of IVIg and anti-D therapy. Cost estimations were based on a process and cost-finding analysis reflecting current practice patterns for the use of IVIg and anti-D therapy in an outpatient clinic. The incidence of ITP was estimated at 65 per 10,000 in human immunodeficiency virus (HIV)-positive individuals and 1.5 per 10,000 in HIV-negative individuals. Hospital discharge data from all 1991 and 1992 hospital discharges in Maryland revealed that both Medicare patients and patients who had other payment options spent less time in hospital compared to Medicaid patients. The limited case study data indicate that anti-D therapy increased platelet counts to greater than 25,000/microL in 82% of evaluable episodes and that IVIg-treated patients reached 25,000/microL in 48% of treated episodes. The estimated cost per treated episode of ITP was $4,269 for IVIg and $2,716 for anti-D therapy, reflecting a cost savings of $1,553 per episode. This retrospective study has shown that the use of anti-D therapy is associated with lower costs compared with IVIg treatment in patients with ITP. The shorter infusion time required for anti-D therapy may also contribute to a better quality of life for patients.

The economic and clinical efficiency of point-of-care testing for critically ill patients: a decision-analysis model.

Our study objective was to assess economic and clinical outcomes of use of a point-of-care (POC) blood analysis device for postoperative coronary artery bypass graft (CABG) patients. A decision analytic model was developed for patients with high expected use of blood analysis, high potential benefit from rapid turn around time of results, a large annual volume of patients, and substantial expense associated with surgery. Published literature and clinical experts provided incidence, outcome, and cost estimates associated with four clinical scenarios potentially influenced by POC testing (ventricular arrhythmias, cardiac arrest, severe postoperative bleeding, and iatrogenic anemia). We found that changes in clinical outcomes were predominantly dependent on comparative turn around time or CABG patient volume. The positive clinical impact of using POC testing was consistently associated with a positive economic impact. POC blood gas analysis may be associated with decreased incidence of adverse clinical events or earlier detection of such events, resulting in significant cost savings. This study also supports previous findings that the costs of STAT blood analysis are more personnel-related than equipment-related.

Markers, cofactors and staging systems in the study of HIV disease progression: a review

This paper is aimed at providing a comprehensive review of markers, cofactors and staging systems used for HIV disease, focusing on some aspects that nowadays could even be considered historical, and advancing in current issues such as the prognostic value of viral load measurements, viral genotypic and phenotypic characterization, and new HIV disease treatment protocols. CD4 cell values, combined with the new viral markers mentioned are promising as a parsimonious predictor set for defining both severity and progression. An adequate predictor of patient resource use for planning purposes still needs to be defined.

Markers, cofactors and staging systems in the study of HIV disease progression: a review.

This paper is aimed at providing a comprehensive review of markers, cofactors and staging systems used for HIV disease, focusing on some aspects that nowadays could even be considered historical, and advancing in current issues such as the prognostic value of viral load measurements, viral genotypic and phenotypic characterization, and new HIV disease treatment protocols. CD4+ cell values, combined with the new viral markers mentioned are promising as a parsimonious predictor set for defining both severity and progression. An adequate predictor of patient resource use for planning purposes still needs to be defined.

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.

Developing a measure of patient perceptions of short-term outcomes of third molar surgery.

PURPOSE: The purpose of the study was to develop an instrument to measure patients' perceptions of their experiences after the removal of third molar teeth. METHODS: Nineteen patients (ages 18 to 25 years) who underwent surgical removal of four third molars after local treatment for mild symptoms of pericoronitis completed a newly developed 14-item instrument each evening for the 14-day period after surgery. A focus group was used to further examine the experiences of a subset of subjects. RESULTS: On the first day postsurgery, patients reported a median level of 81 on the 0 to 100 scale of "limitation of daily activity because of pain" (100 = total interference). This dropped to 21 by day 5, and all but two patients returned completely to normal activities by day 8. During the first 3 days, the median level of "average pain" ranged from 51 to 33 (100 = pain as bad as could be), and all but two patient were pain-free by day 10. Bad taste/breath persisted for between 2 to 4 days; food impaction was experienced by nearly all patients from days 3 through 14. Swelling was encountered by 10 of the patients for the first 2 days and was reported by only one patient after day 5. CONCLUSIONS: This study demonstrated that patients' perceptions of their experiences could be collected using a self-administered instrument, and it confirmed the changes in postsurgical morbidity that occur in healthy, young adults. This instrument and these data will be valuable to those striving to make informed decisions regarding third molar surgery.

Variations in practice patterns: antiviral drug use in hospitalized patients with herpes infections.

This study describes patterns of antiviral drug use for patients hospitalized with chickenpox, herpes simplex, and herpes zoster infections, and also for a subgroup of herpes patients with severe infections (systemic infections, eye infections, encephalitis, hemorrhagic pneumonitis, and other severe conditions). Our findings demonstrate that there is great deal of variation in the use of antiviral drugs for these herpes patients, and that much of this variation is apparently unrelated to medical indications for antiviral drug use. Instead, patterns of use are associated with patient characteristics (age, race) and with hospital characteristics (location, teaching status, number of beds). Because these drugs are effective when used properly, treatment guidelines and protocols may be needed so that improved drug use will produce better patient outcomes.

A model for estimating the impact of changes in children's vaccines.

OBJECTIVES: To assist in strategic planning for the improvement of vaccines and vaccine programs, an economic model was developed and tested that estimates the potential impact of vaccine innovations on health outcomes and costs associated with vaccination and illness. METHODS: A multistep, iterative process of data extraction/integration was used to develop the model and the scenarios. Parameter replication, sensitivity analysis, and expert review were used to validate the model. RESULTS: The greatest impact on the improvement of health is expected to result from the production of less reactogenic vaccines that require fewer inoculations for immunity. The greatest economic impact is predicted from improvements that decrease the number of inoculations required. CONCLUSIONS: Scenario analysis may be useful for integrating health outcomes and economic data into decision making. For childhood infections, this analysis indicates that large cost savings can be achieved in the future if we can improve vaccine efficacy so that the number of required inoculations is reduced. Such an improvement represents a large potential "payback" for the United States and might benefit other countries.

Evaluating the quality of life associated with rifabutin prophylaxis for Mycobacterium avium complex in persons with AIDS: combining Q-TWiST and multiattribute utility techniques.

Our objective was to evaluate the effect of rifabutin prophylaxis in patients with AIDS and CD4 counts of less than 200 per cubic millimetre using a combination of Q-TWiST (quality-adjusted time without symptoms and toxicity) and multiattribute health utility assessment. The design consisted of a secondary analysis of two previously reported multicentre, randomized, placebo-controlled clinical trials conducted in 78 academic, community and Department of Veterans Affairs HIV centres and private practices. 542 patients with AIDS and CD4 counts of less than 200 per cubic millimetre were assigned to rifabutin 300 mg/day and 562 were assigned to a placebo. A modified Q-TWiST approach was used for comparing treatments based on the occurrence and duration of time with and without severe symptoms and clinical endpoints. Health states were constructed to represent combinations of clinical events experienced by study patients. Five physicians assigned utilities for health states using a six-attribute health classification system. These utilities were used to adjust survival for QOL. The rifabutin and placebo groups were compared using estimated quality-of-life-adjusted days. The incidence of MAC was 9% for the rifabutin group and 18% for the placebo group (p < 0.001). Differences, although not statistically significant, were observed for rates of survival and hospitalization. The rifabutin group experienced less anaemia (p < 0.02), and fever and night sweats (p < 0.02) than the placebo group. Average Q-TWiST days were 325 for the rifabutin group and 309 for the placebo group (p < 0.05). Q-TWiST days were significantly lower for patients with MAC bacteraemia (p < 0.04) and hospitalizations (p < (0.003). Rifabutin prophylaxis resulted in fewer MAC infections and greater quality-of-life-adjusted days of survival compared to no rifabutin. Quality-of-life-adjusted survival, based on a combination of the Q-TWiST and multiattribute health utility index, is a feasible approach for evaluating the outcomes of medical treatment. Future studies should, however, use patient-assigned utility weights to compute Q-TWiST scores, since physician generated utilities may differ significantly from those of patients.