Erratum: Cost-effectiveness of everolimus for the treatment of advanced neuroendocrine tumours of gastrointestinal or lung origin in Canada.

[This corrects the article on p. 32 in vol. 25, PMID: 29507481.].

Cost-effectiveness of everolimus for the treatment of advanced neuroendocrine tumours of gastrointestinal or lung origin in Canada.

BACKGROUND: In 2016, everolimus was approved by Health Canada for the treatment of unresectable, locally advanced or metastatic, well-differentiated, non-functional, neuroendocrine tumours (NET) of gastrointestinal (GI) or lung origin in adult patients with progressive disease. This analysis evaluated the cost-effectiveness of everolimus in this setting from a Canadian societal perspective. METHODS: A partitioned survival model was developed to compare the cost per life-year (LY) gained and cost per quality-adjusted life-year (QALY) gained of everolimus plus best supportive care (BSC) versus BSC alone in patients with advanced or metastatic NET of GI or lung origin. Model health states included stable disease, disease progression, and death. Efficacy inputs were based on the RADIANT-4 trial and utilities were mapped from quality-of-life data retrieved from RADIANT-4. Resource utilization inputs were derived from a Canadian physician survey, while cost inputs were obtained from official reimbursement lists from Ontario and other published sources. Costs and efficacy outcomes were discounted 5% annually over a 10-year time horizon, and sensitivity analyses were conducted to test the robustness of the base case results. RESULTS: Everolimus had an incremental gain of 0.616 QALYs (0.823 LYs) and CA$89,795 resulting in an incremental cost-effectiveness ratio of CA$145,670 per QALY gained (CA$109,166 per LY gained). The probability of cost-effectiveness was 52.1% at a willingness to pay (WTP) threshold of CA$150,000 per QALY. CONCLUSIONS: Results of the probabilistic sensitivity analysis indicate that everolimus has a 52.1% probability of being cost-effective at a WTP threshold of CA$150,000 per QALY gained in Canada.

Economic evaluation of everolimus and mycophenolate mofetil versus azathioprine in de novo heart transplantation.

UNLABELLED: Both the proliferation signal inhibitor everolimus (1.5 mg/day) and mycophenolate mofetil (MMF) (3 g/day) have shown superior efficacy versus azathioprine in de novo heart transplantation. The cost-effectiveness of everolimus and MMF versus azathioprine was assessed to 6 months posttransplantation. METHODS: The evaluation was performed from the German health insurance payer perspective. The composite efficacy endpoint in the everolimus trial was death, graft loss/retransplantation, biopsy-proven acute rejection (BPAR) grade>or=3A, rejection with hemodynamic compromise, and loss to follow-up. The composite endpoint in the MMF trial included only death, retransplantation, and BPAR with hemodynamic compromise. To mimic the everolimus endpoint, an estimated number of patients with BPAR>or=3A was added to the MMF trial results, using two mapping scenarios. RESULTS: The incremental 6-month cost versus azathioprine was euro2535 for everolimus and euro3007 for MMF. The absolute reduction in efficacy failure versus azathioprine was 10.4% for everolimus and 9.8% and 10.1% for MMF, respectively, using scenarios 1 and 2. The incremental cost per efficacy failure avoided (ie, the incremental cost versus azathioprine divided by the reduction in efficacy failure) was euro24,457 for everolimus, and euro30,628 and euro29,912 for MMF in scenarios 1 and 2. CONCLUSION: This analysis, based on findings from two clinical trials, suggested that everolimus was more cost-effective than MMF versus azathioprine in the first 6 months after heart transplantation. Data from a head-to-head trial are required to confirm these results.

The incidence and costs of sepsis and pneumonia before and after renal transplantation in the United States.

We compared the graft survival and accumulative costs associated with sepsis and pneumonia pre- and post-transplantation. We analyzed 44 916 first kidney transplants from 1995 to 2001 USRDS where Medicare was the primary payer. We drew five cohorts for each disease from the baseline population: patients who had a disease onset in the first or second years pre-transplantation (cohorts 1 and 2) or post-transplantation (cohorts 3 and 4) and patients who were disease-free (cohort 5). For each cohort, we calculated graft survival and average accumulated Medicare payments (AAMPs) for the two pre- and post-transplantation years. Graft survival: new-onset sepsis and pneumonia both significantly (p <0.01) lowered graft survival during the year of onset. AAMPs: the AAMPs incurred by sepsis- (pneumonia-) free patients during the first and second years post-transplantation were dollar 50,000 and 13,000 (dollar 51,100 and 13,500), respectively. Patients with a sepsis (pneumonia) onset post-transplantation cost on average dollar 48,400 (dollar 38,400) extra (p<0.01). Episodes of sepsis and pneumonia have a strong and independent impact on graft survival and costs.

Retrospective analysis of the health-care costs of bupropion sustained release in comparison with other antidepressants.

OBJECTIVE: The objective of this study was to evaluate the health care costs associated with the treatment of a new episode of depression with bupropion sustained release (SR) rather than with other antidepressants (selective serotonin reuptake inhibitors [SSRIs], tricyclic antidepressants [TCAs], and serotonin norepinephrine reuptake inhibitors [SNRIs]). METHODS: This was a retrospective cohort study based on the private-pay, fee-for-service 1997 and 1998 MEDSTAT MarketScan databases. Individuals were included if they were 18 years of age or older, had an initial prescription for an antidepressant under study with an index prescription date between July 1997 and June 1998, and had a claim for a diagnosis of depression diagnosis within 30 days of the index date. All patients' claims from six months before and after receiving their index antidepressant prescription were examined. Total, outpatient, and pharmacy costs were compared among antidepressant groups using an intent-to-treat analysis with exponential regression models and bootstrapped 95% confidence intervals. RESULTS: A total of 1771 patients were included in the study cohort. The mean age was 41.6 years, and 69.5% of subjects were female. Most patients (75%) continued with the index antidepressant during the 6-month follow-up period. Although the drug acquisition cost was lowest for TCAs, total costs were significantly higher for patients treated with TCAs than for those treated with bupropion SR (p < .05). In comparison with bupropion SR, patients initiating therapy with sertraline had significantly higher mental health payments (p < .05). CONCLUSIONS: Initiating treatment of depression with bupropion SR was associated with lower total mental health care costs compared with TCAs and with sertraline. This study reaffirms that formulary and medical decision-makers should consider the overall impact of antidepressant treatment, including but not limited to drug acquisition costs, other health care costs, and drug efficacy and safety.

The net cost of Alzheimer disease and related dementia: a population-based study of Georgia Medicaid recipients.

The objective of this study was to estimate the direct medical cost of Alzheimer disease (AD) and related dementia to the Georgia Medicaid program. A retrospective, cross-sectional, matched control group design was used. AD cases 50 years of age and older were identified by using International Classification of Diseases (9th edition, Clinical Modification) diagnosis codes from 1994 Georgia Medicaid administrative claims files. For every case, three age- and gender-matched non-AD controls were selected. Differences in average recipient Medicaid expenditures between cases and controls were estimated using weighted least squares regression analysis, adjusting for age, gender, race, Charlson comorbidity index, Medicare eligibility, and months of Medicaid eligibility. A total of 8,671 AD cases were identified (prevalence, 4.4%). The average adjusted annual Medicaid expenditure per AD recipient was $14,492 (U.S.). The net (i.e., excess) average annual Medicaid cost per AD recipient (i.e., the difference in adjusted mean expenditures between cases and controls) was estimated to be approximately $8,200. Excessive nursing home expenditures accounted for most of the additional cost of treating dementia (> 85%), although inpatient hospital, physician, outpatient, and prescription drug expenditures also were higher among patients with AD. Based on these estimates, Georgia Medicaid is projected to spend almost $70 million annually for AD and related dementia. The excessive cost attributable to AD poses a significant burden to the Georgia Medicaid program.

Trends in use of barium enema examination, colonoscopy, and sigmoidoscopy: is use commensurate with risk of disease?

PURPOSE: To assess replacement of barium enema examination with colonoscopy in relation to age- and sex-related risk factors, place of service, physician specialty, and cost. MATERIALS AND METHODS: Between 1985 and 1992, 894,777 insurance claims for barium enema examination and lower gastrointestinal endoscopy were retrospectively examined. Changes in use were investigated. Use of proctosigmoidoscopy and flexible sigmoidoscopy, two office-based endoscopic procedures, was also examined. RESULTS: Use of diagnostic colonoscopy increased from 191 to 406 services per 100,000 persons; colonoscopy with biopsy, from 77 to 183 services; and colonoscopy with lesion removal, from 77 to 202 services. Barium enema examination use declined from 929 to 511 services per 100,000 persons; diagnostic proctosigmoidoscopy, from 854 to 193 services; and diagnostic flexible sigmoidoscopy, from 656 to 620 services. Increases in use of colonoscopy in patients aged younger than 40 years were greater than overall increases. CONCLUSION: Colonoscopy has been replacing barium enema examination as the initial colorectal examination since 1985. Increased use of colonoscopy in patients with lower risk of neoplasia suggests that indications have become overly broad.

Phosphatidylazidothymidine and phosphatidyl-ddC: assessment of uptake in mouse lymphoid tissues and antiviral activities in human immunodeficiency virus-infected cells and in Rauscher leukemia virus-infected mice.

During the early stages of human immunodeficiency virus (HIV) infection, although symptoms are absent and viral replication in peripheral blood mononuclear cells is low, substantial levels of HIV replication can be documented in lymphoid tissue [G. Pantaleo, C. Graziosi, J.F. Demarest, L. Butini, M. Montroni, C.H. Fox, J.M. Orenstein, D.P. Kotler, and A.S. Fauci, Nature (London) 362:355-358, 1993, and J. Embretsen, M. Zupancic, J.L. Ribas, A. Burke, P. Racz, K. Tenner-Tacz, and A.T. Haase, Nature (London) 362:359-362, 1993]. This observation suggests that earlier treatment of HIV infection may be indicated and that strategies for enhancing drug targeting to the lymphoid tissue reservoris of HIV infection may be beneficial. To address this issue, we synthesized dioleoylphosphatidyl-ddC (DOP-ddC) and dipalmitoylphosphatidyl-3'-azido-3'-deoxythymidine (DPP-AZT), phospholipid prodrugs which form lipid bilayers and which are readily incorporated into liposomes. The anti-HIV activity of DOP-ddC was similar to that of ddC in HIV type 1-infected HT4-6C cells, but DPP-AZT was considerably less active than AZT in HT4-6C cells. Liposomes containing DOP-[3H]ddC or DPP-[3H]AZT administered intraperitoneally to mice produced greater levels of total radioactivity over time in plasma, spleen, and lymphoid tissue relative to the results with [3H]ddC and [3H]AZT, respectively. DPP-AZT administered intraperitoneally in liposomes as a single daily dose to mice infected with Rauscher leukemia virus prevented increased spleen weight and reverse transcriptase levels in serum with a dose-response roughly comparable to that of AZT given continuously in the drinking water. DOP-ddC, DPP-AZT, and lipid conjugates of other antiretroviral nucleosides may provide higher levels of drug over time in plasma and in lymph nodes and spleen, important reservoirs of HIV infection, and may represent an interesting alternative approach to antiviral nucleoside treatment of AIDS.

Self-referral in private offices for imaging studies performed in Pennsylvania Blue Shield subscribers during 1991.

PURPOSE: To define the frequency of physician self-referral for diagnostic imaging studies. MATERIALS AND METHODS: High-volume radiographic (n = 65) and ultrasound (US) (n = 29) procedural codes in claims filed by Pennsylvania Blue Shield subscribers were analyzed to determine private-office (nonhospital) utilization of these examinations by radiologists and nonradiologists during 1991. A total of 787,703 radiographic and 159,281 US claims were filed. RESULTS: Nonradiologists self-referred 550,878 radiographic examinations (69.9%) and 99,931 US examinations (62.7%). Patterns of utilization varied considerably by anatomic category: The imaging studies with the highest rates of utilization by nonradiologists were skeletal radiography, vascular US, and obstetric and pelvic US. Aggregate reimbursement allowance by Pennsylvania Blue Shield for all examinations in these 94 codes was approximately $68 million, of which $44 million (65%) went to non-radiologists.

An analysis of cesarean deliveries among Pennsylvania Blue Shield subscribers.

In recent years, increased attention has focused on the relatively high rate of Cesarean deliveries in the U.S. Though the medical necessity and indications for Cesarean deliveries have been heavily debated, there still remains considerable disagreement among professionals about which Cesarean deliveries are inappropriate. To contribute to an understanding of these issues, Pennsylvania Blue Shield prepared a profile of Cesarean deliveries in Pennsylvania relative to Blue Shield's claim experience. The results of the study are presented in this article.

Diagnostic radiology peer review: a method inclusive of all interpreters of radiographic examinations regardless of specialty.

A proposed method of assessing the quality of diagnostic radiographic examinations includes peer review designed to evaluate physicians, including nonradiologists, involved in the performance and interpretation of such examinations. A pilot project evaluated this system with randomly selected Pennsylvania Blue Shield data files of 10 providers billing for chest radiography interpretations during the second quarter of 1989. Of the 98 chest radiographs reviewed blindly, all inadequately marked radiographs and incomplete written reports were produced by nonradiologists. Technical quality of images obtained by radiologists did not significantly differ from that of images obtained by nonradiologists (P = .189). All five interpretive errors that could have seriously affected the patient's health care were produced by nonradiologists (P = .019). Four of these serious errors were made by providers billing for fewer than 25 radiographs. While administrative and time cost limitations are obvious, this method of peer review encompasses all physicians billing for a particular radiographic service, irrespective of specialty.