Real-world comparison of healthcare resource utilization and costs of [177Lu]Lu-DOTA-TATE in patients with progressive neuroendocrine tumors in England: a matched cohort analysis using data from the hospital episode statistics dataset.

OBJECTIVE: To explore the healthcare resource utilization (HCRU) and costs for patients with progressive gastroenteropancreatic neuroendocrine tumors (GEP-NETs) treated with [177Lu]Lu-DOTA-TATE and matched patients treated with somatostatin analogs (SSAs), chemotherapy, or targeted therapies. METHODS: Hospital Episode Statistics (HES) dataset 2016-2018 was used to compare HCRU and costs between the two cohorts. The [177Lu]Lu-DOTA-TATE cohort included patients assigned with a diagnosis code relevant to GEP-NET, a procedure code for imaging or SSAs, and a subsequent code for radionuclide therapy. The non-[177Lu]Lu-DOTA-TATE cohort included patients assigned with a diagnosis code relevant to GEP-NET who had an increased frequency of SSAs or switched from SSAs to chemotherapy or targeted therapies. Cohorts were matched on propensity scores with sex, age at disease progression, and Charlson Comorbidity Index as parameters. Healthcare Resource Group codes were used for costing. RESULTS: A total of 199 matched patients were included. The [177Lu]Lu-DOTA-TATE cohort had lower overall costs (£1,882,028 vs. £3,016,321; p < .0001), non-elective inpatient spells (289 vs. 611 days) and costs (£849,569 vs. £1,707,109; p < .0001 for both), Accident & Emergency costs (£41,978 vs. £62,480; p = .0013), and average length of stay for overall inpatient spells (14.2 vs. 23.3 days; p = .1092) compared with the non-[177Lu]Lu-DOTA-TATE cohort. CONCLUSIONS: These analyses indicate significantly lower overall costs and HCRU for progressive GEP-NET patients treated with [177Lu]Lu-DOTA-TATE. Current research reveals that future real-world analyses would further benefit from using additional databases linked to the HES dataset such as the Clinical Practice Research Datalink and/or National Cancer Registration and Analysis Service database.

Neuroendocrine neoplasms (NENs) are uncommon cancers involving the body's neuroendocrine cells. One type of NEN that is less aggressive with more favorable characteristics and prognosis is known as neuroendocrine tumor (NET). Somatostatin receptors (SSTR) are expressed by most NETs and are important treatment targets. Two-thirds of NETs originate in the body's gastroenteropancreatic system (GEP-NETs). GEP-NET is typically treated in the first instance with somatostatin analogs (SSAs), while other treatments such as chemotherapy, biologic targeted therapy, or Radio Ligand Therapy (RLT), can be offered to patients who have progressed. [¹⁷⁷Lu]Lu-DOTA-TATE is a form of RLT that has recently been approved for use in England, Wales, and Scotland.The purpose of this study is to analyze the utilization of healthcare resources and the costs associated with the management of GEP-NETs patients who have progressed on SSAs. This study is based on hospital data from England as available in the Hospital Episode Statistics dataset 2016­2018.The utilization and costs of healthcare resources were compared between two groups of patients. Following progression, one group received [¹⁷⁷Lu]Lu-DOTA-TATE, while the other group received other therapies (chemotherapy, biologic targeted therapy, or SSA with escalated or more frequent dosing). Statistical techniques were applied to enhance the comparability of analyzed groups of patients.The results revealed that the [¹⁷⁷Lu]Lu-DOTA-TATE group had lower inpatient admissions, outpatient appointments, and Accident & Emergency attendances compared with the non-[¹⁷⁷Lu]Lu-DOTA-TATE group. Furthermore, the overall costs in the [¹⁷⁷Lu]Lu-DOTA-TATE group were lower by 37.6%. This study indicated that patients and hospitals in England and other parts of the United Kingdom may benefit from the use of [¹⁷⁷Lu]Lu-DOTA-TATE. Further research is foreseen involving additional and linked databases, including further clinical outcomes as well.

[177Lu]Lu-DOTA-TATE versus standard of care in adult patients with gastro-enteropancreatic neuroendocrine tumours (GEP-NETs): a cost-consequence analysis from an Italian hospital perspective.

PURPOSE: To assess and compare clinical outcomes and costs, to the Italian healthcare system, of three therapeutic options approved in the management of adult patients with gastro-enteropancreatic neuroendocrine tumours (GEP-NETs). METHODS: We compared the efficacy, safety, and costs of [177Lu]Lu-DOTA-TATE, everolimus (both originator and generic products), and sunitinib in patients with advanced GEP-NETs (NET G1 and G2) that had progressed following treatment with somatostatin analogs (SSAs). A cost-consequence model was developed and validated by a panel of clinical experts from three NET reference centres in Italy. The clinical outcomes included in the model were median progression-free survival and the incidence of grade 3 or 4 adverse events (AEs), as reported in pivotal clinical trials. The costs for acquisition and administration of each treatment, and of managing AEs, were calculated from the perspective of the Italian national health service. Treatment costs per progression-free month were calculated separately for patients with NETs of pancreatic (PanNETs; all three treatments) and gastrointestinal (GI-NETs; [177Lu]Lu-DOTA-TATE and everolimus only) origin. RESULTS: In patients with PanNETs, total costs per progression-free month were €2989 for [177Lu]Lu-DOTA-TATE, €4975 for originator everolimus, €3472 for generic everolimus, and €5337 for sunitinib. In patients with GI-NETs, total costs per progression-free month were €3189 for [177Lu]Lu-DOTA-TATE, €4990 for originator everolimus, and €3483 for generic everolimus. CONCLUSIONS: [177Lu]Lu-DOTA-TATE was associated with lower costs per progression-free month versus relevant treatment options in patients with GI-NETs or PanNETs (NET G1-G2; progressed following SSA treatment), although acquisition and administration costs are higher. These findings provide further economic arguments in the overall context of treatment decision-making.

Use of [177Lu]Lu-DOTA-TATE in the treatment of gastroenteropancreatic neuroendocrine tumours: Results of a UK cost-effectiveness modelling study.

AIM: To evaluate the cost-effectiveness of [177Lu]Lu-DOTA-TATE versus relevant comparators for the treatment of neuroendocrine tumours located in the gastrointestinal tract (GI-NETs) and the pancreas (P-NETs). MATERIALS AND METHODS: A three-state partitioned survival model was developed to perform a cost-utility analysis of [177Lu]Lu-DOTA-TATE versus standard of care (high dose Octreotide LAR), everolimus and sunitinib. Effectiveness data for SoC, everolimus and sunitinib were obtained from published Kaplan-Meier survival curves. Given a lack of head-to-head effectiveness data, matching adjusted indirect comparisons (MAICs) were performed to population-adjust [177Lu]Lu-DOTA-TATE survival data based on prognostic factors and derive estimates of relative effectiveness. Health state utilities were estimated from real-world evidence. Drug acquisition costs were taken from nationally published sources (BNF, NICE), and administration costs were based on treatment protocols in [177Lu]Lu-DOTA-TATE studies, combined with nationally published unit costs (PSSRU, DoH reference costs). Incidence of adverse events were estimated using published sources. A discount rate of 3.5% was applied to both utilities and costs, and deterministic and probabilistic sensitivity analyses were performed. Costs were included from an NHS perspective and presented in 2017/18 GBP (and PPP Euros for base case). RESULTS: In GI-NETs, the incremental cost-effectiveness ratio (ICER) of [177Lu]Lu-DOTA-TATE compared to SoC and everolimus was £26,528 (€27,672) and £24,145 (€25,186) per QALY, respectively. In P-NETs, the ICER of [177Lu]Lu-DOTA-TATE compared to SoC was £22,146 (€23,101) or £28,038 (€29,251) dependent on matched population, and £21,827 (€22,766) and £15,768 (€16,445) compared to everolimus and sunitinib, respectively. CONCLUSIONS: At a willingness to pay threshold of £30,000, [177Lu]Lu-DOTA-TATE is likely to be a cost-effective treatment option for GI-NET and P-NET patients versus relevant treatment comparators (NHS perspective).

Estimation of Health-Related Utilities for 177Lu-DOTATATE in GEP-NET Patients Using Utilities Mapped from EORTC QLQ-C30 to EQ-5D-3L and QLU-C10D Utilities.

BACKGROUND: Gastroenteropancreatic neuroendocrine tumours (GEP-NET) are a rare, life-threatening type of cancer. The survival benefit of 177Lu-DOTATATE has been demonstrated in GEP-NET patients. Health technology assessment bodies require data on health-related utility impacts of treatment. A cancer-specific instrument, EORTC QLQ-C30, was used to collect the data for 177Lu-DOTATATE within clinical studies, but utility-based instruments were not included. OBJECTIVE: The main aim of this study was to compare EQ-5D-3L and QLU-C10D utilities obtained from EORTC QLQ-C30 using two different approaches. A secondary aim was to analyse the EQ-5D-3L and QLU-C10D utilities of patients treated with 177Lu-DOTATATE versus best supportive care. A supplementary aim was to evaluate the effect of 177Lu-DOTATATE on patients' health-related utility over time. METHODS: Three datasets were used for the analysis. NETTER-1 is a clinical trial, whilst ERASMUS and Guy's and St. Thomas (GStT) are real-world datasets. Two mapping algorithms (response mapping and ordinary least square regression) were applied to generate EQ-5D-3L utilities from EORTC QLQ-C30. An algorithm was used to obtain QLU-C10D utilities from EORTC QLQ-C30. RESULTS: In all studies, EQ-5D-3L utilities were higher than QLU-C10D utilities at most time points measured, although the magnitude of the differences was small. In NETTER-1, EQ-5D-3L and QLU-C10D utilities were higher in the 177Lu-DOTATATE arm compared with the octreotide long-acting release (LAR) arm, overall and pre-progression. In all studies, patients' health-related utilities seem to be maintained over time. CONCLUSION: There were small differences between EQ-5D-3L and QLU-C10D utilities, but these did not translate to relative differences over time or between groups. In NETTER-1, patients in the 177Lu-DOTATATE arm had higher health-related utilities than patients in the octreotide LAR arm. Health-related utility may at least remain maintained in patients with GEP-NET receiving 177Lu-DOTATATE.

Symptom Diaries of Patients with Midgut Neuroendocrine Tumors Treated with 177Lu-DOTATATE.

We report the impact of 177Lu DOTATATE treatment on abdominal pain, diarrhea, and flushing, symptoms that patients with advanced midgut neuroendocrine tumors (NETs) often find burdensome. Methods: All patients enrolled in the international randomized phase 3 Neuroendocrine Tumors Therapy (NETTER-1) trial (177Lu-DOTATATE plus standard-dose octreotide long-acting repeatable [LAR], n = 117; high-dose octreotide LAR, n = 114) were asked to record the occurrence of predefined symptoms in a daily diary. Change from baseline in symptom scores (mean number of days with a symptom) was analyzed using a mixed model for repeated measures. Results: Patients (intent-to-treat) who received 177Lu-DOTATATE experienced a significantly greater decline from baseline in symptom scores than patients who received high-dose octreotide LAR. For 177Lu-DOTATATE, the mean decline in days with abdominal pain, diarrhea, and flushing was 4.10, 4.55, and 4.52 days per 4 weeks, respectively, compared with 0.99, 1.44, and 2.54 days for high-dose octreotide LAR. The mean differences were 3.11 days (95% confidence interval, 1.35-4.88; P = 0.0007) for abdominal pain, 3.11 days (1.18-5.04; P = 0.0017) for diarrhea, and 1.98 days (0.08-3.88; P = 0.0413) for flushing, favoring 177Lu-DOTATATE. A positive repeated measures correlation was found between diary-recorded symptom scores and questionnaire-recorded pain, diarrhea, and flushing. Conclusion: In addition to efficacy and quality of life benefits, symptom diaries from NETTER-1 demonstrated that treatment with 177Lu DOTATATE was associated with statistically significant reductions in abdominal pain, diarrhea, and flushing, constituting the core symptoms of patients with progressive midgut NETs, compared with high-dose octreotide LAR, supporting a beneficial effect of 177Lu DOTATATE on HRQoL.

Peptide receptor radiotherapy re-treatment in patients with progressive neuroendocrine tumors: A systematic review and meta-analysis.

BACKGROUND: This review and meta-analysis examined published evidence of peptide receptor radionuclide therapy (PRRT) re-treatment efficacy and safety in patients with advanced neuroendocrine tumors (NETs). METHODS: Embase, MEDLINE, MEDLINE In-Progress, and Cochrane CENTRAL were searched (database inception-present) to identify evidence of efficacy and safety of PRRT re-treatment in adults with NETs previously treated with 177Lu- and/or 90Y-PRRT. Progression-free survival (PFS), overall survival (OS), disease control rate (DCR) from time of re-treatment were assessed. Data were pooled using medians and variance for time-to-event outcomes and inverse-variance weighted proportions (Freeman-Tukey method) for binary outcomes. RESULTS: Of 567 studies screened, 13 reported re-treatment efficacy outcomes. In random-effects meta-analyses of 177Lu-PRRT re-treatment, median PFS (N = 7 studies [414patients]) was 12.52 months (95% CI 9.82-15.22) with moderate heterogeneity across studies (I2 = 50.5%), median OS (N = 2 [194 patients]) was 26.78 months (95% CI 18.73-34.83) with moderate-to-high heterogeneity (I2 = 57.5%), and DCR (N = 8 [347 patients]) was 71% (95% CI 66-75) with high heterogeneity (I2 = 81.5%). PFS was similar with either 177Lu-PRRT re-treatment alone or in combination with 90Y-PRRT. Grade 3/4 adverse events occurred in 5% (95% CI 2-8) of patients receiving 177Lu-PRRT re-treatment (N = 5 [271 patients]) with few grade 3/4 renal toxicities (0% [95% CI 0-1]). Pooled myelodysplastic syndrome and acute myeloid leukemia incidence was 0% (95%CI 0-2). CONCLUSION: Re-treatment with 177Lu-PRRT provided encouraging median PFS in patients with NETs with a safety profile similar to initial PRRT.

Cost-effectiveness of lutetium (177Lu) oxodotreotide vs everolimus in gastroenteropancreatic neuroendocrine tumors in Norway and Sweden.

BACKGROUND: Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) represent a relatively rare and heterogenous group of tumors. Currently available treatment options for patients with progressive GEP-NETs include lutetium (177Lu) oxodotreotide (177Lu-Dotatate) and everolimus [as well as sunitinib for patients with pancreatic NETs (P-NETs)]. AIM: To perform a health economic analysis to determine the cost-effectiveness of 177Lu-Dotatate compared with everolimus in patients with unresectable or metastatic midgut-NETs or P-NETs in both Sweden and Norway. METHODS: Simulations were performed using a three-state partitioned survival model and analyses were performed separately for patients with midgut-NETs and P-NETs. Clinical input data were sourced from an indirect comparison that utilized survival data from clinical trials of 177Lu-Dotatate and everolimus. The analyses were performed from the healthcare payer perspective over a time horizon of 20 years. For Sweden, future costs and clinical outcomes were discounted at 3% per annum. For Norway, a discount rate of 4% per annum was applied. RESULTS: For Sweden, improved survival outcomes and higher lifetime costs with 177Lu-Dotatate resulted in an incremental cost-effectiveness ratio (ICER) of SEK 391194 per quality-adjusted life year (QALY) gained for midgut NETs and SEK 16764 per QALY gained for P-NETs for 177Lu-Dotatate compared with everolimus. For Norway, the corresponding ICERs were NOK 244444 per QALY gained and NOK 106451 per QALY gained, respectively. One-way sensitivity analyses revealed that the results were most sensitive to changes in drug acquisition costs and health state utility values. CONCLUSION: In both Sweden and Norway, from a healthcare provider perspective, 177Lu-Dotatate is likely to be considered cost-effective relative to everolimus for the treatment of patients with unresectable or metastatic, progressive midgut-NETs or P-NETs.

Quality of life in patients with gastroenteropancreatic tumours: A systematic literature review.

BACKGROUND: Gastroenteropancreatic neuroendocrine tumours (GEP-NETs) are slow-growing cancers that arise from diffuse endocrine cells in the gastrointestinal tract (GI-NETs) or the pancreas (P-NETs). They are relatively uncommon, accounting for 2% of all gastrointestinal malignancies. The usual treatment options in advanced GEP-NET patients with metastatic disease include chemotherapy, biological therapies, and peptide receptor radionuclide therapy. Understanding the impact of treatment on GEP-NET patients is paramount given the nature of the disease. Health-related quality of life (HRQoL) is increasingly important as a concept reflecting the patients' perspective in conjunction with the disease presentation, severity and treatment. AIM: To conduct a systematic literature review to identify literature reporting HRQoL data in patients with GEP-NETs between January 1985 and November 2019. METHODS: The PRISMA guiding principles were applied. MEDLINE, Embase and the Cochrane library were searched. Data extracted from the publications included type of study, patient population data (mid-gut/hind-gut/GI-NET/P-NET), sample size, intervention/comparators, HRQoL instruments, average and data spread of overall and sub-scores, and follow-up time for data collection. RESULTS: Forty-three publications met the inclusion criteria. The heterogeneous nature of the different study populations was evident; the percentage of female participants ranged between 30%-60%, whilst average age ranged from 53.8 to 67.0 years. Eight studies investigated GI-NET patients only, six studies focused exclusively on P-NET patients and the remaining studies involved both patient populations or did not report the location of the primary tumour. The most commonly used instrument was the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (n = 28) with consistent results across studies; the GI-NET-specific module Quality of Life Questionnaire-GINET21 was used in six of these studies. A number of randomised trials demonstrated no HRQoL changes between active treatment and placebo arms. The Phase III NETTER-1 study provides the best data available for advanced GEP-NET patients; it shows that peptide receptor radionuclide therapy can significantly improve GEP-NET patients' HRQoL. CONCLUSION: HRQoL instruments offer a means to monitor patients' general disease condition, disease progression and their physical and mental well-being. Instruments including the commonly used European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-C30 and GINET21 lack, however, validation and a defined minimal clinical important difference specifically for GI-NET and P-NET patients.

The Costs of Implementing Vaccination With the RTS,S Malaria Vaccine in Five Sub-Saharan African Countries.

Background. The World Health Organization has recommended pilot implementation of a candidate vaccine against malaria (RTS,S/AS01) in selected sub-Saharan African countries. This exploratory study aimed to estimate the costs of implementing RTS,S in Burkina Faso, Ghana, Kenya, Mozambique, and Tanzania. Methods. Key informants of the expanded program on immunization at all levels in each country were interviewed on the resources required for implementing RTS,S for routine vaccination. Unit prices were derived from the same sources or from international price lists. Incremental costs in 2015 US dollars were aggregated per fully vaccinated child (FVC). It was assumed the four vaccine doses were either all delivered at health facilities or the fourth dose was delivered in an outreach setting. Results. The costs per FVC ranged from US$25 (Burkina Faso) to US$37 (Kenya) assuming a vaccine price of US$5 per dose. Across countries, recurrent costs represented the largest share dominated by vaccines (including wastage) and supply costs. Non-recurrent costs varied substantially across countries, mainly because of differences in needs for hiring personnel, in wages, in cold-room space, and equipment. Recent vaccine introductions in the countries may have had an impact on resource availability for a new vaccine implementation. Delivering the fourth dose in outreach settings raised the costs, mostly fuel, per FVC by less than US$1 regardless of the country. Conclusions. This study provides relevant information for donors and decision makers about the cost of implementing RTS,S. Variations within and across countries are important and the unknown future price per dose and wastage rate for this candidate vaccine adds substantially to the uncertainty about the actual costs of implementation.

Cost-effectiveness analysis of infant pneumococcal vaccination with PHiD-CV in Korea.

BACKGROUND: Streptococcus pneumoniae and non-typeable Haemophilus influenzae (NTHi) can cause invasive pneumococcal diseases (IPD), pneumonia, and acute otitis media (AOM). Both the 10-valent pneumococcal NTHi protein D conjugate vaccine (PHiD-CV) and the 13-valent pneumococcal conjugate vaccine (PCV-13) are included in the National Immunization Program for infants in Korea. This study aimed to evaluate the cost-effectiveness of the 3+1 schedule of PHiD-CV versus that of PCV-13 for National Immunization Program in Korea. METHODS: A published Markov model was adapted to evaluate the cost-effectiveness of vaccinating the 2012 birth cohort with PHiD-CV vs. PCV-13 from the Korean government perspective over 10 y. Best available published data were used for epidemiology, vaccine efficacy and disutilities. Data on incidence and direct medical costs were taken from the national insurance claims database. Sensitivity analyses were conducted to explore the robustness of the results. RESULTS: PHiD-CV was projected to prevent an additional 195,262 cases of pneumococcal diseases and NTHi-related diseases vs. PCV-13, with a substantially greater reduction in NTHi-related AOM and a comparable reduction in IPD and community-acquired pneumonia. Parity-priced PHiD-CV generated a health gain of about 844 quality-adjusted life years and a total cost-saving of approximately 4 million United States Dollars (USD) over 10 y. 93% of probabilistic simulations found PHiD-CV 3+1 to be the dominant vaccine option. CONCLUSION: Compared to PCV-13, PHiD-CV was projected to provide similar prevention against IPD and community-acquired pneumonia but would prevent more cases of AOM. Parity-priced PHiD-CV was anticipated to generate substantial cost-savings and health benefits vs. PCV-13 in Korea.

Cost-effectiveness analysis of routine pneumococcal vaccination in the UK: a comparison of the PHiD-CV vaccine and the PCV-13 vaccine using a Markov model.

OBJECTIVES: In 2010, the 13-valent pneumococcal conjugate vaccine (PCV-13) replaced the 7-valent vaccine (introduced in 2006) for vaccination against invasive pneumococcal diseases (IPDs), pneumonia and acute otitis media (AOM) in the UK. Using recent evidence on the impact of PCVs and epidemiological changes in the UK, we performed a cost-effectiveness analysis (CEA) to compare the pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) with PCV-13 in the ongoing national vaccination programme. DESIGN: CEA was based on a published Markov model. The base-case scenario accounted only for direct medical costs. Work days lost were considered in alternative scenarios. SETTING: Calculations were based on serotype and disease-specific vaccine efficacies, serotype distributions and UK incidence rates and medical costs. POPULATION: Health benefits and costs related to IPD, pneumonia and AOM were accumulated over the lifetime of a UK birth cohort. INTERVENTIONS: Vaccination of infants at 2, 4 and 12 months with PHiD-CV or PCV-13, assuming complete coverage and adherence. OUTCOME MEASURES: The incremental cost-effectiveness ratio (ICER) was computed by dividing the difference in costs between the programmes by the difference in quality-adjusted life-years (QALY). RESULTS: Under our model assumptions, both vaccines had a similar impact on IPD and pneumonia, but PHiD-CV generated a greater reduction in AOM cases (161 918), AOM-related general practitioner consultations (31 070) and tympanostomy tube placements (2399). At price parity, PHiD-CV vaccination was dominant over PCV-13, saving 734 QALYs as well as £3.68 million to the National Health Service (NHS). At the lower list price of PHiD-CV, the cost-savings would increase to £45.77 million. CONCLUSIONS: This model projected that PHiD-CV would provide both incremental health benefits and cost-savings compared with PCV-13 at price parity. Using PHiD-CV could result in substantial budget savings to the NHS. These savings could be used to implement other life-saving interventions.

Cost-Effectiveness Evaluation of the 10-Valent Pneumococcal Non-typeable Haemophilus influenzae Protein D Conjugate Vaccine and 13-Valent Pneumococcal Vaccine in Japanese Children.

INTRODUCTION: Diseases caused by Streptococcus pneumoniae represent a major public health problem. The purpose of this study was to compare, in the Japanese context, the projected health benefits, costs and cost-effectiveness of the latest generation of pneumococcal conjugate vaccines which may provide important insight into the potential public health impact of interventions in the context of local disease-specific epidemiology. METHODS: A Markov model was used to compare two vaccination strategies which involve routine infant immunization with either the 13-valent pneumococcal conjugate vaccine (PCV-13; Prevenar 13™, Pfizer, Pearl River, NY, USA) or the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV; Synflorix™, GlaxoSmithKline Biologicals SA, Rixensart, Belgium) over a time horizon of 5 years from the healthcare provider and societal perspectives. Estimates for key model parameters were obtained from locally available databases and published literature. Incremental benefits in terms of costs and quality-adjusted life-year and cost-effectiveness were assessed. RESULTS: A 3 + 1 vaccination schedule for infants with PHiD-CV is expected to have a similar impact on invasive pneumococcal disease and pneumonia and a larger impact on acute otitis media-related outcomes compared with PCV-13. Assuming price parity for these vaccines, the model projected that vaccination with PHiD-CV would result in cost savings of 1.9 and 3.9 billion Japanese yen from the provider and societal perspectives, respectively. This was largely due to a reduction in highly prevalent acute otitis media. Vaccination with PHiD-CV was expected to generate a gain of 433 quality-adjusted life-years compared to PCV-13 translating into dominance over PCV-13. Sensitivity analyses showed robustness of model outcome to changes in key model parameters and substantiated that the model outcome was consistently driven by the incremental benefit of PHiD-CV in averting acute otitis media. CONCLUSION: In comparison to PCV-13, vaccination with PHiD-CV is projected to be cost saving for Japan from both the healthcare provider and societal perspectives.

Adjunctive psychosocial therapies for the treatment of schizophrenia.

Antipsychotic pharmacotherapy is the standard of care for the treatment of schizophrenia. Although pharmacotherapy effectively improves some symptoms, others can remain. Pharmacotherapy alone also tends to produce only limited improvement in social functioning and quality of life. Supportive psychosocial therapies have been used as adjuncts to pharmacotherapy to help alleviate residual symptoms and to improve social functioning and quality of life. Additionally, therapies with psychoeducational components can focus on improving medication adherence and reducing relapse and rehospitalization. This review describes the major psychosocial therapeutic strategies that have been used effectively in patients with schizophrenia (cognitive-behavioral therapy, family intervention, social skills, and cognitive remediation), with emphasis on their utility in improving medication adherence. Therapies that integrate various psychosocial therapeutic approaches are also discussed. It is concluded that psychosocial therapy is an effective adjunct to pharmacotherapy for schizophrenia. However, these therapies vary significantly in the functional domains that they address. It is therefore important to identify the form of psychosocial intervention most likely to benefit the individual patient, and to recognize that the effectiveness of any psychosocial intervention could be influenced by such factors as the presence and severity of psychotic or affective symptoms or cognitive impairment.

Physician observations and perceptions of positive and negative symptoms of schizophrenia: a multinational, cross-sectional survey.

PURPOSE: To describe physicians' observations and perceptions of patients with schizophrenia and to obtain information about antipsychotic prescribing practices. METHODS: Psychiatrists in the United States and five European countries (France, Germany, Italy, Spain, and the United Kingdom) who prescribed antipsychotics for >or=15 patients with schizophrenia within the preceding 3 months provided data on their patients' demographic and clinical characteristics and their antipsychotic prescribing practices and drug attributes influencing treatment choice. RESULTS: Data were collected from 872 physicians on 6523 patients (85% European, 15% US). Most patients were aged 25-44 years, 63% were men, and 66% were outpatients. About 50% of patients were moderately to grossly dysfunctional; about 50% were unemployed; 34% and 75% were taking conventional or atypical antipsychotics, respectively. Frequently identified positive symptoms included delusions (73%), disordered thought (59%), and hallucinations (59%); common negative symptoms included social withdrawal (54%), impoverished thought (39%), and blunted affect (38%). Reasons for antipsychotic selection included efficacy for positive (90%) or negative symptoms (62%) and tolerability (47%). Inadequate control was reported more frequently for negative (71-77%) than positive (47-60%) symptoms. Adverse events included sedation, weight gain, and extrapyramidal symptoms. CONCLUSIONS: In this large, multinational, cross-sectional survey, physicians reported that positive symptoms were more common than negative symptoms. Treatment for positive symptoms was more successful than that for negative symptoms, with physicians considering treatment inadequate for >70% of patients with negative symptoms.

Fondaparinux or enoxaparin for the initial treatment of symptomatic deep venous thrombosis: a randomized trial.

BACKGROUND: The current standard initial therapies for deep venous thrombosis are low-molecular-weight heparin and unfractionated heparin. In a dose-ranging study of patients with symptomatic deep venous thrombosis, fondaparinux had efficacy and a safety profile similar to those of low-molecular-weight heparin (dalteparin). OBJECTIVE: To evaluate whether fondaparinux has efficacy and safety similar to those of enoxaparin in patients with deep venous thrombosis. DESIGN: Randomized, double-blind study. SETTING: 154 centers worldwide. PATIENTS: 2205 patients with acute symptomatic deep venous thrombosis. INTERVENTION: Fondaparinux, 7.5 mg (5.0 mg in patients weighing <50 kg and 10.0 mg in patients weighing >100 kg) subcutaneously once daily, or enoxaparin, 1 mg/kg of body weight, subcutaneously twice daily for at least 5 days and until vitamin K antagonists induced an international normalized ratio greater than 2.0. MEASUREMENTS: The primary efficacy outcome was the 3-month incidence of symptomatic recurrent venous thromboembolic complications. The main safety outcomes were major bleeding during initial treatment and death. An independent, blinded committee adjudicated all outcomes. RESULTS: 43 (3.9%) of 1098 patients randomly assigned to fondaparinux had recurrent thromboembolic events compared with 45 (4.1%) of 1107 patients randomly assigned to enoxaparin (absolute difference, -0.15 percentage point [95% CI, -1.8 to 1.5 percentage points]). Major bleeding occurred in 1.1% of patients receiving fondaparinux and 1.2% of patients receiving enoxaparin. Mortality rates were 3.8% and 3.0%, respectively. LIMITATIONS: Follow-up was incomplete in 0.4% of fondaparinux-treated patients and 1.0% of enoxaparin-treated patients. CONCLUSIONS: Once-daily subcutaneous fondaparinux was at least as effective (not inferior) and safe as twice-daily, body weight-adjusted enoxaparin in the initial treatment of patients with symptomatic deep venous thrombosis.