Multiple myeloma incidence, mortality, and prevalence estimates and projections, Australia, 1982-2043: a statistical modelling study.

OBJECTIVES: To examine changes in multiple myeloma incidence and mortality rates during 1982-2018, and to estimate its incidence, mortality, and prevalence for 2019-2043. STUDY DESIGN: Population-based statistical modelling study; analysis of and projections based on Australian Institute of Health and Welfare multiple myeloma incidence, mortality, and survival data. SETTING: Australia, 1982-2018 (historical data) and projections to 2043. MAIN OUTCOME MEASURES: Changes in multiple myeloma incidence and mortality rates, 1982-2018, determined by joinpoint regression analysis (age-standardised to 2021 Australian population); projection of rates to 2043 based on age-period-cohort models; estimated 5- and 30-year prevalence of multiple myeloma (modified counting method). RESULTS: The incidence of multiple myeloma increased during 1982-2018 (eg, annual percentage change [APC], 2006-2018, 1.9%; 95% confidence interval [CI], 1.7-2.2%), but the mortality rate declined during 1990-2018 (APC, -0.4%; 95% CI, -0.5% to -0.2%). The age-standardised incidence rate was projected to increase by 14.9% during 2018-2043, from 8.7 in 2018 to 10.0 (95% CI, 9.4-10.7) new cases per 100 000 population in 2043; the mortality rate was projected to decline by 27.5%, from 4.0 to 2.9 (95% CI, 2.6-3.3) deaths per 100 000 population. The annual number of people newly diagnosed with multiple myeloma was estimated to increase by 89.2%, from 2120 in 2018 to 4012 in 2043; the number of deaths from multiple myeloma was projected to increase by 31.7%, from 979 to 1289. The number of people living with multiple myeloma up to 30 years after initial diagnosis was projected to increase by 163%, from 10 288 in 2018 to 27 093 in 2043, including 13 019 people (48.1%) diagnosed during the preceding five years. CONCLUSION: Although the decline in the mortality rate was projected to continue, the projected increases in the incidence and prevalence of multiple myeloma in Australia over the next 25 years indicate that investment in prevention and early detection research, and planning for prolonged treatment and care, are needed.

Economic Evaluation of National Patient Blood Management Clinical Guidelines in Cardiac Surgery.

OBJECTIVES: To the best of our knowledge, no published clinical guidelines have ever undergone an economic evaluation to determine whether their implementation represented an efficient allocation of resources. Here, we perform an economic evaluation of national clinical guidelines designed to reduce unnecessary blood transfusions before, during, and after surgery published in 2012 by Australia's sole public blood provider, the National Blood Authority (NBA). METHODS: We performed a cost analysis from the government perspective, comparing the NBA's cost of implementing their perioperative patient blood management guidelines with the estimated resource savings in the years after publication. The impact on blood products, patient outcomes, and medication use were estimated for cardiac surgeries only using a large national registry. We adopted conservative counterfactual positions over a base-case 3-year time horizon with outcomes predicted from an interrupted time-series model controlling for differences in patient characteristics and hospitals. RESULTS: The estimated indexed cost of implementing the guidelines of A$1.5 million (2018-2019 financial year prices) was outweighed by the predicted blood products resource saving alone of A$5.1 million (95% confidence interval A$1.4 million-A$8.8 million) including savings of A$2.4 million, A$1.6 million, and A$1.2 million from reduced red blood cell, platelet, and fresh frozen plasma use, respectively. Estimated differences in patient outcomes were highly uncertain and estimated differences in medication were financially insignificant. CONCLUSIONS: Insofar as they led to a reduction in red blood cell, platelet, and fresh frozen plasma use during cardiac surgery, implementing the perioperative patient blood management guidelines represented an efficient use of the NBA's resources.

A systematic review and network meta-analysis of incentive- and non-incentive-based interventions for increasing blood donations.

BACKGROUND AND OBJECTIVES: Blood services are tasked with efficiently maintaining a reliable blood supply, and there has been much debate over the use of incentives to motivate prosocial activities. Thus, it is important to understand the relative effectiveness of interventions for increasing donations. MATERIALS AND METHODS: This systematic review used a broad search strategy to identify randomized controlled trials comparing interventions for increasing blood donations. After full-text review, 28 trials from 25 published articles were included. Sufficient data for meta-analysis were available from 27 trials. Monetary incentives were assumed to be equivalent regardless of value, and non-monetary incentives were assumed to be equivalent regardless of type. Non-incentive-based interventions identified included existing practice, letters, telephone calls, questionnaires, and the combination of a letter & telephone call. A network meta-analysis was used to pool the results from identified trials. A subgroup analysis was performed in populations of donors and non-donors as sensitivity analyses. RESULTS: The best performing interventions were letter & telephone call and telephone call-only with odds ratios of 3·08 (95% CI: 1·99, 4·75) and 1·99 (95% CI: 1·47, 2·69) compared to existing practice, respectively. With considerable uncertainty around the pooled effect, we found no evidence that monetary incentives were effective at increasing donations compared to existing practice. Non-monetary incentives were only effective in the donor subgroup. CONCLUSION: When pooling across modes of interventions, letter & telephone call and telephone call-only are effective at increasing blood donations. The effectiveness of incentives remains unclear with limited, disparate evidence identified.

Fresh Red Cells for Transfusion in Critically Ill Adults: An Economic Evaluation of the Standard Issue Transfusion Versus Fresher Red-Cell Use in Intensive Care (TRANSFUSE) Clinical Trial.

OBJECTIVES: Trials comparing the effects of transfusing RBC units of different storage durations have considered mortality or morbidity as outcomes. We perform the first economic evaluation alongside a full age of blood clinical trial with a large population assessing the impact of RBC storage duration on quality-of-life and costs in critically ill adults. DESIGN: Quality-of-life was measured at 6 months post randomization using the EuroQol 5-dimension 3-level instrument. The economic evaluation considers quality-adjusted life year and cost implications from randomization to 6 months. A generalized linear model was used to estimate incremental costs (2016 U.S. dollars) and quality-adjusted life years, respectively while adjusting for baseline characteristics. SETTING: Fifty-nine ICUs in five countries. PATIENTS: Adults with an anticipated ICU stay of at least 24 hours when the decision had been made to transfuse at least one RBC unit. INTERVENTIONS: Patients were randomized to receive either the freshest or oldest available compatible RBC units (standard practice) in the hospital transfusion service. MEASUREMENTS AND MAIN RESULTS: EuroQol 5-dimension 3-level utility scores were similar at 6 months-0.65 in the short-term and 0.63 in the long-term storage group (difference, 0.02; 95% CI, -0.00 to 0.04; p = 0.10). There were no significant differences in resource use between the two groups apart from 3.0 fewer hospital readmission days (95% CI, -5.3 to -0.8; p = 0.01) during follow-up in the short-term storage group. There were no significant differences in adjusted total costs or quality-adjusted life years between the short- and long-term storage groups (incremental costs, -$2,358; 95% CI, -$5,586 to $711) and incremental quality-adjusted life years: 0.003 quality-adjusted life years (95% CI, -0.003 to 0.008). CONCLUSIONS: Without considering the additional supply cost of implementing a freshest available RBC strategy for critical care patients, there is no evidence to suggest that the policy improves quality-of-life or reduces other costs compared with standard transfusion practice.

The Cost-Effectiveness of the Integration of Nalmefene within the UK Healthcare System Treatment Pathway for Alcohol Dependence.

AIMS: To assess the cost-effectiveness of integrating nalmefene within the treatment pathway for alcohol dependence recommended by the National Institute for Health and Care Excellence in the UK. METHODS: A Markov model, taking a UK NHS perspective, followed a cohort with alcohol dependence and high/very high drinking risk levels (HVHDRLs), who do not require immediate detoxification and who continue at HVHDRLs after initial assessment, for 5 years. Costs and quality-adjusted life years (QALYs) from treatment with nalmefene plus psychosocial support versus psychosocial support alone were modelled. The consequent incidence of alcohol-attributable harmful events and disease progression, with the possibility of requiring other options or recurrent treatment, were captured. RESULTS: Nalmefene plus psychosocial support dominated psychosocial support alone, with lower costs and increased QALYs after 5 years. Savings are driven by the higher response to nalmefene, and the subsequent lower cost accumulation for alternatives. CONCLUSIONS: Nalmefene represents a highly cost-effective treatment option in this population. The analysis shows that integrating nalmefene within the current UK clinical treatment pathway for alcohol dependence could reduce the economic burden on the NHS by limiting harmful events and disease progression.

A propensity matched cost analysis of medical emergency team calls led by nurse practitioners versus intensive care registrars.

OBJECTIVES: Nurse practitioner-led MET calls have been shown to improve clinical outcomes versus ICU registrar-led MET calls. However, the cost implications of a nurse practitioner-led MET call system is not known. We conducted cost analysis from the healthcare service perspective to compare the costs of nurse practitioner- and ICU registrar-led MET calls. RESEARCH METHODOLOGY: A retrospective study of MET calls between 1 June 2016 and 9 March 2018 including patients with first MET call during their hospital admission. The cost analysis compared MET calls attended by nurse practitioners against those attended by ICU registrars. MAIN OUTCOME MEASURES: Inpatient costs for nurse practitioner- and ICU registrar-led MET calls. RESULTS: 1,343 MET calls were included in the full dataset with a mean cost per ICU registrar-led MET calls and nurse practitioner led MET calls of AU$19,836 (95 % CI: AU$15,778 - AU$23,895) versus AU$16,404 (95 % CI: AU$14,988 - AU$17,820) respectively and a difference of AU$3,432 (95 % CI: -AU$38 - AU$6,903, p = 0.053). In the propensity-score matched analysis, the mean cost per ICU registrar-led MET calls and nurse practitioner led MET calls was AU$19,009 (95 % CI: AU$15,439 - AU$22,578) and AU$13,937 (95 % CI: AU$12,038 - AU$15,835) respectively, with a difference of AU$5,072 (95 % CI: AU$1,061 - AU$9,082, p = 0.013). A 24-hour nurse practitioners-led MET call service would break even at 101 MET calls leading to ICU admissions per year. CONCLUSION: Nurse practitioners-led MET calls saved significant costs compared to ICU registrar-led MET calls. Assuming that the difference in costs is due to shorter ICU length of stay, a health service that receives more than 101 MET calls leading to ICU admissions per year can save costs with a 24-hour nurse practitioner-led MET call service. IMPLICATIONS FOR CLINICAL PRACTICE: This study helps in identifying the healthcare services where nurse practitioners -led MET systems could be implemented to be cost saving from health service perspective.

Developing and validating a discrete-event simulation model of multiple myeloma disease outcomes and treatment pathways using a national clinical registry.

Multiple myeloma is a haematological malignancy typically characterised by neoplastic plasma cell infiltration of the bone marrow. Treatment for multiple myeloma consists of multi-line chemotherapy with or without autologous stem cell transplantation and has been rapidly evolving in recent years. However, clinical trials are unable to provide patients and clinicians with long-term prognostic information nor policymakers with the full body of evidence needed to perform economic evaluation of new therapies or make reimbursement decisions. To address these limitations of the available evidence, this study aimed to develop and validate the EpiMAP Myeloma model, a discrete-event simulation model of multiple myeloma disease outcomes and treatment pathways. Risk equations were estimated using the Australian and New Zealand Myeloma & Related Diseases Registry after multiple imputation of missing data. Risk equation coefficients were combined with multiple myeloma patients at diagnosis from the Registry to perform the simulation. The model was validated with 100 bootstraps of an out-of-sample prediction analysis using a 70/30 split of the 4,121 registry patients diagnosed between 2009 and 2023, resulting in 2,884 and 1,237 patients in the training and validation cohorts, respectively. For 90% of the 120 months in the 10-year post-diagnosis period, there was no significant difference in overall survival between the validation and simulated cohorts. These results highlight that the EpiMAP Myeloma model is robust at predicting multiple myeloma disease outcomes and treatment pathways in Australia & New Zealand. In the future, clinicians will be able to use the EpiMAP Myeloma model to provide personalised estimates of life expectancy to patients based on their specific characteristics, disease stage, and response to treatment. Policymakers will also be able to use the model to perform economic evaluation, to forecast the number of patients receiving treatment at different stages, and to determine the downstream impact of listing new, effective therapies.

Economic evaluation: immunoglobulin vs prophylactic antibiotics in hypogammaglobulinemia and hematological malignancies.

ABSTRACT: Patients with hematological malignancies are at high risk of developing hypogammaglobulinemia (HGG) and infections. Immunoglobulin (Ig) is one recommended option to prevent these infections, but it is expensive, and its cost-effectiveness compared with other prevention strategies remains unknown. We conducted a trial-based economic evaluation from the Australian health care system perspective to estimate the 12-month cost-effectiveness of prophylactic Ig vs prophylactic antibiotics in 63 adults with HGG and hematological malignancies participating in the RATIONAL feasibility trial. Two analyses were conducted: (1) cost-utility analysis to assess the incremental cost per quality-adjusted life year (QALY) gained; and (2) cost-effectiveness analysis to assess the incremental cost per serious infection prevented (grade ≥3) and per any infection (any grade) prevented. Over 12 months, the total cost per patient was significantly higher in the Ig group than in the antibiotic group (mean difference, AU$29 140; P < .001). Most patients received IVIg, which was the main cost driver; only 2 patients in the intervention arm received subcutaneous Ig. There were nonsignificant differences in health outcomes. Results showed Ig was more costly than antibiotics and associated with fewer QALYs. The incremental cost-effectiveness ratio of Ig vs antibiotics was AU$111 262 per serious infection prevented, but Ig was more costly and associated with more infections when all infections were included. On average and for this patient population, Ig prophylaxis may not be cost-effective compared with prophylactic antibiotics. Further research is needed to confirm these findings in a larger population and considering longer-term outcomes. The trial was registered at the Australian and New Zealand Clinical Trials Registry as #ACTRN12616001723471.

Impact of patient blood management guidelines on blood transfusions and patient outcomes during cardiac surgery.

OBJECTIVE: In March 2012, Australia's National Blood Authority published national patient blood-management guidelines for perioperative care developed by a systematic review and clinical expert opinion. This study assesses how blood transfusions and patient outcomes in cardiac surgery changed after the guidelines were published. METHODS: Blood transfusions and patient outcomes in cardiac surgery were compared before and after implementation of the guidelines using an interrupted time series analysis. The evaluation included red blood cells, platelets, cryoprecipitate, fresh-frozen plasma, 30-day mortality, 30-day readmissions, and hospital and intensive care length of stay. Patient characteristics were controlled for along with hospital characteristics using fixed effects. Different responses across institutional settings were assessed with an expanded difference-in-differences model. RESULTS: After the guidelines were published, our model found a significant reduction in red blood cell, platelet, and fresh-frozen plasma transfusions. There was also a significant reduction in hospital length of stay but no significant impact on cryoprecipitate, 30-day mortality, 30-day readmissions, or intensive care unit length of stay. The subgroup analyses found no differences with regards to institutional settings. CONCLUSIONS: Following the publication of the guidelines, there was a measurable reduction in perioperative blood transfusions in cardiac surgery with an associated reduction in hospital length of stay but no detectable differences in other patient outcomes.

The Cost Effectiveness of Nalmefene for Reduction of Alcohol Consumption in Alcohol-Dependent Patients with High or Very High Drinking-Risk Levels from a UK Societal Perspective.

AIM: To evaluate costs and health outcomes of nalmefene plus psychosocial support, compared with psychosocial intervention alone, for reducing alcohol consumption in alcohol-dependent patients, specifically focusing on societal costs related to productivity losses and crime. METHODS: A Markov model was constructed to model costs and health outcomes of the treatments over 5 years. Analyses were conducted for nalmefene's licensed population: adults with both alcohol dependence and high or very high drinking-risk levels (DRLs) who do not require immediate detoxification and who have high or very high DRLs after initial assessment. The main outcome measure was cost per quality-adjusted life-year (QALY) gained as assessed from a UK societal perspective. Alcohol-attributable productivity loss, crime and health events occurring at different levels of alcohol consumption were taken from published risk-relation studies. Health-related and societal costs were drawn from public data and the literature. Data on the treatment effect, as well as baseline characteristics of the modelled population and utilities, came from three pivotal phase 3 trials of nalmefene. RESULTS: Nalmefene plus psychosocial support was dominant compared with psychosocial intervention alone, resulting in QALYs gained and reduced societal costs. Sensitivity analyses showed that this conclusion was robust. Nalmefene plus psychosocial support led to per-patient reduced costs of £3324 and £2483, due to reduced productivity losses and crime events, respectively. CONCLUSION: Nalmefene is cost effective from a UK societal perspective, resulting in greater QALY gains and lower costs compared with psychosocial support alone. Nalmefene demonstrates considerable public benefits by reducing alcohol-attributable productivity losses and crime events in adults with both alcohol dependence and high or very high DRLs who do not require immediate detoxification and who have high or very high DRLs after initial assessment.

A systematic literature review of utility weights in wet age-related macular degeneration.

OBJECTIVE: The objective of the study was to conduct a systematic review of utility weight estimates relevant to economic models for wet age-related macular degeneration (wAMD). METHODS: A systematic literature search of PubMed, Embase, the Cochrane Library, and EconLit was performed (January 1995-December 2010) and then updated (October 2010-May 2012; February 2012-July 2013) identifying articles reporting utilities in patients with wAMD and visual impairment. Extracted studies were also assessed for compliance with the NICE reference case. RESULTS: Of 2415 articles identified from the searches, 212 articles were reviewed in full, and 17 selected for data extraction. Most studies used time trade-off (TTO) techniques to estimate utilities; other methods included standard gamble, EuroQoL Health Questionnaire 5 Dimensions (EQ-5D); Short-Form 6D Health Status Questionnaire (SF-6D); and Health Utilities Index Mark III (HUI3). Correlation between utility estimates and visual acuity (VA) differed between the instruments. Time trade-off methods were more sensitive to VA changes than standard gamble methods. HUI3 estimates were most highly correlated with VA changes, followed by TTO; no trend was observed between VA and EQ-5D or SF-6D utility weights. Six of the 17 studies complied with the NICE reference case. CONCLUSIONS: Several instruments have been used to elicit utilities from patients with wAMD. Because TTO methods were more sensitive to VA changes than standard gamble and HUI3 estimates were most highly correlated with VA changes, TTO and HUI3 may be suitable methods for economic evaluations in these patients. The EQ-5D and SF-6D were poor indicators of the impact of VA on HRQL.