Navigating the future of Alzheimer's care in Ireland - a service model for disease-modifying therapies in small and medium-sized healthcare systems.

BACKGROUND: A new class of antibody-based drug therapy with the potential for disease modification is now available for Alzheimer's disease (AD). However, the complexity of drug eligibility, administration, cost, and safety of such disease modifying therapies (DMTs) necessitates adopting new treatment and care pathways. A working group was convened in Ireland to consider the implications of, and health system readiness for, DMTs for AD, and to describe a service model for the detection, diagnosis, and management of early AD in the Irish context, providing a template for similar small-medium sized healthcare systems. METHODS: A series of facilitated workshops with a multidisciplinary working group, including Patient and Public Involvement (PPI) members, were undertaken. This informed a series of recommendations for the implementation of new DMTs using an evidence-based conceptual framework for health system readiness based on [1] material resources and structures and [2] human and institutional relationships, values, and norms. RESULTS: We describe a hub-and-spoke model, which utilises the existing dementia care ecosystem as outlined in Ireland's Model of Care for Dementia, with Regional Specialist Memory Services (RSMS) acting as central hubs and Memory Assessment and Support Services (MASS) functioning as spokes for less central areas. We provide criteria for DMT referral, eligibility, administration, and ongoing monitoring. CONCLUSIONS: Healthcare systems worldwide are acknowledging the need for advanced clinical pathways for AD, driven by better diagnostics and the emergence of DMTs. Despite facing significant challenges in integrating DMTs into existing care models, the potential for overcoming challenges exists through increased funding, resources, and the development of a structured national treatment network, as proposed in Ireland's Model of Care for Dementia. This approach offers a replicable blueprint for other healthcare systems with similar scale and complexity.

Economic impact of 21-gene recurrence score testing on early-stage breast cancer in Ireland.

The 21-gene test is a validated multi-gene diagnostic test that predicts chemotherapy (CT) benefit in oestrogen receptor positive (ER+), lymph node-negative (N0) breast cancer (BC) patients (pts). Ireland was the first public health care system to reimburse this test in Europe. Study objectives were to assess the impact of this test on decision-making and to analyse the economic impact of testing. Between October 2011 and February 2013, a national, retrospective, cross-sectional observational study of ER+, N0 BC pts tested with the 21-gene test was conducted. Surveyed breast medical oncologists, provided the assumption for the decision impact analysis that grade (G) 1 pts would not have received CT before testing and G2/3 pts would have received CT before testing. Descriptive statistical analyses were performed. 592 pts were identified; Low, intermediate and high recurrence score were identified in 53, 36 and 10 % pts, respectively. 384 (70 %) pts had G2, 129 (22 %) G3 and 76 (13 %) G1 tumours. Post testing, 345 pts (59 %) experienced a change in CT decision; 339 changed to hormone therapy alone and 6 advised to receive CT. 172 (30 %) pts received CT, 12 (3.9 %) of pts with low scores, 108 (50.9 %) of intermediate risk and 50 (90.9 %) of pts with high risk scores. Net reduction in CT use was 58 % and net savings achieved were €793,565. Since public reimbursement, the introduction of the 21-gene test has resulted in a significant reduction in chemotherapy administration and cost savings for the Irish public healthcare system.

Eribulin for the treatment of advanced or metastatic breast cancer: a NICE single technology appraisal.

The National Institute for Health and Care Excellence (NICE) invited the manufacturer of eribulin (Eisai Ltd) to submit evidence for the clinical and cost effectiveness of eribulin as treatment for patients with locally advanced or metastatic breast cancer (LABC/MBC) pre-treated with at least two chemotherapy regimens. This article summarizes the review of evidence by the Evidence Review Group (ERG) and provides a summary of the NICE Appraisal Committee's (AC's) decision. The clinical evidence was derived from a multi-centred, open-label, randomized, phase III study comparing eribulin with treatment of physician's choice (TPC) in 762 patients with LABC/MBC. Clinical effectiveness results were submitted for two populations: the overall intention-to-treat (ITT) population and a subset (n = 488) that included only patients from North America, Western Europe and Australia (Region 1). For the primary endpoint of overall survival (OS), a primary analysis (after 55 % of patients had died) and an updated analysis (after 77 % of patients had died) were conducted. In the ITT population, treatment with eribulin was associated with a significant improvement in median OS compared with TPC in both primary [difference in median OS 2.5 months; hazard ratio (HR) 0.81, 95 % confidence interval (CI) 0.66-0.99] and updated analyses (2.7 months; HR 0.81, 95 % CI 0.67-0.96). A statistically significant improvement in progression-free survival (PFS) was reported for eribulin compared with TPC when assessed by the investigator (difference in median PFS 1.48 months; HR 0.76, 95 % CI 0.64-0.90), but not when assessed by the ERG (1.44 months; HR 0.87, 95 % CI 0.71-1.05). Gains in OS were greater for Region 1 patients than for the ITT population (3.1 vs. 2.7 months). Health-related quality of life (HRQoL) data suggested a benefit for eribulin responders, but was based on phase II studies. In the eribulin arm, serious adverse events included febrile neutropenia (4.2 %) and neutropenia (1.8 %), with peripheral neuropathy being the most common reason for treatment discontinuation. The manufacturer's economic evaluation using Patient Access Scheme costs reported a base-case incremental cost-effectiveness ratio (ICER) for eribulin versus TPC (Region 1) of £46,050 per quality-adjusted life year gained (corrected to £45,106 when an erroneous data entry was removed). The ERG's revised ICERs were £61,804 for Region 1 and £76,110 for the overall population. The AC concluded that the evidence had not demonstrated sufficient benefit in OS, cost effectiveness or HRQoL and that eribulin was not recommended for use in this patient group.

Assessing the real-world cost-effectiveness of adjuvant trastuzumab in HER-2/neu positive breast cancer.

BACKGROUND: Among women with surgically removed, high-risk HER-2/neu-positive breast cancer, trastuzumab has demonstrated significant improvements in disease-free and overall survival. The objective of this study is to evaluate the cost-effectiveness of the currently recommended 12-month adjuvant protocol of trastuzumab using a Markov modeling approach and real-world cost data. METHODS: A 10-health-state Markov model tracked patients' quarterly transitions between health states in the local and advanced states of breast cancer. Clinical data were obtained from the joint analysis of the National Surgical Adjuvant Breast and Bowel Project and North Central Cancer Treatment Group, as well as from the metastatic study conducted by Norum et al. Clinical outcomes were adjusted for quality of life using utility estimates published in a systematic review. Real cost data were obtained from the British Columbia Cancer Agency and were evaluated from a payer perspective. Costs and utilities were discounted at 5% per year, respectively, for a 28-year time horizon. RESULTS: In the base case analysis, treatment with a 12-month adjuvant trastuzumab regimen resulted in a gain of 1.38 quality-adjusted life years or 1.17 life years gained at a cost of $18,133 per patient. Thus, the cost per QALY gained for the base case is $13,095. Cost per LYG is $15,492. CONCLUSIONS: Over the long term, treatment of HER-2/neu mutation positive breast cancer with a 12-month protocol of trastuzumab in the adjuvant setting is predicted to be cost-effective in a Canadian context.

Renal safety of 1-hour pamidronate infusion for breast cancer and multiple myeloma patients: comparison between clinical trials and population-based database.

PURPOSE: The American Society of Clinical Oncology recommends infusion of pamidronate over 2 hours to avoid renal deterioration, although there are data to suggest that 1-hour infusions may be safe. METHODS: Prevalence of renal deterioration with 1-hour pamidronate infusions from a population database was compared to renal deterioration with 2-hour pamidronate infusions, in randomised, controlled, trials. A cost-minimisation analysis, comparing the 1- and 2-hour pamidronate infusions, and the 15-minute infusion of zoledronic acid, was performed with a sensitivity analysis that varied the opportunity cost of time in the treatment room. RESULTS: Renal deterioration occurred in 7.7% of 169 patients with multiple myeloma and metastatic breast cancer. There is no evidence that this differs from the 10% reported in randomised, controlled, trials (one-tailed binomial test, P = 0.3874). A subgroup analysis showed that renal deterioration occurred in 15 and 1.1% of patients with multiple myeloma and metastatic breast cancer, respectively. The median increase in serum creatinine was 13 and 7% in the multiple myeloma and breast cancer groups, respectively. The respective costs/dose (drug/labour/supplies) of pamidronate and zoledronic acid are 325 dollars and 610 dollars. Cost neutrality occurs if the opportunity cost of chair time is 6.33 dollars/minute for pamidronate 1-hour versus zoledronic acid, and 2.71 dollars/minute for pamidronate 2-hour versus zoledronic acid. If a median 4 dollars/minute is used, the respective costs of pamidronate 1-hour, 2-hour, and zoledronic acid infusions are 685 dollars, 925 dollars, and 790 dollars/cycle. CONCLUSIONS: Prevalence of renal deterioration with 1-hour pamidronate infusions from a population database was not significantly different to 2-hour pamidronate infusions in clinical trials. Our findings suggest further support for the safety of 1-hour pamidronate infusions. Pamidronate via 1-hour infusion is less expensive than zoledronic acid.