Real-world patient-reported outcomes of women receiving initial endocrine-based therapy for HR+/HER2- advanced breast cancer in five European countries.

BACKGROUND: Endocrine therapy (ET)-based regimens are the mainstay of treatment for patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) advanced breast cancer. With the introduction of new treatment classes, it is important to examine patient symptoms and health-related quality of life (HRQoL) at the start of this changing therapeutic landscape. This real-world study describes the patient-reported outcomes (PROs) of women with HR+/HER2- advanced breast cancer receiving ET-based regimens who were naïve to systemic treatment in the advanced setting across five European countries (EU5). METHODS: Data were collected between March and July 2017 from surveyed oncologists and their patients at a single time point using the multinational Adelphi Advanced Breast Cancer Disease Specific Programme™. Patients completed PRO questionnaires on HRQoL (EORTC QLQ-C30), pain severity and interference, and work and activity impairment. A multiple linear regression model explored factors associated with HRQoL. RESULTS: Across EU5, 226 physicians provided data on 781 women with HR+/HER2- advanced breast cancer taking their first ET-based regimen for advanced disease, of whom 252 provided PRO data. This subset had a mean age of 67.1 years, 94% were postmenopausal, 89% were diagnosed with advanced breast cancer at initial presentation, 79% had stage IV disease (66% of these patients had bone metastases and 38% had visceral metastases, including 18% with liver metastases) and 77% were on endocrine-only therapy as their initial treatment for advanced disease. The mean EORTC QLQ-C30 global health score (50.9) was worse than the reference value for patients with advanced breast cancer (60.2). Fatigue, pain, and insomnia were the most severe symptoms, and mean functioning scores were also worse than reference values. "Worst pain" and "pain interference" were moderate/severe for 42 and 80% of patients. Mean activity impairment was 44%, and greater activity impairment was associated with poorer HRQoL. CONCLUSIONS: Despite receiving first-line ET-based regimens for advanced disease, these women had a poor HRQoL and high levels of symptoms, pain, pain interference and activity impairment. New treatments that maintain a stable disease state and reduce activity impairment may have a positive effect on the HRQoL of those living with advanced breast cancer.

Efficacy of duloxetine versus alternative oral therapies: an indirect comparison of randomised clinical trials in chronic low back pain.

INTRODUCTION: The objective of this study was to obtain parameter estimates for the efficacy of duloxetine versus alternative oral therapies for the treatment of chronic low back pain. MATERIALS AND METHODS: Electronic databases were searched to identify randomised, double-blind placebo-controlled trials. Studies reporting pain intensity, with parallel-group design of oral treatments with length of treatment of more than 8 weeks were included. A Bayesian approach to indirect comparisons was applied, using standardised mean difference as a measure of relative treatment effect. RESULTS: Fifteen studies were identified comparing duloxetine with the following oral drug classes: non-scheduled opioids, cyclooxygenase-2 inhibitors, scheduled opioids, selective serotonin reuptake inhibitors, and 'other' (i.e. glucosamine). The primary analysis found scheduled opioids to be more effective than duloxetine for the fixed effects model. However, the estimate of the treatment difference reflected a less than small magnitude of effect (|standardised mean difference| <0.2), and there was no difference for the random effects model. No differences were found in sensitivity analyses involving the subset of patients not receiving concomitant non-steroidal anti-inflammatory medication. CONCLUSION: The available evidence shows that there does not seem to be any difference in efficacy between duloxetine and other oral pharmacological therapies, providing a valuable alternative for this disabling condition.

Cost-effectiveness analysis of abemaciclib with endocrine therapy (ET) versus ET alone for HR+, HER2-, node-positive, high-risk early breast cancer in Italy.

Background: Abemaciclib was recently approved by the European Medicines Agency in combination with adjuvant endocrine therapy (ET) for adult patients with hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2-), node-positive early breast cancer (EBC) at high risk of recurrence. Objective: To evaluate the cost-effectiveness of abemaciclib plus ET vs. ET alone in patients with HR+, HER2-, node-positive EBC at high risk of disease recurrence, from the Italian healthcare system perspective. Methods: A cohort state transition model was developed with five states: invasive disease-free survival (IDFS), nonmetastatic recurrence, remission, metastatic recurrence, and death. The analysis had a time horizon of 30 years. Individual patient-level data from the monarchE trial (NCT03155997) were used to generate IDFS estimates. Resource use included drug acquisition/administration, best supportive care, terminal care, adverse events, hospitalization, post-progression therapy, and associated resource use in the metastatic disease health state. Health state utilities were derived from monarchE patient-level data and other sources, applying Italian tariffs where feasible. Results: The estimated total discounted costs (€39,249 vs. €16,806; difference: €22,443) and quality-adjusted life years (QALYs) (11.49 vs. 10.50; difference: 0.99) were higher for abemaciclib plus ET compared with ET alone. The incremental cost-effectiveness ratio was €22,651 per QALY gained. The likelihood of abemaciclib plus ET being cost-effective vs. ET alone was 99% at a willingness-to-pay threshold of €30,000 per QALY gained. Conclusion: Abemaciclib plus ET is a cost-effective treatment option vs. ET alone for those with HR+, HER2- node-positive EBC at high risk of recurrence in Italy.

Timely symptom management at end of life using 'just in case' boxes.

This article discusses the successful implementation of anticipatory prescribing using 'just in case' boxes (JICB) in primary care across the Grampian region and a subsequent follow up survey one year later. The implementation approach used local educational sessions to primary care clinicians. The survey was distributed to 65 primary care bases to gauge awareness and use of the JICB and thoughts about how the box was used. An estimate of prescription costs was undertaken using stock balance forms. The response rate was 89%. All respondents had heard about the JICB and most had used a JICB. There were 37 positive comments about the benefits to patients, 15 comments about the process and 11 negative comments, often about possible drug wastage. The cost of a prescription was estimated at pounds 22.12. The findings have informed our ongoing educational programme and build on the strong links that exist between primary care and the specialist palliative care service.

Care bundles for acute kidney injury: a balanced accounting of the impact of implementation in an acute medical unit.

In 2009, a National Confidential Enquiry into Patient Outcome and Death report detailed significant shortcomings in recognition and management of patients with acute kidney injury (AKI). As part of a national collaborative to reduce harm from AKI, the Scottish Patient Safety Programme developed two care bundles to improve response ('SHOUT') and review ('BUMP') of AKI. Baseline data from eight patients with AKI on the acute medical unit (AMU) in Ninewells Hospital showed 62% compliance with SHOUT. However, most patients were transferred from AMU within 24 hours so BUMP could not be assessed. Our aim was to achieve >95% compliance with SHOUT on AMU within 2 months. The content of the SHOUT bundle was condensed onto a sticker for the case notes, which was implemented using Plan-Do-Study-Act cycles. Compliance was assessed weekly and feedback obtained from stakeholders concerning their opinion of the sticker, SHOUT bundle and care bundles in general. Use of the sticker was 27% in week 1 but fell to 5% by week 4. Compliance with the bundle varied from 45% to 60% and was only slightly improved by use of the sticker (OR 1.58, 95% CI 0.39 to 6.42). Staff found the sticker burdensome and did not agree that all elements of SHOUT were equally important. This opinion was supported by finding that their compliance with sepsis and hypovolaemia recommendations was 91%-100% throughout, whereas urinalysis was documented in only 55%-63% of patients. Several staff mentioned 'bundle fatigue' and on one day we identified 22 other care bundles or structured improvement forms in AMU. We concluded that the AMU staff had legitimate concerns about the SHOUT care bundle and that our intervention was demotivating. Overcoming bundle fatigue will not be a simple task. We plan to work with staff on integrating AKI into patient safety huddles and on using modelling and recognition of good practice to improve motivation.

Cost effectiveness of cilostazol compared with naftidrofuryl and pentoxifylline in the treatment of intermittent claudication in the UK.

OBJECTIVE: To estimate the cost effectiveness of cilostazol (Pletal) compared to naftidrofuryl and pentoxifylline (Trental) in the treatment of intermittent claudication in the UK. DESIGN AND SETTING: This was a modelling study on the management of patients with intermittent claudication who are 40 years of age or above and have at least six months history of symptomatic intermittent claudication, secondary to lower extremity arterial occlusive disease. The study was performed from the perspective of the UK's National Health Service (NHS). METHODS: Clinical outcomes attributable to managing intermittent claudication were obtained from the published literature and resource utilisation estimates were derived from a panel of vascular surgeons. Using decision analytical techniques, a decision model was constructed depicting the management of intermittent claudication with cilostazol, naftidrofuryl and pentoxifylline over 24 weeks in the UK. The model was used to estimate the cost effectiveness (at 2002/2003 prices) of cilostazol relative to the other treatments. MAIN OUTCOME MEASURES AND RESULTS: Starting treatment with cilostazol instead of naftidrofuryl is expected to increase the percentage improvement in maximal walking distance by 32% (from 57% to 75%) for a 12% increase in NHS costs (from 801 pounds sterling to 895 pounds sterling). Treatment with cilostazol instead of pentoxifylline is expected to increase the percentage improvement in maximal walking distance by 67% (from 45% to 75%) and reduce NHS costs by 2% (from 917 pounds sterling to 895 pounds sterling). Treatment with naftidrofuryl instead of pentoxifylline is expected to increase the percentage improvement in maximal walking distance by 27% (from 45% to 57%) and decrease NHS costs by 14% (from 917 pounds sterling to 801 pounds sterling). CONCLUSION: Within the limitations of our model, starting treatment with cilostazol is expected to be a clinically more effective strategy for improving maximal walking distance at 24 weeks than starting treatment with naftidrofuryl or pentoxifylline and potentially the most cost effective strategy. Moreover, the acquisition cost of a drug should not be used as an indication of the cost effectiveness of a given method of care.

Costs and consequences of using pamidronate compared with zoledronic acid in the management of breast cancer patients in the UK.

OBJECTIVE: To estimate the costs and consequences of using pamidronate compared to zoledronic acid in the prophylactic management of skeletal morbidity among breast cancer patients in the UK. DESIGN AND SETTING: This was a modelling study performed from the perspective of the UK's National Health Service (NHS). METHODS: Published clinical outcomes from a comparative study were combined with resource utilisation estimates derived from a panel of clinicians. This enabled the construction of a decision model depicting the management of patients with breast cancer receiving antineoplastic therapy who are 18 years of age or above and who have at least one bone metastasis (lytic or mixed). There are no significant differences in outcome between using pamidronate and zoledronic acid in breast cancer patients. Therefore, a cost minimisation analysis was performed to identify the treatment strategy that achieves the same outcome for least cost. The expected time attributable to a pamidronate and zoledronic acid infusion was also estimated. MAIN OUTCOME MEASURES AND RESULTS: Starting treatment with pamidronate among patients receiving chemotherapy is expected to lead to a healthcare cost of 6046 pounds over 12 months compared to 6981 pounds with zoledronic acid. In comparison, for patients receiving hormonal therapy, starting treatment with pamidronate is expected to lead to a healthcare cost of 5401 pounds over 12 months compared to 6043 pounds with zoledronic acid. This cost difference is primarily due to the lower acquisition cost of pamidronate and fewer tests among pamidronate-treated patients. Accordingly, pamidronate affords a less expensive management modality. Multivariate analysis showed the expected time attributable to a pamidronate infusion to be 110 to 277 minutes compared with 136 to 296 minutes for a zoledronic acid infusion. CONCLUSION: Use of pamidronate instead of zoledronic acid affords an economic benefit to the NHS. Moreover, published clinical trials show no statistical difference between pamidronate and zoledronic acid at 1 year. Hence, within the limitations of our model and the published evidence, pamidronate is the preferred first-line intravenous bisphosphonate for use in breast cancer patients receiving antineoplastic therapy who are 18 years of age or above and who have at least one bone metastasis (lytic or mixed).

Costs and consequences of botulinum toxin type A use. Management of children with cerebral palsy in Germany.

This study was a retrospective survey of the management of a cohort of children with cerebral palsy at Seepark Hospital, Germany, who did (cases; n=107) and did not (controls; n=107) receive botulinum toxin injections. Data on healthcare resource use and clinical outcomes over 12 months were collected from the date cases received their first injection and from the date controls were first admitted into hospital. Botulinum toxin use led to an 85% reduction in the number of children requiring surgery. Additionally, controls used significantly more healthcare resources than cases, particularly hospital bed days (69.2+/-34.1 vs. 27.5+/-27.9 days; p <0.0001). The total cost of managing cases and controls was 16,700 and 33,800, respectively. In conclusion, use of botulinum toxin released resources for alternative use during the first year following treatment, without any loss of clinical improvement. However, it is unknown how botulinum toxin affected the need for surgery and associated outcomes in subsequent years.

Economic burden of moderate to severe plaque psoriasis in Canada.

BACKGROUND: Psoriasis is a chronic debilitating disease affecting approximately one million Canadians. The objective of this study is to estimate the economic burden in $CDN (2008) of moderate to severe plaque psoriasis among Canadian adults. METHODS: Using a cross-sectional design, direct resource use, costs, lost productivity, and quality of life were obtained for 90 subjects diagnosed with psoriasis in three dermatology clinics in British Columbia, Ontario, and Québec. An Excel-based economic model was developed to project the annual cost of psoriasis, from the societal perspective. RESULTS: The estimated mean annual cost of psoriasis was $7999/subject (95% CI: $3563-$12,434) with direct costs accounting for 57%. Mean lost productivity costs, which accounted for 43% of the mean annual costs of psoriasis, were $3442/subject (95% CI: $1293-$5590). CONCLUSION: Projecting the mean costs per patient to the afflicted population yields an estimated total annual cost of $1.7 billion (95% CI: $0.8-$2.6 billion) attributable to moderate to severe psoriasis in Canada. Understanding the interplay between direct costs, lost productivity, and quality of life is critical for accurately identifying and evaluating effective treatments for this disease.

Joint assessment of intended and unintended effects of medications: an example using vascular endothelial growth factor inhibitors for neovascular age-related macular degeneration.

Objective. To estimate the net health benefits of pegaptanib and ranibizumab by considering the impact of visual acuity and unintended effects (cardiovascular and hemorrhagic events) on quality-of-life among persons with neovascular age-related macular degeneration. Methods. We designed a probabilistic decision-analytic model using published data. It employed 17 visual health states and three for unintended effects. We calculated incremental net health benefits by subtracting the harms of each medication from the benefit using the quality-adjusted life year (QALY). Results. In a hypothetical cohort of 1,000 75-year olds with new-onset bilateral age-related macular degeneration followed for ten years, the mean QALYs per patient is 3.7 for usual care, 4.2 for pegaptanib, and 4.3 for ranibizumab. Net benefits decline with increasing baseline rates of unintended effects. Interpretation. Net health benefits present a quantitative, potentially useful tool to assist patients and ophthalmologists in balancing the benefits and harms of interventions for age-related macular degeneration.

Switching asthma patients to a once-daily inhaled steroid improves compliance and reduces healthcare costs.

OBJECTIVE: To determine the costs and consequences of switching asthma patients, managed in primary care, from a twice-daily inhaled corticosteroid (ICS), to either a once-daily or another twice-daily ICS. DESIGN: This was a case-control study based on an interrogation of the General Practice Research Database in the UK, for patients with a Read code of asthma who were managed between 1990 and 2001, and who had received at least two prescriptions for a twice-daily ICS within 12 months, before switching to a once-daily ICS (cases) or another twice-daily ICS (controls). Data on resource use was collected for one year before and after the switch. Patients were stratified according to whether their treatment step had been stepped up, stepped down or remained unchanged. SETTING: A modelling study performed from the perspective of the UK's National Health Service (NHS). MAIN OUTCOME MEASURES: Compliance with ICS, and the cost of drug and non-drug resource use, for the year before and after the switch. RESULTS: Switching patients managed in primary care to a once-daily ICS increased compliance and reduced NHS costs, irrespective of whether patients' treatment had been stepped up or down. Switching patients to another twice-daily ICS increased compliance to a lesser extent, and increased NHS costs. We believe that this paper offers the first documented association between compliance in asthma and NHS management costs. CONCLUSIONS: Compliance and management costs among patients with asthma managed in primary care appear to be related to both changing treatment and dosing regimen. Within the limitations of our study, the results suggest that patients who are switched to a once-daily ICS rather than another twice-daily preparation are better compliers with their ICS medication. Additionally, patients who become high-compliers after being switched to a once-daily ICS incur lower management costs than patients who become high-compliers after being switched to another twice-daily ICS. These findings should now be investigated further under more controlled conditions.