Transition to secondary progressive multiple sclerosis: The consequences for patients and healthcare systems, a healthcare professional survey.

BACKGROUND AND AIMS: Transition to secondary progressive multiple sclerosis (SPMS) from relapsing-remitting MS (RRMS) is an expected part of the disease trajectory for most patients. However, the transition is challenging to identify due to the gradual nature of progression, and the complications of superimposed relapses, comorbidities, and natural variability in symptoms. This healthcare professional (HCP) survey sought to characterize the transition to and management of SPMS in UK clinical practice. METHODS: Telephone interviews with 20 neurologists and MS specialist nurses from England and Scotland gathered quantitative and qualitative responses. Numerical analyses and theoretical thematic methods were used to identify key emerging themes. RESULTS: The burden SPMS imposes on patients and caregivers was a major theme; discharge from specialist services is common, leading to a sense of abandonment. Respondents acknowledged substantial hesitancy toward identifying SPMS, predominantly due to restricted options of licensed and reimbursed disease-modifying therapies (DMTs) for SPMS compared with RRMS. Currently, HCPs continue DMTs under a label of RRMS, even after recognition of progression. This survey identified MS to be unusual in comparison with other disease areas in that reimbursement guidelines have a direct impact on clinicians' decisions around disease staging. Respondents suggested reimbursed DMTs proven to slow disability progression in SPMS will create a step-change in identifying SPMS, providing rationale to acknowledge progression earlier while removing key obstacles to identification. To aid this change, respondents identified a need for SPMS-specific diagnostic guidance, despite substantial divergence in implementation of current guidance. CONCLUSIONS: In contrast to the current heterogeneity, a more structured and standardized approach to the identification of SPMS, along with guidelines on treatment, will ensure patients can maximally benefit as treatment options for SPMS evolve.

When does economic model type become a decisive factor in health technology appraisals? Learning from the expanding treatment options for relapsing-remitting multiple sclerosis.

OBJECTIVES: Specific economic model types often become de facto standard for health technology appraisal over time. Markov and discrete event simulation (DES) models were compared to investigate the impact of innovative modeling on the cost-effectiveness of disease-modifying therapies (DMTs) in relapsing-remitting multiple sclerosis (RRMS). Fingolimod was compared to dimethyl fumarate (DMF; in highly active [HA] RRMS), alemtuzumab (in HA RRMS) and natalizumab (in rapidly evolving severe RRMS). Comparator DMTs were chosen to reflect different dosing regimens. MATERIALS AND METHODS: Markov and DES models used have been published previously. Inputs were aligned in all relevant respects, with differences in the modeling of event-triggered attributes, such as relapse-related retreatment, which is inherently difficult with a memoryless Markov approach. Outcomes were compared, with and without different attributes. RESULTS: All results used list prices. For fingolimod and DMF, incremental cost-effectiveness ratios (ICERs) were comparable (Markov: £4206/quality-adjusted life year [QALY] gained versus DES: £3910/QALY gained). Deviations were observed when long-term adverse events (AEs) were incorporated in the DES (Markov: £25,412 saved/QALY lost, versus DES: £34,209 saved/QALY lost, fingolimod versus natalizumab; higher ICERs indicate greater cost-effectiveness). For fingolimod versus alemtuzumab, when relapse-triggered retreatment was included in the DES, large cost differences were observed (difference between incremental cost is £35,410 and QALY is 0.10). LIMITATIONS: UK payer perspective, therefore societal approach was not considered. Resource utilization and utilities for both models were not derived from the subpopulations; as the focus is on model type, input limitations that apply to both models are less relevant. CONCLUSIONS: Whilst no model can fully represent a disease, a DES allows an opportunity to include features excluded in a Markov structure. A DES may be more suitable for modeling in RRMS for health technology assessment purposes given the complexity of some DMTs. This analysis highlights the capabilities of different model structures to model event-triggered attributes.

Systematic review of the prevalence of psychiatric illness and sleep disturbance as co-morbidities of HIV infection in the UK.

Psychiatric illness and sleeping disorders are important co-morbidities of human immunodeficiency virus (HIV) infection, which impact both the individual and antiretroviral therapy (ART) selection. This systematic review aimed to assess the prevalence of psychiatric illness and sleep disturbance in people living with HIV (PLHIV) in the UK. Systematic searches for publications reporting epidemiological data for psychiatric co-morbidities and sleep disturbance with HIV were conducted in Embase, MEDLINE, Cochrane Library, eight key conferences (2013-2015), and by hand-searching references of included publications. Data were extracted from publications (2000 onwards) reporting the UK prevalence of depression, anxiety, suicide ideation, or sleep disturbance as a co-morbidity of HIV infection. Comparative UK general population data were obtained from the 2007 Adult Psychiatric Morbidity in England household survey, the 2012 Health Survey for England, and 'PatientBase' (epidemiological database). Sixteen publications met the inclusion criteria. Amongst PLHIV in the UK, the prevalence of depression varied from 17-47%, compared with a reported 2-5% prevalence for the UK general population. A similar disparity was observed in the prevalence of anxiety (22-49% PLHIV versus 4-5% general population), depression or anxiety (50-58% PLHIV versus 27% general population), difficulty sleeping (61% PLHIV versus 10% population), and suicide ideation (31% PLHIV versus 1% general population). This systematic review of UK data demonstrates that rates of psychiatric illness and sleep disturbance are substantially higher amongst PLHIV than in the general population. These data underline the importance of fully considering sleep and psychiatric issues prior to selection and prescription of antiretroviral drugs, as well as the need for ongoing psychiatric and psychological support for PLHIV on ART.

A Systematic Review of Insulin Adherence Measures in Patients with Diabetes.

BACKGROUND: Diabetes care is associated with a considerable burden to the health care system in the United States, and measuring the quality of health care is an important development goal of the Department of Health and Human Services and the Centers for Medicare & Medicaid Services. Diabetes is a priority disease within the National Quality Strategy and should therefore remain a focus in the measurement of health care quality. Despite the importance of measuring quality in diabetes care management, no quality measure is currently associated with adherence to insulin treatment, and measuring adherence to insulin is known to be complicated. OBJECTIVES: To (a) identify methods to measure insulin adherence in patients with diabetes and (b) evaluate whether identified methods could be considered for testing as a quality measure. METHODS: Systematic searches were conducted in the online electronic databases Embase, MEDLINE, and the Cochrane Library, supplemented with additional manual searches to identify publications on insulin adherence from the year 2000 onward. Identified citations were screened for relevance against predefined eligibility criteria, and methods to measure adherence to insulin were extracted from relevant studies into data extraction tables. Methods were critiqued on the feasibility for consideration as a quality measure. RESULTS: Seventy-eight publications met the inclusion criteria and were reviewed. Included studies reported various indirect methods to measure adherence to insulin, using prescription claims or self-report questionnaires. Commonly reported methods included the (adjusted) medication possession ratio, proportion of days covered, persistence, daily average consumption, and the Morisky Medication Adherence Scale. All types of identified methods were associated with measuring challenges varying from accuracy of estimated adherence, complexity of data collection, absence of validated threshold for good adherence, and reliability of adherence outcomes. CONCLUSIONS: Without additional research, none of the identified methods are appropriate for use as a quality measure for insulin adherence. We suggest patient involvement in future research and additional quality measure development. DISCLOSURES: Novo Nordisk paid DRG Abacus to complete the systematic review and manuscript and was involved in the study design, interpretation of data, and decision to publish the findings of the systematic review. Kroes and Webb report personal fees from Novo Nordisk during the conduct of the study and personal fees from DRG Abacus, outside of the submitted work. Webb is employed by DRG Abacus, and Kroes was employed by DRG Abacus at the time of this study. Wisniewski is an employee of Novo Nordisk, which funded the systematic review reported in this article, and also owns stocks in Novo Nordisk. Stolpe has nothing to disclose. Study concept and design were contributed by Kroes, Webb, and Wisniewski, with assistance from Stolpe. Webb took the lead in data collection, along with Kroes, and data interpretation was performed by all the authors. The manuscript was written by Kroes, Webb, and Wisniewski, with assistance from Stolpe, and revised by Kroes, Stolpe, Wisniewski, and Webb.

Second-line single-agent chemotherapy in human epidermal growth factor receptor 2-negative metastatic breast cancer: A systematic review.

BACKGROUND: No 'gold standard' exists for single-agent chemotherapy of human epidermal growth factor receptor 2-negative (HER2-negative) metastatic breast cancer (MBC) in the second-line. The objective of this systematic review is to identify and appraise overall survival (OS), progression-free survival (PFS), time to progression (TTP) and Grade ≥3 adverse event evidence for single-agent chemotherapy in this setting. METHODS: MEDLINE, Embase and the Cochrane Library were searched to October 2013, and PubMed October 2013 to November 2014. Electronic database searches were supplemented with hand searching of reference lists and conferences. Eligible randomised controlled trials (RCTs) employed at least one single-agent chemotherapy treatment, enrolled HER2-negative or unselected MBC patients who had progressed following first-line chemotherapy within the metastatic setting, and reported outcomes of interest for the second-line setting. RESULTS: Fifty-three RCTs were included in total, with most containing mixed populations by HER2 status and treatment line. Fourteen studies reported data specifically for second- and later-line treatment within the metastatic setting. Median overall survival (OS) in most trials was 8-13 months. Only one trial reported a significant difference between studied interventions in the second-line metastatic setting: nab-paclitaxel (n=131) conferred a statistically significant OS advantage vs. three-weekly paclitaxel (n=136) (median OS 13.0 vs. 10.7 months, respectively; hazard ratio 0.73, p=0.024) and improved overall safety. CONCLUSION: One RCT demonstrated significant benefit in this setting in confirmed HER2-negative MBC alongside favourable safety. Treatment line terminology was imprecise. To reliably inform patient treatment decisions, quality-of-life data are needed and precise OS estimation according to underlying patient characteristics.

Impact of weight change on quality of life in adults with overweight/obesity in the United States: a systematic review.

OBJECTIVE: To review published evidence on the impact of weight/BMI change on health-related quality of life (HRQoL) in adults from the US with overweight/obesity. METHODS: The systematic review was conducted in accordance with PRISMA guidelines. MEDLINE, Embase, EconLit, and Cochrane Library databases were reviewed using pre-defined eligibility criteria to identify relevant US studies in adults with overweight/obesity, with ≥1 year follow-up, quantified weight change, and measured HRQoL. This manuscript focuses on HRQoL derived using the Short-Form 36 (SF-36) and Impact of Weight on Quality of Life-Lite (IWQOL-Lite) instruments. RESULTS: In total, 32 of 6793 identified publications reported HRQoL according to SF-36 or IWQOL-Lite; 20 provided adequate data for inclusion in this review. Although study design and outcomes were heterogeneous, improvements in HRQoL were generally observed with weight loss. Bariatric surgery studies provided the most evidence (12 publications) and demonstrated dramatic (≥20%) weight loss and associated HRQoL improvements. Sustained weight loss was associated with maintenance of HRQoL improvements out to 6 years in some studies. In lifestyle and pharmaceutical intervention studies showing weight loss of 5%-10%, some aspects of HRQoL improved, although the association with weight was not typically explored. Across the 20 publications, physical versus mental HRQoL improvements were more commonly statistically significant. CONCLUSION: Overweight/obesity is typically associated with poorer HRQoL than normal weight (BMI 18.5-24.9 kg/m(2)). This systematic review of US literature demonstrated that significant weight loss after bariatric surgery may be associated with improvements in HRQoL. In non-bariatric studies with weight loss of ≥5%, improvements in some aspects of HRQoL were noted, although the causal nature of the relationship is uncertain. Although many SF-36 and IWQOL-Lite domain scores increased, improvements were typically only significant for physical, rather than mental, HRQoL. This systematic review provides evidence supporting that weight loss may improve HRQoL in people with overweight/obesity.

Second-line treatments for the management of advanced renal cell carcinoma: systematic review and meta-analysis.

OBJECTIVES: A systematic review/meta-analysis was conducted to assess the effectiveness and safety of second-line treatments for advanced renal cell carcinoma (RCC), which includes the vascular endothelial growth factor inhibitor axitinib. METHODS: Database searches were conducted to identify randomised controlled trials (RCTs). Indirect comparisons using a fixed-effect Bayesian model were used to assess the relative effectiveness of treatments and reported as hazard ratio (HR) and 95% credible intervals (CrI). RESULTS: Although 24 RCTs met eligibility criteria, only three studies were included in the fixed-effect Bayesian meta-analysis, due to differences in patient inclusion criteria/reported outcomes in the wider dataset. Robust meta-analysis was restricted to the subgroup pretreated with cytokines. In terms of progression-free survival (PFS), axitinib was superior compared with placebo (HR = 0.25, 95% CrI: 0.17 - 0.38), sorafenib (HR = 0.46, 95% CrI: 0.32 - 0.68) and pazopanib (HR = 0.47, 95% CrI: 0.26 - 0.85). An analysis including all patients, regardless of previous first-line treatment, reported similar results. There was no significant difference in PFS between sorafenib and pazopanib. CONCLUSION: Results from the present study suggest that axitinib will be an important treatment option to extend PFS in the management of advanced RCC in the second-line setting. Ongoing research will define the optimal treatment algorithm leading to a patient-focused treatment strategy.