A multisite longitudinal evaluation of patient characteristics associated with a poor response to non-surgical multidisciplinary management of low back pain in an advanced practice physiotherapist-led tertiary service.

BACKGROUND: Non-surgical multidisciplinary management is often the first pathway of care for patients with chronic low back pain (LBP). This study explores if patient characteristics recorded at the initial service examination have an association with a poor response to this pathway of care in an advanced practice physiotherapist-led tertiary service. METHODS: Two hundred and forty nine patients undergoing non-surgical multidisciplinary management for their LBP across 8 tertiary public hospitals in Queensland, Australia participated in this prospective longitudinal study. Generalised linear models (logistic family) examined the relationship between patient characteristics and a poor response at 6 months follow-up using a Global Rating of Change measure. RESULTS: Overall 79 of the 178 (44%) patients completing the Global Rating of Change measure (28.5% loss to follow-up) reported a poor outcome. Patient characteristics retained in the final model associated with a poor response included lower Formal Education Level (ie did not complete school) (Odds Ratio (OR (95% confidence interval)) (2.67 (1.17-6.09), p = 0.02) and higher self-reported back disability (measured with the Oswestry Disability Index) (OR 1.33 (1.01-1.77) per 10/100 point score increase, p = 0.046). CONCLUSIONS: A low level of formal education and high level of self-reported back disability may be associated with a poor response to non-surgical multidisciplinary management of LBP in tertiary care. Patients with these characteristics may need greater assistance with regard to their comprehension of health information, and judicious monitoring of their response to facilitate timely alternative care if no benefits are attained.

"Don't keep me waiting": estimating the impact of reduced vein-to-vein time on lifetime US 3L+ LBCL patient outcomes.

ABSTRACT: Chimeric antigen receptor T-cell therapy (CAR T) has revolutionized the treatment of hematological cancers. Its production requires a complex logistical process, and the time from leukapheresis to patient infusion (known as the vein-to-vein time [V2VT]) can be long during which a patients clinical condition may deteriorate. This study was designed to estimate the benefits of reduced V2VT for third-line or later (3L+) relapsed/refractory large B-cell lymphoma (R/R LBCL) patients treated with CAR T. A mathematical model was developed to estimate the lifetime outcomes of a hypothetical cohort of patients who had either a long or short V2VT. Life-years (LYs), quality-adjusted LYs (QALYs), and costs were estimated. Scenario analyses were performed to assess the robustness of results to key assumptions. The results of the model show that reducing V2VT from 54 days (tisa-cel median V2VT; JULIET) to 24 days (axi-cel median V2VT; ZUMA-1) led to a 3.2-year gain in life expectancy (4.2 vs 7.7 LYs), and 2.4 additional QALYs (3.2 vs 5.6) per patient. Furthermore, a shorter V2VT was shown to be cost-effective under conventional willingness-to-pay thresholds in the United States. Results are driven by a higher infusion rate and a better efficacy of CAR T for those infused. Scenario analyses using a smaller difference in V2VT (24 vs 36 days) produced consistent results. Our study is the first to quantify lifetime V2VT-related outcomes for 3L+ R/R LBCL patients treated with CAR T utilizing currently available evidence. Shorter V2VTs led to improved outcomes, demonstrating the importance of timely infusion achievable by faster manufacturing times and optimization of hospital delivery.

R and Shiny for Cost-Effectiveness Analyses: Why and When? A Hypothetical Case Study.

INTRODUCTION: Health economics models are typically built in Microsoft Excel® owing to its wide familiarity, accessibility and perceived transparency. However, given the increasingly rapid and analytically complex decision-making needs of both the pharmaceutical industry and the field of health economics and outcomes research (HEOR), the demands of cost-effectiveness analyses may be better met by the programming language R. OBJECTIVE: This case study provides an explicit comparison between Excel and R for contemporary cost-effectiveness analysis. METHODS: We constructed duplicate cost-effectiveness models using Excel and R (with a user interface built using the Shiny package) to address a hypothetical case study typical of contemporary health technology assessment. RESULTS: We compared R and Excel versions of the same model design to determine the advantages and limitations of the modelling platforms in terms of (i) analytical capability, (ii) data safety, (iii) building considerations, (iv) usability for technical and non-technical users and (v) model adaptability. CONCLUSIONS: The findings of this explicit comparison are used to produce recommendations for when R might be more suitable than Excel in contemporary cost-effectiveness analyses. We conclude that selection of appropriate modelling software needs to consider case-by-case modelling requirements, particularly (i) intended audience, (ii) complexity of analysis, (iii) nature and frequency of updates and (iv) anticipated model run time.

Patient characteristics associated with a poor response to non-surgical multidisciplinary management of knee osteoarthritis: a multisite prospective longitudinal study in an advanced practice physiotherapist-led tertiary service.

OBJECTIVES: To explore patient characteristics recorded at the initial consultation associated with a poor response to non-surgical multidisciplinary management of knee osteoarthritis (KOA) in tertiary care. DESIGN: Prospective multisite longitudinal study. SETTING: Advanced practice physiotherapist-led multidisciplinary orthopaedic service within eight tertiary hospitals. PARTICIPANTS: 238 patients with KOA. PRIMARY AND SECONDARY OUTCOME MEASURES: Standardised measures were recorded in all patients prior to them receiving non-surgical multidisciplinary management in a tertiary hospital service across multiple sites. These measures were examined for their relationship with a poor response to management 6 months after the initial consultation using a 15-point Global Rating of Change measure (poor response (scores -7 to +1)/positive response (scores+2 to+7)). Generalised linear models with binomial family and logit link were used to examine which patient characteristics yielded the strongest relationship with a poor response to management as estimated by the OR (95% CI). RESULTS: Overall, 114 out of 238 (47.9%) participants recorded a poor response. The odds of a poor response decreased with higher patient expectations of benefit (OR 0.74 (0.63 to 0.87) per 1/10 point score increase) and higher self-reported knee function (OR 0.67 (0.51 to 0.89) per 10/100 point score increase) (p<0.01). The odds of a poor response increased with a greater degree of varus frontal knee alignment (OR 1.35 (1.03 to 1.78) per 5° increase in varus angle) and a severe (compared with mild) radiological rating of medial compartment degenerative change (OR 3.11 (1.04 to 9.3)) (p<0.05). CONCLUSIONS: These characteristics may need to be considered in patients presenting for non-surgical multidisciplinary management of KOA in tertiary care. Measurement of these patient characteristics may potentially better inform patient-centred management and flag the need for judicious monitoring of outcome for some patients to avoid unproductive care.

Transparency in Decision Modelling: What, Why, Who and How?

Transparency in decision modelling is an evolving concept. Recently, discussion has moved from reporting standards to open-source implementation of decision analytic models. However, in the debate about the supposed advantages and disadvantages of greater transparency, there is a lack of definition. The purpose of this article is not to present a case for or against transparency, but rather to provide a more nuanced understanding of what transparency means in the context of decision modelling and how it could be addressed. To this end, we review and summarise the discourse to date, drawing on our collective experience. We outline a taxonomy of the different manifestations of transparency, including reporting standards, reference models, collaboration, model registration, peer review and open-source modelling. Further, we map out the role and incentives for the various stakeholders, including industry, research organisations, publishers and decision makers. We outline the anticipated advantages and disadvantages of greater transparency with respect to each manifestation, as well as the perceived barriers and facilitators to greater transparency. These are considered with respect to the different stakeholders and with reference to issues including intellectual property, legality, standards, quality assurance, code integrity, health technology assessment processes, incentives, funding, software, access and deployment options, data protection and stakeholder engagement. For each manifestation of transparency, we discuss the 'what', 'why', 'who' and 'how'. Specifically, their meaning, why the community might (or might not) wish to embrace them, whose engagement as stakeholders is required and how relevant objectives might be realised. We identify current initiatives aimed to improve transparency to exemplify efforts in current practice and for the future.

Cost Effectiveness of Secukinumab for the Treatment of Active Psoriatic Arthritis in the UK.

OBJECTIVE: The aim was to determine the cost effectiveness of secukinumab, a fully human interleukin-17A inhibitor, for adults in the UK with active psoriatic arthritis (PsA) who are tumour necrosis factor inhibitor (TNFi) naïve and without concomitant moderate-to-severe psoriasis, and who have responded inadequately to conventional systemic disease-modifying anti-rheumatic drugs (csDMARDs). PERSPECTIVE AND SETTING: The study took the perspective and setting of the UK National Health Service (NHS). METHODS: The model structure was a 3-month decision tree leading into a Markov model. Separate analyses based on the number of prior csDMARDs (one and two or more) were conducted, with secukinumab 150 mg compared to standard of care (SoC) and TNFis, respectively, for each subpopulation. Clinical parameters, including response at 3 months, were from the FUTURE 2 trial and a network meta-analysis. Outcomes included total costs and quality-adjusted life years (QALYs) over the 40-year time horizon (3.5% annual discount for both outcomes; cost year 2017), and incremental cost effectiveness ratios (ICERs). RESULTS: The ICER for secukinumab 150 mg versus SoC was £28,748 per QALY gained (one prior csDMARD). Secukinumab 150 mg dominated golimumab, certolizumab pegol and etanercept, and had an ICER of £5680 per QALY gained versus adalimumab and > £1 million saved per QALY foregone versus infliximab (two or more prior csDMARDs). Valuing one QALY at between £20,000 and £30,000, the probability of secukinumab having the highest net monetary benefit was 48.9% (one prior csDMARD) and 88.9% (two or more prior csDMARDs). Parameters related to Health Assessment Questionnaire scores were most influential. CONCLUSIONS: Secukinumab 150 mg at list price appears to represent a cost-effective use of NHS resources for adults with PsA who have responded inadequately to one or two or more prior csDMARDs.

The efficacy and tolerability of nebivolol in hypertensive African American patients.

Hypertensive African Americans often respond poorly to beta-blocker monotherapy, compared with whites. There is evidence, however, that suggests that this response may be different if beta-blockers with vasodilating effects are used. This 12-week, multi-center, double-blind, randomized placebo-controlled study assessed the antihypertensive efficacy and safety of nebivolol, a cardioselective, vasodilating beta1-blocker, at doses of 2.5, 5, 10, 20, or 40 mg once daily in 300 African American patients with stage I or II hypertension (mean sitting diastolic blood pressure [SiDBP] > or =95 mm Hg and < or =109 mm Hg). The primary efficacy end point was the baseline-adjusted change in trough mean SiDBP. After 12 weeks, nebivolol significantly reduced least squares mean SiDBP (P< or =.004) at all doses of 5 mg and higher and sitting systolic blood pressure (P< or =.044) at all doses 10 mg and higher, compared with placebo. The drug was safe and well-tolerated, with no significant difference in the incidence of adverse events compared with placebo. Nebivolol monotherapy provides antihypertensive efficacy, with few significant adverse effects, in hypertensive African Americans.

A randomized, double-blind, placebo-controlled parallel-group study to assess the efficacy and safety of nebivolol, a novel beta-blocker, in patients with mild to moderate hypertension.

This double-blind, multicenter, randomized placebo-controlled study evaluated the antihypertensive efficacy and safety of nebivolol, a selective beta1-adrenoreceptor blocker with vasodilating effects, in patients with mild to moderate hypertension (sitting diastolic blood pressure [SiDBP] > or =95 mm Hg and < or =109 mm Hg). A total of 909 patients were randomized to receive placebo or nebivolol 1.25, 2.5, 5, 10, 20, or 40 mg once daily for up to 84 days. The primary end point was the change in trough SiDBP from baseline to study end. Nebivolol significantly reduced trough SiDBP (8.0-11.2 mm Hg compared with 2.9 mm Hg with placebo; P<.001) and trough sitting systolic blood pressure (a 4.4-9.5-mm Hg decrease compared with a 2.2-mm Hg increase [corrected] with placebo; P< or =.002). The overall adverse event experience was similar in the nebivolol (46.1%) and placebo (40.7%) groups (P=.273). Once-daily nebivolol is an effective antihypertensive in mild to moderate hypertensive patients.

A systematic review of cost-effectiveness modeling of pharmaceutical therapies in neuropathic pain: variation in practice, key challenges, and recommendations for the future.

OBJECTIVES: Complexities in the neuropathic-pain care pathway make the condition difficult to manage and difficult to capture in cost-effectiveness models. The aim of this study is to understand, through a systematic review of previous cost-effectiveness studies, some of the key strengths and limitations in data and modeling practices in neuropathic pain. Thus, the aim is to guide future research and practice to improve resource allocation decisions and encourage continued investment to find novel and effective treatments for patients with neuropathic pain. METHODS: The search strategy was designed to identify peer-reviewed cost-effectiveness evaluations of non-surgical, pharmaceutical therapies for neuropathic pain published since January 2000, accessing five key databases. All identified publications were reviewed and screened according to pre-defined eligibility criteria. Data extraction was designed to reflect key data challenges and approaches to modeling in neuropathic pain and based on published guidelines. RESULTS: The search strategy identified 20 cost-effectiveness analyses meeting the inclusion criteria, of which 14 had original model structures. Cost-effectiveness modeling in neuropathic pain is established and increasing across multiple jurisdictions; however, amongst these studies, there is substantial variation in modeling approach, and there are common limitations. Capturing the effect of treatments upon health outcomes, particularly health-related quality-of-life, is challenging, and the health effects of multiple lines of ineffective treatment, common for patients with neuropathic pain, have not been consistently or robustly modeled. CONCLUSIONS: To improve future economic modeling in neuropathic pain, further research is suggested into the effect of multiple lines of treatment and treatment failure upon patient outcomes and subsequent treatment effectiveness; the impact of treatment-emergent adverse events upon patient outcomes; and consistent and appropriate pain measures to inform models. The authors further encourage transparent reporting of inputs used to inform cost-effectiveness models, with robust, comprehensive and clear uncertainty analysis and, where feasible, open-source modeling is encouraged.