Implementing Multilevel Network Meta-Regression for Time-To-Event Outcomes: A Case Study in Relapsed Refractory Multiple Myeloma.

Objectives: Multilevel network meta-regression (ML-NMR) leverages individual patient data (IPD) and aggregate data from a network of randomized controlled trials (RCTs) to assess the comparative efficacy of multiple treatments, while adjusting for between-study differences. We provide an overview of ML-NMR for time-to-event outcomes and apply it to an illustrative case study, including example R code.

Methods: The case study evaluated the comparative efficacy of idecabtagene vicleucel (ide-cel), selinexor+dexamethasone (Sd), belantamab mafodotin (BM), and conventional care (CC) for patients with triple-class exposed relapsed/refractory multiple myeloma in terms of overall survival.

Challenges of Incorporating Life Cycle Drug Pricing in Cost-Effectiveness Models: A Review of Methods and Modeling Suggestions.

Objectives: This study aimed to conduct a review of existing methods used to incorporate life cycle drug pricing (LCDP) in cost-effectiveness analyses (CEAs), identify common methodological challenges, and suggest modeling approaches for prospectively implementing LCDP in CEA.

Methods: Two complementary searches were conducted in PubMed, combined with hand searching and reference mining, to identify English language full-text articles that explored (1) how drug prices change over time and (2) methods used to apply dynamic pricing in cost-effectiveness models (CEMs). Relevant articles were reviewed, and authors discussed the common methodological practices used in the literature and their associated challenges on prospectively implementing LCDP in CEMs.

Artificial Intelligence to Automate Network Meta-Analyses: Four Case Studies to Evaluate the Potential Application of Large Language Models.

Background: The emergence of artificial intelligence, capable of human-level performance on some tasks, presents an opportunity to revolutionise development of systematic reviews and network meta-analyses (NMAs). In this pilot study, we aim to assess use of a large-language model (LLM, Generative Pre-trained Transformer 4 [GPT-4]) to automatically extract data from publications, write an R script to conduct an NMA and interpret the results.

Methods: We considered four case studies involving binary and time-to-event outcomes in two disease areas, for which an NMA had previously been conducted manually.

Artificial Intelligence to Automate Health Economic Modelling: A Case Study to Evaluate the Potential Application of Large Language Models.

Background: Current generation large language models (LLMs) such as Generative Pre-Trained Transformer 4 (GPT-4) have achieved human-level performance on many tasks including the generation of computer code based on textual input. This study aimed to assess whether GPT-4 could be used to automatically programme two published health economic analyses.

Methods: The two analyses were partitioned survival models evaluating interventions in non-small cell lung cancer (NSCLC) and renal cell carcinoma (RCC).

The Clinical Emergency Data Registry: Structure, Use, and Limitations for Research.

The Clinical Emergency Data Registry (CEDR) is a qualified clinical data registry that collects data from participating emergency departments (EDs) in the United States for quality measurement, improvement, and reporting purposes. This article aims to provide an overview of the data collection and validation process, describe the existing data structure and elements, and explain the potential opportunities and limitations for ongoing and future research use. CEDR data are primarily collected for quality reporting purposes and are obtained from diverse sources, including electronic health records and billing data that are de-identified and stored in a secure, centralized database.

Retrospective Comparison of Survival Projections for CAR T-Cell Therapies in Large B-Cell Lymphoma.

Background: Durable remission has been observed in patients with relapsed or refractory (R/R) large B-cell lymphoma (LBCL) treated with chimeric antigen receptor (CAR) T-cell therapy. Consequently, hazard functions for overall survival (OS) are often complex, requiring the use of flexible methods for extrapolations.

Objectives: We aimed to retrospectively compare the predictive accuracy of different survival extrapolation methods and evaluate the validity of goodness-of-fit (GOF) criteria-based model selection for CAR T-cell therapies in R/R LBCL.

Challenges in conducting fractional polynomial and standard parametric network meta-analyses of immune checkpoint inhibitors for first-line advanced renal cell carcinoma.

Network meta-analyses (NMAs) increasingly feature time-varying hazards to account for non-proportional hazards between different drug classes. This paper outlines an algorithm for selecting clinically plausible fractional polynomial NMA models. The NMA of four immune checkpoint inhibitors (ICIs) + tyrosine kinase inhibitors (TKIs) and one TKI therapy for renal cell carcinoma (RCC) served as case study.

A review of HTA guidelines on societal and novel value elements.

Objectives: Health technology assessment (HTA) organizations vary in terms of how they conduct assessments. We assess whether and to what extent HTA bodies have adopted societal and novel elements of value in their economic evaluations.

Methods: After categorizing "societal" and "novel" elements of value, we reviewed fifty-three HTA guidelines.

Next-generation enhanced-efficiency fertilizers for sustained food security.

Nitrogen losses in agricultural systems can be reduced through enhanced-efficiency fertilizers (EEFs), which control the physicochemical release from fertilizers and biological nitrogen transformations in soils. The adoption of EEFs by farmers requires evidence of consistent performance across soils, crops and climates, paired with information on the economic advantages. Here we show that the benefits of EEFs due to avoided social costs of nitrogen pollution considerably outweigh their costs-and must be incorporated in fertilizer policies.

Economic Threshold Analysis of Supplementing Dairy Cow Diets with Betaine and Fat during a Heat Challenge: A Pre- and Post-Experimental Comparison.

Ex ante economic analysis can be used to establish the production threshold for a proposed experimental diet to be as profitable as the control treatment. This study reports (1) a pre-experimental economic analysis to estimate the milk production thresholds for an experiment where dietary supplements were fed to dairy cows experiencing a heat challenge, and (2) comparison of these thresholds to the milk production results of the subsequent animal experiment. The pre-experimental thresholds equated to a 1% increase in milk production for the betaine supplement, 9% increase for the fat supplement, and 11% increase for fat and betaine in combination, to achieve the same contribution to farm profit as the control diet.

The Potential of Deep Roots to Mitigate Impacts of Heatwaves and Declining Rainfall on Pastures in Southeast Australia.

Declines in growing-season rainfall and increases in the frequency of heatwaves in southern Australia necessitate effective adaptation. The Sustainable Grazing Systems Pasture Model (SGS) was used to model the growth of three pasture species differing in root depth and root distribution under three different climate scenarios at two sites. The modelled metabolisable energy intake (in MJ) was used in a partial discounted net cash flow budget.

Economic Analysis of Offering Different Herbage Allowances to Dairy Cows Fed a Partial Mixed Ration.

The economics of grazing dairy cows offered a range of herbage allowances and fed supplements as a partial mixed ration (PMR) were examined where profit was defined as the margin between total milk income and the cost of pasture plus PMR supplement. The analysis made use of milk production and feed intake data from two dairy cow nutrition experiments, one in early lactation and the other in late lactation. In early lactation and at a PMR intake of 6 kg DM/cow per day, the profit from the cows with access to a medium herbage allowance (25 kg DM/cow per day) was AUD 1.

What Did Time Tell Us? A Comparison and Retrospective Validation of Different Survival Extrapolation Methods for Immuno-Oncologic Therapy in Advanced or Metastatic Renal Cell Carcinoma.

Background: The immuno-oncologic (IO) mechanism of action may lead to an overall survival (OS) hazard that changes over time, producing shapes that standard parametric extrapolation methods may struggle to reflect. Furthermore, selection of the most appropriate extrapolation method for health technology assessment is often based on trial data with limited follow-up.

Objective: To examine this problem, we fitted a range of extrapolation methods to patient-level survival data from CheckMate 025 (NCT01668784, CM-025), a phase III trial comparing nivolumab with everolimus for previously treated advanced renal cell carcinoma (aRCC), to assess their predictive accuracy over time.

Validity of social media for assessing treatment patterns in oncology patients: a case study in melanoma.

There is a need to understand how patients are managed in the real world to better understand disease burden and unmet need. Traditional approaches to gather these data include the use of electronic medical record (EMR) or claims databases; however, in many cases data access policies prevent rapid insight gathering. Social media may provide a potential source of real-world data to assess treatment patterns, but the limitations and biases of doing so have not yet been evaluated.

Comparison of accelerometer-derived physical activity levels between individuals with and without cancer: a UK Biobank study.

To identify the difference in physical activity (PA) levels between individuals with and without cancer, and to estimate all-cause mortality associated with this difference. Current cancer, cancer survivor and cancer-free groups were identified from the UK Biobank. We used multivariate and Cox regression to estimate PA differences and association of PA with all-cause mortality.

Automated extraction of treatment patterns from social media posts: an exploratory analysis in renal cell carcinoma.

The use of health-related social media forums by patients is increasing and the size of these forums creates a rich record of patient opinions and experiences, including treatment histories. This study aimed to understand the possibility of extracting treatment patterns in an automated manner for patients with renal cell carcinoma, using natural language processing, rule-based decisions, and machine learning. Obtained results were compared with those from published observational studies.

Real-world data and the patient perspective: the PROmise of social media?

Understanding the patient perspective is fundamental to delivering patient-centred care. In most healthcare systems, however, patient-reported outcomes are not regularly collected or recorded as part of routine clinical care, despite evidence that doing so can have tangible clinical benefit. In the absence of the routine collection of these data, research is beginning to turn to social media as a novel means to capture the patient voice.

Application of dynamic modeling for survival estimation in advanced renal cell carcinoma.

Objective: In oncology, extrapolation of clinical outcomes beyond trial duration is traditionally achieved by parametric survival analysis using population-level outcomes. This approach may not fully capture the benefit/risk profile of immunotherapies due to their unique mechanisms of action. We evaluated an alternative approach-dynamic modeling-to predict outcomes in patients with advanced renal cell carcinoma.

Agribusiness Perspectives on Transgenic Wheat.

Declining yields of the major human food crops, looming growth in global population and rise of populism, and ill-founded bans on agricultural and horticultural crops and foodstuffs which are genetically modified have potentially serious implications. It makes the chance less than otherwise would be the case that agribusiness value chains in the future will meet the growing demand around the world for more and different foods from more and wealthier people. In the agribusiness value chain, transgenic wheat, meeting a consumer "trigger need" also must meet the "experience" and "credence," risk-related criteria of well-informed consumers.

Simulation Modelling in Ophthalmology: Application to Cost Effectiveness of Ranibizumab and Aflibercept for the Treatment of Wet Age-Related Macular Degeneration in the United Kingdom.

Background: Previously developed models in ophthalmology have generally used a Markovian structure. There are a number of limitations with this approach, most notably the ability to base patient outcomes on best-corrected visual acuity (BCVA) in both eyes, which may be overcome using a different modelling structure. Simulation modelling allows for this to be modelled more precisely, and therefore may provide more accurate and relevant estimates of the cost effectiveness of ophthalmology interventions.

Ranibizumab, verteporfin photodynamic therapy or observation for the treatment of myopic choroidal neovascularization: cost effectiveness in the UK.

Purpose: The aim of this study was to evaluate the cost effectiveness of ranibizumab compared with verteporfin photodynamic therapy (vPDT) or no treatment (observation) in patients with visual impairment due to myopic choroidal neovascularization (CNV).

Methods: A Markov model with health states defined by best-corrected visual acuity and a 3-month cycle length was developed. It had a healthcare provider (UK National Health Service and personal social services) perspective, a lifetime time horizon, and was based on 2011 prices; future costs and health outcomes were discounted at 3.

A UK-based cost-utility analysis of indacaterol, a once-daily maintenance bronchodilator for patients with COPD, using real world evidence on resource use.

Introduction: Chronic Obstructive Pulmonary Disease (COPD) is a chronic, progressive disease that is not curable. However, there are effective treatments available. In the UK, long-acting bronchodilators are first-line treatments for COPD patients requiring maintenance therapy, and there are several options available.