Institute of Group Analysis

Detecting and treating cancer at an early stage is critical for improving patient survival, quality of life, and health system efficiency. Early diagnosis offers substantial clinical benefits, reduces the need for aggressive treatments associated with advanced disease, and lowers healthcare costs. Despite these benefits, disparities in early-stage detection persist across tumor types due to challenges in screening, public awareness, and the aggressive nature of certain cancers. While early-stage diagnosis generally offers a better prognosis than late-stage detection, disease recurrence remains a significant reality and concern. Many patients experience a relapse of cancer despite initial curative treatment, which adversely affects their survival, quality of life, and financial stability. While effective new treatments for early-stage cancers have emerged, including immunotherapy and targeted therapies, barriers to reimbursement and access persist. One challenge is the absence of mature overall survival data at the time of regulatory and reimbursement approvals for most tumor types, which can result in delayed decision-making, reduced patient access, and worse outcomes. This policy paper combines insights from clinicians, health economists, outcomes researchers, and policy experts to address gaps in early-stage cancer care and provide recommendations to enhance diagnosis rates, reduce the burden of recurrence, and optimize access to innovative treatments. Central to these recommendations is the integration of early cancer care into national cancer control plans, including robust data collection and monitoring, as well as improvements in health literacy. A key factor is the use of early clinical endpoints that measure key outcomes in addition to overall survival, providing timely insights into treatment effectiveness that can guide early regulatory and reimbursement decisions prior to reaching overall survival maturity. This paper is a call to action for relevant stakeholders to take a coordinated approach that optimizes outcomes for cancer patients by promoting early detection and treatment.

This study extends a version of the high-dimensional propensity score (HDPS) recently modified for the UK electronic health record setting, by enriching primary care data with hospital data. The performance of this modified approach is assessed via the estimation of a well-established association, the reduced risk of upper gastrointestinal bleeding (UGIB) in cyclo-oxygenase-2 inhibitor (COX-2i) users versus non-steroidal anti-inflammatory drug (NSAID) users. We conducted an active-comparator, new-user cohort study using UK primary care data from the Clinical Practice Research Datalink GOLD database, with linkages to hospitalisation and mortality records. We included individuals with osteoarthritis initiating NSAIDs or COX-2is between 2000-2004. We used Cox proportional hazards models to estimate the hazard ratio (HR) for UGIB, adjusting for confounders using investigator-specified and HDPS-derived propensity scores. Sensitivity analyses were conducted varying the number of HDPS covariates included and the covariate assessment period. We identified 74 443 and 25 742 new users of NSAID and COX-2i users, respectively. The unadjusted HR for UGIB comparing COX-2i and NSAID users was 1.28 (95% CI: 0.95-1.72). Of the included HDPS covariates, 26% originated from the hospitalisation dimension, a source not considered in previous applications indicating the considerable information contained in these data on proxies of potential confounders. The modified-HDPS obtained similar results to the other studies, shifting the HR closer to the expected association (HR 0.86; 95% CI: 0.58-1.26). We demonstrate the ability of the modified-HDPS to obtain similar results to comparable pharmacoepidemiological studies and randomised trials, highlighting the potential benefit of these approaches in UK EHRs more widely and the value of adding hospital data to enrich the pool of covariates available for the HDPS algorithm.

Abstract Sustainability-related considerations play an increasingly important role in competition assessments, as reflected by the European Commission’s 2024–29 mandate situating competition law within the EU’s climate and industrial strategy, the Clean Industrial Deal. During this mandate, the European Commission will revise its 2004 Horizontal Merger Guidelines and 2008 Non-Horizontal Merger Guidelines. Updating the guidelines provides an opportunity to address the relevance of sustainability-related considerations in relation to market definition, competitive assessment, efficiencies, and remedies. We analyse the economic evidence on the role of sustainability-related considerations in merger control, the Commission’s case practice, and its published guidance on merger assessments. We discuss challenges and provide practical recommendations to agency staff and practitioners, with the objective of facilitating the incorporation of sustainability-related considerations in the revised guidelines.

This study investigates the relationship between cold gas efficiency and the H₂/CO ratio in the gasification of various biomass-based waste streams, aiming to optimize the energy and chemical performance of the produced syngas. Experiments were conducted using green waste, olive pomace, and sewage sludge under varying operational conditions, including different temperatures, gasifying agents, and flow rates. The calorific value of the resulting syngas ranged between 5 and 14 MJ/kg, while gas conversion efficiencies varied from 28% to 68%. Maximum syngas quality was achieved at higher temperatures and lower gasifying agent flow rates.The H₂/CO ratio reached up to 5 for green waste, 4 for olive pomace, and 6 for sewage sludge, indicating the potential to produce hydrogen-rich syngas from diverse feedstocks. Cold gas efficiencies were recorded as 92%, 62%, and 73%, respectively. These results demonstrate that waste-specific operational optimization can significantly enhance syngas composition and efficiency. This research contributes to the waste-to-energy literature by providing a comparative assessment of mixed waste gasification under different conditions, with a focus on hydrogen-rich syngas production. The innovative aspect lies in the integrated evaluation of both energy efficiency and H₂/CO balance across multiple feedstocks. The syngas produced can be utilized directly in energy systems such as gas turbines and internal combustion engines or serve as an intermediate for chemical synthesis processes, including methanol and ammonia production. The findings offer a promising approach for sustainable waste management and resource recovery through thermochemical conversion.

Introduction: Treatments for CLL differ in efficacy, safety, treatment duration and monitoring needs, all of which can impact overall treatment experience and outcomes. To better understand patient preferences for various treatment attributes, a comprehensive quantitative analysis was conducted. Methods: A patient survey with a discrete choice experiment (DCE) design was conducted from December 2024 to February 2025 among adults (≥ 18 years) from the United States with confirmed diagnosis of CLL, recruited through online patient panels, physician referrals, and support groups. Treatment attributes were selected based on results of a targeted literature review and clinical inputs. Patients responded to DCE questions on attributes related to efficacy (PFS), safety (impacts of diarrhea, headache, atrial fibrillation, hypertension and tumor lysis syndrome [TLS]/kidney dysfunction on quality of life [QoL]) and treatment convenience (treatment duration: continuous vs. fixed duration with monitoring/hospitalization requirements). A conditional logistic regression model was used to calculate the relative importance of each attribute. Results: A total of 199 patients with CLL completed the survey (median age: 60 years; 91% White; 46% female; 66% with a bachelor’s degree or above; 46% employed; 54% commercially insured; 86% suburban/urban residence; 49% diagnosed ≥ 5 years ago). While 30% of patients had received ≥ 3 lines of therapy, 23% of all patients were treatment-naïve, 25% received 1 line of prior therapy, and 23% received 2 lines of prior therapy. Most patients (88%) reported having experienced ≥ 1 AE from treatment previously, with the most common AEs being headache (53%), fatigue (53%), diarrhea (44%), and nausea and/or vomiting (34%). Based on DCE preference results, patients favored treatments with longer PFS and less impact of headache, atrial fibrillation and TLS/kidney dysfunction on QoL (p < 0.001). Impact of diarrhea and hypertension on QoL and treatment convenience did not have a statistically significant influence on treatment preferences. The top 3 treatment attributes with the highest relative importance to patients were PFS (30%), impact of headache on QoL (26%) and impact of atrial fibrillation on QoL (24%), followed by impact of TLS/kidney dysfunction (10%) on QoL, treatment convenience (5%), and impact of diarrhea (4%) and hypertension (1%) on QoL (Figure). Conclusions: This patient preference survey showed that efficacy measured by PFS, the impact of headache, and impact of atrial fibrillation on QoL, were the most important attributes of treatment for patients with CLL. To support patient-centered care, shared decision-making in CLL treatment selection should incorporate a comprehensive discussion on AEs in addition to efficacy endpoints, as patients may prioritize treatments with less impact of AEs on their QoL. Future studies should assess the impact of shared decision-making on treatment adherence and outcomes. Research funding declaration: This study was funded by BeiGene, Ltd. Keywords: quality of life, late effects, survivorship care; patient and family-centered care; chronic lymphocytic leukemia (CLL) Potential sources of conflict of interest: S. Ailawadhi Consultant or advisory role: GSK, Sanofi, BMS, Takeda, Beigene, Pharmacyclics, Amgen, Janssen, Regeneron, Cellectar, Pfizer Other remuneration: Research funding to institution: GSK, BMS, Pharmacyclics, Amgen, Janssen, Cellectar, AbbVie, and Ascentage S. Challagulla Employment or leadership position: BeiGene USA, Inc. Stock ownership: BeiGene USA, Inc. D. Pilon Employment or leadership position: Analysis Group, Inc. T. I. Totev Employment or leadership position: Analysis Group, Inc. Y. Meng Employment or leadership position: Analysis Group, Inc. L. Diaz Employment or leadership position: Analysis Group, Inc. Z. Chen Employment or leadership position: Analysis Group, Inc. K. Yang Employment or leadership position: BeiGene USA, Inc. Stock ownership: BeiGene USA, Inc.

Immuno-oncology (IO) agents and pemetrexed are approved for the first-line (1L) maintenance treatment (1LMT) of advanced/metastatic non-small cell lung cancer (a/mNSCLC). This international retrospective chart review assessed real-world treatment patterns and outcomes in patients with a/mNSCLC lacking targetable mutations. Oncologists from seven countries (Canada, France, Germany, Italy, Spain, UK, USA) provided deidentified, medical chart-derived data on randomly selected adults with a/mNSCLC who remained stable or responded to 1L chemotherapy + IO. Treatment patterns, overall survival (OS), progression-free survival (PFS), and healthcare resource utilization (HCRU) were compared by maintenance treatment use following propensity score weighting. The effects of adding pemetrexed to IO-containing 1LMT was investigated in patients with non-squamous/mixed histology. Of 942 patients analyzed, 680 initiated 1LMT. After weighting, 1LMT was associated with longer median PFS (17.7 vs 7.1months; HR [95%CI] 0.63 [0.41-0.85]), similar OS (31.7 vs 31.0months; 0.82 [0.47-1.17]), and fewer mean monthly hospitalizations (0.03 vs 0.1; p < 0.01) versus no 1LMT. Among 469 patients with non-squamous/mixed histology who initiated an IO-containing 1LMT, 283 received IO only while 186 received IO + pemetrexed. Median time to treatment discontinuation (20.0 vs 11.0months; p < 0.001), PFS (21.1 vs 11.1months; HR [95%CI] 0.56 [0.37-0.76]), and OS (35.3 vs 27.3months; 0.70 [0.41-0.98]) were longer for patients receiving IO only versus IO + pemetrexed. Fewer patients administered IO only experienced fatigue (28.3% vs 39.8% [IO + pemetrexed]; p < 0.05) and anemia (16.6% vs 31.2%; p < 0.001). 1LMT was associated with significantly longer PFS and similar OS, without substantially increasing HCRU, among the current study population with a/mNSCLC. Adding pemetrexed to 1LM IO did not confer significant clinical benefit in patients with non-squamous/mixed histology and these patients incurred more adverse events. Additional 1LMT options are needed to further improve clinical outcomes.

"HSR25-182: Patient-Physician Communication About Adverse Events and Impact on Quality of Life to Foster Shared Decision-Making in Chronic Myeloid Leukemia" published on 28 Mar 2025 by National Comprehensive Cancer Network.

Biophysical modeling, particularly involving partial differential equations (PDEs), offers significant potential for tailoring disease treatment protocols to individual patients. However, the inverse problem-solving aspect of these models presents a substantial challenge, either due to the high computational requirements of model-based approaches or the limited robustness of deep learning (DL) methods. We propose a novel framework that leverages the unique strengths of both approaches in a synergistic manner. Our method incorporates a DL ensemble for initial parameter estimation, facilitating efficient downstream evolutionary sampling initialized with this DL-based prior. We showcase the effectiveness of integrating a rapid deep-learning algorithm with a high-precision evolution strategy in estimating brain tumor cell concentrations from magnetic resonance images. The DL-Prior plays a pivotal role, significantly constraining the effective sampling-parameter space. This reduction results in a fivefold convergence acceleration and a Dice-score of 95%.

PurposeAdding CDK4/6 inhibitors (CDK4/6is) to endocrine therapy (ET) for HR+/HER2− early breast cancer (EBC) demonstrated statistically significant invasive disease-free survival (iDFS) benefits in monarchE (node positive, high risk, stage II/III) and NATALEE (select N0 and all macroscopic N1, stage II/III). This study evaluated patient preferences for EBC treatment attributes and how these may translate for CDK4/6i selection.MethodsA web-based discrete choice experiment survey was conducted among US-based adult women with self-reported stage II/III HR+/HER2− EBC. Eight attributes were included, informed by 14 qualitative interviews (to identify most relevant attributes), expert clinical input, and differentiating features between CDK4/6is: efficacy (5-year iDFS), adverse events (venous thromboembolic event [VTE], diarrhea, fatigue), number of blood tests, number of electrocardiograms (EKGs), treatment duration, and schedule. Participants selected scenarios that best reflected their preferences from 10 choice cards, each displaying a pair of hypothetical treatment profiles. A conditional logit regression model was used to estimate preference weights and relative importance (RI) of attributes.ResultsA total of 409 women participated. Patient preferences, from high to low RI, were higher efficacy, lower diarrhea risk, lower fatigue risk, shorter treatment duration, and lower VTE risk. Number of blood tests, number of EKGs, and treatment schedule were less important. Utility scores were higher for reconstructed treatment profiles that resembled ribociclib.ConclusionThis study demonstrated that patients prefer adjuvant treatment with higher efficacy and lower risk of adverse events. These data will aid shared decision-making when discussing the addition of CDK4/6is to adjuvant ET for eligible patients with HR+/HER2− EBC.

412 Background: Drug development in esophageal cancer is rapidly evolving, and identifying surrogates for patient outcomes to accelerate clinical drug development remains an important unmet medical need. Although early clinical endpoints such as EFS, disease free survival (DFS) are proven to be valid surrogates for overall survival (OS) in early esophageal (Ajani JA et al. 2022), gastric (Oba K et al. 2013; Wainberg ZA et al. 2023), and gastroesophageal junction tumors (Ronellenfitsch U. et al. 2013) after disease resection, there are no such surrogacy data evaluating patients who underwent non-operative management. Specifically, there has been no prior systemic evaluation of the predictive value of EFS as a surrogate for OS among LA EC patients treated with dCRT. This study evaluated the trial-level correlation between EFS and OS in unresectable LA EC patients receiving dCRT. Methods: A systematic literature review was conducted to identify randomized controlled trials (RCTs) of dCRT interventions in unresectable LA EC (search cutoff date: April 2023). Studies reporting EFS (or similar outcomes such as progression free survival (PFS), defined as time from randomization to local, regional, or distant recurrence, or death) and OS were included. EFS and OS hazard ratios (HRs) of each treatment comparison were extracted. Correlation between the log(HR) of EFS and OS was assessed using weighted linear regression (WLR). The coefficient of determination (R 2 ) was used to evaluate the strength of the correlation. A good surrogate was defined as an R 2 ≥ 0.65 (Ciani et al . 2017) or an R 2 ≥ 0.75 (Lassere et al . 2008). Leave-one-out cross-validations and sensitivity analyses were conducted to assess the robustness of the WLR model and correlation analyses, respectively. Results: The final analysis included 14 between-treatment comparisons from 11 RCTs (total number of patients = 2,812). We found a strong statistical correlation between EFS and OS, with an estimated slope coefficient of 0.91 ( p &lt; 0.001) and R 2 of 0.80 (95% confidence interval [CI]: 0.38, 0.96). In the leave-one-out cross validation, 71.4% of observed OS HRs fell within the predicted 95% CIs. Sensitivity analyses showed R 2 of 0.75 among studies conducted in China and R 2 of 0.73 after including studies that did not report EFS definition. Conclusions: In a pooled analysis of 11 clinical trials corresponding to over 2800 patients, we observed a strong statistical correlation between EFS and OS outcomes. This analysis supports the utility of EFS as a valid surrogate of OS in patients with unresectable LA EC receiving dCRT.