Clinical Drug Investigation最新文献

{"title":"Assessing the Completeness of Adverse Event Reporting in Clinical Trials of Psoriasis Treatments: A Registry-Publication Comparison Study.","authors":"Madeline Rowe, Madison Dinh, Ryan Sherry, Kellen Keefer, Rachel Hazlitt, Ahmed Elghzali, Daniel Archer, Alicia Ito Ford, Matt Vassar","doi":"10.1007/s40261-026-01561-z","DOIUrl":"10.1007/s40261-026-01561-z","url":null,"abstract":"<p><strong>Background and objectives: </strong>The interventional landscape for psoriasis has expanded considerably with the introduction of systemic and biologic agents, intensifying the importance of comprehensive adverse event (AE) documentation to inform safe clinical practice. While regulatory initiatives such as the Food and Drug Administration Amendments Act Final Rule (FDAAA Final Rule) were designed to enhance clinical trial transparency, disparities between AE data presented in ClinicalTrials.gov and peer-reviewed literature continue to occur, potentially complicating interpretation of publicly available harms information used in evidence synthesis and clinical decision-making. Variability in how serious adverse events (SAEs), other adverse events (OAEs), deaths, and treatment discontinuations due to AE are documented can distort safety perceptions and influence clinical practice. This study compares AE reporting between ClinicalTrials.gov and corresponding peer-reviewed publications for psoriasis clinical trials and evaluates whether completeness and concordance differ before versus after implementation of the FDAAA Final Rule.</p><p><strong>Methods: </strong>We performed a cross-sectional analysis using systematic retrieval of psoriasis trials from ClinicalTrials.gov with results posted between 2009 and 2024. Data on AEs-encompassing SAEs, OAEs, treatment discontinuation due to AE, and deaths-were independently abstracted by two reviewers, with disagreements resolved through adjudication. Trials were categorized according to FDA regulatory status, and variations in AE documentation were examined using descriptive statistics, chi-squared tests, Bland-Altman and funnel plots, and regression modeling.</p><p><strong>Results: </strong>The study's primary endpoint was completeness and agreement of AE documentation between ClinicalTrials.gov and corresponding peer-reviewed publications across four predefined domains: SAEs, OAEs, discontinuation due to AE, and death. Pre-Final Rule AE reporting patterns were mixed across domains. After implementation of the FDAAA Final Rule, registry entries more consistently reported SAEs, OAEs, and mortality than corresponding publications. Although death documentation in registry entries showed improvement after the rule's enactment, publications demonstrated persistent inconsistency. Following implementation of the FDAAA Final Rule, SAEs were present in 53% of registry records versus 40% of publications. OAEs were captured in 51% of registry entries but only 22% of publications. Disparities in SAE totals occurred in over 90% of trials, frequently with registry entries recording higher counts. Numerous discrepancies stemmed from incomplete calculations, ambiguous characterizations, or AE information confined to narrative text. Both visual and statistical assessments revealed a pattern of underreporting in publications, with minimal temporal improvement irrespective of trial scale or sponsorship type.</p><p","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":"733-745"},"PeriodicalIF":3.1,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13332884/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147959828","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Milsaperidone: First Approval.","authors":"Matt Shirley","doi":"10.1007/s40261-026-01562-y","DOIUrl":"10.1007/s40261-026-01562-y","url":null,"abstract":"<p><p>Milsaperidone (Bysanti™) is an atypical antipsychotic being developed by Vanda Pharmaceuticals for use in the treatment of schizophrenia, bipolar I disorder, and major depressive disorder. Milsaperidone is an active metabolite of iloperidone (Fanapt^®), an atypical antipsychotic approved in the USA for the treatment of schizophrenia since 2009 and for use in the acute treatment of bipolar I disorder since 2024. With clinical trials demonstrating the pharmacokinetic bioequivalence of milsaperidone and iloperidone, on 20 February 2026, milsaperidone gained approval in the USA for use in the treatment of schizophrenia and in the acute treatment of manic or mixed episodes associated with bipolar I disorder in adults. Additionally, milsaperidone is in phase III clinical evaluation for use in the treatment of major depressive disorder. This article summarizes the milestones in the development of milsaperidone leading to this first approval for schizophrenia and bipolar I disorder in adults.</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":"795-801"},"PeriodicalIF":3.1,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148053060","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Current Strategies and Emerging Paradigms of Immunotherapy in Microsatellite Stable Colorectal Cancer: A Review Article.","authors":"Lu-Ying Zhan, Zhe-Ling Chen, Liu Yang","doi":"10.1007/s40261-025-01520-0","DOIUrl":"10.1007/s40261-025-01520-0","url":null,"abstract":"<p><p>Immunotherapy, especially through the innovative use of immune checkpoint inhibitors (ICIs), has rapidly become an essential component in both first-line and subsequent treatment strategies for cancers that exhibit DNA mismatch repair defects or display high microsatellite instability (dMMR/MSI-H). These therapies harness the power of the immune system to target and destroy cancer cells more effectively. However, the application of ICIs in patients diagnosed with microsatellite stable (MSS) colorectal cancer presents considerable hurdles. These challenges largely arise from the inherent tumor heterogeneity and the complex immune landscape characteristic of the tumor microenvironment. It is crucial to highlight that numerous clinical trials are actively underway, aimed at deepening our understanding of the mechanisms at play and paving the way for future advancements in this arena. This article endeavors to provide an extensive review of the current literature surrounding the application of ICIs in MSS colorectal cancer. We aim to deliver a thorough overview of the present state of immunotherapy for this subset of colorectal cancer, beginning with an exploration of various combination therapy strategies that enhance immune responses. Moreover, we will investigate several adverse prognostic factors that affect MSS colorectal cancer patients undergoing immunotherapy. A particular focus will be placed on the detrimental effects of liver metastasis and the influence of local treatment modalities for liver metastasis on patient clinical outcomes. This narrative review compiles current knowledge to serve as a reference point for identifying potential patient populations that could benefit from immunotherapy in the future, ultimately striving for improved therapeutic approaches and patient outcomes.</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":"701-720"},"PeriodicalIF":3.1,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148053057","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Economic Evaluation of Axicabtagene Ciloleucel as a Second-Line Therapy for Relapsed/Refractory Diffuse Large B-Cell Lymphoma in South Korea: A Cost-Utility Analysis Based on the ZUMA-7 Trial.","authors":"Jiyeon Lee, Minsung Kim, Minseol Jang, Soomi Jo, Seulki Lee, Hae Sun Suh","doi":"10.1007/s40261-026-01557-9","DOIUrl":"10.1007/s40261-026-01557-9","url":null,"abstract":"<p><strong>Background and objectives: </strong>Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma in South Korea, with 30-40% of patients relapsing or becoming refractory after first-line therapy. Axicabtagene ciloleucel (axi-cel) demonstrated superior efficacy over standard-of-care (SoC) salvage chemotherapy plus autologous stem cell transplantation (ASCT) in the ZUMA-7 trial. While approved for second-line use in South Korea, its cost effectiveness has not yet been evaluated in the local healthcare setting. This study aimed to evaluate the cost effectiveness of axi-cel compared with SoC as a second-line treatment for adult patients with relapsed or refractory DLBCL eligible for ASCT from the perspective of the South Korean healthcare system.</p><p><strong>Methods: </strong>A partitioned survival model with a mixture cure approach was developed based on ZUMA-7 data to compare axi-cel with SoC as second-line treatment for transplant-eligible relapsed/refractory DLBCL. The analysis was conducted from the healthcare system perspective over a lifetime horizon, with costs and outcomes discounted at 4.5% annually. Utilities were estimated from EQ-5D-5L data in ZUMA-7 using the South Korean valuation set. Costs included treatment, subsequent therapies, resource use, adverse event management, and end-of-life care. Deterministic and probabilistic sensitivity analyses were conducted. Cost effectiveness was evaluated using a willingness-to-pay threshold of 1.5-2 times the gross domestic product per capita of South Korea.</p><p><strong>Results: </strong>Over a lifetime horizon, axi-cel yielded 8.68 life years (LYs) and 7.61 quality-adjusted life years (QALYs) versus 7.10 LYs and 5.91 QALYs for SoC. Total costs were higher for axi-cel, resulting in an incremental cost of KRW 93.9 million (US dollars (USD) 68,676). The incremental cost-effectiveness ratio (ICER) was KRW 55.5 million (USD 40,583) per QALY gained. Sensitivity analyses showed robust results, with subsequent therapy pattern as the most influential parameter.</p><p><strong>Conclusions: </strong>Axi-cel as second-line treatment for relapsed or refractory DLBCL provided meaningful gains in survival and quality-adjusted life and appeared to be a cost-effective alternative compared to SoC in South Korea.</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":"747-758"},"PeriodicalIF":3.1,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147834646","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cost-Effectiveness Analysis of PCSK9 Inhibitors in Patients with Atherosclerotic Cardiovascular Disease Without Prior Ischemic Events in Italy.","authors":"Giuseppe Musumeci, Lorenzo Pradelli, Kelly Lee, Massimiliano Povero","doi":"10.1007/s40261-026-01559-7","DOIUrl":"10.1007/s40261-026-01559-7","url":null,"abstract":"<p><strong>Background and objective: </strong>Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) are an effective class of lipid-lowering drugs in patients with primary hypercholesterolemia or mixed dyslipidemia. New evidence supported the early use of PCSK9i in patients with atherosclerotic cardiovascular disease without prior ischemic events and not achieving the low-density lipoprotein-cholesterol targets despite being treated with other lipid-lowering therapies. The aim of the study is to evaluate the cost effectiveness of PCSK9i monoclonal antibodies (mAbs) as an add-on treatment in this population over the lifetime horizon from the Italian National Health Service perspective.</p><p><strong>Methods: </strong>A Markov model with a 1-year cycle length was developed to evaluate the incremental cost and effectiveness of maximum tolerated statins plus ezetimibe (MTS+E) with versus without PCSK9i mAbs in high-risk patients with atherosclerotic cardiovascular disease without prior ischemic events. Baseline cardiovascular risk and relative cardiovascular risk reduction attributed to PCSK9i mAbs for major adverse cardiovascular events (i.e., acute coronary syndrome, ischemic stroke, and all-cause mortality) were based on analysis using the US Optum Research database. Costs of drugs and management of cardiovascular events were considered in the analysis. Utility values were sourced from the existing literature. Both deterministic and probabilistic sensitivity analyses were conducted to assess the robustness of the result.</p><p><strong>Results: </strong>The simulated cohort's mean age was 68 years and mean baseline low-density lipoprotein-cholesterol level was 129.7 mg/dL, with female individuals and diabetes mellitus accounting for 50.1% and 34.8%, respectively. The incremental cost and quality-adjusted life-year (QALY) gained of MTS+E with added PCSK9i mAbs versus without PCSK9i mAbs were €61,334 and 2.42 QALY, equivalent to €25,350 per QALY gained. At a willingness-to-pay threshold of €33,000 per QALY gained, MTS+E plus PCSK9i mAbs had about 65% probability of being cost effective versus MTS+E alone.</p><p><strong>Conclusions: </strong>The results demonstrated that PCSK9i mAbs as an add-on therapy to MTS+E are likely to be cost effective when compared with MTS+E alone in high-risk patients with atherosclerotic cardiovascular disease without prior ischemic events from the Italian National Health Service perspective.</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":"771-782"},"PeriodicalIF":3.1,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13332988/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147927180","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regulatory and Ethical Frameworks for First-in-Human Clinical Trials in India: Proceedings of a Codesigned Capacity-Building Workshop.","authors":"Nusrat Shafiq, Ashok Kumar, Jerin Jose Cherian, Taruna Madan, Nilima Kshirsagar, Aparna Mukherjee, Soumya Vij, Pawan Kumar Singh, Geetika Srivastava, Annam Visala, Akhil Kumar, Anita Soman, Harish Kaushik Kotakonda, Sadhna Joglekar, Mahendra Joshi, Venkatesha Udupa, Aruvi Poomali, Nikhil Benroy Noronha, Nithya Gogtay, Manjunath Nookala Krishnamurthy, Satyajit Mohapatra, Nilanjan Saha, Vikram Gota, A K Pradhan, Priyadarshini Chatterjee, Amit Kumar, Animesh Chaturvedi, Mahesh Kumar Balasundaram, Gaurav Prakash, Ashish K Kakkar, Samir Malhotra","doi":"10.1007/s40261-026-01558-8","DOIUrl":"10.1007/s40261-026-01558-8","url":null,"abstract":"<p><p>A two-and-a-half-day workshop on regulatory and ethical issues in first-in-human (FIH) clinical trials in India was held at the Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India, on 7-9 November 2024, under the aegis of the Indian Council of Medical Research (ICMR) Phase I Network. The workshop brought together regulators, academic investigators, and industry representatives to examine the evolving regulatory landscape of early phase trials in India and the operational challenges associated with it. Through interactive sessions, including preparation of investigational new drug (IND) application, mock pre-IND/IND and mock subject expert committee (SEC) meetings, on-site monitoring simulations, and structured hands-on exercises, the workshop navigated regulatory submission pathways, trial reporting, documentation standards, safety oversight, and informed consent processes. A panel discussion on the phase lag policy for FIH studies in India was held with expert personnel from regulatory agencies, ICMR headquarters, industry, and academia. The workshop discussions underscored the need for policy harmonization, enhanced site preparedness, and sustained capacity-building to position India as a leader for early phase clinical research. The present article summarizes the proceeding of the workshop and highlights the critical insights for developing a regulatory and ethical framework to support FIH trials in India.</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":"683-689"},"PeriodicalIF":3.1,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148027839","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacokinetics of Nirmatrelvir/Ritonavir after Multiple Administration in a Phase 1, Open-Label Study in Healthy Chinese Adults and Compared with Non-Chinese Participants.","authors":"Nanyang Li, Jicheng Yu, Jufang Wu, Jing Zhang, Ying Ma, Chunye Zhang, Xiaoran Han, Jackie Gerhart, Shuangchen Cong","doi":"10.1007/s40261-026-01554-y","DOIUrl":"10.1007/s40261-026-01554-y","url":null,"abstract":"<p><strong>Background and objectives: </strong>Nirmatrelvir (PF-07321332) has demonstrated antiviral activity and an acceptable safety profile in clinical studies. This study aimed to demonstrate the pharmacokinetic (PK) profiles of Chinese participants after administration of nirmatrelvir/ritonavir, and to further evaluate the ethnic differences between different races.</p><p><strong>Methods: </strong>This Phase 1, open-label, single-site study assessed the PK, safety, and tolerability of nirmatrelvir 300 mg plus ritonavir 100 mg administered twice daily for 10 days in healthy Chinese adults. In total, 14 Chinese participants were enrolled with an age range of 24 to 43 years. Samples were collected after first-dose administration on day 1 (0, 0.5, 1, 1.5, 2, 4, 6, 8, 12 h after drug administration) and last-dose administration on day 10 (0, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, and 48 h after drug administration) to assess PK parameters after a single dose and multiple doses; pre-dose samples were collected on days 5, 8, and 10 to confirm that steady-state was achieved. All PK samples were assayed with a liquid chromatography-tandem mass spectrometry method to quantify plasma concentration of nirmatrelvir and ritonavir. Study participants were monitored for safety for 28-35 days after the last-dose administration. Adverse events (AEs), clinical safety laboratory tests, vital signs, and 12-lead electrocardiograms were all monitored during study. Results for Chinese participants were compared with results in healthy non-Chinese adult participants who received the same nirmatrelvir/ritonavir dose in other Phase 1 studies.</p><p><strong>Results: </strong>All 14 healthy Chinese adults completed the study. Nirmatrelvir was rapidly absorbed, with a median t_max of approximately 2 h. Geometric mean nirmatrelvir C_max and AUC were 3.08 μg/mL and 19.66 μg·h/mL after the first dose and increased to 4.50 μg/mL and 32.01 μg·h/mL at steady state, with less than 2-fold accumulation and a mean terminal half-life of 6.84 h. Steady-state concentrations were achieved before day 5. Nirmatrelvir/ritonavir was well tolerated; 6 participants (42.9%) reported AEs, 4 of which (28.6%) were treatment-related mild dysgeusia. No serious AEs or discontinuations were reported. The results showed that the PK characteristics of nirmatrelvir/ritonavir in healthy Chinese adults were comparable with results from previous studies in non-Chinese healthy adults, with no apparent clinically significant differences observed between Chinese and non-Chinese participants.</p><p><strong>Conclusions: </strong>In healthy Chinese participants, the PK profile of nirmatrelvir 300 mg plus ritonavir 100 mg twice daily was comparable with that observed in non-Chinese participants, with an overall favorable safety profile, supporting the use of this dosing regimen for the Chinese population.</p><p><strong>Clinicaltrials: </strong></p><p><strong>Gov id: </strong>NCT05339334.</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":"783-793"},"PeriodicalIF":3.1,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13332995/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147833710","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Estimating the Real Option Value of Osimertinib Compared to Standard EGFR-TKI in the Treatment of Advanced NSCLC in the United States.","authors":"Kwame Adjei, Vakaramoko Diaby, Meng Li, Fatimah Sherbeny, Sandra Suther, Askal A Ali","doi":"10.1007/s40261-026-01560-0","DOIUrl":"10.1007/s40261-026-01560-0","url":null,"abstract":"<p><strong>Background and objective: </strong>Real option value (ROV) remains underexplored in epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) for non-small cell lung cancer (NSCLC) even though its impact on economic evaluation is being acknowledged. The objective of this study is to estimate the ROV of osimertinib compared with gefitinib/erlotinib in the treatment of advanced NSCLC.</p><p><strong>Methods: </strong>The ROV was estimated using a three-state Markov model comprising progression-free survival, progressed, and death. The trend approach using NSCLC patients from Surveillance, Epidemiology, and End Results (SEER), and Medicare data, diagnosed between 2011 and 2017, was used. Cox proportional hazards models were fitted in the first 3 years of diagnosis. We assumed that historical survival trends continued beyond 2017 to estimate post-2017 the lung cancer-specific hazard ratio. The estimated hazard ratio was then applied to the transition probabilities from the progressed disease to death to estimate costs and quality-adjusted life years (QALYs), accounting for future improvements in survival. A cycle length of 1 month and a lifetime horizon was used in the analysis. The analysis was conducted from the US health system's perspective and a discount rate of 3% annually was applied.</p><p><strong>Results: </strong>The hazard ratios for all-cause mortality, lung cancer-specific mortality, and other-cause mortality were: 0.835 (95% CI 0.827-0.843; p < 0.001), 0.832 (95% CI 0.824-0.840; p < 0.001), and 0.870 (95% CI 0.841-0.900; p < 0.001), respectively. In the ROV scenario, the incremental cost of osimertinib versus standard EGFR-TKI decreased by 4.40%, from $239,779.95 to $229,226.80. The incremental life years (LYs) and QALYs rose from 1.931 and 1.52 in the conventional setting, to 2.67 and 2.05, respectively. This resulted in 38.34% and 34.86% increase, respectively, from the conventional scenario. The incremental cost effectiveness ratio (ICER) decreased by 29.04% from $157,761.26/QALY in the conventional to $111,942.31/QALY in the option value scenario.</p><p><strong>Conclusion: </strong>This study demonstrates that incorporating ROV into the conventional cost-effectiveness analysis of osimertinib versus standard EGFR-TKI provides a more comprehensive assessment of its value and cost effectiveness. This helps decision-makers better understand the long-term value of first-line treatment choices in advanced EGFR-mutated NSCLC.</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":"721-732"},"PeriodicalIF":3.1,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148053059","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cost Effectiveness of First-Line Therapies for Treatment-Naïve Chronic Lymphocytic Leukaemia in South Africa.","authors":"Rochelle Woudberg, Edina Sinanovic","doi":"10.1007/s40261-026-01538-y","DOIUrl":"10.1007/s40261-026-01538-y","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background and objectives: &lt;/strong&gt;Chronic lymphocytic leukaemia (CLL) is a common adult leukaemia, and selecting the most effective first-line treatment is crucial for optimising patient outcomes and managing healthcare costs. While chemoimmunotherapy (CIT) has been the standard approach, targeted therapies offer promising alternatives for treatment-naïve CLL patients. The objective of this study was to evaluate the cost effectiveness of chemoimmunotherapy compared to targeted therapies for treatment-naïve CLL patients in South Africa.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;A cost-effectiveness analysis was conducted using a Markov model based on three health states: progression-free survival (PFS), progression, and death. The model employed a 15-year time horizon and a 1-month cycle length. Patient-level data were reconstructed, and parametric estimation was used to project long-term clinical outcomes. Cost estimates were derived from national tariffs, reflecting a South African public healthcare perspective, while utilities were sourced from published literature. Outcomes were measured in total costs and quality-adjusted life years (QALYs). Incremental cost-effectiveness ratios (ICERs) were calculated and compared to a willingness-to-pay (WTP) threshold, and sensitivity analyses were conducted to test the robustness of the results.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Among the evaluated treatment strategies, chlorambucil-plus-obinutuzumab (ClbO) had the lowest cost and served as the reference comparator. Both CIT regimens were cost effective, with fludarabine, cyclophosphamide, and rituximab (FCR) yielding an ICER of US$1645.52 per QALY gained and bendamustine-plus-rituximab (BR) had an ICER of US$1716.79 per QALY gained, both below the US$3407 WTP threshold, under the model assumptions. Ibrutinib generated the highest QALYs but at a higher cost, resulting in an ICER of US$19,679.52 per QALY gained and a 0% probability of being cost effective at the WTP threshold, while venetoclax-plus-obinutuzumab (VenO) was extendedly dominated, and therefore eliminated from the results. Sensitivity analyses confirmed the robustness of the findings across variations in key parameters.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;In the South African public healthcare setting, CIT regimens (FCR and BR) represent cost-effective first-line treatment strategies for symptomatic, treatment-naïve CLL. Bendamustine-plus-rituximab emerged as the most decision-robust option under uncertainty, while FCR yielded the lowest point-estimate ICER. Among CIT regimens, FCR may be preferred in fit patients, while BR represents a more decision-robust option in older or unfit populations. Targeted therapies such as ibrutinib and VenO, despite superior clinical efficacy, are not cost effective at current prices. Substantial price reductions, generic entry, or targeted use in high-risk subgroups may improve their value and enable equitable access within South Africa's resource-constrained ","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":"595-607"},"PeriodicalIF":3.1,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13212691/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147456110","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cost-Effectiveness Analysis of Anlotinib Plus Penpulimab Versus Sorafenib in the First-Line Treatment of Unresectable Hepatocellular Carcinoma in China.","authors":"JinDi Liu, Lian Tang, LongXun Zhu, Yong Chen, PanFeng Feng","doi":"10.1007/s40261-026-01543-1","DOIUrl":"10.1007/s40261-026-01543-1","url":null,"abstract":"<p><strong>Background and objectives: </strong>Given the substantial disease burden of unresectable hepatocellular carcinoma (uHCC) in China and the high costs associated with novel combination therapies, this study aims to evaluate, from the perspective of the Chinese healthcare system, the cost effectiveness of anlotinib combined with penpulimab versus sorafenib as first-line treatment for uHCC.</p><p><strong>Methods: </strong>A partitioned survival model was developed using clinical data from the Phase III APOLLO trial. The model employed a 21-day cycle length and a 10-year time horizon. The incremental cost-effectiveness ratio (ICER) of anlotinib plus penpulimab versus sorafenib was calculated and compared against a predefined willingness-to-pay (WTP) threshold-set at three times China's 2024 per capita GDP (40,354.27 US$ per quality-adjusted life year [QALY]) -to determine cost effectiveness. One-way and probabilistic sensitivity analyses were performed to assess the robustness of the model.</p><p><strong>Results: </strong>Compared with the sorafenib group, the anlotinib plus penpulimab group incurred higher costs (44,068.90 US$ vs 38,142.25 US$) but provided greater survival benefits (1.20 QALYs vs 1.03 QALYs), yielding an ICER of 34,862.65 US$/QALY. One-way sensitivity analysis indicated that the utility value in the progressive disease state, the price of penpulimab, and utility value in the progression-free survival state had the most significant impact on the ICER. Probabilistic sensitivity analysis demonstrated robust results, with a 60.6% probability of anlotinib plus penpulimab being cost effective.</p><p><strong>Conclusion: </strong>Our study suggests that anlotinib combined with penpulimab represents a cost-effective first-line treatment option for patients with uHCC from the perspective of the Chinese healthcare system. These results provide critical evidence to inform clinical practice and healthcare reimbursement policy.</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":"631-640"},"PeriodicalIF":3.1,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147484410","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}