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Ribociclib (RIBO) and palbociclib (PALBO), combined with letrozole (LET), have been evaluated as treatments for hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer in separate Phase III randomized controlled trials (RCTs), but not head-to-head. Population differences can lead to biased results by classical indirect treatment comparison (ITC). Matching-adjusted indirect comparison (MAIC) aims to correct these differences. We compared RIBO and PALBO in hormone receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer using MAIC. Patient-level data were available for RIBO (MONALEESA-2), while only published summary data were available for PALBO (PALOMA-2). Weights were assigned to MONALEESA-2 patient data such that mean baseline characteristics matched those reported for PALOMA-2; the resulting matched cohort was used in comparisons. Limited by the results reported in PALOMA-2, progression-free survival (PFS) was the primary comparison. Cox regression models were used to calculate adjusted hazard ratios (HRs) for PFS, before indirect treatment comparison (ITC) was performed with 95% confidence intervals. An exploratory analysis was performed similarly for overall survival using earlier PALBO data (PALOMA-1). Grade 3/4 adverse events were also compared. Racial characteristics, prior chemotherapy setting, and the extent of metastasis were the most imbalanced baseline characteristics. The unadjusted PFS HRs were 0.556 (0.429, 0.721) for RIBO+LET versus LET alone and 0.580 (0.460, 0.720) for PALBO+LET versus LET alone. MAIC adjustment resulted in an HR of 0.524 (0.406, 0.676) for RIBO+LET versus LET. PFS ITC using unadjusted trial data produced an HR of 0.959 (0.681, 1.350) for RIBO versus PALBO, or 0.904 (0.644, 1.268) with MAIC. Unadjusted overall survival HR of RIBO versus PALBO was 0.918 (0.492, 1.710); while exploratory MAIC was 0.839 (0.440, 1.598). ITC of grade 3/4 adverse events yielded a risk ratio of 0.806 (0.604, 1.076). MAIC was performed for RIBO and PALBO in the absence of a head-to-head trial: though not statistically significant, the results favored RIBO.

Background Several reviews have noted shortcomings regarding the quality and reporting of network meta-analyses (NMAs). We suspect that this issue may be partially attributable to limitations in current NMA software which do not readily produce all of the output needed to satisfy current guidelines. Results To better facilitate the conduct and reporting of NMAs, we have created an R package called “BUGSnet” ( B ayesian inference U sing G ibbs S ampling to conduct a Net work meta-analysis). This R package relies upon Just Another Gibbs Sampler (JAGS) to conduct Bayesian NMA using a generalized linear model. BUGSnet contains a suite of functions that can be used to describe the evidence network, estimate a model and assess the model fit and convergence, assess the presence of heterogeneity and inconsistency, and output the results in a variety of formats including league tables and surface under the cumulative rank curve (SUCRA) plots. We provide a demonstration of the functions contained within BUGSnet by recreating a Bayesian NMA found in the second technical support document composed by the National Institute for Health and Care Excellence Decision Support Unit (NICE-DSU). We have also mapped these functions to checklist items within current reporting and best practice guidelines. Conclusion BUGSnet is a new R package that can be used to conduct a Bayesian NMA and produce all of the necessary output needed to satisfy current scientific and regulatory standards. We hope that this software will help to improve the conduct and reporting of NMAs.

To support systematic reviewers new to network meta-analysis (NMA), we (1) identified and described published methods resources for conducting systematic reviews (SRs) with NMA of randomized controlled trials (RCTs); (2) mapped the resources to the typical steps for conducting NMAs; and (3) identified NMA guidance gaps. We performed a scoping review and comprehensively searched major databases, gray literature sources, and websites for methods resources that described or informed any steps in conducting SRs with NMA to guide review authors, particularly those new to the method. Title, abstract, and full-text screening were conducted independently in duplicate using Covidence. NMA resources were narratively described and tabulated by guidance type, review steps, and topic and mapped to the steps of conducting a systematic review with NMA. We considered documents in the 2011–2025 date range and included 90; the majority (39%) were published between 2021 and 2025. Most were classified as guides/guidance (29%), methods/methodology (22%), or reviews (27%). We found that the rate of published guidance around most steps of NMA increased or remained stable over time. Most resources for software were guidance for R and Stata. Guidance documents on assumptions and certainty of evidence were abundant (in excess of 13 documents per topic), whereas fewer guidance documents were available on elements of protocol development and presentation of results. We mapped methods resources across steps in conducting SRs with NMA, identifying areas with sparse guidance. This scoping review provides a comprehensive reference for conducting SRs using NMA, especially for those new to the methods. It highlights the significant increase in guidance since 2011, particularly on evidence certainty and NMA assumptions, and the availability of user-friendly web tools. Future work should focus on advanced NMA guidance and decision tools to aid reviewers in further navigating NMA complexities.

Background Anchored covariate-adjusted indirect comparisons inform reimbursement decisions where there are no head-to-head trials between the treatments of interest, there is a common comparator arm shared by the studies, and there are patient-level data limitations. Matching-adjusted indirect comparison (MAIC), based on propensity score weighting, is the most widely used covariate-adjusted indirect comparison method in health technology assessment. MAIC has poor precision and is inefficient when the effective sample size after weighting is small. Methods A modular extension to MAIC, termed two-stage matching-adjusted indirect comparison (2SMAIC), is proposed. This uses two parametric models. One estimates the treatment assignment mechanism in the study with individual patient data (IPD), the other estimates the trial assignment mechanism. The first model produces inverse probability weights that are combined with the odds weights produced by the second model. The resulting weights seek to balance covariates between treatment arms and across studies. A simulation study provides proof-of-principle in an indirect comparison performed across two randomized trials. Nevertheless, 2SMAIC can be applied in situations where the IPD trial is observational, by including potential confounders in the treatment assignment model. The simulation study also explores the use of weight truncation in combination with MAIC for the first time. Results Despite enforcing randomization and knowing the true treatment assignment mechanism in the IPD trial, 2SMAIC yields improved precision and efficiency with respect to MAIC in all scenarios, while maintaining similarly low levels of bias. The two-stage approach is effective when sample sizes in the IPD trial are low, as it controls for chance imbalances in prognostic baseline covariates between study arms. It is not as effective when overlap between the trials’ target populations is poor and the extremity of the weights is high. In these scenarios, truncation leads to substantial precision and efficiency gains but induces considerable bias. The combination of a two-stage approach with truncation produces the highest precision and efficiency improvements. Conclusions Two-stage approaches to MAIC can increase precision and efficiency with respect to the standard approach by adjusting for empirical imbalances in prognostic covariates in the IPD trial. Further modules could be incorporated for additional variance reduction or to account for missingness and non-compliance in the IPD trial.

Cognitive behavioral therapy (CBT) is recommended for irritable bowel syndrome (IBS). However, it remains unclear whether face-to-face CBT is as effective as digital, self-help, or telephone-delivered CBT for IBS. This study aimed to estimate the relative effects of face-to-face CBT compared with digital, telephone-delivered, and self-help CBT for IBS and to assess whether there are adequate effective sample sizes to support the findings. Ovid MEDLINE, Embase, and the Cochrane Library were searched up to September 27, 2025. Randomized controlled trials of face-to-face, digital, self-help, or telephone-delivered CBT for IBS in adults were included. The primary outcome was the IBS symptom severity scale. The secondary outcomes were IBS quality of life and abdominal pain intensity. A Bayesian random effects model was used for the meta-analysis. The effective and required sample sizes were calculated to estimate whether the sample sizes were adequate. The certainty of evidence was evaluated using the Confidence in Network Meta-Analysis Framework. The risk of bias of included studies was assessed using the Cochrane Collaboration's risk of bias tool (version 2). We analyzed 22 studies involving 3161 participants. The number of participants ranged between 28 and 558. The mean (SD) age of participants was 37.2 (10.6) years, and 78.6% (2485/3161) were women. These randomized controlled trials were published between 2003 and 2025. We found that face-to-face CBT had similar effects compared with digital CBT (mean difference [MD] -0.89, 95% credible interval [CrI] -20.78 to 18.73), self-help CBT (MD -1.73, 95% CrI -21.03 to 17.80), and telephone-delivered CBT (MD -0.76, 95% CrI -20.86 to 19.38) in improving IBS symptom severity scale scores. The comparison between face-to-face CBT and self-help CBT had sufficient effective sample sizes (375/140), whereas the effective sample sizes for comparisons with digital CBT (347/729) and telephone-delivered CBT (140/627) were insufficient. The certainty of evidence was moderate to low. Similarly, in improving quality of life and abdominal pain intensity, face-to-face CBT showed equal effect compared with digital and self-help CBT, with insufficient sample sizes and low to very low evidence certainty. This is the first Bayesian meta-analysis to incorporate effective and required sample size calculations for comparisons among CBT modalities in IBS. We analyzed continuous data of the outcomes. Meanwhile, we computed the effective and required sample sizes, thereby quantifying the informational adequacy of each comparison. Our Bayesian meta-analysis demonstrated significant potential for digital, self-help, and telephone-delivered CBT for patients with IBS, but the effective sample sizes of most comparisons were inadequate. Digital, self-help, and telephone-delivered CBT can serve as important options for managing IBS in clinical practice. Given high heterogeneity, high risk of bias, and inadequate effective sample sizes, more high-quality studies are warranted.

Background In the absence of randomized studies directly comparing chimeric antigen receptor T cell therapies, this study used matching-adjusted indirect comparisons (MAIC) to evaluate the comparative efficacy and safety of lisocabtagene maraleucel (liso-cel) versus axicabtagene ciloleucel (axi-cel) in patients with relapsed or refractory large B cell lymphoma (LBCL). Methods Primary data sources included individual patient data from the TRANSCEND NHL 001 study (TRANSCEND [NCT02631044]; N  = 256 for efficacy set, N  = 269 for safety set) for liso-cel and summary-level data from the ZUMA-1 study (NCT02348216; N  = 101 for efficacy set, N  = 108 for safety set) for axi-cel. Inter-study differences in design, eligibility criteria, baseline characteristics, and outcomes were assessed and aligned to the extent feasible. Clinically relevant prognostic factors were adjusted in a stepwise fashion by ranked order. Since bridging therapy was allowed in TRANSCEND but not ZUMA-1, the initial efficacy and safety analyses included bridging therapy use as a matching factor (TRANSCEND patients who received bridging therapy were removed). Subsequent sensitivity analyses excluded this matching factor. Results The initial analysis showed similar MAIC-weighted efficacy outcomes between TRANSCEND and ZUMA-1 for overall and complete response rates (odds ratio [95% confidence interval (CI)], 1.40 [0.56–3.49] and 1.21 [0.56–2.64], respectively) and for overall survival and progression-free survival (hazard ratio [95% CI], 0.81 [0.44–1.49] and 0.95 [0.58–1.57], respectively). MAIC-weighted safety outcomes favored liso-cel, with significantly lower odds of all-grade and grade ≥ 3 cytokine release syndrome (odds ratio [95% CI], 0.03 [0.01–0.07] and 0.08 [0.01–0.67], respectively) and study-specific neurological events (0.16 [0.08–0.33] and 0.05 [0.02–0.15], respectively). Efficacy and safety outcomes remained similar in sensitivity analyses, which did not include use of bridging therapy as a matching factor. Conclusions After matching and adjusting for clinically relevant prognostic factors, liso-cel demonstrated comparable efficacy and a more favorable safety profile compared with axi-cel in patients with third- or later-line relapsed or refractory LBCL. Trial registration: NCT02631044 and NCT02348216

To date, no head-to-head trials have compared the efficacy of brigatinib and alectinib against anaplastic lymphoma kinase (ALK) rearrangement-positive (ALK-p), ALK-inhibitor-naïve, advanced non-small cell lung cancer (NSCLC) with central nervous system (CNS) metastasis. We conducted an indirect treatment comparison (ITC) between brigatinib and alectinib, with crizotinib as a common comparator, using a Bayesian model with non-informative prior distribution and assessed the between-study heterogeneity of the studies. The primary efficacy endpoint was progression-free survival (PFS), and efficacy was ranked using the surface under the cumulative ranking (SUCRA) curve values. ITC analysis showed that there were no significant differences in PFS between the brigatinib and alectinib arms. However, the SUCRA values revealed that alectinib ranked the highest by efficacy in the overall patient population, whereas brigatinib ranked the highest by efficacy in the CNS metastasis sub-group. Although there were no significant differences in the incidence of G3–5 adverse events between the brigatinib and alectinib arms in the overall patient population, the data were deemed insufficient for the CNS metastasis sub-group analysis. This study provides critical information to clinicians regarding the efficacy of brigatinib for ALK-p, ALK-inhibitor-naïve, advanced NSCLC patients, with and without CNS metastasis. Larger randomized, controlled trials are warranted to confirm our results.

Abstract Background Tarlatamab, a bispecific T-cell engager immunotherapy, showed durable response with promising survival outcomes in patients with previously treated small cell lung cancer (SCLC) in the phase 2 DeLLphi-301 study. Given the lack of a comparator in DeLLphi-301, this analysis aimed to evaluate the relative efficacy of tarlatamab against physicians’ choice of therapies in real-world practice. Patients and Methods This analysis compared the outcomes of patients in DeLLphi-301 who received tarlatamab 10 mg (n = 97) with patients in real-world cancer clinics captured in the Flatiron Health database who received third or later-line comparator therapies for SCLC (n = 184). Propensity score weighting was used to adjust for differences in key prognostic factors between cohorts. Overall survival (OS), progression-free survival (PFS), time to treatment discontinuation (TTD), time to next treatment or death (TTNTD), and objective response rate (ORR) were compared after weighting. Results Tarlatamab was associated with significantly longer OS, PFS, TTD, and TTNTD, and higher ORR vs comparator therapies. After weighting, the hazard ratios (95% confidence interval [CI]) of tarlatamab vs comparator therapies were 0.45 (0.30, 0.68) for OS, 0.61 (0.43, 0.90) for PFS, 0.57 (0.39, 0.84) for TTD, and 0.45 (0.30, 0.66) for TTNTD. The odds ratio for ORR was 2.80 (95% CI, 1.44, 5.83). Conclusion The study findings suggest that tarlatamab offers potential clinical benefits relative to comparator treatments. This analysis underscores the potential of tarlatamab to become a new therapeutic option for previously treated SCLC, a disease that has historically been associated with extremely poor outcomes and limited treatment options.

Background The goal of on-demand treatment for hereditary angioedema attacks is to halt attack progression to minimize morbidity and mortality. Four on-demand treatments have been approved thus far (ecallantide, icatibant, recombinant human C1 esterase inhibitor [rhC1INH], and plasma-derived C1INH). Results from the sebetralstat phase 3 KONFIDENT trial (NCT05259917) have been reported. To put these results into context without head-to-head trials, an indirect treatment comparison (ITC) was conducted to facilitate comparisons of efficacy and safety across treatment options. Methods Based on a systematic literature review and feasibility assessment, only the pivotal trial for intravenous rhC1INH (NCT01188564) reported necessary data for a comparable primary efficacy endpoint (time to beginning of symptom relief) to enable an ITC with oral sebetralstat. Bayesian fixed-effects network meta-analyses models were conducted to indirectly compare the efficacy and safety outcomes of sebetralstat and rhC1INH (NCT01188564, NCT00225147, NCT00262301). A matching-adjusted indirect comparison (MAIC) of efficacy was performed, adjusting for baseline attack severity and demographic characteristics. Results The fixed-effects model found no significant differences in time to beginning of symptom relief between sebetralstat 300 mg and rhC1INH 50 IU/kg (hazard ratio [95% credible interval], 0.96 [0.42–2.15] to 1.19 [0.58–2.45]). After adjusting for baseline attack severity, the MAIC showed numerically favorable results with sebetralstat compared with rhC1INH, regardless of whether baseline demographics were matched. The fixed-effects model found no significant differences in treatment-related treatment-emergent adverse events. All sensitivity analyses returned consistent results. Conclusions This ITC found no significant differences in time to beginning of symptom relief and overall treatment-related treatment-emergent adverse events between sebetralstat and rhC1INH.

Background In the absence of head-to-head analyses, indirect treatment comparisons (ITCs) can be used for comparative treatment evaluations. A previous ITC of atogepant and rimegepant assessed outcomes from US trials for the preventive treatment of migraine. We expand those initial analyses, and use an ITC to evaluate the efficacy, safety, and tolerability, and estimate the number needed to treat (NNT) per additional ≥50% responder for atogepant and rimegepant in Japanese participants. Methods RELEASE (M22-056) and BHV3000-309 were randomized, double-blind, placebo-controlled studies evaluating atogepant compared with placebo and rimegepant compared with placebo for the preventive treatment of episodic migraine (EM) in Japanese participants, respectively. An ITC using a random effects model compared the efficacy, safety, and tolerability of atogepant 60 mg once daily and rimegepant 75 mg once every other day. Estimates of mean differences with 95% confidence intervals (CIs) are presented for monthly migraine days (MMDs), acute medication use days, Migraine-Specific Quality of Life Questionnaire v2.1 (MSQ v2.1) Role Function-Restrictive (RFR) domain score, Migraine Disability Assessment (MIDAS), and European Quality of Life Visual Analog Scale (EQ VAS). Safety and tolerability results are presented as hazard ratios and 95% CIs. The NNT resulting in one additional person achieving a  ≥ 50% reduction from baseline in mean MMDs/monthly headache days was analyzed across three responder definitions. Results Atogepant demonstrated significantly higher mean monthly acute medication use days reduction (−1.68, 95% CI: −2.72 to −0.64; P < 0.002) at weeks 1 to 12 and significantly greater improvement in MSQ v2.1 RFR domain score (5.13, 95% CI: 1.10 to 9.16; P = 0.01) at week 12. Additionally, atogepant demonstrated numerically higher mean MMD reduction at weeks 1 to 12, numerically greater reduction (improvement) in MIDAS at week 12, and numerically lower improvement in EQ VAS at week 12 relative to rimegepant (all P > 0.05). Atogepant demonstrated numerically lower likelihood of treatment-emergent adverse events (TEAEs) (0.70, 95% CI: 0.45 to 1.09) and adverse events (AEs) leading to discontinuation (0.50, 95% CI: 0.03 to 9.46) compared with rimegepant (both P > 0.05). The median NNT (95% CI) versus placebo for a  ≥ 50% reduction from baseline in mean MMDs across weeks 1 to 12 was 2.5 (1.9 to 4.1) for atogepant and 16.6 (6.7 to ∞) for rimegepant. Additional responder definitions were consistent. Conclusions Among Japanese participants with EM, atogepant 60 mg demonstrated significantly or numerically greater improvements in four of five efficacy outcomes and numerically lower TEAEs and AEs leading to discontinuation compared with rimegepant 75 mg. Atogepant 60 mg had substantially lower NNTs per additional ≥50% responder versus placebo than rimegepant 75 mg. Trial Registrations: These studies are registered with ClinicalTrials.gov (NCT05861427, NCT05399485).