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We assessed the impact of respiratory syncytial virus (RSV) preventive characteristics on the intentions of pregnant people and healthcare providers (HCPs) to protect infants with a maternal vaccine or monoclonal antibodies (mAbs). Pregnant people and HCPs who treated pregnant people and/or infants were recruited via convenience sample from a general research panel to complete a cross-sectional, web-based survey, including a discrete choice experiment (DCE) wherein respondents chose between hypothetical RSV preventive profiles varying on five attributes (effectiveness, preventive type [maternal vaccine vs. mAb], injection recipient/timing, type of medical visit required to receive the injection, and duration of protection during RSV season) and a no-preventive option. A best–worst scaling (BWS) exercise was included to explore the impact of additional attributes on preventive preferences. Data were collected between October and November 2022. Attribute-level preference weights and relative importance (RI) were estimated. Overall, 992 pregnant people and 310 HCPs participated. A preventive (vs. none) was chosen 89.2% (pregnant people) and 96.0% (HCPs) of the time (DCE). Effectiveness was most important to preventive choice for pregnant people (RI = 48.0%) and HCPs (RI = 41.7%); all else equal, pregnant people (RI = 5.5%) and HCPs (RI = 7.2%) preferred the maternal vaccine over mAbs, although preventive type had limited influence on choice. Longer protection, protection starting at birth or the beginning of RSV season, and use for both pre-term and full-term babies were ranked highest in importance (BWS). Pregnant people and HCPs strongly preferred a preventive to protect infants against RSV (vs. none), underscoring the need to incorporate RSV preventives into routine care. [ABSTRACT FROM AUTHOR]

A random‐effects model is often applied in meta‐analysis when considerable heterogeneity among studies is observed due to the differences in patient characteristics, timeframe, treatment regimens, and other study characteristics. Since 2014, the journals Research Synthesis Methods and the Annals of Internal Medicine have published a few noteworthy papers that explained why the most widely used method for pooling heterogeneous studies—the DerSimonian–Laird (DL) estimator—can produce biased estimates with falsely high precision and recommended to use other several alternative methods. Nevertheless, more than half of studies (55.7%) published in top oncology‐specific journals during 2015–2022 did not report any detailed method in the random‐effects meta‐analysis. Of the studies that did report the methodology used, the DL method was still the dominant one reported. Thus, while the authors recommend that Research Synthesis Methods and the Annals of Internal Medicine continue to increase the publication of its articles that report on specific methods for handling heterogeneity and use random‐effects estimates that provide more accurate confidence limits than the DL estimator, other journals that publish meta‐analyses in oncology (and presumably in other disease areas) are urged to do the same on a much larger scale than currently documented. [ABSTRACT FROM AUTHOR]

In a recent systematic review, Bastos et al. (Ann Intern Med. 2021;174(4):501–510) compared the sensitivities of saliva sampling and nasopharyngeal swabs in the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection by assuming a composite reference standard defined as positive if either test is positive and negative if both tests are negative (double negative). Even under a perfect specificity assumption, this approach ignores the double-negative results and risks overestimating the sensitivities due to residual misclassification. In this article, we first illustrate the impact of double-negative results in the estimation of the sensitivities in a single study, and then propose a 2-step latent class meta-analysis method for reevaluating both sensitivities using the same published data set as that used in Bastos et al. by properly including the observed double-negative results. We also conduct extensive simulation studies to compare the performance of the proposed method with Bastos et al.'s method for varied levels of prevalence and between-study heterogeneity. The results demonstrate that the sensitivities are overestimated noticeably using Bastos et al.'s method, and the proposed method provides a more accurate evaluation with nearly no bias and close-to-nominal coverage probability. In conclusion, double-negative results can significantly impact the estimated sensitivities when a gold standard is absent, and thus they should be properly incorporated. [ABSTRACT FROM AUTHOR]

Objective: We examined the relationships of work productivity and activity impairment with key patient‐reported outcomes (PROs) assessing pain, disease activity, and health‐related quality of life (HRQoL) in patients with ankylosing spondylitis (AS). Methods: This post hoc analysis pooled available data from baseline to end of the double‐blind phase of phase 2 and 3 placebo‐controlled tofacitinib trials in patients with active AS. A repeated‐measures longitudinal model assessed the relationships (linear or nonlinear) between Work Productivity and Activity Impairment questionnaire in Spondyloarthritis (WPAI:SpA) domains (absenteeism, activity impairment, presenteeism, and productivity loss) as outcomes and key PROs (total back pain, nocturnal spinal pain, Patient Global Assessment of Disease Activity, AS Quality of Life, EuroQol 5‐Dimension 3‐Level [EQ‐5D‐3L], and EQ‐5D Visual Analog Scale [EQ‐5D‐VAS]) as predictors. Results: Data from 330 to 475 patients were available, depending on the analysis. Relationships between WPAI:SpA domains and PROs were approximately linear. The worst PRO scores were associated with a decline in patients' work capacity (measured by activity impairment, presenteeism, and productivity loss [>65%]); the best scores were associated with improvements in WPAI:SpA domains (8%–23%). Incremental PRO improvements were associated with improvement of activity impairment, presenteeism, and productivity loss. Relationships between absenteeism and PROs were the weakest, owing to absenteeism being low in the study population. Conclusion: Evidence of linear relationships between work productivity and activity impairment with patient‐reported pain, disease activity, and HRQoL was observed. Interventions to control pain and disease activity and improve HRQoL are therefore likely to improve work productivity and reduce activity impairment in patients with AS. [ABSTRACT FROM AUTHOR]

Introduction: The coronavirus disease 2019 (COVID-19) pandemic created challenges related to disease management of patients with ulcerative colitis (UC). Methods: The UC Narrative COVID-19 survey was conducted from August to December 2021 among adults with UC from the United States, Canada, Japan, France, and Finland. Patients were questioned on disease management, health care access and experience, and preferences for interactions with their doctor. Data were analyzed descriptively. Results: In total, 584 patients qualified for and completed the survey. Compared with 2019, 25% experienced more flares during the pandemic (from early 2020). Most patients (88%) taking prescription medication were very/somewhat satisfied with their current treatment plan; 53% were hesitant to make changes during the pandemic. Factors that patients agreed helped control UC symptoms during the pandemic included fewer social outings (37%), working from home (29%), and less busy schedules (28%). Greater anxiety/stress (43%) and hesitancy to visit a hospital/office (34%) made the control of UC symptoms more difficult. Compared with 2019, more patients relied on certain alternative support systems during the pandemic. Patients who used in-person and virtual appointments were equally very satisfied/satisfied with the quality of care (both 81%). In-person appointments were preferred by 68% of patients when meeting a new doctor, 55% when experiencing a flare, and 52% for regular check-ups; 41% preferred virtual appointments for UC prescription refills. Conclusion: During the pandemic, most patients were satisfied with their current UC treatment plan and access to care; more patients relied on certain alternative UC management support systems, and many were impacted by anxiety/stress. Plain Language Summary: The coronavirus disease 2019 (COVID-19) pandemic created challenges for patients with ulcerative colitis. These challenges included managing symptoms, lifestyle changes, and access to health care. We asked patients with ulcerative colitis to answer questions about their experience during the pandemic to try to understand how the pandemic was affecting them. A total of 584 patients from the United States, Canada, Japan, France, and Finland took part. Patients were asked questions online. We asked them about their disease activity during the COVID-19 pandemic compared with before the pandemic and how their disease was managed, their access to health care, and their experience during the pandemic. We also asked them about their satisfaction with the types of appointments they had during the pandemic (for example, in-person or virtual meetings), and their interactions and preference for interactions with their doctors. We found that most patients were satisfied with their current treatment plan, their access to health care, and the quality of the care they received. However, many patients experienced greater stress or anxiety, and there was a negative impact on their emotional well-being. During the pandemic, more patients relied on alternative support systems such as online patient portals or virtual appointments, but patients preferred in-person appointments with their doctors in most cases except for refilling prescriptions. This information may help doctors understand the impact of the COVID-19 pandemic on patients with ulcerative colitis, and may help doctors and patients develop treatment plans that include both in-person and virtual appointments. Graphical Plain Language Summary: [ABSTRACT FROM AUTHOR]

Background: Long COVID has become a central public health concern. This study characterized the effectiveness of BNT162b2 BA.4/5 bivalent COVID-19 vaccine (bivalent) against long COVID symptoms. Methods: Symptomatic US adult outpatients testing positive for SARS-CoV-2 were recruited between 2 March and 18 May 2023. Symptoms were assessed longitudinally using a CDC-based symptom questionnaire at Week 4, Month 3, and Month 6 following infection. The odds ratio (OR) of long COVID between vaccination groups was assessed by using mixed-effects logistic models, adjusting for multiple covariates. Results: At Week 4, among 505 participants, 260 (51%) were vaccinated with bivalent and 245 (49%) were unvaccinated. Mean age was 46.3 years, 70.7% were female, 25.1% had ≥1 comorbidity, 43.0% prior infection, 23.0% reported Nirmatrelvir/Ritonavir use. At Month 6, the bivalent cohort had 41% lower risk of long COVID with ≥3 symptoms (OR: 0.59, 95% CI, 0.36–0.96, p = 0.034) and 37% lower risk of ≥2 symptoms (OR: 0.63, 95% CI, 0.41–0.96, p = 0.030). The bivalent cohort reported fewer and less durable symptoms throughout the six-month follow-up, driven by neurologic and general symptoms, especially fatigue. Conclusions: Compared with unvaccinated participants, participants vaccinated with the bivalent were associated with approximately 40% lower risk of long COVID and less symptom burden over the six-month study duration. [ABSTRACT FROM AUTHOR]

For patients with triple-class exposed/refractory multiple myeloma (TCE/R MM), prognosis is poor and effective treatment options are limited. Elranatamab is a novel B-cell maturation antigen (BCMA)- and CD3-directed bispecific antibody which was approved by the US Food and Drug Administration in August 2023 and demonstrated safety and efficacy in patients with TCE/R MM in the phase 2, single-arm MagnetisMM-3 trial (NCT04649359). To compare the effectiveness of elranatamab vs physician's choice of treatment (PCT) in the absence of head-to-head comparative data, a matching-adjusted indirect comparison (MAIC) was conducted. Individual patient data from MagnetisMM-3 (Cohort A [BCMA-naïve] N = 123, 14.7 months of follow-up) were reweighted to match published summary data from two real-world studies of PCT in patients with TCE/R MM (LocoMMotion and MAMMOTH) using a propensity score-type logistic regression. Unanchored MAIC analyses were conducted according to National Institute for Health and Care Excellence (NICE) Decision Support Unit (DSU) 18 guidance. Compared with PCT in LocoMMotion, elranatamab was associated with a significantly higher objective response rate (ORR rate difference: 37.52; 95% CI 26.20–48.83; odds ratio: 4.85; 95% CI 2.85–8.23) and complete or stringent complete response rate (≥CR rate difference: 42.29; 95% CI 31.84–52.74; odds ratio: 184.01; 95% CI 24.66–1372.86), longer progression-free survival (PFS HR 0.32; 95% CI 0.20–0.49), and overall survival (OS HR 0.62; 95% CI 0.40–0.94). Compared with PCT in MAMMOTH, elranatamab was associated with significantly higher ORR (rate difference: 28.14; 95% CI 16.77–39.52; odds ratio: 3.24; 95% CI 1.98–5.32) and ≥ CR (rate difference: 26.22; 95% CI 16.40–36.05; odds ratio: 5.48; 95% CI 2.88–10.44), as well as longer PFS (HR 0.25; 95% CI 0.17–0.37) and OS (HR 0.49; 95% CI 0.33–0.71). Sensitivity analysis results were consistent with the base case. In the MAIC, elranatamab was consistently associated with improved rates and depth of response and significantly longer PFS and OS versus PCT in LocoMMotion and MAMMOTH. [ABSTRACT FROM AUTHOR]

Network meta‐analysis (NMA) is a statistical procedure to simultaneously compare multiple interventions. Despite the added complexity of performing an NMA compared with the traditional pairwise meta‐analysis, under proper assumptions the NMA can lead to more efficient estimates on the comparisons of interventions by combining and contrasting the direct and indirect evidence into a form of evidence that can be used to underpin treatment guidelines. Two broad classes of NMA methods are commonly used in practice: the contrast‐based (CB‐NMA) and the arm‐based (AB‐NMA) models. While CB‐NMA only focuses on the relative effects by assuming fixed intercepts, the AB‐NMA offers greater flexibility on the estimands, including both the absolute and relative effects by assuming random intercepts. A major criticism of the AB‐NMA, on which we aim to elaborate in this paper, is that it does not retain randomization within trials, which may introduce bias in the estimated relative effects in some scenarios. This criticism was drawn under the implicit assumption that a given relative effect is transportable, in which case the data generating mechanism favors the inference based on CB‐NMA, which models the relative effect. In this article, we aim to review, summarize, and elaborate on the underlying assumptions, similarities and differences, and also the advantages and disadvantages, between CB‐NMA and AB‐NMA methods. As indirect treatment comparison is susceptible to risk of bias no matter which approach is taken, it is important to consider both approaches in practice as complementary sensitivity analyses and to provide the totality of evidence from the data. This article is categorized under:Statistical Models > Bayesian ModelsStatistical Models > Generalized Linear ModelsStatistical and Graphical Methods of Data Analysis > Bayesian Methods and Theory [ABSTRACT FROM AUTHOR]

Background: The NCCN/FACT Bladder Symptom Index‐18 (NFBlSI‐18) is a bladder cancer–specific instrument. We aimed to psychometrically evaluate the reliability and validity of NFBlSI‐18 and estimate change thresholds for total, disease‐related symptoms‐physical (DRS‐P), DRS‐emotional (DRS‐E), and function/well‐being (F/WB) scales in patients with locally advanced/metastatic urothelial cancer (la/mUC). Methods: JAVELIN Bladder 100 trial data were analyzed. Anchors to evaluate validity included: 5‐level EuroQoL‐5D utility index (EQ‐5D‐5L UI), visual analog scale (VAS), Eastern Cooperative Oncology Group (ECOG) performance status, and number of symptoms. Responsiveness to change was tested by anchoring to time to tumor progression (TTP), best overall response (BOR), and differences in means between ECOG categories to estimate meaningful between‐group differences. Meaningful within‐group change thresholds were estimated using receiver operating characteristic curve analysis, anchoring to change in EQ‐5D‐5L UI. Significant within‐individual patient change thresholds were estimated with reliable and likely change indexes. Results: Correlations with EQ‐5D‐5L UI and VAS ranged from 0.53 to 0.73. Standardized effect sizes were >0.20. Compared with patients with TTP of ≥6 months, patients with TTP of >0–2 and 3–5 months had larger declines; results for BOR were similar. Thresholds (points) for meaningful between‐group differences were: total, 6–11; DRS‐P, 3–6; and DRS‐E and F/WB, 1. Thresholds (points) for meaningful within‐group worsening were: total, 4; and DRS‐P, 3, and for significant individual change they were: total, 3–9; DRS‐P, 2–6; DRS‐E, 1–3; and F/WB, 2–4. Conclusions: NFBlSI‐18 exhibited evidence of reliability, validity, and responsiveness to assess quality of life in studies of la/mUC, and change thresholds are established for future studies. Plain Language Summary: The NCCN/FACT Bladder Symptom Index‐18 (NFBlSI‐18) is a questionnaire used to assess quality of life for people with advanced bladder cancer.People with advanced bladder cancer who took part in the JAVELIN Bladder 100 study completed the NFBlSI‐18 when they joined the study and after each treatment with avelumab maintenance or best supportive care.This study showed that NFBlSI‐18 is suitable for capturing bladder cancer symptoms and is able to detect important changes in a person's quality of life over time.This study also provides thresholds for changes in NFBlSI‐18 scores, which will be useful for future studies. The NFBlSI‐18 scales demonstrated reliability, validity, and responsiveness to change. This makes it an appropriate questionnaire to use in bladder cancer trials. [ABSTRACT FROM AUTHOR]

Background Skin pain is a common and burdensome symptom of atopic dermatitis (AD), and its severity increases with disease progression. The Pruritus and Symptoms Assessment for Atopic Dermatitis (PSAAD) is a validated 11-item patient-reported instrument developed in accordance with regulatory agency guidance for assessment of the daily symptoms of patients with AD, including skin pain. Objective To establish content validity and evaluate the psychometric properties of the skin pain numerical rating scale (NRS) item of the PSAAD. Methods: The skin pain NRS is a single-item measure from the PSAAD and is used to assess skin pain severity over the past 24 hours with the question "How painful was your skin over the past 24 hours?" on a 10-point scale from 0 (not painful) to 10 (extremely painful). A qualitative validation analysis consisting of concept elicitation (CE) interviews; electronic completion of the PSAAD measure, including the skin pain NRS; and cognitive debriefing (CD) interviews was conducted for adults and adolescents with mild-to-severe AD. Evaluation of psychometric properties of the skin pain NRS--including test-retest reliability, estimation of meaningful within-patient change (MWPC), known-group validity, ability to detect change, construct validity, quality of completion, and ceiling and floor effects--was conducted based on a post hoc qualitative and quantitative analysis of pooled data, with skin pain NRS as part of the PSAAD in the abrocitinib monotherapy phase 3 trials JADE MONO-1 (NCT03349060) and JADE MONO-2 (NCT03575871). Data from patients (≥12 years of age) with moderate-to-severe AD were pooled across all treatment arms. Results: Among 30 CE interviews (adolescents [12-17 years], n=15; adults [≥18 years], n=15) conducted over 2 rounds of testing, 20 of 30 (67%) patients reported skin pain. During CD interviews (n=30), 100% of patients interpreted the skin pain NRS item as intended, and 73% reported it as relevant. The psychometric validation analysis included 736 patients (JADE MONO-1, N=347; JADE MONO-2, N=389). The test-retest reliability of the skin pain NRS was evidenced by large intraclass correlation coefficients (ICC; 0.76 and 0.72 in JADE MONO-1 and MONO-2, respectively) for a single daily skin pain score, which increased to 0.93 and 0.91 for a measurement averaging at least 4 scores per week. Convergent validity was demonstrated by correlations between skin pain and other clinician- and patient-reported AD measures (median correlation >0.4 starting at week 4). The skin pain NRS distinguished between "clear" and "severe" disease severity groups, assessed using the Patient Global Assessment (PtGA) and Investigator's Global Assessment (IGA) as continuous and categorical anchors (P<0.0001); differences were also significant among other disease severity groups using the PtGA and IGA as continuous anchors (P<0.0001). Based on the PtGA and IGA anchor analysis, the estimated MWPC was 1.9 and ranged from 2.7 to 3.9 points using the empirical cumulative distribution function analysis. Ability to detect change was demonstrated by linear relationships between disease severity measures and skin pain scores (correlation of ≥0.5 between the skin pain NRS and the PtGA). More than 90% of patients provided at least 4 daily skin pain scores each week. No floor or ceiling effects were observed. Conclusions: The qualitative and quantitative data from initial PSAAD development and psychometric evaluation of the skin pain NRS from the PSAAD support its content validity, reliability, construct validity, and ability to detect change. These findings corroborate the 4-point improvement in skin pain as the adequate and meaningful cut-off to define a skin pain responder in JADE MONO-1 and MONO-2. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusions identifier Pruritus is a common, bothersome symptom for patients with mild‐to‐moderate plaque psoriasis (PsO), yet no validated scale assesses it in this patient population. We aimed to validate the Peak Pruritus‐Numerical Rating Scale (PP‐NRS) using data from a Phase 2b study investigating the efficacy of brepocitinib in patients with mild‐to‐moderate chronic PsO.Patients completed the PP‐NRS daily from baseline for the first 2 weeks after the dose administration and subsequently only on visit days. Test–retest reliability (intraclass correlation coefficient [ICC]), construct validity (known group validity and convergent validity), ability to detect change, and meaningful within‐patient change (MWPC) were evaluated using correlation and regression analyses.The PP‐NRS demonstrated acceptable test–retest reliability (ICC: 0.86–0.89). Known‐group evidence demonstrated that PP‐NRS scores could discriminate between different degrees of disease severity. Convergent validity was supported by significant correlation coefficients between the PP‐NRS and Patient Global Assessment (PtGA), Dermatology Life Quality Index, and Psoriasis Symptom Inventory, which generally exceeded 0.50. The ability to detect change was evidenced by an approximately linear relationship between changes in PP‐NRS and Physician Global Assessment or PtGA of psoriasis scores. The value of 2.8 was determined as the MWPC for the PP‐NRS.PP‐NRS is a reliable, practical test for assessing pruritus in mild‐to‐moderate PsO clinical trials.NCT03850483. [ABSTRACT FROM AUTHOR]

Aim: To evaluate the impact of palbociclib treatment on health-related quality of life (HRQoL) in patients with hormone receptor-positive, human epidermal growth factor 2-negative advanced breast cancer (HR+/HER2- aBC) or metastatic breast cancer (mBC) in both the clinical and real-world setting. Materials & methods: A systematic literature review was conducted to identify clinical trials and real-world evidence studies up to June 2023 that reported HRQoL outcomes in patients with HR+/HER2- aBC or mBC treated with Palbociclib. Results: 15 unique studies reported across 35 records were identified. Of these, seven were randomized controlled trials (RCTs), three were single-arm clinical trials and five were real-world evidence (RWE) studies. HRQoL was generally found to be maintained in patients with HR+/HER2- aBC or mBC across RCTs, single-arm clinical trials and RWE studies. HRQoL measures across instruments, study types and line of therapy, were largely reported to be at least maintained if not improved from baseline among patients treated with palbociclib and were observed to be comparable or better in the palbociclib group versus monotherapy control arm in RCTs. Similar results were seen for treatment-related outcomes (e.g., sexual functioning, upset by hair loss, systemic therapy side effects etc.), and important individual patient outcomes, including pain, fatigue and physical functioning. Findings were also consistent across key clinical characteristics (visceral metastases, neutropenia), as well as patient populations often underrepresented in clinical trials (Asian patients, older adults). Conclusion: Overall, current evidence suggests that HRQoL is largely preserved with the addition of palbociclib to endocrine therapy in patients with HR+/HER2- aBC or mBC across study types and populations.

Double-zero-event studies (DZS) pose a challenge for accurately estimating the overall treatment effect in meta-analysis. Current approaches, such as continuity correction or omission of DZS, are commonly employed, yet these ad hoc methods can yield biased conclusions. Although the standard bivariate generalized linear mixed model can accommodate DZS, it fails to address the potential systemic differences between DZS and other studies. In this paper, we propose a zero-inflated bivariate generalized linear mixed model (ZIBGLMM) to tackle this issue. This two-component finite mixture model includes zero-inflation for a subpopulation with negligible or extremely low risk. We develop both frequentist and Bayesian versions of ZIBGLMM and examine its performance in estimating risk ratios (RRs) against the bivariate generalized linear mixed model and conventional two-stage meta-analysis that excludes DZS. Through extensive simulation studies and real-world meta-analysis case studies, we demonstrate that ZIBGLMM outperforms the bivariate generalized linear mixed model and conventional two-stage meta-analysis that excludes DZS in estimating the true effect size with substantially less bias and comparable coverage probability., Competing Interests: Conflict of Interest Statement Cappelleri and Chu are employed by Pfizer. They own stocks in their company.

Background: Atopic dermatitis (AD) is a chronic inflammatory skin disease that is associated with allergic comorbidities. However, studies examining comorbidities in childhood AD are incomplete, which may contribute to suboptimal care., Objective: The objective was to compare the risk of developing different allergic and non-allergic comorbidities among children with AD to that of a matched non-AD reference cohort in Sweden., Methods: This was a nationwide population-based cohort study using longitudinal data from primary and specialist care registers. Patients with AD were identified by confirmed diagnosis in primary or specialist care. The non-AD reference cohort was randomly drawn from the general population and matched 1:1 with the AD patients. The risk of developing the following conditions was evaluated: hypersensitivity and allergic disorders, neurological disorders, psychiatric disorders, infections, immunological and inflammatory disorders, Type 1 diabetes (T1D), endocrine and metabolic disorders, skeletal disorders, ocular disorders and malignancies., Results: This study included 165,145 patients with AD (mild-to-moderate [n = 126,681] and severe [n = 38,464]) and an equally sized reference cohort. Patients with AD displayed a higher risk of developing comorbid conditions for all investigated categories, except for T1D and skeletal disorders, compared with the reference cohort. The highest risk compared with the reference cohort was observed for hypersensitivity and allergic disorders (hazard ratio [HR]: 3.87), followed by malignancies (HR: 2.53) and immunological and inflammatory disorders (HR: 2.36). Patients with AD also had higher risk of developing multiple comorbidities (≥2). The risk of comorbidity onset increased alongside AD severity and patients with active AD were associated with increased risk of comorbidity onset compared with patients in remission., Conclusions: The clinical burden of AD is substantial for children with AD and patients are at an increased risk of developing several comorbid conditions extending beyond the atopic march. Our results also showed a positive association between worsening severity of AD and an increased risk of comorbidity onset., (© 2023 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.)

Network meta-analysis (NMA) is a statistical procedure to simultaneously compare multiple interventions. Despite the added complexity of performing an NMA compared with the traditional pairwise meta-analysis, under proper assumptions the NMA can lead to more efficient estimates on the comparisons of interventions by combining and contrasting the direct and indirect evidence into a form of evidence that can be used to underpin treatment guidelines. Two broad classes of NMA methods are commonly used in practice: the contrast-based (CB-NMA) and the arm-based (AB-NMA) models. While CB-NMA only focuses on the relative effects by assuming fixed intercepts, the AB-NMA offers greater flexibility on the estimands, including both the absolute and relative effects by assuming random intercepts. A major criticism of the AB-NMA, on which we aim to elaborate in this paper, is that it does not retain randomization within trials, which may introduce bias in the estimated relative effects in some scenarios. This criticism was drawn under the implicit assumption that a given relative effect is transportable, in which case the data generating mechanism favors the inference based on CB-NMA, which models the relative effect. In this article, we aim to review, summarize, and elaborate on the underlying assumptions, similarities and differences, and also the advantages and disadvantages, between CB-NMA and AB-NMA methods. As indirect treatment comparison is susceptible to risk of bias no matter which approach is taken, it is important to consider both approaches in practice as complementary sensitivity analyses and to provide the totality of evidence from the data., Competing Interests: Conflict of Interest Cappelleri and Chu are employed by Pfizer. They own stocks in their company.