Bayesian Meta-analysis Research Articles

1258 Topical 2-mercaptonicotinoyl glycine (2-MNG): Anti-pigmentation performance versus recognized standards through bayesian meta-analysis in networks

1258 Topical 2-mercaptonicotinoyl glycine (2-MNG): Anti-pigmentation performance versus recognized standards through bayesian meta-analysis in networks

Role of urban vegetation in air phytoremediation: differences between scientific research and environmental management perspectives

Air pollutant removal by urban vegetation is perceived to be a key ecosystem service for mitigating air pollution. However, the effectiveness of air phytoremediation in cities requires more synthesis to inform environmental management. A Bayesian meta-analysis approach was used to quantify the effectiveness of the removal of typical air pollutants—particle matter (PM), nitrogen oxide (NOx), sulfur dioxide (SO2) and ozone (O3)—by synthesizing global field measurement studies. The results revealed that urban vegetation can mitigate the growth of air pollutant concentrations, with reduction rates of 16.5~26.7% for PM, 13.9~36.2% for NOx, and 20.5~47.8% for SO2. However, they failed to significantly mitigate ground-level O3, corresponding to an increase of 5.1~25.9%. The variability in effect sizes was mainly influenced by the distance to nearest highway, ambient concentration, relative humidity, and green coverage. A questionnaire survey conducted in Shenzhen city (China) showed that most environmental managers supposed positive impacts of urban vegetation on all four air pollutants, which was at odds with our findings with respect to O3. This study can inform the lessening of discrepancies between scientific research and environmental managers’ perceptions on how to improve air phytoremediation for urban air pollution mitigation in China and elsewhere.

Summarizing empirical information on between-study heterogeneity for Bayesian random-effects meta-analysis.

In Bayesian meta-analysis, the specification of prior probabilities for the between-study heterogeneity is commonly required, and is of particular benefit in situations where only few studies are included. Among the considerations in the set-up of such prior distributions, the consultation of available empirical data on a set of relevant past analyses sometimes plays a role. How exactly to summarize historical data sensibly is not immediately obvious; in particular, the investigation of an empirical collection of heterogeneity estimates will not target the actual problem and will usually only be of limited use. The commonly used normal-normal hierarchical model for random-effects meta-analysis is extended to infer a heterogeneity prior. Using an example data set, we demonstrate how to fit a distribution to empirically observed heterogeneity data from a set of meta-analyses. Considerations also include the choice of a parametric distribution family. Here, we focus on simple and readily applicable approaches to then translate these into (prior) probability distributions.

Vitamin D status and risk of rheumatoid arthritis: systematic review and meta-analysis

BackgroundVitamin D is important for immunomodulation and may play a role in autoimmune diseases. Studies have reported a high prevalence of vitamin D deficiency in rheumatoid arthritis (RA) patients, and vitamin D status, assessed by circulating 25-hydroxyvitamin D [25(OH)D] concentration, is inversely associated with RA disease activity. However, it is unclear whether vitamin D deficiency increases the risk of later developing RA. We conducted a systematic review and meta-analysis of pre-diagnostic 25(OH)D concentrations and risk of RA.MethodsMedline and Embase databases were searched in December 2021 using various keywords for ‘vitamin D’, ‘rheumatoid arthritis’, and ‘prospective study’. Publications identified from the search were screened for eligibility, studies were excluded if vitamin D status was measured at or after RA diagnosis, and data were extracted from relevant articles. Bayesian meta-analysis was used to estimate the summary relative risk (RR) and 95% credible interval (CrI) for risk of RA in relation to circulating 25(OH)D concentrations, as well as the between-study heterogeneity.ResultsThe search strategy yielded 908 records, of which 4 publications reporting on 7 studies, involving a total of 15,604 participants and 1049 incident RA cases, were included in the meta-analysis. There was no suggestion of an association between 25(OH)D concentration and subsequent risk of RA. The pooled RR per 25 nmol/L increment in 25(OH)D was 0.96 (95% CrI 0.82–1.13; I2 = 52%). No associations were evident in men (RR = 1.02, 95% CrI 0.65–1.61; I2 = 77%, 2 studies) or women (RR = 0.94, 95% CrI 0.73–1.22; I2 = 71%, 4 studies).ConclusionsThis systematic review and meta-analysis did not identify evidence of an association between 25(OH)D and RA risk, but there was notable between-study heterogeneity and a lack of precision. Investigations in large-scale prospective studies with long follow-up or suitably designed Mendelian randomisation studies with consideration of potential non-linear relationships are needed to determine whether vitamin D is involved in RA aetiology.

Radiographic and endoscopic screening to reduce gastric cancer mortality: a systematic review and meta-analysis

Previous systematic reviews naïvely combined biased effects of screening radiography or endoscopy observed in studies with various designs. We aimed to synthesize currently available comparative data on gastric cancer mortality in healthy, asymptomatic adults by explicitly classifying the screening effects through study designs and types of intervention effects. We searched multiple databases through October 31, 2022 for this systematic review and meta-analysis. Studies of any design that compared gastric cancer mortality among radiographic or endoscopic screening and no screening in a community-dwelling adult population were included. The method included a duplicate assessment of eligibility, double extraction of summary data, and validity assessment using the Risk Of Bias In Non-randomized Studies of Interventions tool. Bayesian three-level hierarchical random-effects meta-analysis synthesized data corrected for self-selection bias on the relative risk (RR) for per-protocol (PP) and intention-to-screen (ITS) effects. The study registration number at PROSPERO is CRD42021277126. We included seven studies in which a screening program was newly introduced (median attendance rate, 31%; at moderate-to-critical risk of bias), and seven cohort and eight case-control studies with ongoing screening programs (median attendance rate, 21%; all at critical risk of bias); thus, data of 1,667,117 subjects were included. For the PP effect, the average risk reduction was significant for endoscopy (RR 0.52; 95% credible interval: 0.39-0.79) but nonsignificant for radiography (0.80; 0.60-1.06). The ITS effect was not significant for both radiography (0.98; 0.86-1.09) and endoscopy (0.94; 0.71-1.28). The magnitude of the effects depended on the assumptions for the self-selection bias correction. Restricting the scope to East Asian studies only did not change the results. In limited-quality observational evidence from high-prevalence regions, screening reduced gastric cancer mortality; however, the effects diminished at a program level. National Cancer Center Japan; and Japan Agency for Medical Research and Development.

Global mean potassium intake: a systematic review and Bayesian meta-analysis

PurposeIncreasing potassium intake, especially in populations with low potassium intake and high sodium intake, has emerged as an important population-level intervention to reduce cardiovascular events. Current guideline recommendations, such as those made by the World Health Organisation, recommend a potassium intake of > 3.5 g/day. We sought to determine summary estimates for mean potassium intake and sodium/potassium (Na/K) ratio in different regions of the world.MethodsWe performed a systematic review and meta-analysis. We identified 104 studies, that included 98 nationally representative surveys and 6 multi-national studies. To account for missingness and incomparability of data, a Bayesian hierarchical imputation model was applied to estimating summary estimates of mean dietary potassium intake (primary outcome) and sodium/potassium ratio.ResultsOverall, 104 studies from 52 countries were included (n = 1,640,664). Mean global potassium intake was 2.25 g/day (57 mmol/day) (95% credible interval (CI) 2.05–2.44 g/day), with highest intakes in Eastern and Western Europe (mean intake 3.53g/day, 95% CI 3.05–4.01 g/day and 3.29 g/day, 95% CI 3.13–3.47 g/day, respectively) and lowest intakes in East Asia (mean intake 1.89 g/day; 95% CI 1.55–2.25 g/day). Approximately 31% (95% CI, 30–41%) of global population included have an estimated potassium intake > 2.5 g/day, with 14% (95% CI 11–17%) above 3.5 g/day.ConclusionGlobal mean potassium intake (2.25 g/day) falls below current guideline recommended intake level of > 3.5 g/day, with only 14% (95% CI 11–17%) of the global population achieving guideline-target mean intake. There was considerable regional variation, with lowest mean potassium intake reported in Asia, and highest intake in Eastern and Western Europe.

Comparative efficacy of psychosocial interventions for opioid-dependent people receiving methadone maintenance treatment: A network meta-analysis.

To estimate the efficacy of multiple psychosocial interventions for opioid-dependent people receiving methadone maintenance treatment (MMT). Systematic review and network meta-analysis of randomized controlled trials (RCTs) reporting the effect of psychosocial intervention for opioid-dependent people receiving MMT in outpatient clinics. We searched multiple data sources (Medline, Embase, Web of Science, PsycINFO and Cochrane Library) from inception to January 2022, finding 21 RCTs evaluating a total of 2862 people with opioid dependence receiving MMT. The primary outcome was the opioid-positive rate (assessed by urinalysis) and the secondary outcome was treatment discontinuation (the number of patients who terminated the study for any reason). We performed random-effects Bayesian meta-analysis. We used relative ranking using surface under the cumulative ranking method and certainty of evidence using grading of recommendations, assessment, development and evaluations. Cognitive-behavioral therapy (CBT) [odds ratio (OR) =0.66, 95% credible interval (CI) =0.66-0.96; low certainty] and educational and behavioral counseling (EBC) (OR =0.28, 95% CI =0.12-0.25; high certainty) were more effective than treatment as usual (TAU) in efficacy. In terms of treatment discontinuation, at the end of the follow-up period there was no statistical significance among psychosocial interventions. According to the ranking probabilities, EBC might be the most effective treatment and behavioral couples' therapy (BCT) might be the best discontinuation treatment. Educational and behavioral counseling and cognitive-behavioral therapy appear to be the most effective psychosocial interventions for opioid-dependent people receiving methadone maintenance treatment.

The correlation between proprioceptive drift and subjective embodiment during the rubber hand illusion: A meta-analytic approach.

In the rubber hand illusion (RHI), participants see a fake hand touched synchronously with their real hand, which is hidden from view. The three-way interaction between vision, touch, and proprioception induces the sensation that the dummy hand belongs to oneself (i.e., subjective embodiment) and the illusory displacement of the real hand towards the fake one (i.e., proprioceptive drift). In the literature, there are mixed results (some positive and some null) regarding the existence of a relationship between subjective embodiment and proprioceptive drift. We conducted a Bayesian meta-analysis to tackle this issue quantitatively. Evidence strongly favours the presence of a correlation between subjective embodiment and proprioceptive drift, supporting the model proposed by Botvinick and Cohen in 1998. However, the correlation is around .35, a value suggesting that the two indices capture different facets of the RHI. This result clarifies the association between the illusory effects produced by the RHI and may be helpful for designing studies having appropriate statistical power.

Association of rs9939609 in FTO with BMI among Polynesian peoples living in Aotearoa New Zealand and other Pacific nations.

The fat mass and obesity associated (FTO) locus consistently associates with higher body mass index (BMI) across diverse ancestral groups. However, previous small studies of people of Polynesian ancestries have failed to replicate the association. In this study, we used Bayesian meta-analysis to test rs9939609, the most replicated FTO variant, for association with BMI with a large sample (n = 6095) of Aotearoa New Zealanders of Polynesian (Māori and Pacific) ancestry and of Samoan people living in the Independent State of Samoa and in American Samoa. We did not observe statistically significant association within each separate Polynesian subgroup. Bayesian meta-analysis of the Aotearoa New Zealand Polynesian and Samoan samples resulted in a posterior mean effect size estimate of +0.21 kg/m2, with a 95% credible interval [+0.03 kg/m2, +0.39 kg/m2]. While the Bayes Factor (BF) of 0.77 weakly favors the null, the BF = 1.4 Bayesian support interval is [+0.04, +0.20]. These results suggest that rs9939609 in FTO may have a similar effect on mean BMI in people of Polynesian ancestries as previously observed in other ancestral groups.

Partial Vs Full Range of Motion Resistance Training: A Systematic Review and Meta-Analysis

Abstract
 Background: Range of motion (ROM) during resistance training is of growing interest and is potentially used to elicit differing adaptations (e.g. muscle hypertrophy and muscular strength and power). To date, attempts at synthesising the data on ROM during resistance training have primarily focused on muscle hypertrophy in the lower body.
 Objective: Our aim was to meta-analyse and systematically review the effects of ROM on a variety of outcomes including hypertrophy, strength, sport, power and body-fat type outcomes. Following pre-registration and consistent with PRISMA guidelines, a systematic review of PubMed and SportsDISCUS was performed. Data was extracted and a Bayesian multi-level meta-analysis was performed. A range of exploratory sub-group and moderator analyses were performed.
 Results: The main model revealed a trivial SMD (0.12; 95% CI: –0.02, 0.26) in favour of full ROM compared to partial ROM. When grouped by outcome, SMDs all favoured full ROM, but SMDs were trivial to small (all between 0.05 to 0.2). Sub-group analyses suggested there may be a muscle hypertrophy benefit to partial ROM training at long muscle lengths compared to using a full ROM (–0.28; 95% CI: –0.81, 0.16). Analysis also suggested the existence of a specificity aspect to ROM, such that training in the ROM being tested as an outcome resulted in greater strength adaptations. No clear differences were found between upper- and lower-body adaptations when ROM was manipulated.
 Conclusions: Overall, our results suggest that using a full or long ROM may enhance results for most outcomes (strength, speed, power, muscle size, and body composition). Differences in adaptations are trivial to small. As such, partial ROM resistance training might present an efficacious alternative for variation and personal preference, or where injury prevents full-ROM resistance training.

Is personalized treatment selection a promising avenue in bpd research? A meta-regression estimating treatment effect heterogeneity in RCTs of BPD.

Psychotherapy is the first-line treatment for borderline personality disorder (BPD) in evidence-based care. The effects are, on average, medium; however, nonresponse rates point to differential treatment effects. Personalized treatment selection has the potential to improve outcomes, but they depend on the heterogeneity of treatment effects (HTEs), which this article seeks to establish. Using an extensive database of randomized controlled trials on psychotherapy for BPD, we determined a reliable estimate of this heterogeneity in treatment effects by (a) applying Bayesian variance ratio meta-analysis and (b) estimating the HTE. In total, 45 studies were included in our study. HTE was found for all psychological treatments, although with low degrees of certainty. Across all psychological treatment and control group types, the estimate for the intercept was 0.10, indicating a 10% higher variance of endpoint values in the intervention groups after controlling for differences in posttreatment means. The results suggest that, while there might be sufficient heterogeneity in treatment effects, the estimates are uncertain, and future research is needed to gain more accurate boundaries for HTE. Personalizing psychological treatments for BPD by using treatment selection approaches could have positive effects, but the current evidence does not allow for a precise estimate of potential outcome improvement. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Effectiveness of the mindfulness–acceptance–commitment approach: a meta-analysis

ABSTRACT The presented study evaluates the evidence base underpinning the use of the Mindfulness–Acceptance–Commitment approach (MAC) in applied sport psychology. To assess the effectiveness of the MAC protocol on improving mindfulness and psychological flexibility, and on enhancing sport performance and well-being among athletes, we used Robust Bayesian Meta-Analysis with Publication Selection Model-Averaging (RoBMAPSMA). In total, there were eleven controlled trials included in the meta-analysis. Results of the RoBMAPSMA show: a moderate model-averaged effect size estimate for developing mindfulness with strong evidence (g = 0.64, 95% CI 0.00–0.91, BFes = 25.35); a small model-averaged effect size estimate for experiential acceptance with anecdotal evidence (g = 0.36, 95% CI 0.00–0.92, BFes = 2.32); and a small model-averaged effect size estimate for improving sport performance with moderate evidence (g = 0.37, 95% CI 0.00–0.79, BFes = 3.27). Only one study assessed the effectiveness of the MAC protocol on well-being and averaged effect sizes ranged from 0.01 to 0.82. Based on the results of the meta-analysis, the Mindfulness–Acceptance–Commitment protocol can be effective in improving mindfulness. In addition, results suggest that the MAC protocol might be effective in improving sport performance. Currently available trials, however, do not provide sufficient evidence supporting the MAC protocol's effectiveness in developing psychological flexibility, experiential acceptance, and promoting well-being among athletes.

Association of Funisitis with Short-Term Outcomes of Prematurity: A Frequentist and Bayesian Meta-Analysis.

The fetal systemic inflammatory response associated with intra-amniotic inflammation may play a key role in the pathogenesis of complications of preterm birth. Funisitis is the histologic equivalent of the fetal inflammatory response, whereas chorioamnionitis represents a maternal inflammatory response. We conducted a frequentist and Bayesian model average (BMA) meta-analysis of studies investigating the effects of funisitis on short-term outcomes of prematurity. Thirty-three studies (12,237 infants with gestational age ≤ 34 weeks) were included. Frequentist meta-analysis showed that funisitis was associated with an increased risk of any bronchopulmonary dysplasia (BPD), moderate/severe BPD, retinopathy of prematurity (ROP), intraventricular hemorrhage (IVH), periventricular leukomalacia (PVL), any sepsis, early-onset sepsis (EOS), and mortality. However, Bayesian meta-analysis showed that the evidence in favor of the alternative hypothesis (i.e., funisitis is associated with an increased risk of developing the outcome) was strong for any IVH, moderate for severe IVH and EOS, and weak for the other outcomes. When the control group was restricted to infants having chorioamnionitis without funisitis, the only outcome associated with funisitis was any IVH. In conclusion, our data suggest that the presence of funisitis does not add an additional risk to preterm birth when compared to chorioamnionitis in the absence of fetal inflammatory response.

Deep prostate-specific antigen response and overall survival in patients with metastatic castration-sensitive prostate cancer: A systematic review and meta-analysis.

195 Background: Preliminary data suggests that patients with metastatic castration-sensitive prostate cancer (mCSPC) who achieve deep prostate-specific antigen (PSA) response may have improved survival. This finding may have implications for developing treatment de-escalation strategies. Thus, we assessed the overall survival by deep PSA response in mCSPC patients receiving intensified treatments. Methods: MEDLINE and EMBASE were systematically searched from each database’s inception through 1st October 2022. Trials assessing androgen deprivation therapy intensification (doublets, triplets) and reporting overall survival (OS) by deep PSA response were considered eligible for inclusion. Deep PSA response was defined as the PSA level of less than 0.1 or 0.2 ng/ml within eight months after initiation of intensified treatment. Precomputed effect estimates of OS (deep PSA response vs no deep PSA response) were pooled using an inverse-variance approach after logarithmic transformation; a random-effects meta-analysis was conducted within the Bayesian framework using empirical informative priors for heterogeneity parameter as specified by Turner et al. Summary effect was expressed as hazard ratios (HR) with the corresponding 95% credible intervals (CrI). A sensitivity analysis was conducted using the Der Simonian-Lairds random-effects meta-analysis with Hartung-Knapp (HK) adjustment. Results: Five RCTs (PEACE-1, ARASENS, CHAARTED, LATITUDE, TITAN) with 2533 patients were included in this systematic review. A total of 1335 patients experienced a deep PSA response, while 1218 did not achieve a deep PSA response after the initiation of intensified treatment. The pooled incidence of deep PSA response was 49.45% (95% confidence interval: 37.75-61.18). Bayesian meta-analysis showed significantly improved OS in overall mCSPC patient population who achieved a deep PSA response after intensified treatment with either triplet or doublet therapy as compared to those who did not achieve a deep PSA response (HR: 0.39; 95% CI: 0.30-0.50) as shown. The results were consistent with HK adjustment. Conclusions: Excellent overall survival in patients with deep PSA response may offer an opportunity to guide treatment de-escalation trials in carefully selected mCSPC patients. [Table: see text]

Effectiveness of written corrective feedback in developing L2 accuracy: A Bayesian meta-analysis

Corrective feedback on second language (L2) writing has remained one of the most heavily studied areas in applied linguistics, yet clear guidance for practitioners about how to provide it most effectively remains limited. Previous studies have meta-analysed written corrective feedback (WCF) research revealing conflicting findings in how WCF affects development in L2 writers’ accuracy over time. This study provides a needed update in light of a recent increase in (quasi)experimental WCF studies. It features several methodological advances by introducing a Bayesian approach to conducting a meta-analysis, which provides a more valid picture of the generalizable effects. The analysis allows distinction – for the first time at a meta-analytic level – between short-, medium-, and long-term effects of WCF. Results aggregate data from an initial 52 primary studies that utilized control groups revealing robust evidence of the durability of moderate effectiveness of WCF over time and deeper insight into the relative effectiveness of various types of WCF (e.g. direct, indirect, metalinguistic – all yielding similar effect sizes) across research contexts, writing task types, target error types, and instructional characteristics. We conclude with recommendations to help continue methodological advances in this domain.

Rate of Complete Spectacle Independence with a Trifocal Intraocular Lens: A Systematic Literature Review and Meta-Analysis.

A systematic literature review and meta-analysis was conducted to identify and obtain a precise single summary estimate on complete spectacle independence after bilateral implantation of a trifocal intraocular lens (IOL) (AcrySof PanOptix, TFNTXX/TFATXX) for patients undergoing cataract surgery. A search was conducted in PubMed from January 2017 to September 2021. Relevant congress presentations were also searched to include data from completed studies not yet published. Search terms included the intervention (TFNTXX, TFATXX, PanOptix) and outcomes of interest (patient-reported spectacle independence rates). A Bayesian random-effects meta-analysis was conducted, providing a pooled estimate (median and its 95% credible interval) of complete spectacle independence rates among cataract surgery patients. Subgroup analyses evaluated spectacle independence after cataract surgery across different working distances (near, intermediate, far). Nineteen unique clinical studies were identified. Based on a meta-analysis of 13 studies (N = 513 patients), the complete spectacle independence rate after cataract surgery with TFNTXX/TFATXX IOL was 91.6% (95% credible interval 86.8-95.9%). Additionally, the spectacle independence rates at each focal point (N = 13 studies, 603 patients) were 89.6% (near), 96.3% (intermediate), and 95.9% (far). This meta-analysis demonstrated that at least nine out of ten patients receiving TFNTXX/TFATXX trifocal IOL during cataract surgery can expect to achieve complete spectacle independence. This study provides informative data for clinicians and patients to feel confident in the use of trifocal intraocular lenses as presbyopia-correcting IOLs that offer high rates of complete spectacle independence.

Chronic Adaptations to Eccentric Cycling Training: A Systematic Review and Meta-Analysis.

This study aimed to investigate the effects of eccentric cycling (ECCCYC) training on performance, physiological, and morphological parameters in comparison to concentric cycling (CONCYC) training. Searches were conducted using PubMed, Embase, and ScienceDirect. Studies comparing the effect of ECCCYC and CONCYC training regimens on performance, physiological, and/or morphological parameters were included. Bayesian multilevel meta-analysis models were used to estimate the population's mean difference between chronic responses from ECCCYC and CONCYC training protocols. Group levels and meta-regression were used to evaluate the specific effects of subjects and study characteristics. Fourteen studies were included in this review. The meta-analyses showed that ECCCYC training was more effective in increasing knee extensor strength, vastus lateralis fiber cross-sectional area, and six-minute walking distance compared to CONCYC. Moreover, ECCCYC was as effective as CONCYC in decreasing body fat percentage. CONCYC was more effective in increasing V˙O2max and peak power output attained during concentric incremental tests. However, group-level analyses revealed that ECCCYC was more effective than CONCYC in improving V˙O2max in patients with cardiopulmonary diseases. ECCCYC is a viable modality for exercise interventions aiming to improve parameters of muscle strength, hypertrophy, functional capacity, aerobic power, and body composition, with more advantages than CONCYC training in improving neuromuscular variables.

Robust Bayesian meta-analysis: Addressing publication bias with model-averaging.

Meta-analysis is an important quantitative tool for cumulative science, but its application is frustrated by publication bias. In order to test and adjust for publication bias, we extend model-averaged Bayesian meta-analysis with selection models. The resulting robust Bayesian meta-analysis (RoBMA) methodology does not require all-or-none decisions about the presence of publication bias, can quantify evidence in favor of the absence of publication bias, and performs well under high heterogeneity. By model-averaging over a set of 12 models, RoBMA is relatively robust to model misspecification and simulations show that it outperforms existing methods. We demonstrate that RoBMA finds evidence for the absence of publication bias in Registered Replication Reports and reliably avoids false positives. We provide an implementation in R so that researchers can easily use the new methodology in practice. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

What are small, medium and large effect sizes for exercise treatments of tendinopathy? A systematic review and meta-analysis

ObjectiveTo quantify and describe effect size distributions from exercise therapies across a range of tendinopathies and outcome domains to inform future research and clinical practice through conducting a systematic review...

321 Cancer risk with topical pimecrolimus and tacrolimus for atopic dermatitis: systematic review and Bayesian meta-analysis

Abstract Atopic dermatitis affects millions worldwide and is effectively managed by topical treatments, including topical calcineurin inhibitors, pimecrolimus and tacrolimus. In 2005 and 2011, the FDA released reviews associating topical calcineurin inhibitors with a theoretical cancer risk, albeit an uncertain association. We systematically reviewed the risk of cancer in patients with atopic dermatitis exposed to topical calcineurin inhibitors. We systematically identified randomized controlled trials, comparative, and non-comparative non-randomized studies from database inception to 6 June 2022, from MEDLINE, EMBASE, GREAT, LILACS, ICTRP, FDA, EMA, company registers and relevant citations. We included studies in any language addressing the risk of cancer in patients with atopic dermatitis exposed to topical calcineurin inhibitors for greater than 3 weeks. We excluded split-body studies. We conducted a Bayesian meta-analysis and used the GRADE approach to determine the certainty of the evidence. A multidisciplinary panel including patients, advocacy groups and care providers, set an a priori threshold of 1 in 1000 risk difference as a clinically important effect. We analysed 121 studies (52 randomized controlled trials and 69 non-randomized studies) including 3.4 million patents followed for a mean of 11 months (range: 0.7–120). The absolute risk of any cancer with topical calcineurin inhibitor exposure was neither different from controls (absolute risk 4.70 per 1000 with topical calcineurin inhibitor exposure vs. 4.56 per 1000 without; odds ratio 1.03 [95% credible interval 0.94–1.11], moderate-certainty evidence) nor the general US population (4.6 per 1000). Findings were similar in infants, children, and adults, and were robust to trial sequential, subgroup and sensitivity analyses. Among infants, children and adults with atopic dermatitis, moderate-certainty evidence shows that topical calcineurin inhibitors do not increase the risk of cancer. These findings support the safe use of topical calcineurin inhibitors in the management of patients with atopic dermatitis. Our findings provide actional information to inform updated clinical practice guidelines, product labels and continuing education for care providers, to clarify the safe usage of topical calcineurin inhibitors.