Supplementary Materials for EBIA-CT: CAM interventions

S1. PRIOR checklist

overall_section	precise_section	item_number	item	location_reported
Title	Title	1	Identify the report as an overview of reviews	we identified it as large-scale synthesis in the title as the term overview/umbrella review is not know by all readers, and more clearly as umbrella review in abstract
Abstract	Abstract	2	Provide a comprehensive and accurate summary of the purpose, methods, and results of the overview of reviews.	abstract
Introduction	Rationale	3	Describe the rationale for conducting the overview of reviews in the context of existing knowledge.	first paragraphs of the introduction
Introduction	Objectives	4	Provide an explicit statement of the objective(s) or question(s) addressed by the overview of reviews.	last paragraph of the introduction
Methods	Eligibility criteria	5a	Specify the inclusion and exclusion criteria for the overview of reviews. If supplemental primary studies were included, this should be stated, with a rationale.	paragraph entitled ‘Search strategy and eligibility criteria’
Methods	Eligibility criteria	5b	Specify the definition of ‘systematic review’ as used in the inclusion criteria for the overview of reviews.	paragraph entitled ‘Search strategy and eligibility criteria’
Methods	Information sources	6	Specify all databases, registers, websites, organizations, reference lists, and other sources searched or consulted to identify systematic reviews and supplemental primary studies (if included). Specify the date when each source was last searched or consulted.	paragraph entitled ‘Search strategy and eligibility criteria’
Methods	Search strategy	7	Present the full search strategies for all databases, registers and websites, such that they could be reproduced. Describe any search filters and limits applied.	paragraph entitled ‘Search strategy and eligibility criteria’
Methods	Selection process	8a	Describe the methods used to decide whether a systematic review or supplemental primary study (if included) met the inclusion criteria of the overview of reviews	paragraph entitled ‘Search strategy and eligibility criteria’
Methods	Selection process	8b	Describe how overlap in the populations, interventions, comparators, and/or outcomes of systematic reviews was identified and managed during study selection.	paragraph entitled ‘Overlapping meta-analyses’
Methods	Data collection process	9a	Describe the methods used to collect data from reports	paragraph entitled ‘Data extraction and checking’
Methods	Data collection process	9b	If applicable, describe the methods used to identify and manage primary study overlap at the level of the comparison and outcome during data collection. For each outcome, specify the method used to illustrate and/or quantify the degree of primary study overlap across systematic reviews.	not applicable, we selected 1 SR/MA per PICO
Methods	Data collection process	9c	If applicable, specify the methods used to manage discrepant data across systematic reviews during data collection.	paragraphs entitled ‘Data extraction and checking’ and ‘Overlapping meta-analyses’
Methods	Data items	10	List and define all variables and outcomes for which data were sought. Describe any assumptions made and/or measures taken to identify and clarify missing or unclear information.	paragraph entitled ‘Search strategy and eligibility criteria’
Methods	Risk of bias assessment	11a	Describe the methods used to assess risk of bias or methodological quality of the included systematic reviews.	paragraph entitled ‘Assessment of the methodological quality’
Methods	Risk of bias assessment	11b	Describe the methods used to collect data on (from the systematic reviews) and/or assess the risk of bias of the primary studies included in the systematic reviews. Provide a justification for instances where flawed, incomplete, or missing assessments are identified but not re-assessed.	paragraph entitled ‘Assessment of the methodological quality’
Methods	Risk of bias assessment	11c	Describe the methods used to assess the risk of bias of supplemental primary studies (if included).	not applicable
Methods	Synthesis methods	12a	Describe the methods used to summarize or synthesize results and provide a rationale for the choice(s).	paragraph entitled ‘Data analysis’
Methods	Synthesis methods	12b	Describe any methods used to explore possible causes of heterogeneity among results.	paragraph entitled ‘Data analysis’
Methods	Synthesis methods	12c	Describe any sensitivity analyses conducted to assess the robustness of the synthesized results.	paragraph entitled ‘Data analysis’
Methods	Reporting bias assessment	13	Describe the methods used to collect data on (from the systematic reviews) and/or assess the risk of bias due to missing results in a summary or synthesis (arising from reporting biases at the levels of the systematic reviews, primary studies, and supplemental primary studies, if included).	not applicable
Methods	Certainty assessment	14	Describe the methods used to collect data on (from the systematic reviews) and/or assess certainty (or confidence) in the body of evidence for an outcome.	paragraph entitled ‘Assessment of the certainty of evidence’
Results	Systematic review and supplemental primary study selection	15a	Describe the results of the search and selection process, including the number of records screened, assessed for eligibility, and included in the overview of reviews, ideally with a flow diagram.	paragraph entitled ‘Results of the searches.’
Results	Characteristics of systematic reviews and supplemental primary studies	15b	Provide a list of studies that might appear to meet the inclusion criteria, but were excluded, with the main reason for exclusion.	paragraph entitled ’’Characteristics of the meta-analytic reports retained in the umbrella review” + Supplementary materials
Results	Characteristics of systematic reviews and supplemental primary studies	16	Cite each included systematic review and supplemental primary study (if included) and present its characteristics.	Supplementary materials
Results	Primary study overlap	17	Describe the extent of primary study overlap across the included systematic reviews.	not applicable, because we removed reports that combined several intervention types
Results	Risk of bias in systematic reviews, primary studies, and supplemental primary studies	18a	Present assessments of risk of bias or methodological quality for each included systematic review.	paragraph entitled ’’Description of the meta-analyses included in the primary analysis” + Supplementary materials
Results	Risk of bias in systematic reviews, primary studies, and supplemental primary studies	18b	Present assessments (collected from systematic reviews or assessed anew) of the risk of bias of the primary studies included in the systematic reviews.	paragraph entitled ’’Results of our primary analysis” + Supplementary materials
Results	Risk of bias in systematic reviews, primary studies, and supplemental primary studies	18c	Present assessments of the risk of bias of supplemental primary studies (if included).	paragraph entitled ’’Results of our primary analysis” + Supplementary materials
Results	Summary or synthesis of results	19a	For all outcomes, summarize the evidence from the systematic reviews and supplemental primary studies (if included). If meta-analyses were done, present for each the summary estimate and its precision and measures of statistical heterogeneity. If comparing groups, describe the direction of the effect.	paragraph entitled ’’Results of our primary analysis” + Supplementary materials
Results	Summary or synthesis of results	19b	If meta-analyses were done, present results of all investigations of possible causes of heterogeneity.	not applicable (moderators are not consistently reported across meta-analyses)
Results	Summary or synthesis of results	19c	If meta-analyses were done, present results of all sensitivity analyses conducted to assess the robustness of synthesized results.	Supplementary materials (e.g., sensitivity analysis excluding NRCT)
Results	Reporting biases	20	Present assessments (collected from systematic reviews and/or assessed anew) of the risk of bias due to missing primary studies, analyses, or results in a summary or synthesis (arising from reporting biases at the levels of the systematic reviews, primary studies, and supplemental primary studies, if included) for each summary or synthesis assessed.	Supplementary materials
Results	Certainty of evidence	21	Present assessments (collected or assessed anew) of certainty (or confidence) in the body of evidence for each outcome	paragraph entitled ’’Results of our primary analysis” + Supplementary materials
Discussion	Discussion	22a	Summarize the main findings, including any discrepancies in findings across the included systematic reviews and supplemental primary studies (if included).	paragraph entitled ’’Results of our primary analysis” + “Overlapping meta-analyses” + Supplementary materials
Discussion	Discussion	22b	Provide a general interpretation of the results in the context of other evidence.	Discussion section
Discussion	Discussion	22c	Discuss any limitations of the evidence from systematic reviews, their primary studies, and supplemental primary studies (if included) included in the overview of reviews. Discuss any limitations of the overview of reviews methods used.	Discussion section
Discussion	Discussion	22d	Discuss implications for practice, policy, and future research (both systematic reviews and primary research). Consider the relevance of the findings to the end users of the overview of reviews, e.g., healthcare providers, policymakers, patients, among others.	Discussion section
Other information	Registration and protocol	23a	Provide registration information for the overview of reviews, including register name and registration number, or state that the overview of reviews was not registered.	Title page (prospero number)
Other information	Registration and protocol	23b	Indicate where the overview of reviews protocol can be accessed, or state that a protocol was not prepared.	Title page (prospero number)
Other information	Registration and protocol	23c	Describe and explain any amendments to information provided at registration or in the protocol. Indicate the stage of the overview of reviews at which amendments were made.	Supplementary materials
Other information	Support	24	Describe sources of financial or non-financial support for the overview of reviews, and the role of the funders or sponsors in the overview of reviews.	paragraph entitled ’’Funding. ”
Other information	Competing interests	25	Declare any competing interests of the overview of reviews’ authors.	paragraph entitled ’’Conflict of Interest. ”
Other information	Author information	26a	Provide contact information for the corresponding author.	paragraph entitled ’’
Other information	Author information	26b	Describe the contributions of individual authors and identify the guarantor of the overview of reviews.	online manager
Other information	Availability of data and other materials	26	Report which of the following are available, where they can be found, and under which conditions they may be accessed: template data collection forms; data collected from included systematic reviews and supplemental primary studies; analytic code; any other materials used in the overview of reviews.	All raw data are available : “Data availability.”

S2. Search strategies

S3. Classification of age groups

1. Homogeneous Preschool (<6yo): The 85th percentile of the distribution of the age is <6yo.

2. Homogeneous School-age (6-12yo): The 25th percentile of the distribution of the age is >=6yo and the 75th percentile of the distribution of the age is < 13yo.

3. Homogeneous Adolescents (13-19yo): The 25th percentile of the distribution of the age is >=13yo and the 75th percentile of the distribution of the age is < 20yo.

4. Homogeneous Adults (>=20yo): The 15th percentile of the distribution of the age is >=18yo (because 18 is considered as the adult age in many countries).

S4. Data extraction

For each trial included in the meta-analysis, the first author and at least one member of the research team independently extracted data contained in the meta-analytic report. Comparisons of the extractions were made using the metaConvert R package. Extracted data included the characteristics of participants, such as the number of participants, the average age or age range, the mean total IQ or total IQ range, and the percentage of female participants. It also included data on characteristics of interventions (such as the intervention name, dosage, and length) and outcomes (such as the outcome category, the method used to assess the outcome, and the tool name). Finally, we also extracted information on the study design (NRCT vs. RCT), the type of control group (treatment as usual, eclectic, waiting list/delayed, or active control treatment), the risk of bias, and the effect size (effect size metrics, value, 95% confidence interval, standard error, or variance). When information about a clinical trial, including the age of participants, risk of bias, dosage/duration of an intervention, or type of control group, was absent from one meta-analysis but present in one or more other meta-analyses, the missing information was systematically filled in using the data from the meta-analysis with the highest methodological quality for which the information was available.

S5. Data quality checks

A subsequent critical step following the extraction of data was to either complete or verify the information gathered about the clinical trials included in the meta-analyses. In instances where information pertaining to the same clinical trial differed between two meta-analyses (for instance, if one classified a clinical trial as an RCT and the other as an NRCT), or when the age of the participants in a clinical trial was absent from all available meta-analyses, we proceeded to consult the full text of the clinical trial with the intention of completing or correcting the relevant information. Furthermore, this approach was employed for the estimation of effect sizes that were deemed suspect (e.g., a standardized mean difference exceeding 5, a narrow confidence interval associated with a small sample size). When the full-texts of these clinical trials were not accessible (for example, when the link provided in the references was no longer available), the authors of the meta-analyses were contacted in order to obtain the data. When we did not receive an answer from our request, or when an error was spotted in the estimation of the effect sizes, the meta-analysis was excluded from all our analyses. All calculations about effect sizes were performed using the metaConvert R package.

S6. Strategy overlapping

When facing with overlapping meta-analyses, i.e., independent meta-analyses that assessed the same PICO (population, intervention, comparator, outcome) combination, we reported the results of one meta-analysis in our primary analysis, and we reported the results of all other meta-analyses in a secondary analysis aiming to explore their concordance. To select the unique meta-analysis per PICO for our primary analysis, we started to identify all recent reviews (published after January 1st, 2018) that included CCTs with homogeneous age groups, and we selected the meta-analysis with the highest methodological quality at 5 key AMSTAR criteria (that regarded the presence of preregistration, a complete search strategy, a duplicate data selection and extraction, and a risk of bias assessment). When no recent meta-analyses with homogeneous age groups were available, we selected meta-analyses published before 2018 with homogeneous age groups, and ultimately, we selected meta-analyses that pooled together trials with heterogeneous age groups.

S7. Data analytic strategy

All analyses were performed in the R environment (version 4.1.1) using the ‘metaumbrella’ package.22 We used the standardized mean difference (SMD) as the main effect size measure for the assessment of efficacy and Risk Ratio (RR) for the assessment of safety measures (i.e., acceptability, tolerability, and adverse events). For meta-analyses of mean difference (MD) and Odds Ratio (OR), we harmonized effect size metrics by converting individual RCTs effect sizes into SMD and RR, respectively, prior to conducting calculations. For the meta-analysis of OR and RR, we systematically re-estimated the effect size from the contingency table when available, as meta-analytic reports frequently use different analytic strategies to handle situations with no events in a group. Regardless of the metric used (RR or SMD), the direction of the effect was reversed when needed, such that a positive effect size (RR>1 or SMD>0) systematically reflected an improvement, i.e., a symptom reduction, a competence improvement or a higher safety.

We re-ran all meta-analyses comparing intervention and control groups using random-effects models. To estimate between-study heterogeneity variance (τ²), we employed restricted maximum likelihood (REML) estimators for SMD and Paul-Mandel estimators for OR or RR. Pooled effect sizes were reported with 95% confidence intervals derived from the standard normal quantile (Wald) method. Heterogeneity was assessed using I² statistics, Q-statistics, τ² values, and 95% prediction intervals. To evaluate small-study effects, we applied Egger’s regression asymmetry test,23 analyzed excess statistical significance bias,24 and quantified the proportion of participants in studies with high risk of selective reporting bias. Where meta-analyses included dependent effect sizes, we resolved dependency using the standardized data aggregation method proposed by Borenstein and colleagues.25

S8. Dependent effect sizes

In cases where a given paper reported separate meta-analyses evaluating the impact of an identical intervention on disparate measures of the same outcome, the effect sizes of the trials included multiple times in the separate meta-analyses were aggregated into a single, unified effect size through the application of the standard Borenstein’s aggregating approach (Borenstein et al. 2009). Then, all these indenpendent effect sizes that are quantifying the effects of the same intervention on the same outcome were pooled together.

For example, if a meta-analytic report conducted two meta-analyses exploring the effects of an intervention on the total scores of the CARS-2 and the ADOS-2, we properly aggregated the effect sizes of the trials included multiple times in these two meta-analyses and we pooled all the independent effect sizes into a single meta-analysis exploring the effects of the intervention on ‘Overall ASD symptoms’.

S9. Included studies

res_included = res_search %>%
      filter(Inclusion == "Included")
if (word) {
  res_included[,1:2]
} else {
kbl(res_included[,1:2]) %>%
    kable_styling(bootstrap_options = c("striped", "hover", "condensed", "responsive"), position = "left") %>%
    scroll_box(width = "100%", height = "500px")
}

Reference	Inclusion
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Maw, S. S., & Haga, C. (2018). Effectiveness of cognitive, developmental, and behavioural interventions for Autism Spectrum Disorder in preschool-aged children: A systematic review and meta-analysis. Heliyon, 4(9).	Included
Siafis, S., Çıray, O., Wu, H., Schneider-Thoma, J., Bighelli, I., Krause, M., … & Leucht, S. (2022). Pharmacological and dietary-supplement treatments for autism spectrum disorder: a systematic review and network meta-analysis. Molecular autism, 13(1), 1-17.	Included
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Barahona-Correa, J. B., Velosa, A., Chainho, A., Lopes, R., & Oliveira-Maia, A. J. (2018). Repetitive Transcranial Magnetic Stimulation for Treatment of Autism Spectrum Disorder: A Systematic Review and Meta-Analysis. Frontiers in Integrative Neuroscience, 12. doi:10.3389/fnint.2018.00027Â	Included
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Wang, Y., Wang, M. J., Rong, Y., He, H. Z., & Yang, C. J. (2019). Oxytocin therapy for core symptoms in autism spectrum disorder: An updated meta-analysis of randomized controlled trials. Research in Autism Spectrum Disorders, 64, 63-75.	Included
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Salazar de Pablo, G., Pastor Jordá, C., Vaquerizo-Serrano, J., Moreno, C., Cabras, A., Arango, C., Hernández, P., Veenstra-VanderWeele, J., Simonoff, E., Fusar-Poli, P., Santosh, P., Cortese, S., & Parellada, M. (2023). Systematic Review and Meta-analysis: Efficacy of Pharmacological Interventions for Irritability and Emotional Dysregulation in Autism Spectrum Disorder and Predictors of Response. Journal of the American Academy of Child and Adolescent Psychiatry, 62(2), 151–168. https://doi.org/10.1016/j.jaac.2022.03.033	Included
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Wang S, Chen D, Yang Y, Zhu L, Xiong X, Chen A. Effectiveness of physical activity interventions for core symptoms of autism spectrum disorder: A systematic review and meta-analysis. Autism Res. 2023;16(9):1811-1824. doi:10.1002/aur.3004	Included
Ojeda, Á., Barahona-Fuentes, G., Villagra Órdenes, F. et al. Effects of Physical Education on Socializing and Communicating Among Children and Preadolescents with Autism Spectrum Disorder: a Systematic Review and Meta-Analysis. Rev J Autism Dev Disord (2023). https://doi.org/10.1007/s40489-023-00410-5	Included
He X, Liu W, Tang F, Chen X, Song G. Effects of Probiotics on Autism Spectrum Disorder in Children: A Systematic Review and Meta-Analysis of Clinical Trials. Nutrients. 2023;15(6):1415. Published 2023 Mar 15. doi:10.3390/nu15061415	Included
Zhang M, Wu Y, Lu Z, et al. Effects of Vitamin D Supplementation on Children with Autism Spectrum Disorder: A Systematic Review and Meta-analysis. Clin Psychopharmacol Neurosci. 2023;21(2):240-251. doi:10.9758/cpn.2023.21.2.240	Included
Madigand J, Rio M, Vandevelde A. Equine assisted services impact on social skills in autism spectrum disorder: A meta-analysis. Prog Neuropsychopharmacol Biol Psychiatry. 2023;125:110765. doi:10.1016/j.pnpbp.2023.110765	Included
Liu A, Gong C, Wang B, Sun J, Jiang Z. Non-invasive brain stimulation for patient with autism: a systematic review and meta-analysis. Front Psychiatry. 2023;14:1147327. Published 2023 Jun 29. doi:10.3389/fpsyt.2023.1147327	Included
Kiani Z, Farkhondeh T, Aramjoo H, et al. Oxytocin Effect in Adult Patients with Autism: An Updated Systematic Review and Meta-Analysis of Randomized Controlled Trials. CNS Neurol Disord Drug Targets. 2023;22(6):906-915. doi:10.2174/1871527321666220517112612	Included
Jia S, Guo C, Li S, Zhou X, Wang X, Wang Q. The effect of physical exercise on disordered social communication in individuals with autism Spectrum disorder: a systematic review and meta-analysis of randomized controlled trials. Front Pediatr. 2023;11:1193648. Published 2023 Jun 30. doi:10.3389/fped.2023.1193648	Included
Li, Y., Feng, Y., Zhong, J. et al. The Effects of Physical Activity Interventions in Children with Autism Spectrum Disorder: a Systematic Review and Network Meta-analysis. Rev J Autism Dev Disord (2023). https://doi.org/10.1007/s40489-023-00418-x	Included
Rahim F, Toguzbaeva K, Qasim NH, Dzhusupov KO, Zhumagaliuly A, Khozhamkul R. Probiotics, prebiotics, and synbiotics for patients with autism spectrum disorder: a meta-analysis and umbrella review. Front Nutr. 2023;10:1294089. Published 2023 Dec 11. doi:10.3389/fnut.2023.1294089	Included
Iffland M, Livingstone N, Jorgensen M, Hazell P, Gillies D. Pharmacological intervention for irritability, aggression, and self-injury in autism spectrum disorder (ASD). Cochrane Database Syst Rev. 2023;10(10):CD011769. Published 2023 Oct 9. doi:10.1002/14651858.CD011769.pub2	Included
Xiao N, Shinwari K, Kiselev S, Huang X, Li B, Qi J. Effects of Equine-Assisted Activities and Therapies for Individuals with Autism Spectrum Disorder: Systematic Review and Meta-Analysis. Int J Environ Res Public Health. 2023 Feb 1;20(3):2630. doi: 10.3390/ijerph20032630. PMID: 36767996; PMCID: PMC9915993.	Included

nrow(res_included)

## [1] 53

S10. Excluded studies

res_excluded = res_search %>%
      filter(Inclusion == "Excluded")
nrow(res_excluded)

## [1] 148

if (word) {
  kbl(res_excluded)
} else {
kbl(res_excluded) %>%
    kable_styling(bootstrap_options = c("striped", "hover", "condensed", "responsive"), position = "left") %>%
    scroll_box(width = "100%", height = "500px")
}

Reference	Inclusion	Reasons_exclusion
Ameis, S. H., Kassee, C., Corbett-Dick, P., Cole, L., Dadhwal, S., Lai, M.-C., … Correll, C. U. (2018). Systematic review and guide to management of core and psychiatric symptoms in youth with autism. Acta Psychiatrica Scandinavica. doi:10.1111/acps.12918Â	Excluded	Not a meta-analysis
Burns, C., Lang, R., & Ledbetter Cho, K. (2017). Meta-analysis of single-case experimental design studies involving children with or at risk of autism spectrum disorder suggests intervention is effective during first three years of life. Evidence-Based Communication Assessment and Intervention, 11(3-4), 119–123. doi:10.1080/17489539.2017.1401038Â	Excluded	Comment
Charman T, Howlin P, Aldred C, et al. Research into early intervention for children with autism and related disorders: methodological and design issues. Report on a workshop funded by the Wellcome Trust, Institute of Child Health, London, UK, November 2001. Autism. 2003;7(2):217-225. doi:10.1177/1362361303007002008	Excluded	Not a meta-analysis
Classen S, Monahan M. Evidence-based review on interventions and determinants of driving performance in teens with attention deficit hyperactivity disorder or autism spectrum disorder. Traffic Inj Prev. 2013;14(2):188-193. doi:10.1080/15389588.2012.700747	Excluded	Not a meta-analysis
Cook, R., & Botting, D. (1997). Use of orthomolecular therapy for those with behavioural problems and mental handicap: A review. Complementary Therapies in Medicine, 5(4), 228–232. doi:10.1016/s0965-2299(97)80035-0Â	Excluded	Not a meta-analysis
Correll CU, Cortese S, Croatto G, et al. Efficacy and acceptability of pharmacological, psychosocial, and brain stimulation interventions in children and adolescents with mental disorders: an umbrella review. World Psychiatry. 2021;20(2):244-275. doi:10.1002/wps.20881	Excluded	Not a meta-analysis of controlled studies
Correll CU, Cortese S, Croatto G, et al. Efficacy and acceptability of pharmacological, psychosocial, and brain stimulation interventions in children and adolescents with mental disorders: an umbrella review. World Psychiatry. 2021;20(2):244-275. doi:10.1002/wps.20881	Excluded	Not a meta-analysis of controlled studies
Cortese S, Wang F, Angriman M, Masi G, Bruni O. Sleep Disorders in Children and Adolescents with Autism Spectrum Disorder: Diagnosis, Epidemiology, and Management. CNS Drugs. 2020;34(4):415-423. doi:10.1007/s40263-020-00710-y	Excluded	Not a meta-analysis of controlled studies
Cuomo BM, Vaz S, Lee EAL, Thompson C, Rogerson JM, Falkmer T. Effectiveness of Sleep-Based Interventions for Children with Autism Spectrum Disorder: A Meta-Synthesis. Pharmacotherapy. 2017;37(5):555-578. doi:10.1002/phar.1920	Excluded	Not a meta-analysis of controlled studies
Dhir S, Teo WP, Chamberlain SR, Tyler K, Yücel M, Segrave RA. The Effects of Combined Physical and Cognitive Training on Inhibitory Control: A Systematic Review and Meta-Analysis. Neurosci Biobehav Rev. 2021;128:735-748. doi:10.1016/j.neubiorev.2021.07.008	Excluded	Outcome not included in the UR
Guo, S., Zhou, K. L., Dong, S., Xue, X. N., Wei, P. D., Yang, J. Y., Fu, G. B., Liu, Z. B., & Cui, X. (2021). Efficacy and safety of massage therapy for autism spectrum disorders: A protocol for systematic review and meta-analysis. Medicine, 100(19), e25874.	Excluded	Not a meta-analysis
Elliott, S. J., Marshall, D., Morley, K., Uphoff, E., Kumar, M., & Meader, N. (2021). Behavioural and cognitive behavioural therapy for obsessive compulsive disorder (OCD) in individuals with autism spectrum disorder (ASD). The Cochrane database of systematic reviews, 9(9), CD013173. https://doi.org/10.1002/14651858.CD013173.pub2	Excluded	Not a meta-analysis of controlled studies
Vaquerizo-Serrano, J., Salazar De Pablo, G., Singh, J., & Santosh, P. (2021). Catatonia in autism spectrum disorders: A systematic review and meta-analysis. European psychiatry : the journal of the Association of European Psychiatrists, 65(1), e4. https://doi.org/10.1192/j.eurpsy.2021.2259	Excluded	Not a meta-analysis of controlled studies
Jiang X, Song M, Qin W, Xiao J, Xu X, Yuan Q. Nonpharmaceutical therapy for autism spectrum disorder: A protocol for systematic review and network meta-analysis. Medicine (Baltimore). 2022;101(7):e28811. doi:10.1097/MD.0000000000028811	Excluded	Protocol
Kirkendall, N., & Palokas, M. (2017). Behavioral and/or pharmacological interventions for managing sleep disturbances in children with autism spectrum disorder. JBI Database of Systematic Reviews and Implementation Reports, 15(10), 2495–2501. doi:10.11124/jbisrir-2016-003310Â	Excluded	Protocol
Lasheras2021	Excluded	Not a meta-analysis
Masi, A., Lampit, A., DeMayo, M. M., Glozier, N., Hickie, I. B., & Guastella, A. J. (2017). A comprehensive systematic review and meta-analysis of pharmacological and dietary supplement interventions in paediatric autism: moderators of treatment response and recommendations for future research. Psychological medicine, 47(7), 1323–1334.	Excluded	Mixed intervention types
Masi, A., Lampit, A., Glozier, N., Hickie, I. B., & Guastella, A. J. (2015). Predictors of placebo response in pharmacological and dietary supplement treatment trials in pediatric autism spectrum disorder: a meta-analysis. Translational psychiatry, 5(9), e640. https://doi.org/10.1038/tp.2015.143	Excluded	Not a meta-analysis of controlled studies
Pervin M, Ahmed HU, Hagmayer Y. Effectiveness of interventions for children and adolescents with autism spectrum disorder in high-income vs. lower middle-income countries: An overview of systematic reviews and research papers from LMIC. Front Psychiatry. 2022;13:834783. Published 2022 Aug 4. doi:10.3389/fpsyt.2022.834783	Excluded	Not a meta-analysis of controlled studies
Rosson S, de Filippis R, Croatto G, et al. Brain stimulation and other biological non-pharmacological interventions in mental disorders: An umbrella review. Neurosci Biobehav Rev. 2022;139:104743. doi:10.1016/j.neubiorev.2022.104743	Excluded	Not a meta-analysis of controlled studies
Sandbank, M., Bottema-Beutel, K., Crowley, S., Cassidy, M., Dunham, K., Feldman, J. I., Crank, J., Albarran, S. A., Raj, S., Mahbub, P., & Woynaroski, T. G. (2020). Project AIM: Autism intervention meta-analysis for studies of young children. Psychological bulletin, 146(1), 1–29.	Excluded	Updated later
Sturmey P. Treatment of psychopathology in people with intellectual and other disabilities. Can J Psychiatry. 2012;57(10):593-600. doi:10.1177/070674371205701003	Excluded	Not a meta-analysis of controlled studies
Xiong, T., Chen, H., Luo, R., & Mu, D. (2016). Hyperbaric oxygen therapy for people with autism spectrum disorder (ASD). Cochrane Database of Systematic Reviews, (10).	Excluded	Not a meta-analysis
Abo Almaali HMM, Gelewkhan A, Mahdi ZAA. Analysis of Evidence-Based Autism Symptoms Enhancement by Acupuncture. J Acupunct Meridian Stud. 2017;10(6):375-384. doi:10.1016/j.jams.2017.09.001	Excluded	Not a meta-analysis
Aithal S, Moula Z, Karkou V, Karaminis T, Powell J, Makris S. A Systematic Review of the Contribution of Dance Movement Psychotherapy Towards the Well-Being of Children With Autism Spectrum Disorders. Front Psychol. 2021;12:719673. Published 2021 Oct 8. doi:10.3389/fpsyg.2021.719673	Excluded	Not a meta-analysis
Akhter M, Khan SM, Firdous SN, Tikmani P, Khan A, Rafique H. A narrative review on manifestations of gluten free casein free diet in autism and autism spectrum disorders. J Pak Med Assoc. 2022;72(10):2054-2060. doi:10.47391/JPMA.3971	Excluded	Not a meta-analysis
Applewhite B, Cankaya Z, Heiderscheit A, Himmerich H. A Systematic Review of Scientific Studies on the Effects of Music in People with or at Risk for Autism Spectrum Disorder. Int J Environ Res Public Health. 2022;19(9):5150. Published 2022 Apr 23. doi:10.3390/ijerph19095150	Excluded	Not a meta-analysis
Auvichayapat N, Auvichayapat P. Transcranial Direct Current Stimulation in Treatment of Child Neuropsychiatric Disorders: Ethical Considerations. Front Hum Neurosci. 2022;16:842013. Published 2022 Jul 8. doi:10.3389/fnhum.2022.842013	Excluded	Not a meta-analysis
Azari, H., Morovati, A., Gargari, B.P. et al. An Updated Systematic Review and Meta-Analysis on the Effects of Probiotics, Prebiotics and Synbiotics in Autism Spectrum Disorder. Rev J Autism Dev Disord (2022). https://doi.org/10.1007/s40489-022-00348-0	Excluded	Pre/post effect sizes within the experimental group
Bang M, Lee SH, Cho SH, et al. Herbal Medicine Treatment for Children with Autism Spectrum Disorder: A Systematic Review. Evid Based Complement Alternat Med. 2017;2017:8614680. doi:10.1155/2017/8614680	Excluded	Not a meta-analysis
Bozzatello, Rocca, Mantelli, & Bellino. (2019). Polyunsaturated Fatty Acids: What is Their Role in Treatment of Psychiatric Disorders? International Journal of Molecular Sciences, 20(21), 5257. doi:10.3390/ijms20215257Â	Excluded	Not a meta-analysis of controlled studies
Cao J, Chai-Zhang TC, Huang Y, Eshel MN, Kong J. Potential scalp stimulation targets for mental disorders: evidence from neuroimaging studies. J Transl Med. 2021;19(1):343. Published 2021 Aug 10. doi:10.1186/s12967-021-02993-1	Excluded	Not a meta-analysis of controlled studies
Cardoso, C., Kingdon, D., & Ellenbogen, M. A. (2014). A meta-analytic review of the impact of intranasal oxytocin administration on cortisol concentrations during laboratory tasks: Moderation by method and mental health. Psychoneuroendocrinology, 49, 161–170. doi:10.1016/j.psyneuen.2014.07.014Â	Excluded	Not on ASD
Chan, J. S., Deng, K., & Yan, J. H. (2020). The effectiveness of physical activity interventions on communication and social functioning in autistic children and adolescents: A meta-analysis of controlled trials. Autism, 136236132097764. doi:10.1177/1362361320977645Â	Excluded	Mixed intervention types
Christie2022	Excluded	Pre/post effect sizes within the experimental group
Cugusi, L., & Carta, M. G. (2020). Conventional exercise interventions for adults with intellectual disabilities: A systematic review and meta‐analysis. Translational Sports Medicine. doi:10.1002/tsm2.195Â	Excluded	Not on ASD
Droboniku, M. J., & Mychailyszyn, M. P. (2021). Animal Interaction Affecting Core Deficit Domains Among Children with Autism: A Meta-Analysis. Journal of Autism and Developmental Disorders. doi:10.1007/s10803-021-04891-3Â	Excluded	Pre/post effect sizes within the experimental group
Feng K, Zhao Y, Yu Q, Deng J, Wu J, Liu L. Can probiotic supplements improve the symptoms of autism spectrum disorder in children?: A protocol for systematic review and meta analysis. Medicine (Baltimore). 2021;100(10):e18621. doi:10.1097/MD.0000000000018621	Excluded	Protocol
Ferreira, J. P., Ghiarone, T., Júnior, C. R. C., Furtado, G. E., Carvalho, H. M., Rodrigues, A. M., & Toscano, C. V. A. (2019). Effects of Physical Exercise on the Stereotyped Behavior of Children with Autism Spectrum Disorders. Medicina (Kaunas, Lithuania), 55(10), 685.	Excluded	Pre/post effect sizes within the experimental group
Fifer, S. (2018). Meta-Analysis of the Efficacy of Neurofeedback (Doctoral dissertation, Walden University).	Excluded	Mixed outcomes
Geretsegger, M., Elefant, C., Mössler, K. A., & Gold, C. (2014). Music therapy for people with autism spectrum disorder. Cochrane Database of Systematic Reviews. doi:10.1002/14651858.cd004381.pub3Â	Excluded	Updated later
Gold, C., Wigram, T., & Elefant, C. (2006). Music therapy for autistic spectrum disorder. Cochrane Database of Systematic Reviews. doi:10.1002/14651858.cd004381.pub2Â	Excluded	Updated later
Guo S, Zhou KL, Dong S, et al. Efficacy and safety of massage therapy for autism spectrum disorders: A protocol for systematic review and meta-analysis. Medicine (Baltimore). 2021;100(19):e25874. doi:10.1097/MD.0000000000025874	Excluded	Protocol
Hayduke, D., & Nye, A. (2019). C-60 The Efficacy of Weighted Blankets for Quantity and Quality of Sleep in Autism Spectrum Disorder: A Meta-Analysis. Archives of Clinical Neuropsychology, 34(6), 1089–1089. doi:10.1093/arclin/acz034.222Â	Excluded	Not enough information to replicate
Healy, S., Nacario, A., Braithwaite, R. E., & Hopper, C. (2018). The effect of physical activity interventions on youth with autism spectrum disorder: A meta-analysis. Autism Research, 11(6), 818–833. doi:10.1002/aur.1955Â	Excluded	Mixed outcomes
Hemangi Narayan Narvekar, Harshada Narayan Narvekar, Canine-assisted Therapy in Neurodevelopmental Disorders: A Scoping Review, European Journal of Integrative Medicine, Volume 50, 2022, 102112, ISSN 1876-3820, https://doi.org/10.1016/j.eujim.2022.102112.	Excluded	Not a meta-analysis of controlled studies
Howells, K., Sivaratnam, C., May, T., Lindor, E., McGillivray, J., & Rinehart, N. (2019). Efficacy of Group-Based Organised Physical Activity Participation for Social Outcomes in Children with Autism Spectrum Disorder: A Systematic Review and Meta-analysis. Journal of Autism and Developmental Disorders. doi:10.1007/s10803-019-04050-9Â	Excluded	Mixed intervention types
Sinha, Y., Silove, N., Wheeler, D., & Williams, K. (2006). Auditory integration training and other sound therapies for autism spectrum disorders: a systematic review. Archives of disease in childhood, 91(12), 1018–1022. https://doi.org/10.1136/adc.2006.094649	Excluded	Not a meta-analysis of controlled studies
Millward, C., Ferriter, M., Calver, S., & Connell-Jones, G. (2008). Gluten- and casein-free diets for autistic spectrum disorder. The Cochrane database of systematic reviews, (2), CD003498. https://doi.org/10.1002/14651858.CD003498.pub3	Excluded	Retracted
Shahrestani, S., Kemp, A. H., & Guastella, A. J. (2013). The impact of a single administration of intranasal oxytocin on the recognition of basic emotions in humans: a meta-analysis. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 38(10), 1929–1936. https://doi.org/10.1038/npp.2013.86	Excluded	Not on ASD
Brondino, N., De Silvestri, A., Re, S., Lanati, N., Thiemann, P., Verna, A., Emanuele, E., & Politi, P. (2013). A Systematic Review and Meta-Analysis of Ginkgo biloba in Neuropsychiatric Disorders: From Ancient Tradition to Modern-Day Medicine. Evidence-based complementary and alternative medicine : eCAM, 2013, 915691. https://doi.org/10.1155/2013/915691	Excluded	Not on ASD
Hofmann, S. G., Fang, A., & Brager, D. N. (2015). RETRACTED: Effect of intranasal oxytocin administration on psychiatric symptoms: A meta-analysis of placebo-controlled studies. Psychiatry research, 228(3), 708–714. https://doi.org/10.1016/j.psychres.2015.05.039 (Retraction published Psychiatry Res. 2018 May;263:299)	Excluded	Retracted
van IJzendoorn, M. H., & Bakermans-Kranenburg, M. J. (2016). The Role of Oxytocin in Parenting and as Augmentative Pharmacotherapy: Critical Issues and Bold Conjectures. Journal of neuroendocrinology, 28(8), 10.1111/jne.12355. https://doi.org/10.1111/jne.12355	Excluded	Not a meta-analysis of controlled studies
Tan, M. L., Ho, J. J., & Teh, K. H. (2016). Polyunsaturated fatty acids (PUFAs) for children with specific learning disorders. The Cochrane database of systematic reviews, 9(9), CD009398. https://doi.org/10.1002/14651858.CD009398.pub3	Excluded	Not on ASD
Hollis, J. L., Sutherland, R., Williams, A. J., Campbell, E., Nathan, N., Wolfenden, L., Morgan, P. J., Lubans, D. R., Gillham, K., & Wiggers, J. (2017). A systematic review and meta-analysis of moderate-to-vigorous physical activity levels in secondary school physical education lessons. The international journal of behavioral nutrition and physical activity, 14(1), 52. https://doi.org/10.1186/s12966-017-0504-0	Excluded	Not on ASD
Khaleghi, A., Zarafshan, H., Vand, S. R., & Mohammadi, M. R. (2020). Effects of Non-invasive Neurostimulation on Autism Spectrum Disorder: A Systematic Review. Clinical psychopharmacology and neuroscience : the official scientific journal of the Korean College of Neuropsychopharmacology, 18(4), 527–552. https://doi.org/10.9758/cpn.2020.18.4.527	Excluded	Not a meta-analysis
Khaleghi, A., Zarafshan, H., Vand, S. R., & Mohammadi, M. R. (2020). Effects of Non-invasive Neurostimulation on Autism Spectrum Disorder: A Systematic Review. Clinical psychopharmacology and neuroscience : the official scientific journal of the Korean College of Neuropsychopharmacology, 18(4), 527–552. https://doi.org/10.9758/cpn.2020.18.4.527	Excluded	Not a meta-analysis
Lam, N. S. K., Long, X. X., Li, X., Saad, M., Lim, F., Doery, J. C., Griffin, R. C., & Galletly, C. (2022). The potential use of folate and its derivatives in treating psychiatric disorders: A systematic review. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 146, 112541. https://doi.org/10.1016/j.biopha.2021.112541	Excluded	Not a meta-analysis of controlled studies
Gao, X., Su, X., Han, X., Wen, H., Cheng, C., Zhang, S., Li, W., Cai, J., Zheng, L., Ma, J., Liao, M., Ni, W., Liu, T., Liu, D., Ma, W., Han, S., Zhu, S., Ye, Y., & Zeng, F. F. (2022). Unsaturated Fatty Acids in Mental Disorders: An Umbrella Review of Meta-Analyses. Advances in nutrition (Bethesda, Md.), 13(6), 2217–2236. https://doi.org/10.1093/advances/nmac084	Excluded	Not a meta-analysis of controlled studies
Huang, Y., Huang, X., Ebstein, R. P., & Yu, R. (2021). Intranasal oxytocin in the treatment of autism spectrum disorders: A multilevel meta-analysis. Neuroscience & Biobehavioral Reviews, 122, 18–27. doi:10.1016/j.neubiorev.2020.12.028Â	Excluded	Mixed outcomes
Huang, Y., Zhang, B., Cao, J., Yu, S., Wilson, G., Park, J., & Kong, J. (2020). Potential Locations for Noninvasive Brain Stimulation in Treating Autism Spectrum Disorders—A Functional Connectivity Study. Frontiers in Psychiatry, 11. doi:10.3389/fpsyt.2020.00388Â	Excluded	Not a meta-analysis of controlled studies
Huashuang Z, Yang L, Chensheng H, et al. Prevalence of Adverse Effects Associated With Transcranial Magnetic Stimulation for Autism Spectrum Disorder: A Systematic Review and Meta-Analysis. Front Psychiatry. 2022;13:875591. Published 2022 May 23. doi:10.3389/fpsyt.2022.875591	Excluded	Not a meta-analysis of controlled studies
Hwang, B., & Hughes, C. (2000). Journal of Autism and Developmental Disorders, 30(4), 331–343. doi:10.1023/a:1005579317085Â	Excluded	Not a meta-analysis
James S, Stevenson SW, Silove N, Williams K. Chelation for autism spectrum disorder (ASD). Cochrane Database Syst Rev. 2015;5(5):CD010766. Published 2015 May 11. doi:10.1002/14651858.CD010766.pub2	Excluded	Not a meta-analysis
Johnstone, J. M., Hughes, A., Goldenberg, J. Z., Romijn, A. R., & Rucklidge, J. J. (2020). Multinutrients for the Treatment of Psychiatric Symptoms in Clinical Samples: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Nutrients, 12(11), 3394. doi:10.3390/nu12113394Â	Excluded	Not on ASD
Kandeel M, El-Deeb W. The Application of Natural Camel Milk Products to Treat Autism-Spectrum Disorders: Risk Assessment and Meta-Analysis of Randomized Clinical Trials. Bioinorg Chem Appl. 2022;2022:6422208. Published 2022 May 27. doi:10.1155/2022/6422208	Excluded	Retracted
Koch, S. C., Riege, R. F. F., Tisborn, K., Biondo, J., Martin, L., & Beelmann, A. (2019). Effects of Dance Movement Therapy and Dance on Health-Related Psychological Outcomes. A Meta-Analysis Update. Frontiers in Psychology, 10. doi:10.3389/fpsyg.2019.01806Â	Excluded	Not enough information to replicate
Lee B, Lee J, Cheon JH, Sung HK, Cho SH, Chang GT. The Efficacy and Safety of Acupuncture for the Treatment of Children with Autism Spectrum Disorder: A Systematic Review and Meta-Analysis [published correction appears in Evid Based Complement Alternat Med. 2023 Feb 4;2023:9840285]. Evid Based Complement Alternat Med. 2018;2018:1057539. Published 2018 Jan 11. doi:10.1155/2018/1057539	Excluded	Probable errors in calculations
Lee, M. S., Choi, T.-Y., Shin, B.-C., & Ernst, E. (2011). Acupuncture for Children with Autism Spectrum Disorders: A Systematic Review of Randomized Clinical Trials. Journal of Autism and Developmental Disorders, 42(8), 1671–1683. doi:10.1007/s10803-011-1409-4Â	Excluded	Not a meta-analysis
Lefevre A, Hurlemann R, Grinevich V. Imaging neuropeptide effects on human brain function. Cell Tissue Res. 2019;375(1):279-286. doi:10.1007/s00441-018-2899-6	Excluded	Not a meta-analysis
Leppanen, J., Ng, K. W., Tchanturia, K., & Treasure, J. (2017). Meta-analysis of the effects of intranasal oxytocin on interpretation and expression of emotions. Neuroscience & Biobehavioral Reviews, 78, 125–144. doi:10.1016/j.neubiorev.2017.04.010Â	Excluded	Only one study
Liang X, Li R, Wong SHS, et al. The Effects of Exercise Interventions on Executive Functions in Children and Adolescents with Autism Spectrum Disorder: A Systematic Review and Meta-analysis. Sports Med. 2022;52(1):75-88. doi:10.1007/s40279-021-01545-3	Excluded	Outcome not included in the UR
Littell, J. H., Pigott, T. D., Nilsen, K. H., Green, S. J., & Montgomery, O. L. (2021). Multisystemic Therapy® for social, emotional, and behavioural problems in youth age 10 to 17: An updated systematic review and meta‐analysis. Campbell Systematic Reviews, 17(4), e1158.	Excluded	Not on ASD
Liu, C., Li, T., Wang, Z., Zhou, R., & Zhuang, L. (2019). Scalp acupuncture treatment for childrenʼs autism spectrum disorders. Medicine, 98(13), e14880. doi:10.1097/md.0000000000014880Â	Excluded	Probable errors in calculations
Lowenthal 2019	Excluded	Not enough information to replicate
Main, P. A., Angley, M. T., O’Doherty, C. E., Thomas, P., & Fenech, M. (2012). The potential role of the antioxidant and detoxification properties of glutathione in autism spectrum disorders: a systematic review and meta-analysis. Nutrition & metabolism, 9, 35. https://doi.org/10.1186/1743-7075-9-35	Excluded	Not a meta-analysis of controlled studies
Maujean, A., Pepping, C. A., & Kendall, E. (2015). A systematic review of randomized controlled trials of animal-assisted therapy on psychosocial outcomes. Anthrozoös, 28(1), 23–36. https://doi.org/10.2752/089279315X14129350721812	Excluded	Not a meta-analysis
McLay, L.-L. K., & France, K. (2014). Empirical research evaluating non-traditional approaches to managing sleep problems in children with autism. Developmental Neurorehabilitation, 1–12. doi:10.3109/17518423.2014.904452Â	Excluded	Not a meta-analysis
Miyahara M. (2013). Meta review of systematic and meta analytic reviews on movement differences, effect of movement based interventions, and the underlying neural mechanisms in autism spectrum disorder. Frontiers in integrative neuroscience, 7, 16.	Excluded	Not a meta-analysis of controlled studies
Monteiro CE, Da Silva E, Sodré R, et al. The Effect of Physical Activity on Motor Skills of Children with Autism Spectrum Disorder: A Meta-Analysis. Int J Environ Res Public Health. 2022;19(21):14081. Published 2022 Oct 28. doi:10.3390/ijerph192114081	Excluded	Outcome not included in the UR
Nimer, J., & Lundahl, B. (2007). Animal-assisted therapy: A meta-analysis. Anthrozoös, 20(3), 225–238. https://doi.org/10.2752/089279307X224773	Excluded	Not on ASD
Nogueira HA, de Castro CT, da Silva DCG, Pereira M. Melatonin for sleep disorders in people with autism: Systematic review and meta-analysis. Prog Neuropsychopharmacol Biol Psychiatry. 2023;123:110695. doi:10.1016/j.pnpbp.2022.110695	Excluded	Probable errors in calculations
Nye, C., & Brice, A. (2005). Combined vitamin B6-magnesium treatment in autism spectrum disorder. Cochrane Database of Systematic Reviews. doi:10.1002/14651858.cd003497.pub2Â	Excluded	Not a meta-analysis of controlled studies
Park, E. Y., Kim, W. H., & Blair, K. S. C. (2021). Effectiveness of interventions involving physical activities for individuals with autism spectrum disorder: a meta-analysis. Education and Training in Autism and Developmental Disabilities, 56(3), 354-367.	Excluded	Meta-analysis of SCD
Peled-Avron, L., Abu-Akel, A., & Shamay-Tsoory, S. (2020). Exogenous effects of oxytocin in five psychiatric disorders: a systematic review, meta-analysis and a personalized approach through the lens of the social salience hypothesis. Neuroscience & Biobehavioral Reviews. doi:10.1016/j.neubiorev.2020.04.023Â	Excluded	Probable errors in calculations
Peng S, Fang Y, Othman AT, Liang J. Meta-analysis and systematic review of physical activity on neurodevelopment disorders, depression, and obesity among children and adolescents. Front Psychol. 2022;13:940977. Published 2022 Nov 30. doi:10.3389/fpsyg.2022.940977	Excluded	Not enough information to replicate
Quan L, Xu X, Cui Y, et al. A systematic review and meta-analysis of the benefits of a gluten-free diet and/or casein-free diet for children with autism spectrum disorder. Nutr Rev. 2022;80(5):1237-1246. doi:10.1093/nutrit/nuab073	Excluded	Pre/post effect sizes within the experimental group
Rehn AK, Caruso VR, Kumar S. The effectiveness of animal-assisted therapy for children and adolescents with autism spectrum disorder: A systematic review. Complement Ther Clin Pract. 2023;50:101719. doi:10.1016/j.ctcp.2022.101719	Excluded	Not a meta-analysis
Romero-Martínez Á, Bressanutti S, Moya-Albiol L. A Systematic Review of the Effectiveness of Non-Invasive Brain Stimulation Techniques to Reduce Violence Proneness by Interfering in Anger and Irritability. J Clin Med. 2020;9(3):882. Published 2020 Mar 24. doi:10.3390/jcm9030882	Excluded	Not a meta-analysis
Rossignol DA, Frye RE. Melatonin in autism spectrum disorders: a systematic review and meta-analysis. Dev Med Child Neurol. 2011;53(9):783-792. doi:10.1111/j.1469-8749.2011.03980.x	Excluded	Probable errors in calculations
Rossignol DA, Frye RE. The Effectiveness of Cobalamin (B12) Treatment for Autism Spectrum Disorder: A Systematic Review and Meta-Analysis. J Pers Med. 2021;11(8):784. Published 2021 Aug 11. doi:10.3390/jpm11080784	Excluded	Only one study
Rossignol, D. A., & Frye, R. E. (2021). Cerebral Folate Deficiency, Folate Receptor Alpha Autoantibodies and Leucovorin (Folinic Acid) Treatment in Autism Spectrum Disorders: A Systematic Review and Meta-Analysis. Journal of personalized medicine, 11(11), 1141. https://doi.org/10.3390/jpm11111141	Excluded	Not a meta-analysis of controlled studies
Ruan, H., Eungpinichpong, W., Wu, H., Shen, M., & Zhang, A. (2022). Medicine Insufficient Evidence for the Efficacy of Massage as Intervention for Autism Spectrum Disorder: A Systematic Review. Evidence-based complementary and alternative medicine : eCAM, 2022, 5328320.	Excluded	Not a meta-analysis
Salehi A, Hashemi N, Imanieh MH, Saber M. Chiropractic: Is it Efficient in Treatment of Diseases? Review of Systematic Reviews. Int J Community Based Nurs Midwifery. 2015;3(4):244-254.	Excluded	Not a meta-analysis of controlled studies
Sefen, J. A. N., Al-Salmi, S., Shaikh, Z., AlMulhem, J. T., Rajab, E., & Fredericks, S. (2020). Beneficial Use and Potential Effectiveness of Physical Activity in Managing Autism Spectrum Disorder. Frontiers in Behavioral Neuroscience, 14. doi:10.3389/fnbeh.2020.587560Â	Excluded	Not a meta-analysis
Shi, Z. M., Lin, G. H., & Xie, Q. (2016). Effects of music therapy on mood, language, behavior, and social skills in children with autism: A meta-analysis. Chinese Nursing Research, 3(3), 137-141.	Excluded	Probable errors in calculations
Shuai B, Jin H, Lin Y, et al. Safety and efficacy of complementary and alternative medicine in the treatment of autism spectrum disorder: A protocol for systematic review and meta-analysis. Medicine (Baltimore). 2020;99(45):e23128. doi:10.1097/MD.0000000000023128	Excluded	Protocol
Shuai B, Jin H, Lin Y, et al. Safety and efficacy of complementary and alternative medicine in the treatment of autism spectrum disorder: A protocol for systematic review and meta-analysis. Medicine (Baltimore). 2020;99(45):e23128. doi:10.1097/MD.0000000000023128	Excluded	Protocol
Silva EAD Junior, Medeiros WMB, Torro N, et al. Cannabis and cannabinoid use in autism spectrum disorder: a systematic review. Trends Psychiatry Psychother. 2022;44:e20200149. Published 2022 Jun 13. doi:10.47626/2237-6089-2020-0149	Excluded	Not a meta-analysis
Smith JR, DiSalvo M, Green A, et al. Treatment Response of Transcranial Magnetic Stimulation in Intellectually Capable Youth and Young Adults with Autism Spectrum Disorder: A Systematic Review and Meta-Analysis [published online ahead of print, 2022 Sep 26]. Neuropsychol Rev. 2022;10.1007/s11065-022-09564-1. doi:10.1007/s11065-022-09564-1	Excluded	Pre/post effect sizes within the experimental group
Sowa, M., & Meulenbroek, R. (2012). Effects of physical exercise on autism spectrum disorders: A meta-analysis. Research in autism spectrum disorders, 6(1), 46-57.	Excluded	Pre/post effect sizes within the experimental group
Sun CK, Cheng YS, Hung KC. N-acetylcysteine is effective as add-on therapy to risperidone-based combination for children with autistic disorders. Aust N Z J Psychiatry. 2022;56(1):91-92. doi:10.1177/00048674211041932	Excluded	Comment
Sung MC, Ku B, Leung W, MacDonald M. The Effect of Physical Activity Interventions on Executive Function Among People with Neurodevelopmental Disorders: A Meta-Analysis. J Autism Dev Disord. 2022;52(3):1030-1050. doi:10.1007/s10803-021-05009-5	Excluded	Outcome not included in the UR
Tan, B. W. Z., Pooley, J. A., & Speelman, C. P. (2016). A Meta-Analytic Review of the Efficacy of Physical Exercise Interventions on Cognition in Individuals with Autism Spectrum Disorder and ADHD. Journal of Autism and Developmental Disorders, 46(9), 3126–3143. doi:10.1007/s10803-016-2854-xÂ	Excluded	Outcome not included in the UR
Tarr, C. W., Rineer-Hershey, A., & Larwin, K. (2020). The effects of physical exercise on stereotypic behaviors in autism: Small-n meta-analyses. Focus on Autism and Other Developmental Disabilities, 35(1), 26-35.	Excluded	Not enough information to replicate
Teh, E. J., Vijayakumar, R., Tan, T. X. J., & Yap, M. J. (2022). Effects of Physical Exercise Interventions on Stereotyped Motor Behaviours in Children with ASD: A Meta-Analysis. Journal of autism and developmental disorders, 52(7), 2934–2957.	Excluded	Probable errors in calculations
Trzmiel, T., Purandare, B., Michalak, M., Zasadzka, E., & Pawlaczyk, M. (2019). Equine assisted activities and therapies in children with autism spectrum disorder: A systematic review and a meta-analysis. Complementary therapies in medicine, 42, 104–113.	Excluded	Pre/post effect sizes within the experimental group
Vancampfort D, Scheewe T, van Damme T, Deenik J. Effect van bewegen op psychiatrische symptomen en lichamelijke gezondheid bij mensen met psychiatrische aan-doeningen; systematische review van recente meta-analyses [The efficacy of physical activity on psychiatric symptoms and physical health in people with psychiatric disorders: a systematic review of recent meta-analyses]. Tijdschr Psychiatr. 2020;62(11):936-945.	Excluded	Not a meta-analysis
Varigonda, A. L., Edgcomb, J. B., & Zima, B. T. (2021). The impact of exercise in improving executive function impairments among children and adolescents with ADHD, autism spectrum disorder, and fetal alcohol spectrum disorder: a systematic review and meta-analysis. Archives of Clinical Psychiatry (São Paulo), 47, 146-156.	Excluded	Pre/post effect sizes within the experimental group
Wang, L., Peng, J. L., Qiao, F. Q., Cheng, W. M., Lin, G. W., Zhang, Y., Gao, T. G., Sun, Y. Y., Tang, W. Z., & Wang, P. (2021). Clinical Randomized Controlled Study of Acupuncture Treatment on Children with Autism Spectrum Disorder (ASD): A Systematic Review and Meta-Analysis. Evidence-based complementary and alternative medicine : eCAM, 2021, 5549849.	Excluded	Probable errors in calculations
Whipple, J. (2004). Music in Intervention for Children and Adolescents with Autism: A Meta-Analysis. Journal of Music Therapy, 41(2), 90–106. doi:10.1093/jmt/41.2.90Â	Excluded	Meta-analysis of SCD
Wigton, R., Radua, J., Allen, P., Averbeck, B., Meyer-Lindenberg, A., McGuire, P., Shergill, S. S., & Fusar-Poli, P. (2015). Neurophysiological effects of acute oxytocin administration: systematic review and meta-analysis of placebo-controlled imaging studies. Journal of psychiatry & neuroscience : JPN, 40(1), E1–E22	Excluded	Not a meta-analysis
Williams, K. J., Wray, J. J., & Wheeler, D. M. (2005). Intravenous secretin for autism spectrum disorder. Cochrane Database of Systematic Reviews. doi:10.1002/14651858.cd003495.pub2Â	Excluded	Updated later
Williams, K., Wray, J. A., & Wheeler, D. M. (2012). Intravenous secretin for autism spectrum disorders (ASD). The Cochrane database of systematic reviews, 2012(4), CD003495.	Excluded	Not a meta-analysis
Xiao N, Shinwari K, Kiselev S, Huang X, Li B, Qi J. Effects of Equine-Assisted Activities and Therapies for Individuals with Autism Spectrum Disorder: Systematic Review and Meta-Analysis. Int J Environ Res Public Health. 2023 Feb 1;20(3):2630. doi: 10.3390/ijerph20032630. PMID: 36767996; PMCID: PMC9915993.	Excluded	Not enough information to replicate
Yang, Y. J., Siao, M. R., Tsai, F. T., & Luo, H. J. (2015). Effect of physical activity interventions on children and adolescents with autism spectrum disorder: a systematic review and meta-analysis. Physiotherapy, 101, e1685-e1686.	Excluded	Not enough information to replicate
Yi et al 2020 IOP Conf. Ser.: Earth Environ. Sci. 440 042094	Excluded	Probable errors in calculations
Zhang, M., Liu, Z., Ma, H., & Smith, D. M. (2020). Chronic Physical Activity for Attention Deficit Hyperactivity Disorder and/or Autism Spectrum Disorder in Children: A Meta-Analysis of Randomized Controlled Trials. Frontiers in behavioral neuroscience, 14, 564886.	Excluded	Outcome not included in the UR
Zhang, Y., Zeng, J., Wu, D., Li, X., Chen, Y., Dai, S., Wang, B., Qi, Y., & Lu, J. (2021). Effect and safety of acupuncture for autism spectrum disorders: A protocol for systematic review and meta-analysis. Medicine, 100(11), e22269.	Excluded	Protocol
Zhao M, Chen S, You Y, Wang Y, Zhang Y. Effects of a Therapeutic Horseback Riding Program on Social Interaction and Communication in Children with Autism. International Journal of Environmental Research and Public Health. 2021; 18(5):2656	Excluded	Only one study
Zhukova, M. A., Talantseva, O. I., Logvinenko, T. I., Titova, O. S., & Grigorenko, E. L. (2020). Complementary and Alternative Treatments for Autism Spectrum Disorders: A Review for Parents and Clinicians. Clinical Psychology & Special Education/Kliniceska I Special’naa Psihologia, 9(3).	Excluded	Not a meta-analysis of controlled studies
Charry-Sánchez JD, Pradilla I, Talero-Gutiérrez C. Effectiveness of Animal-Assisted Therapy in the Pediatric Population: Systematic Review and Meta-Analysis of Controlled Studies. J Dev Behav Pediatr. 2018 Sep;39(7):580-590. doi: 10.1097/DBP.0000000000000594. PMID: 29994814.	Excluded	Not on ASD
Rehn AK, Caruso VR, Kumar S. The effectiveness of animal-assisted therapy for children and adolescents with autism spectrum disorder: A systematic review. Complement Ther Clin Pract. 2023 Feb;50:101719. doi: 10.1016/j.ctcp.2022.101719. Epub 2023 Jan 1. PMID: 36599281.	Excluded	Not a meta-analysis
Nuria Prades, Eva Varela, Itziar Flamarique, Ramon Deulofeu & Inmaculada Baeza (2023) Water-soluble vitamin insufficiency, deficiency and supplementation in children and adolescents with a psychiatric disorder: a systematic review and meta-analysis, Nutritional Neuroscience, 26:2, 85-107, DOI: 10.1080/1028415X.2021.2020402	Excluded	Not a meta-analysis of controlled studies
Soares A, Shiozawa P, Trevizol AP, Paula CS, Lowenthal R, Cordeiro Q. Effects of augmentation agents in autistic disorder patients treated with risperidone: a systematic review and a meta-analysis. Trends Psychiatry Psychother. 2016;38(2):114-116. doi:10.1590/2237-6089-2015-0068	Excluded	Mixed intervention types
Soares, A., Shiozawa, P., Trevizol, A. P., Paula, C. S. D., Lowenthal, R., & Cordeiro, Q. (2016). Effects of augmentation agents in autistic disorder patients treated with risperidone: a systematic review and a meta-analysis. Trends in psychiatry and psychotherapy, 38, 114-116.	Excluded	Mixed intervention types
Yu Z, Zhang P, Tao C, Lu L, Tang C. Efficacy of nonpharmacological interventions targeting social function in children and adults with autism spectrum disorder: A systematic review and meta-analysis. PLoS One. 2023;18(9):e0291720. Published 2023 Sep 19. doi:10.1371/journal.pone.0291720	Excluded	Probable errors in calculations
Sam, K. L., Chow, B. C., & Tong, K. K. (2015). Effectiveness of exercise-based interventions for children with autism: A systematic review and meta-analysis. International Journal of Learning and Teaching, 1(2), 98-103.	Excluded	Mixed intervention types
Lun T, Lin S, Chen Y, et al. Acupuncture for children with autism spectrum disorder: A systematic review and meta-analysis. Medicine (Baltimore). 2023;102(8):e33079. doi:10.1097/MD.0000000000033079	Excluded	Outcome not included in the UR
Beavers A, Fleming A, Shahidullah JD. Animal-assisted therapies for autism. Curr Probl Pediatr Adolesc Health Care. 2023;53(11):101478. doi:10.1016/j.cppeds.2023.101478	Excluded	Not a meta-analysis of controlled studies
Lavín-Pérez AM, Rivera-Martín B, Lobato-Rincón LL, Villafaina-Domínguez S, Collado-Mateo D. Benefits of animal-Assisted interventions in preschool children: A systematic review. Clin Child Psychol Psychiatry. 2023;28(2):850-873. doi:10.1177/13591045221142115	Excluded	Not a meta-analysis of controlled studies
Michele Mussap1 , Rossella Tomaiuolo2 New insights on biomarkers reflecting the genetic deficiency of folate cycle in autism spectrum disorder Biochimica Clinica 2023; 47(2) 125-126	Excluded	Not a meta-analysis of controlled studies
JAMEY https://www.biorxiv.org/content/10.1101/2023.02.08.527718v2.full.pdf	Excluded	Not a meta-analysis of controlled studies
Zhang J, Zhu G, Wan L, et al. Effect of fecal microbiota transplantation in children with autism spectrum disorder: A systematic review. Front Psychiatry. 2023;14:1123658. Published 2023 Mar 2. doi:10.3389/fpsyt.2023.1123658	Excluded	Not a meta-analysis
Ji YQ, Tian H, Zheng ZY, Ye ZY, Ye Q. Effectiveness of exercise intervention on improving fundamental motor skills in children with autism spectrum disorder: a systematic review and meta-analysis. Front Psychiatry. 2023;14:1132074. Published 2023 Jun 12. doi:10.3389/fpsyt.2023.1132074	Excluded	Outcome not included in the UR
Rice LJ, Cannon L, Dadlani N, et al. Efficacy of cannabinoids in neurodevelopmental and neuropsychiatric disorders among children and adolescents: a systematic review. Eur Child Adolesc Psychiatry. Published online March 3, 2023. doi:10.1007/s00787-023-02169-w	Excluded	Not a meta-analysis
Zhang J, Zhu G, Wan L, et al. Effect of fecal microbiota transplantation in children with autism spectrum disorder: A systematic review. Front Psychiatry. 2023;14:1123658. Published 2023 Mar 2. doi:10.3389/fpsyt.2023.1123658	Excluded	Not a meta-analysis of controlled studies
Lewandowska-Pietruszka Z, Figlerowicz M, Mazur-Melewska K. Microbiota in Autism Spectrum Disorder: A Systematic Review. Int J Mol Sci. 2023;24(23):16660. Published 2023 Nov 23. doi:10.3390/ijms242316660	Excluded	Not a meta-analysis of controlled studies
Fan MSN, Li WHC, Ho LLK, Phiri L, Choi KC. Nature-Based Interventions for Autistic Children: A Systematic Review and Meta-Analysis. JAMA Netw Open. 2023;6(12):e2346715. Published 2023 Dec 1. doi:10.1001/jamanetworkopen.2023.46715	Excluded	Mixed intervention types
Wong T, Falcomata TS, Barnett M. The Collateral Effects of Antecedent Exercise on Stereotypy and Other Nonstereotypic Behaviors Exhibited by Individuals with Autism Spectrum Disorder: A Systematic Review. Behav Anal Pract. 2022;16(2):407-420. Published 2022 Sep 19. doi:10.1007/s40617-022-00746-0	Excluded	Not a meta-analysis
Ye, Y.; Ning, K.; Wan, B.; Shangguan, C. The Effects of the Exercise Intervention on Fundamental Movement Skills in Children with Attention Deficit Hyperactivity Disorder and/or Autism Spectrum Disorder: A Meta-Analysis. Sustainability 2023, 15, 5206. https://doi.org/10.3390/ su15065206	Excluded	Outcome not included in the UR
Romano K, Shah AN, Schumacher A, Zasowski C, Zhang T, Bradley-Ridout G, Merriman K, Parkinson J, Szatmari P, Campisi SC, Korczak DJ. The gut microbiome in children with mood, anxiety, and neurodevelopmental disorders: An umbrella review. Gut Microbiome (Camb). 2023 Sep 20;4:e18. doi: 10.1017/gmb.2023.16. PMID: 39295902; PMCID: PMC11406386.	Excluded	Not a meta-analysis of controlled studies
Xiong M, Li F, Liu Z, et al. Efficacy of Melatonin for Insomnia in Children with Autism Spectrum Disorder: A Meta-analysis. Neuropediatrics. 2023;54(3):167-173. doi:10.1055/s-0043-1761437	Excluded	Probable errors in calculations
Nogueira HA, de Castro CT, da Silva DCG, Pereira M. Melatonin for sleep disorders in people with autism: Systematic review and meta-analysis. Prog Neuropsychopharmacol Biol Psychiatry. 2023;123:110695. doi:10.1016/j.pnpbp.2022.110695	Excluded	Probable errors in calculations
Meng XR, Cao X, Sun ML, Deng H, He LY, Liu J. [Re-evaluation of systematic reviews of acupuncture and moxibustion for childhood autism]. Zhongguo Zhen Jiu. 2023 Feb 12;43(2):223-31. Chinese. doi: 10.13703/j.0255-2930.20220526-k0002. PMID: 36808520.	Excluded	Not a meta-analysis of controlled studies
Kandeel M, El-Deeb W. The Application of Natural Camel Milk Products to Treat Autism-Spectrum Disorders: Risk Assessment and Meta-Analysis of Randomized Clinical Trials. Bioinorg Chem Appl. 2022 May 27;2022:6422208. doi: 10.1155/2022/6422208. Retraction in: Bioinorg Chem Appl. 2023 Oct 4;2023:9807391. doi: 10.1155/2023/9807391. PMID: 35669459; PMCID: PMC9166988.	Excluded	Retracted
Kisely S, Connor M, Somogyi AA, Siskind D. A systematic literature review and meta-analysis of the effect of psilocybin and methylenedioxymethamphetamine on mental, behavioural or developmental disorders. Aust N Z J Psychiatry. 2023;57(3):362-378. doi:10.1177/00048674221083868	Excluded	Only one study
Parrella NF, Hill AT, Enticott PG, Barhoun P, Bower IS, Ford TC. A systematic review of cannabidiol trials in neurodevelopmental disorders. Pharmacol Biochem Behav. 2023;230:173607. doi:10.1016/j.pbb.2023.173607	Excluded	Not a meta-analysis of controlled studies

tab_excluded = res_excluded %>%
  group_by(Reasons_exclusion) %>%
  summarise(n=n()) %>%
  arrange(n)

paste0("n-eligible = ", nrow(res_included) + sum(tab_excluded$n[tab_excluded$Reasons_exclusion %in% c("Probable errors in calculations", "Not enough information to replicate")]))

## [1] "n-eligible = 72"

tab_excluded

## # A tibble: 15 x 2
##    Reasons_exclusion                                       n
##    <chr>                                               <int>
##  1 Comment                                                 2
##  2 Meta-analysis of SCD                                    2
##  3 Mixed outcomes                                          3
##  4 Only one study                                          4
##  5 Retracted                                               4
##  6 Updated later                                           4
##  7 Mixed intervention types                                7
##  8 Not enough information to replicate                     7
##  9 Protocol                                                7
## 10 Outcome not included in the UR                          9
## 11 Pre/post effect sizes within the experimental group     9
## 12 Not on ASD                                             10
## 13 Probable errors in calculations                        12
## 14 Not a meta-analysis                                    33
## 15 Not a meta-analysis of controlled studies              35

S11. Main analysis

Table

res_p = res_m %>% filter(IN_meta == 1)

if (word) {
  res_p
} else {
DT::datatable(res_p,
      rownames = FALSE,
      extensions = 'Buttons',
      class = "display",
      options = list(
        # dom = c('t'),
        scrollX = TRUE,
        scrollCollapse = TRUE,

        scrollY = "500px",
        pageLength = nrow(res_p),
        columnDefs = list(
          list(width = '100px',
               targets = "_all"),
          list(className = 'dt-center',
               targets = "_all")),
        dom = c('tB'),
        buttons = c('copy', 'csv', 'excel','pdf')
        ))
}

Plot

Primary outcomes (core symptoms and safety)

# {.tabset .tabset-pills}
paste("--- contouring = GRADE (larger = higher evidence) ---")

## [1] "--- contouring = GRADE (larger = higher evidence) ---"

paste("--- colouring = effect size (green = positive effect, grey = negligeable effect, red = negative effect) ---")

## [1] "--- colouring = effect size (green = positive effect, grey = negligeable effect, red = negative effect) ---"

paste("--- star = statistical significance (p<0.05) ---")

## [1] "--- star = statistical significance (p<0.05) ---"

res_p$intervention_spell = factor (res_p$intervention_spell)

res_p$intervention_spell <- factor(res_p$intervention_spell, levels = sort(unique(as.character(res_p$intervention_spell)), decreasing = TRUE))

res_sum = res_p %>%
    filter(Outcome %in% c(ASD_symptoms, safety))

p1 <- ggplot(res_sum, aes(Outcome_rank, intervention_spell)) +
    geom_point(shape = 21, size = 5,
               fill="transparent",
               aes(stroke = GRADE_rank,
                   color = col_contour)) +
    geom_point(shape = 21, aes(size = n_studies,
                   fill = col_sig,
                   color = col_sig)) +
    geom_point(data = res_sum %>% filter(as.numeric(p_value) < 0.05),
               aes(Outcome_rank, intervention_spell),
               colour = "#000000",
               size = 2,
               shape=8) +
    theme_bw() + 
    facet_grid(.~ age_rank, switch = "x") +
    theme(axis.ticks.x=element_blank(),
          axis.text.x=element_text(size = 7, angle = 55, hjust = 0),
        legend.position = "none",
        axis.title.x = element_blank(),
        axis.title.y = element_blank())+
    scale_x_discrete(position = "top", 
                     expand = expansion(mult = c(0.09, 0.09))) +
    scale_y_discrete(expand = expansion(mult = c(0.05, 0.05)), drop = FALSE) +
    scale_size_continuous(range = c(2, 5)) +
    theme(plot.margin = unit(c(10,10,10,10), "mm"))+ 
    scale_fill_manual(values = c("#DC5746" = "#DC5746", "#DD8378" = "#DD8378", "#DEADA7" = "#DEADA7", "#D4D4D4" = "#D4D4D4", "#A2CDAE" = "#BCEBBC", "#68CD84" = "#73C289", "#30CC5C" = "#09A302", "white" = "white", "transparent" = "transparent", "black" = "black")) +
    scale_colour_manual(values = c("#DC5746" = "#DC5746", "#DD8378" = "#DD8378", "#DEADA7" = "#DEADA7", "#D4D4D4" = "#D4D4D4", "#A2CDAE" = "#BCEBBC", "#68CD84" = "#73C289", "#30CC5C" = "#09A302", "white" = "white", "transparent" = "transparent", "black" = "black", small="black", large="white")) 

p1

Secondary outcomes (key ASD-related outcomes)

paste("--- contouring = GRADE (larger = higher evidence) ---")

## [1] "--- contouring = GRADE (larger = higher evidence) ---"

paste("--- colouring = effect size (green = positive effect, grey = negligeable effect, red = negative effect) ---")

## [1] "--- colouring = effect size (green = positive effect, grey = negligeable effect, red = negative effect) ---"

paste("--- star = statistical significance (p<0.05) ---")

## [1] "--- star = statistical significance (p<0.05) ---"

res_sum_add = res_p %>%
    filter(!Outcome %in% c(ASD_symptoms, safety))

p2 <- ggplot(res_sum_add, aes(Outcome_rank, intervention_spell)) +
    geom_point(shape = 21, size = 5.5,
               fill="transparent",
               aes(stroke = GRADE_rank,
                   color = col_contour)) +
    geom_point(shape = 21, aes(size = n_studies,
                   fill = col_sig,
                   color = col_sig)) +
    geom_point(data = . %>% filter(as.numeric(p_value) < 0.05),
               aes(Outcome_rank, intervention_spell),
               colour = "#000000",
               size = 2,
               shape=8) +
    theme_bw() + 
    facet_grid(.~ age_rank, switch = "x") +
    theme(axis.ticks.x=element_blank(),
          axis.text.x=element_text(size = 7, angle = 55, hjust = 0),
        legend.position = "none",
        axis.title.x = element_blank(),
        axis.title.y = element_blank())+
    scale_x_discrete(position = "top", 
                     expand = expansion(mult = c(0.09, 0.09))) +
    scale_y_discrete(expand = expansion(mult = c(0.05, 0.05)), drop = FALSE) +
    scale_size_continuous(range = c(2, 5)) +
    theme(plot.margin = unit(c(10,10,10,10), "mm"))+ 
    scale_fill_manual(values = c("#DC5746" = "#DC5746", "#DD8378" = "#DD8378", "#DEADA7" = "#DEADA7", "#D4D4D4" = "#D4D4D4", "#A2CDAE" = "#BCEBBC", "#68CD84" = "#73C289", "#30CC5C" = "#09A302", "white" = "white", "transparent" = "transparent", "black" = "black")) +
    scale_colour_manual(values = c("#DC5746" = "#DC5746", "#DD8378" = "#DD8378", "#DEADA7" = "#DEADA7", "#D4D4D4" = "#D4D4D4", "#A2CDAE" = "#BCEBBC", "#68CD84" = "#73C289", "#30CC5C" = "#09A302", "white" = "white", "transparent" = "transparent", "black" = "black", small="black", large="white")) 

p2

S12. Overlapping

Overall picture

res_m$GRADE_order = as.character(res_m$GRADE)
res_m$GRADE_order[res_m$GRADE_order == "High"] <- "4"
res_m$GRADE_order[res_m$GRADE_order == "Moderate"] <- "3"
res_m$GRADE_order[res_m$GRADE_order == "Low"] <- "2"
res_m$GRADE_order[res_m$GRADE_order == "Very low"] <- "1"
res_m$GRADE_order = as.numeric(as.character(res_m$GRADE_order))
interval_overlap_percentage <- function(lower1, upper1, lower2, upper2) {
  overlap = max(0, min(upper1, upper2) - max(lower1, lower2))
  total_length = (upper1 - lower1) + (upper2 - lower2) - overlap
  percentage_overlap = (overlap / total_length) * 100
  return(percentage_overlap)
}


res_over <- res_m %>%
  group_by(PICO_amstar) %>%
  filter(n() > 1) %>%
  mutate(n_SRMA = length(unique(paper))) %>%
  group_by(PICO_amstar) %>%
  mutate(
   eG_meta_IN = eG[IN_meta == 1],
   GRADE_meta_IN = GRADE[IN_meta == 1],
   p_value_meta_IN = p_value[IN_meta == 1],
    n = n(),
    n_SRMA = unique(n_SRMA),
    paper = collapsunique(paper),
    min_es = min(eG),
    max_es = max(eG),
    dif_es = max(eG) - min(eG),
    max_grade = head(sort(GRADE_order), 1),
    min_grade = tail(sort(GRADE_order), 1),
    prop_sig = sum(as.numeric(p_value) < 0.05) / n(),
    avg_percentage_overlap = mean(map_dbl(combn(n(), 2, simplify = FALSE), function(idx) {
    interval_overlap_percentage(
      ci_lo_g[idx[1]], ci_up_g[idx[1]], 
      ci_lo_g[idx[2]], ci_up_g[idx[2]])
  })),
    min_percentage_overlap = min(map_dbl(combn(n(), 2, simplify = FALSE), function(idx) {
    interval_overlap_percentage(
      ci_lo_g[idx[1]], ci_up_g[idx[1]], 
      ci_lo_g[idx[2]], ci_up_g[idx[2]])
  }))
  ) %>%
  arrange(PICO_amstar)

overlap_factors_disc = res_over %>% 
  filter(abs(as.numeric(GRADE_order) - as.numeric(GRADE_order)) >= 2 | 
      (abs(eG_meta_IN - eG) >= 0.30 & 
           sum(as.numeric(p_value_meta_IN) < 0.05,
               as.numeric(p_value) < 0.05) == 1) |
          as.numeric(avg_percentage_overlap) < 20) %>%
  select(PICO_amstar, Factor, IN_meta) 

res_over_disc = res_over %>%
  filter(PICO_amstar %in% overlap_factors_disc$PICO_amstar)

# length(unique(res_over_disc$PICO_amstar))

if (word) {
  res_over %>%
    kbl()
} else {
DT::datatable(res_over)  
}

Figure

res_m$inter_out = paste0(res_m$Intervention, " - ", res_m$Outcome)
metaumbrella::forest(res_m %>% filter(Factor %in% res_over_disc$Factor) %>%
    as.data.frame(),
       layout = "RevMan5",
       squaresize = 0.7,
       weight.study = "same",
       subgroup = "inter_out",
       subgroup.name = "",
       leftcols = c("paper", "Age", "GRADE", 
                    "n_studies",  "rob_num", "I2", "effect.ci"),
       leftlabs = c("Paper", "Age", "GRADE",
                    "n-studies", "Low RoB", "I²", "eSMD + 95% CI"),
       smlab = "Key overlapping situations"
)