scholarly journals Anti-Tumor Activity and Safety of Multikinase Inhibitors in Advanced and/or Metastatic Thyroid Cancer: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials

2019 ◽  
Vol 52 (01) ◽  
pp. 25-31 ◽  
Author(s):  
Marina Tsoli ◽  
Krystallenia I. Alexandraki ◽  
Maria-Eleni Spei ◽  
Gregory A. Kaltsas ◽  
Kosmas Daskalakis
Keyword(s):  
Clinical Trials ◽  
Thyroid Cancer ◽  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Objective Response ◽  
Risk Of Bias ◽  
Controlled Trials ◽  
Cochrane Central Register ◽  
Multikinase Inhibitors ◽  
Metastatic Thyroid Cancer

AbstractMany trials have demonstrated prime antitumor activity of novel, small molecule multikinase inhibitors (MKIs) in advanced and/or metastatic thyroid cancer (TC). In this work, the PubMed, EMBASE, Cochrane Central Register of Controlled Trials, Web of Science, SCOPUS, and clinicaltrials.gov databases were searched. Quality/risk of bias were assessed using GRADE criteria. Randomized clinical trials (RCTs) comparing two or more systemic therapies in patients with advanced and/or metastatic thyroid cancer were assessed. A total of 1347 articles and 548 clinical trials in clinicaltrials.gov were screened. We included seven relevant RCTs comprising 1934 unique patients assigned to different MKIs. Two separate network meta-analyses included four RCTs in radioiodine refractory well-differentiated thyroid cancer (RR-WDTC) and three RCTs in medullary thyroid cancer (MTC), respectively; all with a low risk of bias. We identified three therapies for RR-WDTC: sorafenib [disease control rate (DCR) odds ratio (OR): 0.11 (95% CI: 0.03–0.40); progression-free survival (PFS) hazard ratio (HR): 1.99 (95% CI: 1.62–2.46)], vandetanib [DCR_OR:0.26 (95% CI: 0.06–1.24); PFS_HR: 0.99 (95% CI: 0.82–1.20)] and lenvatinib [DCR_OR: 0.26 (95% CI: 0.05–1.33); PFS_HR: 0.99 (95% CI: 0.81–1.22)]; and the following therapies for MTC: vandetanib 300 mg [objective response rate (ORR)_OR: 3.31 (95% CI: 0.68–16.22); vandetanib 150 mg ORR_OR: 0.60 (95% CI: 0.16–2.33)]; and cabozantinib [ORR_OR: 85.32 (95% CI: 5.22–1395.15)]. Serious side effect (SE) analysis per organ/system demonstrated a varying MKI SE profile across both RR-WDTC and MTC diagnoses, more commonly involving metabolic/nutritional disorders [OR: 2.07 [95% CI: 0.82–5.18)] and gastrointestinal SE [OR: 1.63 (95% CI: 1.0–2.66)]. This network meta-analysis on advanced and/or metastatic TC points towards a higher efficacy of lenvatinib in RR-WDTC. The included MKIs exhibit a varying SE profile across different organs/systems favoring a patient-tailored approach with the anticipated toxicities guiding clinicians’ decisions.

scholarly journals Randomized Controlled Trials of Early Ambulatory Hydroxychloroquine in the Prevention of COVID-19 Infection, Hospitalization, and Death: Meta-Analysis

2020 ◽  
Author(s):  
Joseph A. Ladapo ◽  
John E. McKinnon ◽  
Peter A. McCullough ◽  
Harvey Risch
Keyword(s):  
Systematic Review ◽  
Clinical Trials ◽  
Side Effects ◽  
Fixed Effects ◽  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Controlled Trials ◽  
Cochrane Central Register ◽  
Randomized Controlled ◽  
Exposure Prophylaxis

Objective--To determine if hydroxychloroquine (HCQ) reduces the incidence of new illness, hospitalization or death among outpatients at risk for or infected with SARS-CoV-2 (COVID-19). Design--Systematic review and meta-analysis of randomized clinical trials. Data sources--Search of MEDLINE, EMBASE, PubMed, medRxiv, PROSPERO, and the Cochrane Central Register of Controlled Trials. Also review of reference lists from recent meta-analyses. Study selection--Randomized clinical trials in which participants were treated with HCQ or placebo/standard-of-care for pre-exposure prophylaxis, post-exposure prophylaxis, or outpatient therapy for COVID-19. Methods--Two investigators independently extracted data on trial design and outcomes. Medication side effects and adverse reactions were also assessed. The primary outcome was COVID-19 hospitalization or death. When unavailable, new COVID-19 infection was used. We calculated random effects meta-analysis according to the method of DerSimonian and Laird. Heterogeneity between the studies was evaluated by calculation of Cochran Q and I2 parameters. An Egger funnel plot was drawn to investigate publication bias. We also calculated the fixed effects meta-analysis summary of the five studies. All calculations were done in Excel, and results were considered to be statistically significant at a two-sided threshold of P=.05. Results--Five randomized controlled clinical trials enrolling 5,577 patients were included. HCQ was associated with a 24% reduction in COVID-19 infection, hospitalization or death, P=.025 (RR, 0.76 [95% CI, 0.59 to 0.97]). No serious adverse cardiac events were reported. The most common side effects were gastrointestinal. Conclusion--Hydroxychloroquine use in outpatients reduces the incidence of the composite outcome of COVID-19 infection, hospitalization, and death. Serious adverse events were not reported and cardiac arrhythmia was rare. Systematic review registration--This review was not registered.

scholarly journals Dental Composite Restorations Repair: A Systematic Review and Meta-analysis

2021 ◽  
pp. 707-738
Author(s):  
Abdulmohsen Al Rabiah ◽  
Alamri Zahrah ◽  
Tuwaym Malath ◽  
Al Daghri Ebtihal ◽  
Al Suhaibani Daniyah ◽  
...  
Keyword(s):  
Systematic Review ◽  
Clinical Trials ◽  
Prospective Cohort ◽  
Randomized Clinical Trials ◽  
Assessment Tool ◽  
Risk Of Bias ◽  
Dental Composite ◽  
Controlled Trials ◽  
Cochrane Central Register ◽  
Bias Assessment

Background: Controversy exists in the literature regarding the most optimal repair procedure for improving the adhesion between the repair resin and the existing resin composite materials. Hence the aim of the present study was to do a systematic review and to analyze the adhesion potential of resin-based composites to similar and dissimilar composites and aimed to determine the possible dominant factors affecting the bond strength results. Materials & Methods: Randomized clinical trials (RCTs) and prospective cohort design were searched through electronic databases including MEDLINE, PubMed, Web of Science, and the Cochrane Central Register of Controlled Trials for randomized clinical trials (RCTs) until July 2020 that compared different methods of composite restoration repair and a minimum mean follow-up time of 1 year. There were no restrictions on a particular treatment indication or outcome measures. Two authors independently conducted screening, risk of bias assessment, and data extraction of eligible trials in duplicate. We applied the Cochrane risk of bias assessment tool to consider the risk of bias. Results: We identified 10 articles; two of them were RCTs, and eight prospective cohort studies. There were 530 participants, with 990 teeth, dealing with resin-based composite (RBC) restorations. The intervention of defective restorations ranged from minimal intervention to total restoration replacement. The evaluation criteria were also varied with different evaluation protocols. The low number and heterogeneity of RCTs did not allow for meta-analyses. Conclusions: Although different repair protocols are mentioned in the literature according to the included studies, an appropriate and definitive conclusion can't be drawn. However, it seems repairs versus replacements should be considered as the first line of treatment when all factors lead to repair rather than replacement. Further randomized controlled trials with high methodological quality need to be conducted in order to establish evidence-based recommendations, particularly for RBC repair.

scholarly journals Cardiovascular Toxicities Secondary to Biotherapy and Molecular Targeted Therapies in Neuroendocrine Neoplasms: A Systematic Review and Meta-Analysis of Randomized Placebo-Controlled Trials

Cancers ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 2159
Author(s):  
Charalampos Aktypis ◽  
Maria-Eleni Spei ◽  
Maria Yavropoulou ◽  
Göran Wallin ◽  
Anna Koumarianou ◽  
...  
Keyword(s):  
Systematic Review ◽  
Clinical Trials ◽  
Adverse Effects ◽  
Targeted Therapies ◽  
Safety Profile ◽  
Meta Analysis ◽  
Mtor Inhibitors ◽  
Risk Of Bias ◽  
Neuroendocrine Neoplasms ◽  
Controlled Trials

A broad spectrum of novel targeted therapies with prime antitumor activity and/or ample control of hormonal symptoms together with an overall acceptable safety profile have emerged for patients with metastatic neuroendocrine neoplasms (NENs). In this systematic review and quantitative meta-analysis, the PubMed, EMBASE, Cochrane Central Register of Controlled Trials and clinicaltrials.gov databases were searched to assess and compare the safety profile of NEN treatments with special focus on the cardiovascular adverse effects of biotherapy and molecular targeted therapies (MTTs). Quality/risk of bias were assessed using GRADE criteria. Placebo-controlled randomized clinical trials (RCTs) in patients with metastatic NENs, including medullary thyroid cancer (MTC) were included. A total of 3695 articles and 122 clinical trials registered in clinicaltrials.gov were screened. We included sixteen relevant RCTs comprising 3408 unique patients assigned to different treatments compared with placebo. All the included studies had a low risk of bias. We identified four drug therapies for NENs with eligible placebo-controlled RCTs: somatostatin analogs (SSAs), tryptophan hydroxylase (TPH) inhibitors, mTOR inhibitors and tyrosine kinase inhibitors (TKI). Grade 3 and 4 adverse effects (AE) were more often encountered in patients treated with mTOR inhibitors and TKI (odds ratio [OR]: 2.42, 95% CI: 1.87–3.12 and OR: 3.41, 95% CI: 1.46–7.96, respectively) as compared to SSAs (OR:0.77, 95% CI: 0.47–1.27) and TPH inhibitors (OR:0.77, 95% CI: 0.35–1.69). MTOR inhibitors had the highest risk for serious cardiac AE (OR:3.28, 95% CI: 1.66–6.48) followed by TKIs (OR:1.51, 95% CI: 0.59–3.83). Serious vascular AE were more often encountered in NEN patients treated with mTOR inhibitors (OR: 1.72, 95% CI: 0.64–4.64) and TKIs (OR:1.64, 95% CI: 0.35–7.78). Finally, patients on TKIs were at higher risk for new-onset or exacerbation of pre-existing hypertension (OR:3.31, 95% CI: 1.87–5.86). In conclusion, SSAs and TPH inhibitors appear to be safer as compared to mTOR inhibitors and TKIs with regards to their overall toxicity profile, and cardiovascular toxicities in particular. Special consideration should be given to a patient-tailored approach with anticipated toxicities of targeted NEN treatments together with assessment of cardiovascular comorbidities, assisting clinicians in treatment selection and early recognition/management of cardiovascular toxicities. This approach could improve patient compliance and preserve cardiovascular health and overall quality of life.

scholarly journals Short Segment versus Long Segment Pedicle Screws Fixation in Management of Thoracolumbar Burst Fractures: Meta-Analysis

2017 ◽  
Vol 11 (1) ◽  
pp. 150-160 ◽  
Author(s):  
Tarek Ahmed Aly
Keyword(s):  
Pedicle Screw ◽  
Screw Fixation ◽  
Meta Analysis ◽  
Pedicle Screw Fixation ◽  
Risk Of Bias ◽  
Controlled Trials ◽  
Cochrane Central Register ◽  
Thoracolumbar Burst Fractures ◽  
Burst Fractures ◽  
Significant Difference

<p>Posterior pedicle screw fixation has become a popular method for treating thoracolumbar burst fractures. However, it remains unclear whether additional fixation of more segments could improve clinical and radiological outcomes. This meta-analysis was performed to evaluate the effectiveness of fixation levels with pedicle screw fixation for thoracolumbar burst fractures. MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, Springer, and Google Scholar were searched for relevant randomized and quasirandomized controlled trials that compared the clinical and radiological efficacy of short versus long segment for thoracolumbar burst fractures managed by posterior pedicle screw fixation. Risk of bias in included studies was assessed using the Cochrane Risk of Bias tool. Based on predefined inclusion criteria, Nine eligible trials with a total of 365 patients were included in this meta-analysis. Results were expressed as risk difference for dichotomous outcomes and standard mean difference for continuous outcomes with 95% confidence interval. Baseline characteristics were similar between the short and long segment fixation groups. No significant difference was identified between the two groups regarding radiological outcome, functional outcome, neurologic improvement, and implant failure rate. The results of this meta-analysis suggested that extension of fixation was not necessary when thoracolumbar burst fracture was treated by posterior pedicle screw fixation. More randomized controlled trials with high quality are still needed in the future.</p>

Dexamethasone in Patients with Spontaneous Intracerebral Hemorrhage: An Updated Meta-Analysis

2020 ◽  
Vol 49 (5) ◽  
pp. 495-502
Author(s):  
Stephanie Wintzer ◽  
Josef Georg Heckmann ◽  
Hagen B. Huttner ◽  
Stefan Schwab
Keyword(s):  
Clinical Trials ◽  
High Risk ◽  
Intracerebral Hemorrhage ◽  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Risk Of Bias ◽  
Spontaneous Intracerebral Hemorrhage ◽  
Control Groups ◽  
Language Data ◽  
Negative Effect

<b><i>Background:</i></b> Spontaneous intracerebral hemorrhage (ICH) is a frequent cerebrovascular disorder and still associated with high mortality and poor clinical outcomes. The purpose of this review was to update a 15-year-old former meta-analysis on randomized clinical trials (RCTs) addressing the question of whether ICH patients treated with dexamethasone have better outcomes than controls. <b><i>Methods:</i></b> The electronic databases PubMed, SCOPUS, and Cochrane as well as web platforms on current clinical trials were searched for the years 1970–2020 without constriction on language. Data were extracted and outcomes were pooled for conventional and cumulative meta-analysis using a commercial software program (www.Meta-Analysis.com). <b><i>Results:</i></b> Finally, 7 RCTs were identified and analyzed including 248 participants in the dexamethasone groups and 242 in the control groups. Five studies showed a high risk of bias. The overall relative risk (RR) for death was 1.32 (95% confidence interval [CI] 0.99–1.76; <i>p</i> = 0.06) and did not differ significantly between the 2 groups. After exclusion of studies with high risk of bias, the RR for death was 1.37 (95% CI 0.54–3.42; <i>p</i> = 0.51). The RR for poor outcome did not differ significantly between the 2 groups analyzed for all included studies (RR = 0.69; 95% CI 0.47–1; <i>p</i> = 0.05) and after exclusion of studies with high risk of bias (RR = 0.7; 95% CI 0.45–1.08; <i>p</i> = 0.11). The RR for complications did not differ significantly including all studies (RR = 1.29; 95% CI 0.77–2.17; <i>p</i> = 0.34) and after exclusion of studies with high risk of bias (RR = 1.27; 95% CI 0.18–8.89; <i>p</i> = 0.81). The cumulative statistics delivered no other results; however, it pointed out fewer complications over time in the dexamethasone group. <b><i>Conclusion:</i></b> Clear evidence of a beneficial or negative effect of dexamethasone is still lacking. Modern RCTs or observational studies with propensity design are necessary to evaluate the efficacy and safety of treatment with dexamethasone in patients with ICH.

scholarly journals Effectiveness of orthodontic temporary anchorage devices in canine retraction and anchorage preservation during the two-step technique: a systematic review and meta-analysis

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Haonan Tian ◽  
Congman Xie ◽  
Min Lin ◽  
Hongmei Yang ◽  
Aishu Ren
Keyword(s):  
Systematic Review ◽  
Meta Analysis ◽  
Risk Of Bias ◽  
Controlled Trials ◽  
Cochrane Central Register ◽  
Canine Retraction ◽  
Temporary Anchorage Devices ◽  
The Mean ◽  
Mean Differences ◽  
Implant Anchorage

Abstract Background Temporary anchorage devices have been used for decades in orthodontic practice for many applications. The aim of this systematic review was to assess the effectiveness of orthodontic temporary anchorage devices in canine retraction during the two-step technique. Methods A search was systematically performed for articles published prior to June 30, 2019 in five electronic databases (PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science, Scopus). The risk of bias was assessed using the Cochrane risk of bias tool for randomized controlled trials (RCTs) and the risk of bias in nonrandomized studies of interventions (ROBINS-I) tool for controlled clinical trials (CCTs). The Grading of Recommendation, Assessment, Development and Evaluation (GRADE) approach was used for the quality assessment. Data concerning the mean difference in mesial molar movement and extent of canine retraction were extracted for statistical analysis. The mean differences and 95% confidence intervals were analyzed for continuous data. A meta-analysis with a random-effects model for comparable outcomes was carried out. Results Three RCTs and five CCTs were finally included. Meta-analysis showed a significant increase not only in anchorage preservation in the implant anchorage group in both the maxilla (1.56 mm, 95% CI: 1.14 to 1.98, P < 0.00001) and the mandible (1.62 mm, 95% CI: 1.24 to 2.01, P < 0.00001) but also in canine retraction in the implant anchorage group in both the maxilla (0.43 mm, 95% CI: 0.16 to 0.69, P = 0.001) and the mandible (0.26 mm, 95% CI: 0.02 to 0.49, P = 0.03). Conclusions There is very low-quality evidence showing that implant anchorage is more efficient than conventional anchorage during canine retraction. Additional high-quality studies are needed.

scholarly journals Network Meta-Analysis of Different Clinical Commonly Used Drugs for the Treatment of Hypertrophic Scar and Keloid

2021 ◽  
Vol 8 ◽  
Author(s):  
Sha Yang ◽  
Yujia J. Luo ◽  
Cong Luo
Keyword(s):  
Clinical Trials ◽  
Randomized Controlled Trials ◽  
Topical Treatment ◽  
Hypertrophic Scar ◽  
Meta Analysis ◽  
Treatment Strategies ◽  
Controlled Trials ◽  
Cochrane Central Register ◽  
Randomized Controlled ◽  
Silicone Gels

Background: There is no uniform treatment for pathological scars, including keloids and hypertrophic scars, in clinic currently. Previously, multiple randomized controlled trials have examined the clinical efficacy of different treatments. Nonetheless, the results are inconsistent, and many treatments have not been directly compared. This makes it difficult to conclude which approach is more favorable, in terms of efficacy and safety, for the treatment of pathological scarring. This study aimed at evaluating the efficacy of different injection and topical treatment strategies for hypertrophic scar and keloid.Methods: Relevant literature from PubMed, Medline, Embase, Scopus, the Cochrane Central Register of Controlled Trials (CCRCT), and WHO International Clinical Trials Registry Platform (WHO-ICTRP) were searched, from database inception through November 2020. Randomized clinical trials evaluating different treatment strategies of pathological scars, including triamcinolone acetonide (TAC), verapamil (VER), 5-fluorouracil (5-FU), botulinum toxin A (BTA), bleomycin (BLM), and silicone gels were included in the study.Results: The network meta-analysis included a total of 2,009 patients from 29 studies. A network meta-analysis of injection and topical treatment strategies showed that the efficacy of TAC combined with BTA was best in the treatment of pathological scars. Combination therapies of TAC with 5-FU and TAC with BTA significantly improved the clinical efficiency. However, there was no statistically significant difference between other treatment strategies. The order of efficacy predicted by the surface under the cumulative ranking (SUCRA) curve was as follows: TAC+BTA (82.2%) &gt; TAC+5-FU (69.8%) &gt; BTA (67.3%) &gt; 5-FU+silicone (59.4%) &gt; TAC+silicone (58.3%) &gt; 5-FU (49.8%) &gt; BLM (42.0%) &gt; TAC (26.7%) &gt; VER (26.2%) &gt; silicone (18.3%). There was no publication bias revealed based on the funnel diagram.Conclusion: This study recommends intralesional injection of TAC-BTA and TAC-5-FU combined therapies. But for patients who cannot tolerate the side effects, the use of silicone gels in combination with TAC is recommended. However, these conclusions need to be further confirmed by more randomized controlled trials.

scholarly journals Relationship between hormonal contraceptives and sleep among women of reproductive age: a systematic review protocol

BMJ Open ◽  
2021 ◽  
Vol 11 (10) ◽  
pp. e045819
Author(s):  
Jinhui Ma ◽  
Megan Cheng ◽  
Lehana Thabane ◽  
Caihong Ma ◽  
Ning Zhang ◽  
...  
Keyword(s):  
Systematic Review ◽  
Meta Analysis ◽  
Research Question ◽  
Risk Of Bias ◽  
Reproductive Age ◽  
Hormonal Contraceptives ◽  
Controlled Trials ◽  
Cochrane Central Register ◽  
Women Of Reproductive Age

IntroductionThe aetiology of sleep disruptions is unknown, but hormonal fluctuations during the menstrual cycle, pregnancy and menopause have been shown to potentially affect how well a woman sleeps. The aim of this systematic review was to investigate whether hormonal contraceptives are associated with a decreased quality of sleep and increased sleep duration in women of reproductive age.MethodsThis review will analyse data from randomised controlled trials or non-randomised comparative studies investigating the association between hormonal contraceptives and sleep outcomes among women of reproductive age. Reviews addressing the same research question with similar eligibility criteria will be included. A literature search will be performed using the MEDLINE, Embase and Cochrane Central Register of Controlled Trials databases from inception to 7 March 2021. The Cochrane Collaboration’s Risk of Bias for Randomised Trials V.2.0 and The Risk of Bias for Non-randomised Studies of Interventions tool will be used to assess risk of bias for each outcome in eligible studies. Two reviewers will independently assess eligibility of studies and risk of bias and extract the data. All extracted data will be presented in tables and narrative form. For sleep measures investigated by two or more studies with low heterogeneity, we will conduct random-effects meta-analysis to estimate the magnitude of the overall effect of hormonal contraceptives. If studies included in this systematic review form a connected network, a network meta-analysis will be conducted to estimate the comparative effect of different contraceptives. The Grading of Recommendations, Assessment, Development, and Evaluation approach will be used to summarise the quality of evidence. Our protocol follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Protocols 2015 guidelines.Ethics and disseminationEthics approval is not required as data were sourced from previously reported studies. The findings of this review will be published in a peer-reviewed journal and presented at relevant conferences.PROSPERO registration numberCRD42020199958.

scholarly journals Vaccines to prevent COVID-19: a protocol for a living systematic review with network meta-analysis including individual patient data (The LIVING VACCINE Project)

2020 ◽  
Vol 9 (1) ◽  
Author(s):  
Steven Kwasi Korang ◽  
Sophie Juul ◽  
Emil Eik Nielsen ◽  
Joshua Feinberg ◽  
Faiza Siddiqui ◽  
...  
Keyword(s):  
Systematic Review ◽  
Clinical Trials ◽  
Randomized Clinical Trials ◽  
Individual Patient Data ◽  
Viral Vector ◽  
Meta Analysis ◽  
Risk Of Bias ◽  
Serious Adverse Events ◽  
Meta Analyses ◽  
Harmful Effects

Abstract Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19) which has rapidly spread worldwide. Several human randomized clinical trials assessing potential vaccines are currently underway. There is an urgent need for a living systematic review that continuously assesses the beneficial and harmful effects of all available vaccines for COVID-19. Methods/design We will conduct a living systematic review based on searches of major medical databases (e.g., MEDLINE, EMBASE, CENTRAL) and clinical trial registries from their inception onwards to identify relevant randomized clinical trials. We will update the literature search once a week to continuously assess if new evidence is available. Two review authors will independently extract data and conduct risk of bias assessments. We will include randomized clinical trials comparing any vaccine aiming to prevent COVID-19 (including but not limited to messenger RNA; DNA; non-replicating viral vector; replicating viral vector; inactivated virus; protein subunit; dendritic cell; other vaccines) with any comparator (placebo; “active placebo;” no intervention; standard care; an “active” intervention; another vaccine for COVID-19) for participants in all age groups. Primary outcomes will be all-cause mortality; a diagnosis of COVID-19; and serious adverse events. Secondary outcomes will be quality of life and non-serious adverse events. The living systematic review will include aggregate data meta-analyses, trial sequential analyses, network meta-analyses, and individual patient data meta-analyses. Within-study bias will be assessed using Cochrane risk of bias tool. The Grading of Recommendations, Assessment, Development and Evaluations (GRADE) and Confidence in Network Meta-Analysis (CINeMA) approaches will be used to assess certainty of evidence. Observational studies describing harms identified during the search for trials will also be included and described and analyzed separately. Discussion COVID-19 has become a pandemic with substantial mortality. A living systematic review assessing the beneficial and harmful effects of different vaccines is urgently needed. This living systematic review will regularly inform best practice in vaccine prevention and clinical research of this highly prevalent disease. Systematic review registration PROSPERO CRD42020196492

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