key: cord-0742107-qsh3nyw7 authors: Arab-Zozani, M.; Hassanipour, S.; GHoddoosi-Nejad, D. title: Favipiravir for treating novel coronavirus (COVID-19) patients: protocol for a systematic review and meta-analysis of controlled trials date: 2020-05-01 journal: nan DOI: 10.1101/2020.04.27.20081471 sha: 40878c70ff24ace8f6351bcf1151b56865334e98 doc_id: 742107 cord_uid: qsh3nyw7 Introduction An outbreak of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) was reported in Wuhan, China in mid-December 2019, and declared a pandemic by the World Health Organization (WHO) on March 11, 2020. Due to the unknown nature of the disease and the lack of specific drugs, several potential treatments were used for patients. This systematic review and meta-analysis will evaluate studies of the effects of Favipiravir in COVID-19 pneumonia. Methods and analysis We will search electronic databases including LitCovid hub, PubMed, Scopus, ISI web of Sciences, Cochrane, and Embase using keywords related to COVID-19 and Favipiravir. We will search the reference lists of all included studies and reviews. We will also search for clinical trial registries, such as clinicaltrial.gov for the ongoing clinical trials. Two investigators (MAZ and SH) will independently screen titles, abstracts, and full-text of included studies based on eligibility criteria. These investigators will also independently extract data and appraise the quality of studies. All potential discrepancies will be resolved through consultation with the third reviewer. Data synthesis will be conducted using the Review Manager software (version 5.3) or CMA (version 2). Statistical heterogeneity will be assessed using a standard I2 test. A funnel plot, Egger test, and Begg test will be used for asymmetry to explore possible publication bias. Ethics and dissemination The findings of this systematic review with proportional meta-analysis will help to identify the safety and efficacy of Favipiravir for COVID-19 patients. Knowledge gained from this research will also assist physicians in selecting better treatment options and developing a guideline in this field. • The small number of studies published in this field when writing a protocol can be one of 22 the most important limitations. CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted May 1, 2020. of specific drugs, several potential treatments were used for patients. This systematic review and 33 meta-analysis will evaluate studies of the effects of Favipiravir in COVID-19 pneumonia. 34 Methods and analysis 35 We will search electronic databases including LitCovid hub, PubMed, Scopus, ISI web of 36 Sciences, Cochrane, and Embase using keywords related to COVID-19 and Favipiravir. We will 37 search the reference lists of all included studies and reviews. We will also search for clinical trial 38 registries, such as clinicaltrial.gov for the ongoing clinical trials. Two investigators (MAZ and 39 SH) will independently screen titles, abstracts, and full-text of included studies based on 40 eligibility criteria. These investigators will also independently extract data and appraise the 41 quality of studies. All potential discrepancies will be resolved through consultation with the 42 third reviewer. Data synthesis will be conducted using the Review Manager software (version 43 5.3) or CMA (version 2). Statistical heterogeneity will be assessed using a standard I 2 test. A 44 funnel plot, Egger's test, and Begg's test will be used for asymmetry to explore possible 45 publication bias. 46 Ethics and dissemination 47 The findings of this systematic review with proportional meta-analysis will help to identify the 48 safety and efficacy of Favipiravir for COVID-19 patients. Knowledge gained from this research 49 will also assist physicians in selecting better treatment options and developing a guideline in this 50 field. 51 PROSPERO registration number: CRD42020180032 52 . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted May 1, 2020. . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted May 1, 2020. Farsi languages or whose full text is not accessible will be excluded from the study. Also, studies 93 that have insufficient or incomplete data will not be incorporated. After importing records to EndNote X7 software and removing duplicate records, two reviewers 105 (SH and DGh) will independently screen titles, abstracts and full-texts of included studies based 106 on predefined eligibility criteria to identify studies concerning safety and efficacy of Favipiravir 107 . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted May 1, 2020. . https://doi.org/10.1101/2020.04.27.20081471 doi: medRxiv preprint 5 among patients with COVID-19. A kappa (κ) statistic will be used to calculate the extent of 108 inter-observer agreement on the independent inclusion of articles. All potentials discrepancies 109 will be resolved by consultation with a third reviewer (MA-Z). 110 Two reviewers (SH and DGh) will independently extract data from included studies using a pre-112 piloted data extraction form. We will pilot this form using at least three examples of included 113 studies, and if there is an agreement above 90%, it will be approved. The data extraction form 114 includes the following items; authors name, year of the publication, study design, study sample, 115 country of origin, mean age of participants, gender, the severity of diseases, comorbidities, type 116 of intervention and dose, control group, follow up, randomization, blinding, allocation 117 concealment, primary and secondary outcomes, and adverse events. All potentials discrepancies 118 will be resolved by consultation with a third reviewer (MA-Z). Two reviewers (SH and DGh) will independently assess the risk of bias among the included 121 studies. We will assess the risk of bias of the included studies using Cochrane Collaboration 122 criteria including seven items of selection bias (random sequence generation and allocation 123 concealment), performance bias, detection bias, attrition bias, reporting bias, and other bias. Any 124 discrepancies will be resolved by consultation with a third reviewer (MA-Z). Statistical analyses will be carried out using the RevMan software (version 5.3) or CMA (version 127 2). We will conduct analyses employing risk ratios (RR) and mean differences (MD) with 95% 128 confidence intervals for dichotomous continuous data, respectively. Statistical heterogeneity will 129 be tested using Cochran's Q statistic and quantified using the I² statistic. If possible, we will 130 perform subgroup analyses based on dose, follow up time, level of disease and age group. The 131 Mantel-Haenszel method and the DerSimonian and Laird inverse variance method will be used 132 for dichotomous outcomes and continuous outcomes, respectively. The fix or random-effects 133 model will be used to pool the data based on the level of heterogeneity and the number of studies 134 . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted May 1, 2020. . https://doi.org/10.1101/2020.04.27.20081471 doi: medRxiv preprint 6 in each unit of analyses. A funnel plot, Egger's test, and Begg's test will be used for asymmetry 135 to explore possible publication bias. 136 Patients and public involvement 137 We will not collect primary data, then, ethical approval will not be required. CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted May 1, 2020. . https://doi.org/10.1101/2020.04.27.20081471 doi: medRxiv preprint The COVID-19 epidemic Preventing a covid-19 pandemic The epidemiological characteristics of an outbreak of 2019 novel 171 coronavirus diseases (COVID-19) in China. Zhonghua liu xing bing xue za zhi= Zhonghua 172 liuxingbingxue zazhi Clinical course and risk factors for 174 mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. The 175 Lancet Organization declares global emergency: A review of the 2019 novel coronavirus (COVID-19) Drug targets for corona 184 virus: A systematic review Targeting the Ebola Virus: A Systematic Review Favipiravir, an anti-influenza drug against life-threatening RNA 188 virus infections Preferred 190 reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015 statement. 191 Systematic reviews International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity Preferred reporting items for systematic 193 reviews and meta-analyses: the PRISMA statement. Annals of internal medicine Keep up with the latest coronavirus research Medical overuse in the 198 Iranian healthcare system: a systematic review protocol Responding to Covid-19-a once-in-a-century pandemic? Discovering drugs to treat coronavirus disease 2019 (COVID-19) 58-60. the author/funder, who has granted medRxiv a license to display the preprint in perpetuity The authors declare that they have no competing interests.