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A stride by step guide for conducting a systematic review and meta-analysis with simulation data
Tropical Medicine and Health volume 47, Article number:46 (2019) Cite this article
Abstract
Background
The massive affluence of studies relating to tropical medicine and wellness has increased strikingly over the terminal few decades. In the field of tropical medicine and health, a well-conducted systematic review and meta-assay (SR/MA) is considered a viable solution for keeping clinicians abreast of current bear witness-based medicine. Understanding of SR/MA steps is of paramount importance for its conduction. It is not easy to be done as there are obstacles that could face the researcher. To solve those hindrances, this methodology study aimed to provide a stride-by-pace arroyo mainly for beginners and junior researchers, in the field of tropical medicine and other health care fields, on how to properly conduct a SR/MA, in which all the steps here depicts our experience and expertise combined with the already well-known and accepted international guidance.
We suggest that all steps of SR/MA should be done independently past 2–3 reviewers' give-and-take, to ensure data quality and accuracy.
Determination
SR/MA steps include the development of research question, forming criteria, search strategy, searching databases, protocol registration, title, abstract, total-text screening, transmission searching, extracting data, quality cess, data checking, statistical analysis, double data checking, and manuscript writing.
Introduction
The amount of studies published in the biomedical literature, specially tropical medicine and health, has increased strikingly over the last few decades. This massive abundance of literature makes clinical medicine increasingly circuitous, and knowledge from various researches is often needed to inform a particular clinical determination. However, bachelor studies are often heterogeneous with regard to their design, operational quality, and subjects under study and may handle the research question in a different way, which adds to the complexity of prove and conclusion synthesis [ane].
Systematic review and meta-analyses (SR/MAs) have a loftier level of evidence as represented by the show-based pyramid. Therefore, a well-conducted SR/MA is considered a viable solution in keeping health clinicians ahead regarding contemporary show-based medicine.
Differing from a systematic review, unsystematic narrative review tends to exist descriptive, in which the authors select frequently articles based on their bespeak of view which leads to its poor quality. A systematic review, on the other paw, is defined as a review using a systematic method to summarize evidence on questions with a detailed and comprehensive plan of written report. Furthermore, despite the increasing guidelines for effectively conducting a systematic review, we constitute that bones steps oft start from framing question, so identifying relevant work which consists of criteria evolution and search for manufactures, appraise the quality of included studies, summarize the testify, and interpret the results [2, iii]. However, those simple steps are not easy to be reached in reality. There are many troubles that a researcher could be struggled with which has no detailed indication.
Conducting a SR/MA in tropical medicine and health may exist difficult especially for young researchers; therefore, understanding of its essential steps is crucial. It is not piece of cake to be done as there are obstacles that could face the researcher. To solve those hindrances, we recommend a menses diagram (Fig. i) which illustrates a detailed and step-by-step the stages for SR/MA studies. This methodology report aimed to provide a step-past-step arroyo mainly for beginners and inferior researchers, in the field of tropical medicine and other health care fields, on how to properly and succinctly comport a SR/MA; all the steps here depicts our feel and expertise combined with the already well known and accepted international guidance.
Detailed flow diagram guideline for systematic review and meta-analysis steps. Note: Star icon refers to "2–3 reviewers screen independently"
Methods and results
Detailed steps for conducting whatsoever systematic review and meta-analysis
We searched the methods reported in published SR/MA in tropical medicine and other healthcare fields as well the published guidelines like Cochrane guidelines {Higgins, 2011 #7} [4] to collect the best low-bias method for each pace of SR/MA conduction steps. Furthermore, we used guidelines that we apply in studies for all SR/MA steps. We combined these methods in social club to conclude and conduct a detailed menstruum diagram that shows the SR/MA steps how being conducted.
Whatsoever SR/MA must follow the widely accepted Preferred Reporting Items for Systematic Review and Meta-analysis statement (PRISMA checklist 2009) (Additional file five: Tabular array S1) [5].
We proposed our methods co-ordinate to a valid explanatory simulation example choosing the topic of "evaluating condom of Ebola vaccine," equally information technology is known that Ebola is a very rare tropical disease but fatal. All the explained methods feature the standards followed internationally, with our compiled experience in the bear of SR abreast it, which we think proved some validity. This is a SR under behave by a couple of researchers teaming in a research group, moreover, as the outbreak of Ebola which took identify (2013–2016) in Africa resulted in a significant mortality and morbidity. Furthermore, since there are many published and ongoing trials assessing the safety of Ebola vaccines, we thought this would provide a cracking opportunity to tackle this hotly debated outcome. Moreover, Ebola started to burn again and new fatal outbreak appeared in the Democratic Democracy of Congo since August 2018, which caused infection to more than grand people according to the Earth Health Organization, and 629 people have been killed till now. Hence, it is considered the second worst Ebola outbreak, after the first 1 in West Africa in 2014, which infected more than than 26,000 and killed near 11,300 people along outbreak form.
Research question and objectives
Like other study designs, the research question of SR/MA should be viable, interesting, novel, ethical, and relevant. Therefore, a clear, logical, and well-defined enquiry question should be formulated. Usually, ii common tools are used: PICO or SPIDER. PICO (Population, Intervention, Comparison, Outcome) is used mostly in quantitative evidence synthesis. Authors demonstrated that PICO holds more sensitivity than the more specific SPIDER approach [6]. SPIDER (Sample, Phenomenon of Involvement, Design, Evaluation, Inquiry blazon) was proposed equally a method for qualitative and mixed methods search.
Nosotros here recommend a combined arroyo of using either one or both the SPIDER and PICO tools to recall a comprehensive search depending on time and resources limitations. When we use this to our causeless research topic, being of qualitative nature, the use of SPIDER approach is more valid.
PICO is usually used for systematic review and meta-analysis of clinical trial study. For the observational written report (without intervention or comparator), in many tropical and epidemiological questions, it is unremarkably enough to use P (Patient) and O (consequence) only to formulate a research question. We must indicate conspicuously the population (P), then intervention (I) or exposure. Next, it is necessary to compare (C) the indicated intervention with other interventions, i.due east., placebo. Finally, nosotros need to analyze which are our relevant outcomes.
To facilitate comprehension, we choose the Ebola virus disease (EVD) as an instance. Currently, the vaccine for EVD is beingness developed and under phase I, Ii, and III clinical trials; we desire to know whether this vaccine is safe and can induce sufficient immunogenicity to the subjects.
An example of a inquiry question for SR/MA based on PICO for this outcome is as follows: How is the safe and immunogenicity of Ebola vaccine in man? (P: healthy subjects (human), I: vaccination, C: placebo, O: safety or adverse effects)
Preliminary inquiry and thought validation
We recommend a preliminary search to place relevant articles, ensure the validity of the proposed idea, avert duplication of previously addressed questions, and assure that we accept enough manufactures for conducting its analysis. Moreover, themes should focus on relevant and of import health-care issues, consider global needs and values, reflect the current science, and be consistent with the adopted review methods. Gaining familiarity with a deep understanding of the report field through relevant videos and discussions is of paramount importance for meliorate retrieval of results. If nosotros ignore this stride, our study could exist canceled whenever we detect out a similar study published before. This means we are wasting our fourth dimension to deal with a problem that has been tackled for a long time.
To do this, we can showtime by doing a simple search in PubMed or Google Scholar with search terms Ebola AND vaccine. While doing this step, nosotros identify a systematic review and meta-analysis of determinant factors influencing antibody response from vaccination of Ebola vaccine in non-human primate and human [7], which is a relevant paper to read to get a deeper insight and place gaps for better formulation of our inquiry question or purpose. We can still comport systematic review and meta-analysis of Ebola vaccine considering we evaluate safety as a different outcome and different population (but human).
Inclusion and exclusion criteria
Eligibility criteria are based on the PICO arroyo, study design, and date. Exclusion criteria mostly are unrelated, duplicated, unavailable full texts, or abstruse-only papers. These exclusions should be stated in accelerate to refrain the researcher from bias. The inclusion criteria would be articles with the target patients, investigated interventions, or the comparison between two studied interventions. Briefly, it would be articles which incorporate information answering our enquiry question. But the most important is that it should be clear and sufficient information, including positive or negative, to respond the question.
For the topic we have chosen, we can make inclusion criteria: (i) any clinical trial evaluating the safety of Ebola vaccine and (2) no restriction regarding land, patient age, race, gender, publication language, and date. Exclusion criteria are as follows: (1) study of Ebola vaccine in not-human subjects or in vitro studies; (2) report with data non reliably extracted, duplicate, or overlapping information; (3) abstract-simply papers equally preceding papers, conference, editorial, and author response theses and books; (4) manufactures without available total text available; and (5) case reports, example series, and systematic review studies. The PRISMA flow diagram template that is used in SR/MA studies tin can exist found in Fig. two.
PRISMA flow diagram of studies' screening and option
Search strategy
A standard search strategy is used in PubMed, and then later information technology is modified co-ordinate to each specific database to go the all-time relevant results. The basic search strategy is congenital based on the research question formulation (i.e., PICO or PICOS). Search strategies are constructed to include gratis-text terms (e.g., in the championship and abstract) and whatsoever advisable discipline indexing (east.g., MeSH) expected to remember eligible studies, with the assistance of an expert in the review topic field or an data specialist. Additionally, we propose not to apply terms for the Outcomes as their inclusion might hinder the database being searched to retrieve eligible studies because the used outcome is not mentioned plainly in the articles.
The improvement of the search term is made while doing a trial search and looking for another relevant term within each concept from retrieved papers. To search for a clinical trial, nosotros can use these descriptors in PubMed: "clinical trial"[Publication Type] OR "clinical trials as topic"[MeSH terms] OR "clinical trial"[All Fields]. Later on some rounds of trial and refinement of search term, nosotros formulate the final search term for PubMed as follows: (ebola OR ebola virus OR ebola virus disease OR EVD) AND (vaccine OR vaccination OR vaccinated OR immunization) AND ("clinical trial"[Publication Type] OR "clinical trials as topic"[MeSH Terms] OR "clinical trial"[All Fields]). Because the written report for this topic is express, nosotros practice non include outcome term (safety and immunogenicity) in the search term to capture more than studies.
Search databases, import all results to a library, and exporting to an excel canvas
According to the AMSTAR guidelines, at least two databases have to be searched in the SR/MA [eight], simply every bit you increase the number of searched databases, you get much yield and more accurate and comprehensive results. The ordering of the databases depends generally on the review questions; being in a study of clinical trials, you will rely more often than not on Cochrane, mRCTs, or International Clinical Trials Registry Platform (ICTRP). Here, we propose 12 databases (PubMed, Scopus, Web of Science, EMBASE, GHL, VHL, Cochrane, Google Scholar, Clinical trials.gov, mRCTs, POPLINE, and SIGLE), which help to cover almost all published articles in tropical medicine and other wellness-related fields. Among those databases, POPLINE focuses on reproductive health. Researchers should consider to choose relevant database according to the inquiry topic. Some databases practice not support the employ of Boolean or quotation; otherwise, at that place are some databases that have special searching manner. Therefore, we need to modify the initial search terms for each database to get appreciated results; therefore, manipulation guides for each online database searches are presented in Additional file five: Table S2. The detailed search strategy for each database is constitute in Additional file v: Tabular array S3. The search term that we created in PubMed needs customization based on a specific feature of the database. An example for Google Scholar advanced search for our topic is as follows:
- one.
With all of the words: ebola virus
With at least one of the words: vaccine vaccination vaccinated immunization
Where my words occur: in the title of the commodity
- 2.
With all of the words: EVD
With at least one of the words: vaccine vaccination vaccinated immunization
Where my words occur: in the championship of the article
Finally, all records are collected into one Endnote library in society to delete duplicates and then to it export into an excel sheet. Using remove duplicating function with ii options is mandatory. All references which have (1) the same title and writer, and published in the same year, and (2) the same title and writer, and published in the same journal, would be deleted. References remaining later this step should be exported to an excel file with essential information for screening. These could be the authors' names, publication yr, journal, DOI, URL link, and abstruse.
Protocol writing and registration
Protocol registration at an early on phase guarantees transparency in the research process and protects from duplication bug. Besides, it is considered a documented proof of team plan of action, research question, eligibility criteria, intervention/exposure, quality cess, and pre-analysis program. Information technology is recommended that researchers send it to the principal investigator (PI) to revise it, then upload information technology to registry sites. There are many registry sites available for SR/MA similar those proposed by Cochrane and Campbell collaborations; nevertheless, nosotros recommend registering the protocol into PROSPERO as it is easier. The layout of a protocol template, co-ordinate to PROSPERO, tin can exist found in Additional file v: File S1.
Championship and abstract screening
Decisions to select retrieved articles for farther assessment are based on eligibility criteria, to minimize the chance of including non-relevant manufactures. According to the Cochrane guidance, ii reviewers are a must to practice this step, but as for beginners and junior researchers, this might exist slow; thus, we propose based on our experience that at least three reviewers should piece of work independently to reduce the gamble of error, peculiarly in teams with a large number of authors to add more scrutiny and ensure proper conduct. Mostly, the quality with three reviewers would be better than 2, as two simply would have different opinions from each other, so they cannot decide, while the third opinion is crucial. And hither are some examples of systematic reviews which we conducted following the same strategy (by a different grouping of researchers in our research group) and published successfully, and they feature relevant ideas to tropical medicine and illness [ix,10,11].
In this step, duplications volition be removed manually whenever the reviewers find them out. When there is a doubt about an article decision, the squad should be inclusive rather than exclusive, until the main leader or PI makes a decision after discussion and consensus. All excluded records should be given exclusion reasons.
Full text downloading and screening
Many search engines provide links for gratuitous to access full-text articles. In instance not found, we tin can search in some enquiry websites equally ResearchGate, which offer an option of direct total-text asking from authors. Additionally, exploring archives of wanted journals, or contacting PI to buy information technology if available. Similarly, ii–3 reviewers piece of work independently to make up one's mind about included total texts co-ordinate to eligibility criteria, with reporting exclusion reasons of articles. In case any disagreement has occurred, the terminal determination has to be made past discussion.
Manual search
I has to frazzle all possibilities to reduce bias past performing an explicit hand-searching for retrieval of reports that may take been dropped from first search [12]. We employ v methods to brand manual searching: searching references from included studies/reviews, contacting authors and experts, and looking at related articles/cited articles in PubMed and Google Scholar.
Nosotros draw here three consecutive methods to increase and refine the yield of manual searching: firstly, searching reference lists of included articles; secondly, performing what is known as commendation tracking in which the reviewers track all the articles that cite each 1 of the included manufactures, and this might involve electronic searching of databases; and thirdly, like to the citation tracking, we follow all "related to" or "similar" articles. Each of the abovementioned methods can exist performed by two–3 independent reviewers, and all the possible relevant article must undergo further scrutiny confronting the inclusion criteria, after post-obit the aforementioned records yielded from electronic databases, i.e., championship/abstruse and total-text screening.
Nosotros suggest an independent reviewing by assigning each member of the teams a "tag" and a distinct method, to compile all the results at the cease for comparison of differences and discussion and to maximize the retrieval and minimize the bias. Similarly, the number of included manufactures has to be stated before addition to the overall included records.
Data extraction and quality assessment
This step entitles information collection from included full-texts in a structured extraction excel sheet, which is previously airplane pilot-tested for extraction using some random studies. Nosotros recommend extracting both adapted and non-adjusted data because it gives the most immune confounding factor to be used in the analysis by pooling them later on [13]. The procedure of extraction should exist executed past 2–3 independent reviewers. Mostly, the sail is classified into the study and patient characteristics, outcomes, and quality assessment (QA) tool.
Information presented in graphs should exist extracted by software tools such every bit Spider web plot digitizer [xiv]. Nigh of the equations that can be used in extraction prior to analysis and estimation of standard deviation (SD) from other variables is found inside Boosted file 5: File S2 with their references as Hozo et al. [15], Xiang et al. [sixteen], and Rijkom et al. [17]. A variety of tools are available for the QA, depending on the design: ROB-2 Cochrane tool for randomized controlled trials [eighteen] which is presented as Boosted file 1: Effigy S1 and Additional file 2: Figure S2—from a previous published article data—[19], NIH tool for observational and cross-sectional studies [xx], ROBINS-I tool for non-randomize trials [21], QUADAS-2 tool for diagnostic studies, QUIPS tool for prognostic studies, Intendance tool for case reports, and ToxRtool for in vivo and in vitro studies. We recommend that 2–3 reviewers independently appraise the quality of the studies and add to the data extraction class earlier the inclusion into the assay to reduce the gamble of bias. In the NIH tool for observational studies—accomplice and cantankerous-sectional—as in this EBOLA instance, to evaluate the risk of bias, reviewers should rate each of the xiv items into dichotomous variables: yeah, no, or not applicative. An overall score is calculated past adding all the items scores as aye equals one, while no and NA equals nada. A score will be given for every newspaper to classify them every bit poor, off-white, or good conducted studies, where a score from 0–5 was considered poor, 6–ix as fair, and 10–14 as good.
In the EBOLA case example above, authors can excerpt the following information: proper noun of authors, state of patients, yr of publication, study design (case report, cohort written report, or clinical trial or RCT), sample size, the infected indicate of time subsequently EBOLA infection, follow-up interval after vaccination fourth dimension, efficacy, safety, adverse effects after vaccinations, and QA canvas (Additional file 6: Data S1).
Data checking
Due to the expected human error and bias, we recommend a data checking footstep, in which every included article is compared with its counterpart in an extraction sheet by bear witness photos, to find mistakes in data. We advise assigning articles to 2–3 independent reviewers, ideally not the ones who performed the extraction of those articles. When resources are limited, each reviewer is assigned a dissimilar article than the one he extracted in the previous stage.
Statistical analysis
Investigators use different methods for combining and summarizing findings of included studies. Before analysis, at that place is an important step called cleaning of data in the extraction canvass, where the analyst organizes extraction canvass data in a form that can be read by analytical software. The analysis consists of 2 types namely qualitative and quantitative analysis. Qualitative analysis mostly describes data in SR studies, while quantitative analysis consists of 2 main types: MA and network meta-analysis (NMA). Subgroup, sensitivity, cumulative analyses, and meta-regression are advisable for testing whether the results are consistent or not and investigating the effect of certain confounders on the result and finding the best predictors. Publication bias should exist assessed to investigate the presence of missing studies which tin affect the summary.
To illustrate bones meta-analysis, we provide an imaginary data for the research question well-nigh Ebola vaccine condom (in terms of agin events, 14 days after injection) and immunogenicity (Ebola virus antibodies rise in geometric mean titer, 6 months after injection). Assuming that from searching and data extraction, we decided to exercise an analysis to evaluate Ebola vaccine "A" safety and immunogenicity. Other Ebola vaccines were not meta-analyzed because of the limited number of studies (instead, it volition be included for narrative review). The imaginary data for vaccine safe meta-assay can be accessed in Additional file 7: Information S2. To do the meta-analysis, nosotros tin use costless software, such as RevMan [22] or R package meta [23]. In this instance, nosotros volition use the R package meta. The tutorial of meta package tin be accessed through "General Parcel for Meta-Analysis" tutorial pdf [23]. The R codes and its guidance for meta-assay done tin be found in Additional file 5: File S3.
For the analysis, nosotros presume that the study is heterogenous in nature; therefore, we cull a random effect model. We did an assay on the prophylactic of Ebola vaccine A. From the data tabular array, we can meet some adverse events occurring after intramuscular injection of vaccine A to the subject area of the study. Suppose that nosotros include six studies that fulfill our inclusion criteria. We can do a meta-analysis for each of the agin events extracted from the studies, for case, arthralgia, from the results of random effect meta-analysis using the R meta package.
From the results shown in Boosted file 3: Effigy S3, we tin see that the odds ratio (OR) of arthralgia is i.06 (0.79; ane.42), p value = 0.71, which ways that at that place is no association between the intramuscular injection of Ebola vaccine A and arthralgia, as the OR is about one, and besides, the P value is insignificant as information technology is > 0.05.
In the meta-analysis, we tin also visualize the results in a forest plot. It is shown in Fig. 3 an case of a forest plot from the simulated analysis.
Random effect model wood plot for comparison of vaccine A versus placebo
From the forest plot, we can run into six studies (A to F) and their respective OR (95% CI). The green box represents the effect size (in this case, OR) of each study. The bigger the box means the study weighted more (i.e., bigger sample size). The blue diamond shape represents the pooled OR of the half-dozen studies. We can see the blue diamond cross the vertical line OR = 1, which indicates no significance for the association as the diamond almost equalized in both sides. We can confirm this also from the 95% conviction interval that includes one and the p value > 0.05.
For heterogeneity, we see that I 2 = 0%, which means no heterogeneity is detected; the study is relatively homogenous (information technology is rare in the real written report). To evaluate publication bias related to the meta-analysis of agin events of arthralgia, we can use the metabias function from the R meta package (Additional file 4: Figure S4) and visualization using a funnel plot. The results of publication bias are demonstrated in Fig. 4. We run across that the p value associated with this test is 0.74, indicating symmetry of the funnel plot. We can confirm it by looking at the funnel plot.
Publication bias funnel plot for comparison of vaccine A versus placebo
Looking at the funnel plot, the number of studies at the left and right side of the funnel plot is the aforementioned; therefore, the plot is symmetry, indicating no publication bias detected.
Sensitivity analysis is a process used to discover how dissimilar values of an independent variable volition influence the significance of a particular dependent variable by removing 1 study from MA. If all included study p values are < 0.05, hence, removing any study will not modify the significant association. It is simply performed when there is a significant association, and then if the p value of MA done is 0.seven—more than one—the sensitivity analysis is not needed for this case study example. If there are 2 studies with p value > 0.05, removing whatever of the two studies will issue in a loss of the significance.
Double data checking
For more balls on the quality of results, the analyzed data should exist rechecked from full-text data by evidence photos, to permit an obvious check for the PI of the study.
Manuscript writing, revision, and submission to a periodical
Writing based on four scientific sections: introduction, methods, results, and discussion, mostly with a conclusion. Performing a characteristic table for written report and patient characteristics is a mandatory step which can be establish equally a template in Additional file 5: Tabular array S3.
After finishing the manuscript writing, characteristics table, and PRISMA flow diagram, the squad should send it to the PI to revise it well and answer to his comments and, finally, choose a suitable journal for the manuscript which fits with considerable impact factor and fitting field. Nosotros need to pay attending past reading the author guidelines of journals before submitting the manuscript.
Discussion
The role of bear witness-based medicine in biomedical research is rapidly growing. SR/MAs are also increasing in the medical literature. This paper has sought to provide a comprehensive arroyo to enable reviewers to produce high-quality SR/MAs. We promise that readers could gain general knowledge about how to conduct a SR/MA and take the confidence to perform one, although this kind of study requires complex steps compared to narrative reviews.
Having the bones steps for conduction of MA, at that place are many avant-garde steps that are practical for certain specific purposes. One of these steps is meta-regression which is performed to investigate the clan of any confounder and the results of the MA. Furthermore, there are other types rather than the standard MA like NMA and MA. In NMA, we investigate the difference between several comparisons when in that location were not enough information to enable standard meta-analysis. It uses both straight and indirect comparisons to conclude what is the best between the competitors. On the other manus, mega MA or MA of patients tend to summarize the results of independent studies past using its individual subject data. As a more detailed assay can be done, information technology is useful in conducting repeated mensurate assay and time-to-effect analysis. Moreover, it can perform analysis of variance and multiple regression analysis; notwithstanding, information technology requires homogenous dataset and it is time-consuming in conduct [24].
Conclusions
Systematic review/meta-assay steps include evolution of inquiry question and its validation, forming criteria, search strategy, searching databases, importing all results to a library and exporting to an excel sheet, protocol writing and registration, title and abstract screening, full-text screening, manual searching, extracting data and assessing its quality, data checking, conducting statistical analysis, double data checking, manuscript writing, revising, and submitting to a journal.
Availability of information and materials
Not applicable.
Abbreviations
- NMA:
-
Network meta-analysis
- PI:
-
Principal investigator
- PICO:
-
Population, Intervention, Comparison, Outcome
- PRISMA:
-
Preferred Reporting Items for Systematic Review and Meta-assay statement
- QA:
-
Quality assessment
- SPIDER:
-
Sample, Phenomenon of Interest, Design, Evaluation, Research blazon
- SR/MAs:
-
Systematic review and meta-analyses
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Funding
This written report was conducted (in part) at the Joint Usage/Research Heart on Tropical Disease, Institute of Tropical Medicine, Nagasaki University, Nippon.
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NTH and GMT were responsible for the idea and its design. The figure was washed past GMT. All authors contributed to the manuscript writing and approval of the final version.
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Additional files
Boosted file one:
Figure S1. Risk of bias assessment graph of included randomized controlled trials. (TIF twenty kb)
Boosted file 2:
Figure S2. Risk of bias assessment summary. (TIF 69 kb)
Additional file 3:
Figure S3. Arthralgia results of random issue meta-assay using R meta package. (TIF 20 kb)
Additional file 4:
Figure S4. Arthralgia linear regression test of funnel plot asymmetry using R meta package. (TIF xiii kb)
Additional file 5:
Table S1. PRISMA 2009 Checklist. Table S2. Manipulation guides for online database searches. Table S3. Detailed search strategy for twelve database searches. Table S4. Baseline characteristics of the patients in the included studies. File S1. PROSPERO protocol template file. File S2. Extraction equations that can be used prior to analysis to get missed variables. File S3. R codes and its guidance for meta-analysis done for comparison between EBOLA vaccine A and placebo. (DOCX 49 kb)
Boosted file 6:
Data S1. Extraction and quality assessment data sheets for EBOLA instance example. (XLSX 1368 kb)
Additional file seven:
Information S2. Imaginary information for EBOLA case instance. (XLSX x kb)
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Tawfik, G.M., Dila, K.A.Due south., Mohamed, M.Y.F. et al. A step past step guide for conducting a systematic review and meta-analysis with simulation data. Trop Med Health 47, 46 (2019). https://doi.org/x.1186/s41182-019-0165-six
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DOI : https://doi.org/10.1186/s41182-019-0165-six
Keywords
- Search
- Data
- Extraction
- Analysis
- Study
- Results
Source: https://tropmedhealth.biomedcentral.com/articles/10.1186/s41182-019-0165-6
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