The effectiveness of microneedling compared to placebo in the treatement of melasma: A systematic review and meta-analysis.

1. * Review title. The effectiveness of microneedling compared to placebo in the treatement of melasma: A systematic review and meta-analysis. 2. * Anticipated or actual start date. Give the date when the systematic review commenced, or is expected to commence. 28/02/2020 3. * Anticipated completion date. Give the date by which the review is expected to be completed. 20/04/2020 4. * Stage of review at time of this submission. Review stage Started Completed Preliminary searches Piloting of the study selection process Formal screening of search results against eligibility criteria Data extraction Risk of bias (quality) assessment Data analysis Provide any other relevant information about the stage of the review here (e.g. Funded proposal, protocol not yet finalised). 5. * Named contact. The named contact acts as the guarantor for the accuracy of the information presented in the register record. Adrian Bailey Email salutation (e.g. "Dr Smith" or "Joanne") for correspondence: Mr Bailey 6. * Named contact email. Give the electronic mail address of the named contact. abail082@uottawa.ca 7. Named contact address PLEASE NOTE this information will be published in the PROSPERO record so please do not enter private information Give the full postal address for the named contact. 4512 Appleton Side Road 8. Named contact phone number. Give the telephone number for the named contact, including international dialling code. 6138585029 9. * Organisational affiliation of the review. Full title of the organisational affiliations for this review and website address if available. This field may be completed as 'None' if the review is not affiliated to any organisation. University of Ottawa 10. * Review team members and their organisational affiliations. Give the personal details and the organisational affiliations of each member of the review team. Affiliation refers to groups or organisations to which review team members belong. NOTE: email and country are now mandatory fields for each person. Adrian Bailey - University of Ottawa Heidi Li - University of Ottawa 11. * Funding sources/sponsors. Give details of the individuals, organizations, groups or other legal entities who take responsibility for initiating, managing, sponsoring and/or financing the review. Include any unique identification numbers assigned to the review by the individuals or bodies listed. None 12. * Conflicts of interest. List any conditions that could lead to actual or perceived undue influence on judgements concerning the main topic investigated in the review. None 13. Collaborators. Give the name and affiliation of any individuals or organisations who are working on the review but who are not listed as review team members. NOTE: email and country are now mandatory fields for each person. None 14. * Review question. State the question(s) to be addressed by the review, clearly and precisely. Review questions may be specific or broad. It may be appropriate to break very broad questions down into a series of related more specific questions. Questions may be framed or refined using PI(E)COS where relevant. P = adult patients (>18 years old) with melasma I = microneedling C = control intervention (topical treatments, oral tranexamic acid, placebo) O = Melasma Area and Severity Index or modified Melasma Area and Severity Index S = Randomized controlled trial, Prospective studies 15. * Searches. State the sources that will be searched. Give the search dates, and any restrictions (e.g. language or publication period). Do NOT enter the full search strategy (it may be provided as a link or attachment.) A systematic search without date restrictions was conducted in MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials on March 4th, 2020, using a search strategy developed in conjunction with a librarian specializing in systematic review searches. The search strategy was consistent across all databases. 16. * Condition or domain being studied. Give a short description of the disease, condition or healthcare domain being studied. This could include health and wellbeing outcomes. Melasma is an acquired, symmetrical disorder of hypermelanosis that affects the sun-exposed areas of the skin. To-date, there does not exist a satisfactory treatment for melasma. A variety of topical and systemic treatments have been attempted, including laser therapy, oral and topical tranexamic acid, and combination therapies. In particular, many studies have explored the use of microneedling in melasma and have shown promising results. However, to-date, the literature lacks a systematic review and meta-analysis on the effectiveness of microneedling in the treatment of melasma. 17. * Participants/population. Give summary criteria for the participants or populations being studied by the review. The preferred format includes details of both inclusion and exclusion criteria. Adult patients with melasma (>18 years old). Pediatric patients are excluded. 18. * Intervention(s), exposure(s). Give full and clear descriptions or definitions of the nature of the interventions or the exposures to be reviewed. Microneedling, either alone or in combination with another therapy. Ex. Platelet rich plasma, tranexamic acid (oral and topical), vitamin C, depigmentation serum. 19. * Comparator(s)/control. Where relevant, give details of the alternatives against which the main subject/topic of the review will be compared (e.g. another intervention or a non-exposed control group). The preferred format includes details of both inclusion and exclusion criteria. Any control. Ex. Placebo, microinjections. 20. * Types of study to be included. Give details of the types of study (study designs) eligible for inclusion in the review. If there are no restrictions on the types of study design eligible for inclusion, or certain study types are excluded, this should be stated. The preferred format includes details of both inclusion and exclusion criteria. All English-language full-text articles that report on microneedling or microneedling combined with another intervention, such as tranexamic acid, lasers, and platelet plasma, for the treatment of melasma are included. Eligible study designs include prospective cohort, randomized controlled trials (RCT), and quasi-randomized clinical trials. Included studies are required to be comparative, either through split-faced design or experimental and control group design. Studies that used microinjections or radiofrequency microneedling are excluded. Studies using baseline as a comparison are excluded along with retrospective cohort, case-reports, case series, reviews, and grey literature. 21. * Main outcome(s). Give the pre-specified main (most important) outcomes of the review, including details of how the outcome is defined and measured and when these measurement are made, if these are part of the review inclusion criteria. Outcome = Melasma Area and Severity Index. All variations of the MASI score (MASI and modified MASI) are accepted and will be directly compared. 175 words remaining * Measures of effect Please specify the effect measure(s) for you main outcome(s) e.g. relative risks, odds ratios, risk difference, and/or 'number needed to treat. Mean difference between Melasma Area and Severity Index (MASI) scores at baseline and endpoint for both the intervention and control groups. 22. * Additional outcome(s). List the pre-specified additional outcomes of the review, with a similar level of detail to that required for main outcomes. Where there are no additional outcomes please state ‘None’ or ‘Not applicable’ as appropriate to the review N/A * Measures of effect Please specify the effect measure(s) for you additional outcome(s) e.g. relative risks, odds ratios, risk difference, and/or 'number needed to treat. N/A 23. * Data extraction (selection and coding). Describe how studies will be selected for inclusion. State what data will be extracted or obtained. State how this will be done and recorded. In order to be included in the meta-analysis, studies have to provide the difference between Melasma Area and Severity Index (MASI) scores at baseline and endpoint for both the intervention and control groups or provide sufficient data for these values to be calculated. All variations of the MASI score (MASI and modified MASI) are accepted and directly compared. Studies using baseline as a comparison are excluded. In the next step, the characteristics and results of the studies will be extracted. This will include demographic data of each of the studies (authors, country of origin, date of publication) and details of the study’s design (age range, number, and sex of participants, interventions in the control group and experimental arm). The difference in MASI scores (mean and standard deviation) of the intervention and control groups between baseline and endpoint for each of the studies will be extracted or calculated. If necessary, ImageJ will be used to estimate values from figures, and corresponding authors will be contacted for missing data. Data will be stored and compared using Excel Software in duplicates. 24. * Risk of bias (quality) assessment. Describe the method of assessing risk of bias or quality assessment. State which characteristics of the studies will be assessed and any formal risk of bias tools that will be used. The Cochrane risk of bias tool 2 (reference) will be used to assess the quality of the included studies. Studies of any risk of bias will be included in the meta-analysis, but separate analysis will be conducted with these studies excluded. 25. * Strategy for data synthesis. Provide details of the planned synthesis including a rationale for the methods selected. This must not be generic text but should be specific to your review and describe how the proposed analysis will be applied to your data. Review Manager Software (version 5.3) will be used. The DerSimonian-Laird random-effects model for the

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