Denniston, Alastair

Downie, Laura

Haque, Sayeed

Hill, Lisa J

Jalal, Zahraa

Mahmood, Sajid

Paudyal, Vibhu

Shahzad, Haris

English

University of Birmingham Research Portal

  University of BirminghamA systematic review and meta-analysis on treatmentnon-adherence and non-persistence to intravitrealanti-vascular endothelial growth factor therapyMahmood, Sajid; Shahzad, Haris ; Haque, Sayeed; Denniston, Alastair; Paudyal, Vibhu;Downie, Laura; Hill, Lisa J; Jalal, ZahraaLicense:None: All rights reservedDocument VersionPublisher's PDF, also known as Version of recordCitation for published version (Harvard):Mahmood, S, Shahzad, H, Haque, S, Denniston, A, Paudyal, V, Downie, L, Hill, LJ & Jalal, Z 2020, 'A systematicreview and meta-analysis on treatment non-adherence and non-persistence to intravitreal anti-vascularendothelial growth factor therapy', PROSPERO.<https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020216205>Link to publication on Research at Birmingham portalGeneral rightsUnless a licence is specified above, all rights (including copyright and moral rights) in this document are retained by the authors and/or thecopyright holders. The express permission of the copyright holder must be obtained for any use of this material other than for purposespermitted by law.•	Users may freely distribute the URL that is used to identify this publication.•	Users may download and/or print one copy of the publication from the University of Birmingham research portal for the purpose of privatestudy or non-commercial research.•	User may use extracts from the document in line with the concept of ‘fair dealing’ under the Copyright, Designs and Patents Act 1988 (?)•	Users may not further distribute the material nor use it for the purposes of commercial gain.Where a licence is displayed above, please note the terms and conditions of the licence govern your use of this document.When citing, please reference the published version.Take down policyWhile the University of Birmingham exercises care and attention in making items available there are rare occasions when an item has beenuploaded in error or has been deemed to be commercially or otherwise sensitive.If you believe that this is the case for this document, please contact UBIRA@lists.bham.ac.uk providing details and we will remove access tothe work immediately and investigate.Download date: 28. Jun. 2022PROSPEROInternational prospective register of systematic reviewsA systematic review and meta-analysis on treatment non-adherence and non-persistenceto intravitreal anti-vascular endothelial growth factor therapySajid Mahmood, Haris Shahzad, Sayeed Haque, Alastair K. Denniston, Vibhu Paudyal, Laura E. Downie,Lisa J Hill, Zahraa Jalal CitationSajid Mahmood, Haris Shahzad, Sayeed Haque, Alastair K. Denniston, Vibhu Paudyal, Laura E.Downie, Lisa J Hill, Zahraa Jalal. A systematic review and meta-analysis on treatment non-adherence and non-persistence to intravitreal anti-vascular endothelial growth factor therapy.PROSPERO 2020 CRD42020216205 Available from: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020216205 Review question1. What is the prevalence of non-adherence and non-persistence to intravitreal anti-vascular endothelialgrowth factor (anti-VEGF) therapy? 2. What are the barriers/reasons associated with non-adherence and non-persistence to anti-VEGF therapy?Are they the same in different disease states? 3. What are the strategies/interventions to tackle non-adherence and non-persistence to anti-VEGF therapy? SearchesAn electronic search of databases will be conducted for research articles published from the start of thedatabases until December 2020: PubMed, Embase, MEDLINE, CINAHL Plus (The Cumulative Index toNursing and Allied Health Professionals), Scopus, Cochrane Library (The Cochrane Database for SystematicReviews), PsycINFO, Web of Science and Google Scholar Types of study to be includedThere will be no restriction to study design regarding primary research articles (original research). Condition or domain being studiedAnti-VEGF therapy non-adherence and non-persistence, barriers to adherence and persistence tomedication and therapy follow up. Participants/populationInclusion: Patients treated with intravitreal Anti-VEGF therapy for ocular diseases (for example: AMD,diabetic retinopathy).Exclusion: Patients not on intravitreal Anti-VEGF therapy, or treated with Anti-VEGF therapy but not forocular conditions. Intervention(s), exposure(s)Intervention(s), exposures(s) Anti-VEGF therapy Inclusion: Any study with patients on anti-VEGF therapy and ocular diseases which require anti-VEGFtherapy. Patients receiving intravitreal injections such as with the following medications ranibizumab,Lucentis, aflibercept, Eylea, Zaltrap, Avastin, bevacizumab. Studies reporting rates of non-adherence and/ornon-persistence to anti-VEGF therapy and studies including strategies/interventions to tackle non-adherenceand/or non-persistence. Studies assessing reasons and barriers to non-adherence and non-persistence toanti-VEGF therapies and regimens. No eligibility restrictions will be placed based on the type of anti-VEGFused or the relevant ocular disease and the treatment regimen of anti-VEGF used. Exclusion: Studies will be excluded if they are review or expert opinion articles, case studies and series.Where duplicate papers are identified, the research paper with the most completely reported data will beincluded. Studies not reporting outcomes such as non-adherence and non-persistence and studies not                               Page: 1 / 4PROSPEROInternational prospective register of systematic reviewsreporting barriers to treatment with anti-VEGF medications and studies with patients receiving otherintravitreal injections not anti-VEGF. Comparator(s)/controlNot applicable Main outcome(s)Degree/prevalence of non-adherence and non-persistence to anti-VEGF therapy.* Measures of effectRate and prevalence of non-adherence and non-persistence to anti-VEGF therapy. Additional outcome(s)Distinguish non-adherence and non-persistence by patient, physician and centre-related reasons, as well asintentional and non-intentional causes, investigate strategies/interventions to improve medication adherenceand treatment follow up in patients on anti-VEGF therapy. Identify specific barriers associated with non-adherence to Anti-VEGF therapy.* Measures of effectReasons and barriers, intentional and non-intentional non-adherence and non-persistence. Data extraction (selection and coding)The search will be done in two steps. Firstly, studies will be identified by initial screening of titles andabstract. Then full text screening will be done for the selected articles. The screening process will be carriedout independently by two reviewers; any conflict regarding the selected articles will be resolved by consultingthe third reviewer. A data extraction tool will be developed based on aims and objectives. The extractionparameters will be the study name, name of investigator, year of study, location, study design, source ofdata, study duration, population size, gender ratio, mean age, intervention and regimen, definition of non-adherence and non-persistence used, non-adherence by gender, overall non-adherence to anti-VEGFtherapy, reasons/barriers for non-adherence and non-persistence, medication used, frequency of follow-up,participant population and disease type. Risk of bias (quality) assessmentSince different types of studies will be included, the assessment will be carried out using the NationalInstitute of Health (NIH) quality assessment tool. This will include assessment of quality around consideringthe risk of potential biases such as information bias, measurement bias or other confounding factors. Theprocess will be undertaken by two reviewers independently, with any disagreements resolved by consensus.For RCTs we will use Cochrane risk-of-bias tool for randomized trials. Strategy for data synthesisNarrative synthesis of the quantitative data along with thematic data synthesis of the qualitative data will bedone. The synthesis process will be carried out in three stages. The quantitative and the qualitative synthesiswill be carried out in parallel and then third synthesis where combining the results of the two previoussynthesis will take place.Meta-analysis will be performed on eligible studies included in this review. For outcomes includingprevalence/rate of non-adherence and non-persistence. Meta-analysis for prevalence of non-adherence and non-persistence:Pooled prevalence of non-adherence non-persistence along with their 95% Confidence Intervals will beestimated using random effects models. The results will be presented using forest plots. Heterogeneityamong the studies will be described using I² statistics along with ?² test 95% prediction intervals will also bepresented to show the variability of the pooled estimates. P value level < 0.05 will be considered as the levelof statistical significance. The random effects method will be used to measure the heterogeneity level.Measuring I² value and 95% Confidence Interval will show statistical heterogeneity. If there is sufficienthomogeneity across included studies, forest plots and the meta-analyses will be created using RevMan®.                               Page: 2 / 4PROSPEROInternational prospective register of systematic reviewsFactors/reasons/barriers associated with non-adherence will be analysed using World Health Organization’smultidimensional adherence model (MAM). We will categorise factors associated with non-adherenceaccording to the five domains of the MAM which are: 1) socioeconomic factors, 2) health care system-relatedfactors, 3) condition-related factors, 4) treatment-related factors, and 5) patient-related factors. Analysis of subgroups or subsetsSub-group analyses will also be undertaken if eligible studies are found for example for different diseasestates (for example: as AMD, diabetic retinopathy, myopia maculopathy). Contact details for further informationZahraa Jalalz.jalal@bham.ac.uk Organisational affiliation of the reviewUniversity of Birmingham Review team members and their organisational affiliationsDr Sajid Mahmood. Department of Pharmacy, Quaid-i-Azam University Islamabad. PakistanMr Haris Shahzad. School of Medicine, Institute of Clinical Sciences, University of Birmingham, Birmingham,UK.Dr Sayeed Haque. Institute of Applied Health Research University of Birmingham, Birmingham, UK.Professor Alastair K. Denniston. University Hospitals Birmingham NHS Foundation Trust, Queen ElizabethHospital BirminghamDr Vibhu Paudyal. School of Pharmacy, Institute of Clinical Sciences, University of Birmingham, Birmingham,UK.Assistant/Associate Professor Laura E. Downie. Department of Optometry and Vision Sciences, University ofMelbourne, Parkville, Victoria, AustraliaDr Lisa J Hill. School of Biomedical Sciences, Institute of Clinical Sciences, University of BirminghamDr Zahraa Jalal. School of Pharmacy, Institute of Clinical Sciences, University of Birmingham, Birmingham,UK. Type and method of reviewMeta-analysis, Systematic review Anticipated or actual start date28 October 2020 Anticipated completion date15 February 2021 Funding sources/sponsorsNone Conflicts of interest LanguageEnglish CountryEngland Stage of reviewReview Ongoing Subject index terms statusSubject indexing assigned by CRD Subject index termsHumans; Intravitreal Injections; Vascular Endothelial Growth Factors                                Page: 3 / 4PROSPEROInternational prospective register of systematic reviewsDate of registration in PROSPERO06 November 2020 Date of first submission25 October 2020 Stage of review at time of this submission Stage Started CompletedPreliminary searches Yes NoPiloting of the study selection process Yes NoFormal screening of search results against eligibility criteria No NoData extraction No NoRisk of bias (quality) assessment No NoData analysis No NoThe record owner confirms that the information they have supplied for this submission is accurate andcomplete and they understand that deliberate provision of inaccurate information or omission of data may beconstrued as scientific misconduct.The record owner confirms that they will update the status of the review when it is completed and will addpublication details in due course. Versions06 November 2020 PROSPEROThis information has been provided by the named contact for this review. CRD has accepted this information in goodfaith and registered the review in PROSPERO. The registrant confirms that the information supplied for this submissionis accurate and complete. CRD bears no responsibility or liability for the content of this registration record, anyassociated files or external websites. Powered by TCPDF (www.tcpdf.org)                               Page: 4 / 4

A systematic review and meta-analysis on treatment non-adherence and non-persistence to intravitreal anti-vascular endothelial growth factor therapy

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A systematic review and meta-analysis on treatment non-adherence and non-persistence to intravitreal anti-vascular endothelial growth factor therapy

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