We will use the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocol PRISMA-P 2015 Checklist (Multimedia Appendix 1) and the Cochrane protocol guide to develop the protocol. In order to establish Medical Subject Headings (MeSH), subject heading, and keywords (Multimedia Appendix 2), a clear research question will be developed and a Population, Intervention, Comparator, and Outcome framework will be completed. To provide replicable and transparent methods, we will describe the following 6 stages in detail: (1) Literature search; (2) article selection; (3) data extraction; (4) quality appraisal; (5) data analysis; and (6) data synthesis.

Systematic scoping reviews intend to promptly gather and provide evidence on essential concepts pertaining to broad research subjects [26]. As opposed to systematic reviews that answer narrow and specific questions, scoping reviews may answer broad questions and provide evidence that lie outside of the effectiveness of an intervention [25]. Thus, where systematic reviews may not be conducted due to evidence deficiency, systematic scoping reviews have been proven to be valuable [27].

Although scoping reviews do not require a strict methodological approach, methodological frameworks have been developed by Arksey and O’Malley in 2005 and by Levac, Colquhoun, and O’Brien in 2010 [26,27].

Following preliminary and exploratory reading on somatic and gene therapy trials involving pediatric patients with ophthalmic conditions, no synthesis of evidence around the technological advances used in these trials was found, demonstrating a research gap. In light of this evidence paucity, we formulated the following research question: What are the range of health care information and communication technologies applied to achieve patient-centered care in children undergoing somatic and gene therapies for ocular diseases?

We will systematically searche MEDLINE/PubMed, Embase, and Scopus through the Imperial College London library. Subsequent to the identification of MeSH, subject headings, and keywords, the medical librarian at Imperial College London will be asked to review the search strategy. Search terms will consist of MeSH and keywords linked to (1) pediatric population; (2) digital technologies; (3) traditional care; and (4) outcomes. No restrictions will be applied on publication date, publication status, or study location. Subsequent to the MEDLINE/PubMed search, the search strategy will be converted to Embase and Scopus searches. The search strategy may be requested from the first author once finalized. Following database searches, results will be imported to EndNote, a reference software. Once the included studies are determined, we will thoroughly search their bibliographic citations to identify supplemental relevant studies.

The following Population, Intervention, Comparator, and Outcome framework was developed for the purpose of the review’s research question.

EndNote X8.2 (Clarivate Analytics) will be used for the collection of bibliographic references. Following the assemblage of references following database searches, duplicates will be removed using a deduplication tool on the bibliographic software. Where duplicates are not removed automatically by means of the EndNote software, reviewers will examine and compare findings thoroughly. Upon agreement, duplicates will be removed. Authors of included studies will be contacted if required.

In the first phase of the selection process, 2 reviewers will independently perform screening of titles and abstracts. Following elimination of papers with discernible ineligibility, eligibility of the remaining papers will be assessed in the second phase of the study selection process through full-text reading. Disagreements on study eligibility will be resolved through discussion between reviewers. If no consensus is reached, a third reviewer will assist in the selection process. In the final phase of the selection process, bibliographic references of included studies will be reviewed, thereby identifying additional potentially relevant papers. A PRISMA flow diagram will be used to illustrate the selection process, as well as exclusion reasons, demonstrating the review’s transparency and replicability.

The methodological quality of included studies will be assessed by 2 independent reviewers. If, following discussion, reviewers cannot reach consensus on the risk of bias pertaining to included studies, a third reviewer will be asked to aid in decision making.

To assess the methodological quality of included studies, the Cochrane Collaboration Risk of Bias Tool will be applied. The following 6 criteria will be evaluated in each included study: (1) random sequence generation (selection bias); (2) allocation concealment (selection bias); (3) blinding (performance bias and detection bias); (4) incomplete outcome data (attrition bias); (5) selective reporting (reporting bias); and (6) other bias.

Following criteria assessment, risk of bias of included studies will be determined, and studies will be judged as “high risk,” “low risk,” or “unclear risk.” To illustrate the methodological quality of the review’s included studies, a Risk of Bias Graph and a Risk of Bias Summary will be presented.

Subsequent to data extraction, results will first be synthesized numerically or by means of a descriptive statistic. Providing an overview of the quantity and type of included papers, the descriptive analysis will consist of the following information: (1) intervention type, control group, sample size; (2) characteristics of the population involved including, age, gender, ocular disease targeted, location; and (3) intervention outcomes including, health treatment and process outcomes

Results will also be synthesized narratively. Using the PRISMA-P 2015 Checklist, data will be presented in a tabular format to supplement the narrative synthesis. This will consist of a synthesis of all included papers that will enable guidance and allow assessment of potential heterogeneity between included studies. To ensure the reliability of our findings, narrative synthesis reporting will be conducted in a transparent manner.

Providing a holistic analysis of the intervention, the quality of the studied intervention will be determined by evaluating through outcome measures, as well as satisfaction of health care professionals and patients and the complexity of the intervention. Recommendations regarding future research, policy, and practice will be developed by the authors. Details of this stage are currently being developed by the research team and may be subjected to iterations or further updates following review commencement. We intend to finalize this stage in December 2017.

The review intends to provide evidence on technology applied to genetic and somatic cell therapy trials in children with ocular diseases. In addition to developing recommendations that will enable collaboration between key stakeholders, we aim to provide a comprehensive overview that will facilitate decision making and improve pediatric health care. Thus, we aspire to move evidence into practice, or translate research into medical practice, through the circulation of our review findings. We predict that the review will also provide insight to other researchers as additional research gaps that may need to be addressed will be identified by means of evidence gathered in the proposed review.

Responding to a research gap, the review will provide evidence on technological advances related to somatic and gene therapy trials in children. We will perform rigorous and systematic search of multiple health and medicine databases. No restrictions applied on publication date, status, or location. The review will identify unmet needs of pediatric patients with ophthalmologic disorders, thereby informing policy makers and donors. On completion of the review, additional research gaps will be identified, thereby guiding the conduct of future systematic reviews. Review findings will enhance the management of pediatric patients undergoing somatic and gene therapies by identifying digital technologies that improve patient safety, engagement, and satisfaction. The effectiveness of digital technologies on treatment outcomes will be assessed.

Language restrictions will be imposed (non-English papers will be excluded). As the review will outline the existing electronic processes applied in somatic and gene therapy trials for children, quality appraisal will not be conducted on identified papers.

We believe consulting experts will provide valuable insight regarding the development of recommendations, challenges that need to be addressed, and potential solutions. In addition to consulting pediatric somatic and gene therapy experts and researchers, regulatory authorities and eHealth experts at Imperial College London, the University of Oxford, and Stanford University will be consulted throughout the conduction of the review. This will allow the reviewers to obtain guidance that has not been provided in the searched literature. Their feedback on the protocol and review findings will be requested prior to completion of the final report. Through multiple consultations, we intend to engage subject experts in the development and design of the systematic review in addition to the subsequent action plan. It is intended that by means of various consultations, we will develop strategies facilitating the uptake of novel technological advancements by researchers, health care practitioners, and patients in the field of personalized medicine.

The review intends to provide evidence on the digital technologies used in data analysis and interpretation in pediatric somatic and gene therapy trials. The review intends to develop and circulate strategies to promote their uptake, enhance patient safety and enhance development of personalized medicine within health care systems. In order to enable informed decision-making skills of consumers and improve health care quality and access, results will be actively communicated to health care providers, patients, and other relevant stakeholders. To ensure transparency, replicability, and applicability of the proposed systematic review, we intend to distribute our work from the initial stage (protocol) to the final product.

Genomics is reshaping health systems. While advancements in technologies are enabling the personalization and customization of care, there is paucity around the evidence of their utilization and impact in somatic and gene therapy trials in children. As eHealth and mobile health resources have the potential to empower patients through enhancement of decision-making skills and patient engagement, the review intends to exhibit how their utilizations may be maximized in pediatric somatic and gene therapy trials to improve the quality of pediatric ophthalmology.