Online randomised trials with children: A scoping review protocol

Introduction

Digital technologies are increasingly important in most aspects of daily life. Health research is especially well poised to benefit from the possibilities these technologies offer. In the last decade, there has been rapid growth in randomised controlled trials (RCTs) and clinical trials using remote and digital methodologies^1–3. The COVID-19 pandemic has spotlighted these remote methods by emphasizing how useful and innovative they can be. While traditional or centralised trials remain invaluable and necessary, decentralised trials may offer increased or different benefits to trial participants, researchers and health professionals. Decentralised trials include any study where data are collected in an alternative manner to a centralised trial. They often use alternative data collection locations, such as mobile or local health clinics, employ digital technologies, for example, wearable devices, or leverage online methods. Decentralised trials can potentially reach people in geographically remote areas, recruit larger and more diverse populations, improve trial participant retention, and may decrease trial costs and research waste^2,4,5.

Recruitment and retention of trial participants are two of the most common hurdles faced by research teams conducting trials with adults⁶. Paediatric trials often encounter the same hurdles as those involving adults and have additional challenges, especially those of a logistical and ethical nature. In their Cochrane systematic review discussing strategies to improve recruitment in trials, Treweek et al. identified the lack of, and critical need for, the “development and evaluation”^6(p22) of strategies for recruitment to paediatric trials. Pica and Bourgeois⁷ found that the two most common reasons researchers conducting paediatric RCTs cited for discontinuation or non-publication of a trial were participant recruitment and “conduct problems”^7(p3), which they defined as technical or logistical issues in completing the trial. They found that 19% of registered paediatric trials went unfinished, and a further 30% went unpublished, resulting in substantial research waste and undue burden to their participants⁷. RCTs can be onerous for participants, which can affect their willingness to enrol or remain in them⁸. Consent forms for RCTs are customarily long documents written in legal jargon, and participants often do not fully comprehend or read them⁹. Given the opportunities online trials offer both participants and researchers for increased engagement and recruitment, and decreased research waste, it is important to examine how these tools can and are directed at paediatric research.

Price et al.¹⁰ published a systematic review of online trials with adults in 2019, outlining the need for more rigorous reporting of methodologies, but after a preliminary search of MEDLINE, Epistemonikos, and the Cochrane Database of Systematic Reviews, no such reviews, systematic or otherwise, were identified for online trials involving children. Overall, paediatric trials are published less often than adult trials despite paediatric disease making up 26.2% of all-cause disability-adjusted life years¹¹. Groff et al.¹¹ found of 4146 published RCTs, only 14.2% (591) were conducted with children and 18.3% (761) enrolled both children and adults. This may be because working with children introduces the added challenges of gaining consent from caregivers and children, recruiting children from non-traditional family groups where all caregivers must give consent, and differing international laws regarding the age of health or digital consent. As exclusively online, decentralised trials are still not common, and those with children even less so, there is a gap in the literature describing the methods and processes employed by them. This scoping review will identify, describe, and characterize how online, decentralised trials with children are conducted. The objectives of this scoping review are: (a) to determine what methods and tools have been used to create and conduct online trials with children and (b) to identify the gaps in the knowledge in this field.

Early in the field, Bull et al.¹² conducted a randomised trial via social media with 16- to 25- year-olds. The researchers used multiple forms of recruitment, including online personal channels, blogs, websites, and in-person recruitment efforts and then conducted the rest of the trial online¹². This type of research is termed ‘hybrid’, meaning it is conducted partially online and partially through other channels. Systematic reviews have reported on internet-based trials developed for young people and adolescents to address tobacco-, alcohol-, and drug- use, but many of these have an offline component, such as recruitment or consent acquisition^4,13. Khan et al.¹⁴ published a systematic review of web-based interventions for children and young people with neurodevelopmental disorders and identified ten papers that met their inclusion criteria. Most of these trials were also hybrid as they recruited predominantly from clinics, but they demonstrate the trend towards decentralised trial development¹⁴.

While there are numerous publications from ‘hybrid’ trials, a growing body of work is being done entirely online. Notably, Rhodes et al.³ published recently on three of the studies they are developing or have already completed via their website ‘Discoveries Online’¹⁵. The paper describes their methods for overcoming the barriers involved in conducting their online studies using a webcam and participants’ guardians uploading their data for analysis by the research team³. Similarly, both MIT and Yale have developed websites for parents and their young children to take part in online trials, which can be accessed at the ‘LookIt’¹⁶ and the ‘Child Lab’ websites¹⁷, respectively. The website ‘Children Helping Science’¹⁸ hosts online trials from multiple groups, mostly academic, for parents and children to access and take part in. Gijbels et al.¹⁹ also reported on three ‘researcher-moderated’ virtual studies discussing the various elements needed to produce valid, trustworthy results. Although some trials will never lend themselves to being entirely online, the number that are accomplishing this is swiftly increasing.

Methods

Given the exploratory nature of our objectives, a scoping review is the most appropriate approach for this study²⁰. The protocol’s organization and development are informed by the Preferred Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR)²¹, the JBI Manual for Evidence Synthesis’ scoping review chapter²², and Peters et al.²³ and addresses the following steps: identifying a research question, identifying relevant studies, selecting studies, charting the data, and collating, summarising and reporting results. This scoping review protocol is registered with Open Science Framework (https://doi.org/10.17605/OSF.IO/WHJXY). A preprint of the protocol is available at medRXiv: doi: https://doi.org/10.1101/2022.04.15.22273742.

Discussion

This scoping review aims to identify and characterize how online randomised trials with children have been designed and implemented, and identify the gaps in the research. The review will employ a thorough and robust search strategy, chart the desired data, and summarise it in order to establish how these trials are managed. Our aim is that this review will allow for recommendations for future research directions and help guide researchers to improve the execution of these trials.

The challenges faced by researchers in these types of trials differ depending on the participants’ ages, the interventions used, and the primary objectives of the studies. Sensitivity, technological knowledge, and forethought are required to protect the child and find the appropriate digital tools for recruitment. In trials where maintaining the child's autonomy is critical, it can be a complex balance also to involve the caregivers to ensure legal and ethical integrity. Collecting and validating unique, individual data sets digitally requires additional verification steps compared to what a centralised trial might demand. Finally, and arguably most importantly, confirming informed consent and assent from both caregivers and children online calls for transparency, caution, and creativity in some cases. These additional challenges can be daunting for researchers to tackle; however, trialists have made innovative advances in online research with children in the last decade.

Our interest in this field stems from the ability of decentralised trials to reach a larger participant base, potentially decrease research waste, and expand inclusivity in paediatric trials. However, we acknowledge that internet-based trials inherently exclude some populations. There remains a digital divide through either disadvantage, infrastructure availability, or personal choice. We have chosen to focus on entirely online, decentralised trials to describe their benefits and challenges, and it is outside the scope of this work to address and include trials that are not internet-based.

Data availability