This protocol has been written in accordance with the recommendation of Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA-P) 2015 Protocol (24).
Main Objective of the Review
The purpose of this study is to define the key features of rRCTs by identifying RCTs that utilise a registry, establish the common registry linked trial activities in each rRCT and categorise them.
Eligibility Criteria
Study designs
Registry based randomised controlled trials, specifically utilising a patient registry (10) to facilitate key clinical trial procedures will be eligible for inclusion. This can include any clinical trial procedure or process embedded within the study protocol, clearly described within the trial publication. Both ongoing and completed studies will be eligible for inclusion. Articles published in the English language only will be included in this systematic review. No other filters will be applied (Table 1).
Participants
Studies including adult and children participants (including the parents/guardians of children) enrolled to completed or ongoing rRCTs are eligible. There is no age limit for participants.
Interventions
rRCTs investigating the treatment of any disease/pharmacological and non-pharmacological agents will be included. Randomisation within trials can be at the individual or cluster level.
Comparator
Studies will not be included or excluded from this systematic review based on comparator or control.
Outcome of Interest
Studies will not be included or excluded based on clinical outcome measures however studies must utilise a patient registry to acquire at least one study outcome measure.
Table 1. Selection Criteria of Published Studies Eligible for Review
Inclusion Criteria:
- rRCTs incorporating a patient registry to facilitate key trial procedures.
- rRCTs where randomisation is at individual or cluster level.
- rRCTs including collection of at least one outcome measure from a patient registry.
Exclusion Criteria:
- Non randomised trials.
- Trials using public health registries.
- Primary trials only - RCTs accessing registries to acquire long term follow up data will be excluded.
Search Methods
Electronic Searches
The following databases will be searched, using a combination of subject headings, MeSH and free text terms:
- MEDLINE/PubMed EBSCO
- EMBASE (OVID interface)
- CINAHLPlus EBSCO
- Scopus - Elsevier
- CENTRAL
- Cochrane Library (Cochrane Database of Systematic Reviews)
Additional Searches
The following additional sources will be searched:
- WHO International Clinical Trials Registry Platform (ICTRP): A search of the ICTRP will be conducted to extract any planned or ongoing trials.
- Reference Lists: The reference lists of included studies (snowballing-backward), citing articles (snowballing-forward) and reference lists of published systematic reviews in the field will be completed.
- Google Scholar: Google Scholar will be searched to ensure that relevant articles were not missed.
Search Strategy
The initial search be completed in PubMed and will be based on the following syntax, using the following terms:
Search terms will be adapted as appropriate for each database. The literature search and screening process will take place over six weeks. The completed search will be repeated prior to submission of the manuscript to ensure the most up to date rRCTs, if published, are retrieved and included.
Study Screening
NOS will systematically compile and import titles and abstracts of all electronic search results to Endnote, separating each database by group. Duplicate studies will be electronically removed by means of EndNote software. The remaining studies will be imported to Rayyan QCRI Software for screening (25). The screening process will involve two reviewers (NOS and FS). Both reviewers will independently review all titles, abstracts and relevant full texts for eligibility. Should discord arise during the literature screening process, the reviewers will meet to resolve any disagreement by consensus and where this is not possible a third reviewer (JE) will be consulted. All ambiguous citations will be included for full text review and where possible study authors will be contacted for clarification.
Data Extraction and Management
Following screening, all data regarding registry based trial activities will be extracted and imported to a standardized data extraction form. Data to be extracted is included in Table 2. Trial authors will be contacted where clarification is required in cases where relevant data is not available within an article. Where contact is not possible, ambiguous information as detailed in articles will be highlighted and included in the data extraction table.
Table 2
Variable |
1. Trial Title, Author and Year |
|
2. Disease Under Investigation
|
|
3. Planned Sample Size (PSS)
or Total Enrolled (TE)
|
|
4. Registry Name
|
|
5. Registry Description
|
|
6. Role of Registry within Trial
|
|
7. Role of Registry within Trial
|
|
8. Indicators of Study Quality
|
Study Quality Assessment
NOS and FS will independently assess risk of bias for each included study, using Version 2 of the Cochrane risk-of-bias tool for randomised trials (RoB 2) (26). The risk of bias will be assessed according to the following domains: allocation concealment, blinding of participants and personnel, blinding of outcome assessment, incomplete outcome data, selective outcome reporting, similarity of baseline characteristics, and any other bias. A proposed judgement about the risk of bias arising from each domain is generated by an algorithm, based on answers to the signalling questions. Judgement can be 'Low' or 'High' risk of bias, or can express 'Some Concerns’. We will not exclude studies on the grounds of their risk of bias, but will clearly report the risk of bias when presenting the results of the studies.
Data Synthesis
A thematic analysis of the data will be conducted. This approach, known as a narrative synthesis, will be adopted based on the Guidance on the Conduct of Narrative Synthesis in Systematic Reviews (27). We will focus on the reported, documented information within each article, specifically regarding registry linked trial activities, conducting a thematic analysis of the study text, to define the key, critical features of rRCTS. We will perform a meta-analysis if appropriate, but we expect interventions will be substantially different between studies therefore it is unlikely a meta-analysis will be undertaken.