Objectives
This is a protocol for a Cochrane review (intervention). The objectives are as follows:
To determine if lower blood pressure (BP) targets (i.e. ≤ 130/85 mmHg), compared with standard BP targets (i.e. ≤ 140 to 160/90 to 100 mmHg) are associated with reduction in mortality and morbidity in people with elevated BP and diabetes mellitus.
Background
Description of the condition
Elevated blood pressure (BP), or hypertension (i.e. systolic BP ≥ 140 mmHg or diastolic BP ≥ 90 mmHg, or both) is independently associated with diabetes mellitus, and both conditions substantially increase cardiovascular disease risk (e.g. stroke, heart failure, myocardial infarction), chronic kidney disease, and all‐cause mortality [1, 2, 3, 4]. Globally, 589 million (one in nine) adults aged 20 to 79 years are living with diabetes mellitus [5], and hypertension is frequently detected in an estimated 70% to 80% of people with diabetes mellitus [6]. The concurrence of hypertension and diabetes mellitus may accelerate the development and progression of macrovascular (i.e. injury to the large blood vessels of the heart or brain due to a blockage or stoppage in blood flow, e.g. myocardial infarction, stroke) and microvascular (i.e. damage to the small blood vessels of the kidneys or eyes, e.g. nephropathy, retinopathy) complications [7, 8, 9, 10]. Consequently, lowering BP is important for reducing cardiovascular morbidity and all‐cause mortality among individuals with elevated BP and diabetes mellitus [1, 3, 4, 11, 12].
Description of the intervention and how it might work
Using antihypertensives to lower BP in people with diabetes mellitus and hypertension reduces the risk of cardiovascular complications [1, 8, 13]. Antihypertensives may reduce vascular stress (i.e. physical strain and injury to blood vessels) and endothelial dysfunction (i.e. damage to the thin layer of cells lining the blood vessels in the body), along with mitigating activation of the renin‐angiotensin‐aldosterone system which regulates BP and the volume of the blood, oxidative stress (i.e. an imbalance that leads to damage to the cells in the body), and systemic inflammation (i.e. a continual state of defence by the immune system) [1, 10]. A central question in treating hypertension for people living with diabetes is how low BP should be to achieve clinical benefit.
In clinical practice, a target BP is used as the goal of antihypertensive therapy and guides treatment decisions regarding the intensity of the antihypertensive regimen [14]. Lower systolic BP targets (e.g. < 120 mmHg) have been proposed for people with diabetes mellitus, who are at increased risk of cardiovascular disease and chronic kidney disease [15]; however, evidence on the clinical benefits of such targets compared with standard targets (e.g. <140 mmHg) remains inconsistent [16, 17, 18, 19].
The goal of lower BP targets would be a further reduction in cardiovascular disease risk and renal complications, compared with a standard BP target. However, achieving lower BP targets may require higher doses or a greater number of antihypertensive medications, or both, potentially increasing treatment costs and medication burden. Excessive BP lowering may also increase the risk of adverse cardiovascular outcomes [18, 20, 21, 22, 23, 24, 25, 26, 27].
Why it is important to do this review
Clinical practice guidelines recommend lowering BP in people with elevated BP and diabetes mellitus; however, the optimal BP targets in this population remain uncertain [28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39]. Lower BP targets have been recommended for individuals with elevated BP and diabetes mellitus because of their increased risk of cardiovascular disease and kidney disease outcomes [8, 10]. For example, guidelines, including those from Diabetes Canada, the European Society of Cardiology, and the American Heart Association/American College of Cardiology, recommend systolic BP targets below 130 mmHg in people with diabetes mellitus, particularly among individuals at high cardiovascular risk, including those with cardiovascular disease, subclinical organ damage, or chronic kidney disease [34, 35, 37].
In prior Cochrane reviews and meta‐analyses of randomised controlled trials (RCTs), treatment with BP targets < 130/85 mmHg among people with hypertension did not reduce mortality or cardiovascular morbidity compared with standard BP targets (systolic BP < 140 to 160 mmHg and diastolic BP < 90 to 100 mmHg). Similarly, sensitivity analyses in people with diabetes mellitus provided little to no evidence of differences for lower BP targets, compared to standard BP targets [40, 41].
Recent systematic reviews and meta‐analyses report heterogeneous findings regarding the effects of intensive BP lowering in people with diabetes mellitus. While some reviews suggest that lower systolic BP targets may reduce the risk of cardiovascular mortality, major cardiovascular events, including fatal and non‐fatal stroke [4, 27, 42, 43], evidence regarding all‐cause mortality, chronic kidney disease, and other cardiovascular events remains inconsistent [42, 44, 45, 46]. Current evidence also suggests that lowering systolic BP to between 130 and 140 mmHg may provide cardiovascular benefit, while intensive lowering below this threshold may offer limited additional benefit [27, 47].
Given the continued uncertainty regarding optimal BP targets in people with elevated BP and diabetes mellitus, this review aims to investigate the benefits and harms of lower BP targets (≤ 130/85 mmHg), compared with standard BP targets (systolic BP ≤ 140 to 160 mmHg and diastolic BP ≤ 90 to 100 mmHg). In addition, this review will complement related reviews evaluating BP targets in adults with hypertension [41], chronic kidney disease [48], and cardiovascular disease [49].
Objectives
To determine if lower blood pressure (BP) targets (i.e. ≤ 130/85 mmHg), compared with standard BP targets (i.e. ≤ 140 to 160/90 to 100 mmHg) are associated with reduction in mortality and morbidity in people with elevated BP and diabetes mellitus.
Methods
We will follow the Methodological Expectations for Cochrane Intervention Reviews (MECIR) when conducting the review [50], and PRISMA 2020 for reporting [51]. We will report amendments to the protocol and the reason for the amendment. This may include decisions about eligibility criteria, subgroup analyses, and any parts of the protocol that were not implemented. We will document this information in the 'Differences between protocol and review' section of the review or as supplementary material.
Criteria for considering studies for this review
Types of studies
We will consider only RCTs (i.e. randomisation at the individual level), and include published trials, conference abstracts, and other unpublished trials, irrespective of the language of publication.
Cross‐over trials will not be eligible for inclusion due to the possibility of carryover effects distorting effect estimates, as BP target interventions are likely to have sustained effects.
Types of participants
We will include non‐pregnant and non‐lactating adults (≥ 18 years) with diabetes mellitus and elevated BP (i.e. systolic BP ≥ 140 mmHg or diastolic BP ≥ 90 mmHg, or both) [3], documented in a standard way on at least two occasions, or already receiving treatment for elevated BP or treatment for nephropathy that includes BP‐lowering drugs. We will include trials if people with elevated BP diabetes mellitus were randomised to one of the two BP targets described below, irrespective of their BP at enrolment, any concomitant disease including baseline cardiovascular risk, or geographical location.
We will consider studies that include a subset of eligible participants for inclusion. If data for the eligible subgroup are not reported separately, we will attempt to contact the corresponding author to retrieve relevant data, including age‐stratified data for adults (≥ 18 years), if applicable. If trial authors are unable to provide subgroup‐specific data, or correspondence is not successful, we will categorise such studies as awaiting classification [52].
Types of interventions
We will include trials of individuals randomised to a lower (≤ 130/85 mmHg) compared with a standard (≤ 140 to 160/90 to 100 mmHg) systolic/diastolic BP target. We will include trials irrespective of dose, type, duration, frequency, delivery intensity, or route of administration of medications administered as part of the intervention. For trials that report mean arterial blood pressure (MAP), a MAP < 107 mmHg, 102 mmHg, or 98 mmHg will be considered similar to systolic/diastolic BP < 140/90 mmHg, 135/85 mmHg, or 135/80 mmHg, respectively [53].
Studies that include co‐interventions (e.g. antihypertensive or antidiabetic medications) will be eligible if the same co‐intervention is administered in both the intervention and comparison group.
Outcome measures
Critical outcomes
All‐cause mortality.
Number of people with at least one serious adverse event (i.e. any unfavourable medical occurrence that is considered serious, is life‐threatening/results in death, requires hospitalisation or prolongation of hospitalisation, or results in significant disability [54]).
Total cardiovascular serious adverse events.
Important outcomes
Systolic BP achieved (mmHg).
Diastolic BP achieved (mmHg).
Withdrawals due to adverse effects (i.e. number or proportion of participants who discontinued treatment due to adverse effects).
Number of antihypertensive drugs needed per participant (i.e. average number of antihypertensive medications required per participant in the intervention and control groups).
Timing of outcome assessment
For all‐cause mortality, number of people with at least one serious adverse event, total cardiovascular serious adverse events, and withdrawals due to adverse effects, we will extract cumulative events occurring at any time from randomisation to the primary endpoint of the trial. For systolic BP achieved, diastolic BP achieved, and number of antihypertensive drugs per participant, where outcomes are assessed at multiple time points, we will use the outcome measurement at the primary endpoint of the trial.
Search methods for identification of studies
Electronic searches
We will search the following databases without language or publication status restrictions:
Cochrane Hypertension Group Specialised Register via the Cochrane Register of Studies (CRS‐Web);
Cochrane Central Register of Controlled Trials (CENTRAL) via the Cochrane Register of Studies (CRS‐Web);
Ovid MEDLINE ALL (2013 to present);
Ovid Embase (2013 to present);
US National Institutes of Health Ongoing Trials Register ClinicalTrials.gov (www.clinicaltrials.gov);
World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) (apps.who.int/trialsearch).
The Cochrane Hypertension Information Specialist (CIS) will model the search strategies for databases on the core search strategy designed for MEDLINE. Where appropriate, the CIS will combine the subject strategy adaptations with the sensitivity and precision‐maximising search strategy designed by Cochrane for identifying RCTs (as described in the Cochrane Handbook for Systematic Reviews of Interventions) [55]. We will run searches of MEDLINE and Embase from 2013, to capture trials published since the last published version of this review [40]. As records from those databases, as well as from ClinicalTrials.gov and WHO ICTRP, are regularly added to CENTRAL and the Hypertension Specialised Register, we will search the other databases listed above from 2023 to present. We will also incorporate results from a broader, related review on BP targets not limited to people with diabetes that was updated in 2020 and which is currently being updated in parallel with this review [41]. The MEDLINE search strategy is presented in Supplementary material 1.
Searching other resources
We will check the reference lists of included studies and any relevant systematic reviews identified for further references to relevant trials.
We will check the included studies for retractions and errata via PubMed (www.ncbi.nlm.nih.gov/pubmed) and the Retraction Watch Database (retractiondatabase.org), report the search dates in the review, and exclude retracted studies.
We will search Epistemonikos (www.epistemonikos.org) for related systematic reviews.
We will attempt to contact authors of relevant papers regarding any further published or unpublished work.
We will attempt to contact authors of trials reporting incomplete information to provide the missing information.
We will search Clarivate Web of Science for papers that cite studies included in the review.
Data collection and analysis
It is unlikely that review authors will be involved in trials included in this review. Any review authors who are involved in the publication of an included study will be excluded from study screening, data extraction, risk of bias assessment, GRADE assessment, and resolution of any related disagreements [50].
We will identify English translation support for trials in languages other than English from individuals fluent in the relevant language. We may also use translation software, including Google Translate, or identify volunteers via Cochrane Engage [56] to assist with translation, screening, and/or data extraction, if applicable. To ensure accuracy, a review author will verify all translated study information or study data. If an eligible trial includes multiple studies, we will collate the studies and treat merged studies as a single study with one identifier [57].
Selection of studies
Three review authors (DL, GG, DS) will independently evaluate trial eligibility via title and abstract screening using Covidence [58]. The same three review authors will independently perform full‐text screening, with any disagreements resolved by discussion with the senior review author (WT). If limited information is reported on the study design, or eligible studies are available as conference abstracts only, we will attempt to contact trialists to request additional study information.
We will report records identified, included, or excluded, in addition to the reasons for trial exclusion, in the PRISMA 2020 flow diagram [51].
Data extraction and management
Three authors (DL, GG, DS) will independently extract data from the included trials using a data extraction form that we will pilot‐test with at least two included studies. If available, we will extract information on study characteristics (e.g. trial funding, study duration, study location/setting, publication date, inclusion criteria, and exclusion criteria), study methods (e.g. randomisation methods, allocation concealment, sample size), study participants (e.g. age, gender/sex, PROGRESS‐Plus characteristics (e.g. socioeconomic status, race/ethnicity/culture/language, geographical location) [59], baseline BP, existing comorbidities, number of participants randomised, number of participants lost to follow‐up/withdrawn), intervention (e.g. lower, intensive, or tight BP targets (e.g. systolic BP < 120 mmHg)), comparator (e.g. normal, usual, or standard BP targets (e.g. systolic BP < 140 mmHg)), and outcome data. If applicable, we will contact trial authors to retrieve missing or additional study information. Any discrepancies will be resolved by discussion among review authors or by recourse to the senior review author (WT). One review author (DL) will enter all study data into RevMan software [60], which a second review author (GG) will verify.
Risk of bias assessment in included studies
Two of three review authors (DL, GG, DS) will independently assess risk of bias in the included studies using Cochrane's RoB 1 tool, following the methods described in the Cochrane Handbook for Systematic Reviews of Interventions [61]. We will assess the risk of bias based on the following risk of bias domains: sequence generation, allocation concealment, blinding (participants, personnel, caregivers), incomplete outcome data, selective outcome reporting, and other sources of bias. We will contact trial authors to retrieve relevant missing information or for clarification. We will assess methodological quality across all six risk of bias domains and assign an overall judgement of low, high, or unclear risk of bias. We will use Microsoft Excel to document the risk of bias judgements [62]. Any disagreements between review authors will be resolved by the senior review author (WT) or by recourse to a third review author (JW).
Measures of treatment effect
Dichotomous data
We will report dichotomous data (i.e. all‐cause mortality, number of people with at least one serious adverse event, total cardiovascular serious adverse events, withdrawals due to adverse effects) using risk ratio (RR) and 95% confidence intervals (CIs). When there is a statistically significant difference between treatments for any outcome, we will estimate the absolute risk reduction (ARR) and absolute risk increase (ARI). In order to estimate the number of patients needed to treat to provide one additional benefit or to produce one additional harm, we will calculate the number needed to treat for an additional beneficial outcome (NNTB) and the number needed to treat for an additional harmful outcome (NNTH), respectively.
Continuous data
For continuous outcomes (i.e. systolic BP achieved, diastolic BP achieved, number of antihypertensive drugs needed per participant), we will extract the mean and standard deviation (SD) [63]. If effect measures are not reported on the same scale, we will convert data into the required direction and format to approximate the mean and SDs. If outcomes are measured on the same scale, we will summarise data using mean difference (MD) and 95% CIs. If different scales are used to measure the same outcome, we will estimate the standardised mean difference (SMD) and 95% CIs.
If applicable, for trials with multiple time points, we will consider the assessment time point immediately after trial completion [64].
Unit of analysis issues
The randomised participant will be the primary unit of analysis according to the intention‐to‐treat principle.
Cross‐over trials
We will not include cross‐over trials in this review.
Multiple intervention arms
In included trials with more than two intervention groups, we will only include arms that meet the a priori inclusion criteria. If intervention arms are sufficiently similar, we will form a single pair‐wise intervention group [65]. We will report all intervention groups in the table of 'Characteristics of included studies' table.
Dealing with missing data
We will attempt to contact trial investigators for missing information or clarification as needed, including for unpublished data or studies available as abstract only [63]. We will contact the corresponding author via email, sending two email reminders if needed. If we receive no response, or trial investigators are unable to provide the missing information, we will compute summary data from relevant statistics reported.
In cases where we are unable to retrieve data or compute data appropriately for an outcome of interest, and we determine that this leads to a high risk of bias, we will report the extent of missingness and investigate its effect on the certainty of evidence. We will also address the implications of missingness on the findings of the review in the 'Discussion' section.
Reporting bias assessment
To assess selective reporting bias, three review authors (DL, GG, DS) will independently search trial registries, associated study protocols, and clinical study reports to evaluate potential discrepancies in the methods or outcomes of included studies, if applicable. If at least 10 studies are included in the meta‐analysis, we will use funnel plots to assess the risk of publication bias. We will investigate funnel plot asymmetry through visual inspection and conduct the Egger's test (P values < 0.10 to be identified as statistically significant) where appropriate to explore the presence of small‐study effects [66].
Synthesis methods
Quantitative synthesis of outcomes will be based on an intention‐to‐treat analysis. We will pool dichotomous outcomes using the Mantel–Haenszel method and report results as RRs with 95% CIs. We will analyse continuous outcomes using the inverse‐variance method and report results as MDs (or SMDs, where applicable) with 95% CIs.
We will conduct meta‐analyses for relevant outcomes when participants, interventions, and comparisons are sufficiently similar for pooling to make sense. We will use RevMan software to synthesise and analyse data [60]. We will use a fixed‐effect meta‐analysis to combine the same outcomes across included trials investigating a similar underlying effect, that is the methods, interventions, and participant characteristics, including setting, are judged to be sufficiently similar. However, if there is clinical (e.g. participants, interventions, comparisons, outcomes) and methodological (e.g. study design limitations) heterogeneity, we will use the random‐effects model to estimate the average intervention effect. We will use the Restricted Maximum Likelihood estimator to estimate between‐study variance (Tau²). When there are at least three studies, and the estimate of heterogeneity is more than zero, we will use the Hartung‐Knapp‐Sidik‐Jonkman method to calculate a CI for the effect estimate. On the other hand, in pooled analysis of two studies, or where the estimate of heterogeneity is equal to zero, we will use the Wald‐type method [63].
If meta‐analysis is inappropriate or not possible, we will report the synthesis of intervention effects using the Synthesis Without Meta‐analysis (SWiM) guideline [67].
Investigation of heterogeneity and subgroup analysis
To test for heterogeneity of treatment effect between trials (i.e. statistical heterogeneity), we will use the Chi² and I² statistics [68]. We will consider a Chi² value less than 0.05 or an I² value greater than 50% as indicative of significant statistical heterogeneity.
We will examine methodological heterogeneity by assessing differences in study design and risk of bias across included studies. We will evaluate clinical heterogeneity by considering diversity in participant characteristics, interventions and comparators, outcome definitions, and outcome assessment time points.
Where substantial statistical, clinical, and/or methodological heterogeneity, is identified, we will explore potential reasons for it through sensitivity and subgroup analyses.
We will use critical outcomes to perform the following subgroup analyses including at least 10 trials, irrespective of the risk of bias, when possible.
BP targets: systolic BP achieved versus diastolic BP achieved.
Age: < 65 years versus ≥ 65 years versus not reported.
Duration of elevated BP/hypertension: < 10 years versus ≥ 10 years versus not reported.
Number of antihypertensive medications: < 5 versus ≥ 5.
Duration of diabetes mellitus: < 10 years versus ≥ 10 years versus not reported.
Sex: male versus female versus mixed versus not reported.
For subgroup effects examined statistically, we will assess differences between subgroups using the formal test for subgroup differences available within RevMan and report the Chi² value, P value, and interaction test I² statistic, to determine whether these effects would lead to differing clinical interpretations [63].
Sensitivity analysis
We plan to assess the robustness of effect estimates in the review through the following sensitivity analyses [50, 63].
Risk of bias: excluding studies judged to have an overall high risk of bias.
Attrition: excluding studies with high rates of missing data (> 20%).
Funding: excluding industry‐sponsored trials.
If the resulting effect estimate leads to a different clinical interpretation compared to the original effect estimate, we will judge results to be sensitive to these exclusions.
Certainty of the evidence assessment
We will use the GRADE approach to investigate the certainty of the evidence for each estimate of intervention effect for the following outcomes:
all‐cause mortality;
number of people with at least one serious adverse event;
total cardiovascular serious adverse events;
withdrawals due to adverse effects [69].
We will evaluate the following domains: study design limitations/risk of bias, consistency of effect, imprecision, indirectness, and publication bias. The certainty of evidence may be downgraded by one level for serious limitations or by two levels for very serious limitations, for each domain. Hence, for each outcome, we will assess the certainty of the evidence as high, moderate, low or very low.
Two review authors (DL, GG) will independently perform GRADE assessments, with any disagreements/discrepancies resolved by consensus or through discussion with the senior review author (WT) or a third review author (JW). We will provide justification for our judgements, and document a summary of the amount of data, the magnitude of the effect size, and the overall certainty of the evidence, in the summary of findings table.
Equity considerations
We will extract any relevant equity‐related factors that may influence clinical outcomes and how BP target strategies are implemented, including age, sex/gender, and characteristics captured within the INCLUDE Ethnicity framework and PROGRESS‐Plus framework (e.g. Place of residence, Race/ethnicity/culture/ancestry, Occupation, Gender, Religion, Education, Socioeconomic status, and Social capital, plus other context‐specific factors including comorbidity burden) [59]. We will follow guidance by the PRO EDI Initiative to report these characteristics in the 'Characteristics of included studies' table [70], and discuss the availability and distribution of equity‐related data in the 'Equity assessment' section of the final review. We will not conduct specific subgroup analyses by equity‐relevant factors; however, we will describe any relevant findings narratively in the 'Results' and 'Discussion' sections of the review.
Where reported, we will narratively describe the representation of diabetes types (e.g. type 1 versus type 2 diabetes mellitus) across included studies and consider whether this affects the applicability of the evidence to people with type 1 or type 2 diabetes mellitus. If sufficient data are available, we will explore whether findings differ according to diabetes type.
Consumer involvement
Throughout the review process, we will engage family physicians and other clinical decision‐makers involved in the provision of care for individuals with elevated BP or diabetes mellitus, or both. This may include stakeholder input by helping to contextualise the planned analyses from a clinical and policy perspective. We will seek feedback during interpretation of the findings to enhance the relevance and applicability of the review. Where appropriate, we will also explore opportunities to incorporate participant or caregiver perspectives, including feedback on PROGRESS‐Plus considerations [59], and review of the Plain language summary for readability.
Supporting Information
Supplementary materials are available with the online version of this article: 10.1002/14651858.CD016392.
Supplementary materials are published alongside the article and contain additional data and information that support or enhance the article. Supplementary materials may not be subject to the same editorial scrutiny as the content of the article and Cochrane has not copyedited, typeset or proofread these materials. The material in these sections has been supplied by the author(s) for publication under a Licence for Publication and the author(s) are solely responsible for the material. Cochrane accordingly gives no representations or warranties of any kind in relation to, and accepts no liability for any reliance on or use of, such material.
Supplementary material 1 Search strategies
New
Additional information
Acknowledgements
We would like to thank Jose Agustin Arguedas, who wrote the initial version of this protocol.
We would like to thank Viriam Leiva, who contributed to the initial version of this protocol.
The authors would like to acknowledge the Cochrane Hypertension Group's advice and assistance.
Editorial and peer‐reviewer contributions
The following people conducted the editorial process for this article:
Sign‐off Editor (final editorial decision): Rupa Sarkar, Editor‐in‐Chief, Cochrane;
Managing Editor (selected peer reviewers, provided editorial guidance to authors, edited the article): Sue Marcus, Cochrane Central Editorial Service;
Editorial Assistant (conducted editorial policy checks, selected peer reviewers, collated peer‐reviewer comments, and supported the editorial team): Cynthia Stafford, Cochrane Central Editorial Service;
Copy Editor (copy editing and production): Lisa Winer, Cochrane Central Production Service;
Peer reviewers (provided comments and recommended an editorial decision): Dr Shweta Agrawal, Assistant Professor, Periodontology and Oral Implantology, B P Koirala Institute of Health Sciences, Nepal (patient and public review), Lindsay Robertson, Cochrane (methods review), Jo Platt, Central Editorial Information Specialist (search review).
Contributions of authors
Jose A Arguedas developed the basis for and wrote the initial version of the protocol.
Viriam Leiva contributed to development of the initial version of the protocol.
Doreen Y Larvie developed and was responsible for writing the current draft of the protocol.
Anshula Ambasta provided methodological input and reviewed and approved the final version of the protocol.
Ciprian Jauca provided methodological input and reviewed and approved the final version of the protocol.
Douglas Salzwedel developed the search strategy, provided methodological input, and reviewed and approved the final version of the protocol.
James Wright helped formulate the idea for the protocol, assisted with methodological expertise, and reviewed and approved the final version of the protocol.
Guillaume Grenet provided methodological input, clinical expertise, and reviewed and approved the final version of the protocol.
Colleen Fuller provided clinical input regarding the equity framework and applicability considerations, and reviewed and approved the final version of the protocol.
Wade Thompson contributed to the development of the Background and Methods sections, and reviewed and approved the final version of the protocol.
Declarations of interest
Doreen Y Larvie declares no conflicts of interest.
Anshula Ambasta declares no conflicts of interest.
Ciprian Jauca declares no conflicts of interest.
Douglas Salzwedel declares no conflicts of interest.
James Wright declares no conflicts of interest.
Guillaume Grenet declares no conflicts of interest.
Colleen Fuller declares no conflicts of interest.
Wade Thompson declares no conflicts of interest.
Sources of support
Internal sources
No sources of support provided
External sources
No sources of support provided
Registration and protocol
This protocol is an update to a protocol that was initially registered in the Cochrane Database of Systematic Reviews [71].
Data, code and other materials
Data sharing is not applicable to this article as it is a protocol, so no datasets were generated or analysed.
Disclosure of artificial intelligence use
We will not use AI platforms, systems, or tools for any review process or in the preparation of the manuscript.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Supplementary material 1 Search strategies
Data Availability Statement
Data sharing is not applicable to this article as it is a protocol, so no datasets were generated or analysed.