Criteria for considering studies for this review
Types of studies
We will include randomised controlled trials (RCTs), irrespective of publication status or language of publication. Non-parallel design studies (e.g. split-mouth) are not appropriate for this type of investigation, because they may introduce 'carry-across effects' which potentially allow interventions to have effects on experimental units other than those which they were assigned to. There will be no restriction in the length of follow-up for inclusion.
Types of participants
We will include studies of individuals, of any age, receiving orthodontic treatment using fixed appliances with the adjunctive use of non-surgical interventions to accelerate tooth movement. Studies including patients treated with orthognathic surgery, or involving participants with cleft lip or palate or other craniofacial syndromes or deformities, will be excluded.
Types of interventions
Active interventions: Any form of fixed appliance orthodontic treatment incorporating the use of non-surgical adjunctive interventions for accelerating tooth movement.
Control: Any form of fixed appliance orthodontic treatment without the use of non-surgical adjunctive interventions for accelerating tooth movement.
Types of outcome measures
Harms arising during the course of orthodontic treatment including gingival and periodontal problems, anchorage loss and iatrogenic damage to teeth (e.g. caries or decalcification, root resorption).
Patient-centred outcomes: impact of fixed appliances on daily life, quality of life and pain experience.
Improvement in occlusion adjudged using Peer Assessment Rating (PAR) or other validated scale recorded at the completion of active orthodontic treatment.
Prolonged stability of treatment outcome using validated methods (e.g. Little's irregularity index).
Cost of treatment.
Safety of the adjunctive intervention.
Search methods for identification of studies
For the identification of studies included or considered for this review, we will develop detailed search strategies for each database that is to be searched. These will be based on the search strategy developed for MEDLINE but revised appropriately for each database (Appendix 1).
We will search the following databases:
the Cochrane Oral Health Group's Trial Register (to present);
the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, current issue);
MEDLINE via OVID (1946 to present);
EMBASE via OVID (1980 to present);
LILACS via BIREME (1980 to present).
The MEDLINE subject search will be linked to the Cochrane Highly Sensitive Search Strategy (CHSSS) for identifying randomised trials in MEDLINE: sensitivity maximising version (2008 revision) as referenced in Chapter 22.214.171.124 and detailed in box 6.4.c of theCochrane Handbook for Systematic Reviews of Interventions, Version 5.1.0 (updated March 2011) (Higgins 2011).
Searching other resources
We will examine the reference lists of relevant articles and will contact the investigators of included studies by electronic mail to ask for details of additional published and unpublished trials.
The following journals have been identified as important to be handsearched as part of this review:
American Journal of Orthodontics and Dentofacial Orthopedics
The Angle Orthodontist
European Journal of Orthodontics
Journal of Orthodontics
Orthodontics and Craniofacial Research.
Issues of these journals, published within the past 12 months, will be handsearched by the review authors if handsearching has not already been carried out as part of the Cochrane worldwide handsearching programme.
We will conduct searches using the following databases to identify ongoing trials:
metaRegister of Controlled Trials (mRCT) (to present);
US National Institutes of Health Register (to present);
World Health Organization International Clinical Trials Registry Platform Search Portal (ICTRP) (to present).
We will also contact manufacturers for unpublished or ongoing trials or both.
There will be no language restrictions applied in the searches of the electronic databases.
Data collection and analysis
Selection of studies
Two review authors (Ahmed el-Angbawi (AE), Grant T McIntyre (GM) or David R Bearn (DB)) will independently assess the titles and abstracts of studies identified by the searches. Full copies will be obtained of all relevant and potentially relevant studies, and those appearing to meet the inclusion criteria yet for which there are insufficient data in the title and abstract to make a clear decision. The full text papers will be assessed independently by two review authors (AE, GM, DB). Any disagreement on the eligibility of an included study will be resolved through discussion and consensus, or if necessary in conjunction with a third review author. From this group, the studies not meeting the inclusion criteria will be recorded, with reasons for exclusion, in the 'Characteristics of excluded studies' section of the review.
Data extraction and management
We will use data extraction forms recording the year of publication, country of origin and details of the participants including demographic characteristics and the criteria for inclusion. The study details will be entered into the 'Characteristics of included studies' tables in Review Manager (RevMan) 5.2 (RevMan 2012). Data will be extracted independently, and in duplicate, by two review authors (AE, GM) and only included if consensus is met; any disagreements will be resolved by consulting with a third review author.
The following details will be also extracted if reported.
Trial methods: (a) allocation method; (b) sample size calculation; (c) masking of participants, trial lists and outcome assessors; (d) exclusion of participants after randomisation and the proportion and reasons for sample attrition at follow-up.
Participants: (a) country of origin and study setting; (b) sample size; (c) age; (d) gender; (e) inclusion and exclusion criteria.
Intervention: (a) type; (b) materials and techniques used; (c) time of follow-up.
Control: (a) type; (b) materials and techniques used; (c) time of follow-up.
Outcomes: (a) primary and secondary outcomes mentioned in the Types of outcome measures section of this review.
Where stated, sources of funding will be recorded. The review authors will use this information to aid their assessment of investigator reporting bias and the validity of included trials.
Assessment of risk of bias in included studies
Two review authors (AE and Padhraig Fleming (PF)) will independently assess the risk of bias for the selected trials using The Cochrane Collaboration's tool for assessing risk of bias as described in section 8.5 of theCochrane Handbook for Systematic Reviews of Interventions, Version 5.1.0 (updated March 2011) (Higgins 2011). This works by producing a risk of bias table for each included study in two parts. For each domain, the first part is a description of what was reported to have happened, whilst the second part is a judgement of low, high or unclear for that domain. The three authors will meet and compare their judgement gradings with any inconsistencies in the assessments between the review authors discussed and resolved.
The following domains will be assessed as at low, high or unclear risk of bias:
sequence generation (selection bias);
allocation concealment (selection bias);
blinding of participants and personnel (performance bias);
blinding of outcome assessors (detection bias);
incomplete outcome data addressed (attrition bias);
free of selective outcome reporting (reporting bias);
free of other bias.
We will categorise and report the overall risk of bias of the included studies according to the following:
low risk of bias (plausible bias unlikely to seriously alter the results) if all domains are assessed as at low risk of bias;
unclear risk of bias (plausible bias that raises some doubt about the results) if one or more domains are assessed as at unclear risk of bias; or
high risk of bias (plausible bias that seriously weakens confidence in the results), if one or more domains are assessed as at high risk of bias.
Measures of treatment effect
Mean differences with 95% confidence intervals will be calculated for continuous data; including overall treatment time and number of visits required. Odds ratios and 95% confidence intervals will be calculated for dichotomous outcomes (e.g. adverse effects).
The review authors will contact the trials corresponding authors for original data to allow calculation of standardised rates when not reported.
Unit of analysis issues
We anticipate that some of the included studies may present data from repeated or multiple site observations or both on participants which may lead to unit of analysis errors; if this is the case, we will follow the advice provided in section 9.3.4 of theCochrane Handbook for Systematic Reviews of Interventions (Higgins 2011).These will be considered as cluster-randomised trials, as per section 16.3.7 of the Cochrane Handbook for Systematic Reviews of Interventions, with sensitivity analyses being conducted to investigate the robustness of their conclusions, especially where intracluster (or intraclass) correlation coefficients (ICCs) are borrowed from external sources (Higgins 2011).
Dealing with missing data
In studies where data are unclear or missing the principal investigators will be contacted. If missing data are unavailable we will follow the advice given in section 16.1.2 of the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011).
We will make the assumptions of any methods used to cope with missing data explicit: for example, that the data are assumed missing at random, or that missing values were assumed to have a particular value such as a poor outcome. We will perform sensitivity analyses to assess how sensitive results are to reasonable changes in the assumptions that are made, as per section 9.7 of the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011) and address the potential impact of missing data on the findings of the review in the discussion.
Assessment of heterogeneity
We will assess clinical heterogeneity by examining the characteristics of the studies, the similarity between the types of participants, the interventions and the outcomes as specified in the criteria for included studies. Statistical heterogeneity will be assessed using a Chi2 test and the I2 statistic. We will consider heterogeneity to be significant for the Chi2 test when the P value is less than 0.10 (Higgins 2003) and I2 values of 30% to 60% will indicate moderate, 60% to 90% substantial and 75% to 100% considerable heterogeneity.
Assessment of reporting biases
We plan to assess publication bias according to the recommendations on testing for funnel plot asymmetry if a sufficient number of studies assessing similar interventions are identified for inclusion in this review, as described in section 10.4.3.1 of theCochrane Handbook for Systematic Reviews of Interventions, Version 5.1.0 (Higgins 2011). If asymmetry is identified, we will attempt to assess other possible causes and these will be explored in the discussion if appropriate.
Pooling of data and meta-analysis will only be carried out if there is sufficient homogeneity between studies with similarities in the types of participants, interventions and outcomes. A weighted treatment effect will be calculated and the results will be expressed as mean differences and 95% confidence intervals for continuous outcomes, and odds ratios and 95% confidence intervals for dichotomous outcomes. In general, the random-effects model will be used for meta-analyses; however, if meta-analyses involve less than four studies, a fixed-effect model will be used.
Subgroup analysis and investigation of heterogeneity
If a sufficient number of studies are included and we identify moderate, substantial or considerable heterogeneity (see Assessment of heterogeneity), we plan to carry out the following subgroup analyses according to: type of non-surgical method used, and age category (adolescents versus adults).
Data analysis will be restricted to studies where missing data have not been imputed. Sensitivity analysis will be performed on studies at low risk of bias. Furthermore, we plan to carry out sensitivity analyses to assess the robustness of the results of the review by repeating the analyses with the following adjustment: exclusion of studies with a high risk of bias.
Presentation of main results
Using GRADEPro software (http://ims.cochrane.org/gradepro), we will produce a summary of findings table of the following outcomes listed according to priority.
Rate of tooth movement.
Duration of orthodontic treatment, and number of visits during active treatment (scheduled and unscheduled), and duration of appointments.
Improvement in occlusion.
Patient-centred outcomes: impact of fixed appliances on daily life, quality of life and pain experience.
Patient satisfaction measured using validated questionnaires or scales.
Harm arising during the course of orthodontic treatment: including gingival and periodontal problems, anchorage loss and iatrogenic damage to teeth (e.g. caries or demineralisation, root resorption).
The quality of the evidence will be assessed with reference to the overall risk of bias for the included studies, the directness of the evidence, the inconsistency of the results, the precision of the estimates, the risk of publication bias and the magnitude of the effect. The quality of the body of evidence for each of the primary outcomes will be categorised as high, moderate, low or very low.