Background and objectives

CONSORT item 2a is “scientific background and explanation of rationale.”

Example: “A significant problem continues to relate to bond failures, estimated at 6% to 25%, depending on the placement technique and the observation period… Although light-cured materials offer longer working times and improved moisture control, no randomized controlled trial has been published investigating the importance of these theoretical advantages.”

Explanation: It is good practice at the planning stage of the trial to first search the literature to identify the available evidence on the topic of interest. This evidence can be limited or abundant, and identification of a high-quality systematic review, if available, is desirable. A recent high-quality systematic review, which summarizes the existing evidence, can serve as a reference in terms of what is known and what remains unclear regarding the efficacy and safety of the intervention of interest. The Declaration of Helsinki considers research on human subjects without thorough knowledge of the existing literature as unethical. It is also unethical to plan a trial to answer a question that has already been answered. A trial is justified when there is genuine uncertainty (equipoise), based on the existing evidence, regarding the effectiveness of the intervention at hand.

In the RCT example, a systematic review is not cited, but the authors explicitly stated that no RCT has been published investigating the theoretical advantages of light curing vs chemical curing.

CONSORT item 2b is “specific objectives or hypotheses.”

Example: “In this study, we aimed to compare the survival of mandibular lingual retainers placed by using either chemical or photopolymerization after orthodontic treatment.”

Explanation: The objectives are the questions that the trial was designed to answer. They often relate to the efficacy of a particular therapeutic or preventive intervention. Hypotheses are prespecified questions being tested to help meet the objectives. Hypotheses are more specific than objectives and are amenable to explicit statistical evaluations. In practice, objectives and hypotheses are not always easily differentiated.

Trial design

CONSORT item 3a is “description of the trial design (eg, parallel, factorial) including the allocation ratio.”

Example: “This was a parallel-group, randomized, active controlled trial with a 1:1 allocation ratio.”

Explanation: The most common type of trial design is the parallel design; however, other designs such as cross-over, cluster randomized, noninferiority, factorial, and hybrids of those exist and should be specified. A study design commonly used in dentistry is the split-mouth design, as well as studies including elements of clustered designs. Such designs occur when several observations are collected from each patient from multiple sites and tissues such as the number of teeth or periodontal sites or structures. Different trial designs have characteristics that may influence the conduct and analysis of the trial; these details should, therefore, be described clearly. It is important that specific details (design and allocation ratio) are given as shown under this subheading.

CONSORT item 3b is “important changes to methods after trial commencement (such as eligibility criteria), with reasons.”

Example: “No changes to the methods after trial commencement occurred.”

Explanation: Changes between the study protocol and how the trial was actually done are common and should be documented appropriately. Possible reasons for changes—eg, to eligibility criteria or duration of follow up—include new external evidence, inability to recruit a sufficient number of patients, and financial constraints. For some “adaptive” trials, the protocol allows for limited changes following prespecified rules, when the sample size and duration of the trial are not determined before commencement. The protocol should indicate the adjustments planned under the different change scenarios, and the changes should be documented, explained, and justified in the published article. Any modifications to the trial design should be fully reported to help the reader interpret the results, whether they were anticipated in the protocol or in response to changing circumstances.

The RCT at hand reported no changes after the commencement of the trial; however, no published protocol allowed this to be verified, and this is reported at the end of the abstract.

Participants

CONSORT item 4a is “eligibility criteria for participants.”

Example: “The following selection criteria were applied: no active caries, restorations, or fractures on the mandibular anterior teeth; no periodontal disease; and adequate oral hygiene.”

Explanation: Eligibility criteria and information on participants and settings should be outlined clearly because they have implications for the relevance of the trial results to other settings (generalizability). Because eligibility criteria are applied before randomization, they do not affect the internal validity (methodologic quality) of a trial. The common distinction between inclusion and exclusion criteria is unnecessary; the same criterion can be phrased to include or exclude participants.

CONSORT item 4b is “settings and locations where the data were collected.”

Example: “Consecutive patients who had completed orthodontic treatment with fixed appliances were recruited at the private practice of the first author (N.P.) from April 2009 to November 2010.”

Explanation: A clear description of the setting and locations where the data were collected is important to allow the reader to decide whether the findings are relevant to her or his own setting. Information on the geographic location, the number of participating centers, the available facilities, the involved care providers, and their levels of expertise should also be clearly described. Trial results may differ substantially, for example, between centers with state-of-the-art facilities with highly trained personnel and studies undertaken by relative novices in poorly equipped clinics.

Interventions

CONSORT item 5 is “interventions for each group with sufficient details to allow replication, including how and when they were actually administered.”

Example: “All patients received a soft bonded lingual retainer of 0.022-in (Tru-Chrome multi-stranded wire; Rocky Mountain Orthodontics, Denver, Colo) that was fabricated intraorally… In the chemical polymerization group, Maximum Cure 2-part liquid adhesive (Reliance Orthodontic Products, Itasca, Ill) was mixed and applied on the wire and the teeth, and Excel 2-part paste (Reliance Orthodontic Products) was mixed, loaded on a syringe dispenser, and applied. The dental floss was removed after 7 minutes. In the photopolymerization group, a light-cured liquid (Assure; Reliance Orthodontic Products) and a paste in 2 layers (Flow-Tain; Reliance Orthodontic Products) were placed on the wire and the adjacent enamel, and light-cured for 9 seconds per tooth with a plasma light (Ortholite; 3M Unitek, Monrovia, Calif).”

Explanation: A clear description of each intervention in sufficient detail to allow a knowledgeable researcher to duplicate the experiment should be provided. For example, in a multicenter trial, as a minimum, the exact method of standardization of the administration, the duration, and the timing of the treatment should be outlined. A pharmacologic intervention would require explanation of the drug administered in conjunction with the mode of delivery, dosage, and frequency, and whether the control or placebo was indistinguishable from the “active pill” in terms of shape, color, smell, and taste. For other types of interventions, the CONSORT extension for nonpharmacologic trials describes the reporting requirements. Some important issues are the standardization of the delivery of the interventions, description of the various components of the interventions, and how adherence of the care providers to the protocol was assessed. A clear description further facilitates the implementation of valid comparisons and informed decisions regarding the inclusion of the primary study in systematic reviews.

Outcomes

CONSORT item 6a is “completely defined prespecified primary and secondary outcome measures, including how and when they were assessed.”

Example: “The main outcome was any first-time failure of the lingual retainer. The secondary outcome was the pattern of failure based on the adhesive remnant… The patients were advised to visit the orthodontist initially at 1, 3, and 6 months after retainer placement, followed by scheduled appointments at 12, 18, and 24 months… When scheduled appointments were unfeasible, particularly approaching the end of the trial, an assessment of retainer integrity was made over the telephone.”

Explanation: It is common for trials to have several outcomes, often identified as primary and secondary. All outcomes should be clearly defined and prespecified with an explicit description of how and when they were assessed. The definition of each outcome should be clear enough to allow other investigators to use the same outcome in a trial or to be confident of the similarities and differences of the outcome in the context of a systematic review. Declaration of prespecified outcomes, especially the primary outcome, is important, since, like registration and protocol prepublication, it mitigates against the problem of selective reporting of “interesting” outcomes. This is more likely when multiple outcomes or multiple time points of data collection are planned. Additionally, recording of several outcomes, and consequently multiple testing, invokes the problems associated with multiplicity and misleading interpretations.

When assessing the evidence for or against the effectiveness of an intervention, the balance of benefits and harms is an important consideration. A clear description of harms that were recorded should be provided. In nonpharmacologic trials, it is particularly important to specify the skills and the number of persons assessing the outcomes.

CONSORT item 6b is “any changes to trial outcomes after the trial commenced, with reasons.”

Example: “There were no outcome changes after trial commencement.”

Explanation: Reviews of publications show that discrepancies between planned and presented outcomes are common. Outcomes initially planned to be the primary outcomes in the original trial protocol may be portrayed as secondary outcomes, whereas new primary outcomes can be introduced in the published article. Selective outcome reporting and presentation of “interesting” findings has also been documented. Therefore, clear descriptions of any outcome changes with the reasons for the alterations will enhance transparency. No outcome changes are reported in the RCT described; however, there is no prepublished protocol to confirm this.

Sample size

CONSORT item 7a is “how sample size was determined.”

Example: “Calculation of sample size was based on the ability to detect a clinically relevant difference in the risk of first-time failure (primary outcome) of 20% between the 2 trial arms (15% vs 35% with α = 0.05 and power of 85%). Foek et al found a 35% failure rate for light-cured lingual retainers; we used this value as our reference for the sample calculation. This calculation indicated that 93 participants were required in each arm; this was rounded up to 110 to account for losses to follow-up.”

Explanation: RCTs should have enough power to detect a clinically important difference between the treatment groups if such a difference exists, or to confirm the lack of a difference. It is an obligation of the investigators to conduct appropriate sample-size calculations driven by clinical importance and reasonable assumptions.

Authors should provide enough information so that a knowledgeable reader can reproduce the sample-size calculation. The sample-size calculation is usually based on the primary outcome, which should be clearly identified. For continuous outcomes, the authors should report the expected result in the control group, the expected difference of the intervention group from the control, the standard deviations, and the alpha and power levels. For binary outcomes, the same information is required, except for the standard deviation. In designs where clustering effects are expected, the value of the intracluster correlation coefficient should be provided. For split-mouth designs, common in orthodontics, the assumed correlations between sites should be specified. Finally, any provisions for expected losses to follow-up should also be described. Authors should ideally explain the rationale for the values used in the calculation.

A post hoc analysis to justify the sample size is considered inappropriate: power can be judged by inspecting the effect size and confidence intervals and the uncertainty that they convey.

CONSORT item 7b is “when applicable, explanation of any interim analyses and stopping guidelines.”

Example: “Not applicable.”

Explanation: Participants can be recruited and treated over a prolonged period. If an obvious difference between interventions emerges early in the trial, the study may be stopped prematurely for ethical reasons. This eventuality can be addressed by inspection of the interim results, ideally by an independent data-monitoring committee. However, performing multiple statistical examinations without appropriate corrections can lead to erroneous results and interpretations. Authors should report whether they or a data-monitoring committee took several “looks” at the data; if so, how many were there, what triggered them, what statistical methods were used (including any formal stopping rule), and whether they were planned before the start of the trial, before the data-monitoring committee saw any interim data by allocation, or some time thereafter.

No interim analyses or stopping guidelines were reported in the example study.