Clinical Trials Clinical trials include intervention studies where the assignment to the treatment or control condition is controlled by the investigator and the outcomes to be measured are clearly defined at the time the trial is designed. Features of randomized clinical trials include randomization (in which participants are randomly assigned to exposures), unbiased assessment of outcome, and analysis of all participants based on the assigned exposure (an “intention to treat” analysis).
There are many different types of clinical trials, including studies designed to evaluate treatments, prevention techniques, community interventions, quality-of-life improvements, and diagnostic or screening approaches (3). Since 2007, investigators conducting randomized clinical trials are expected to register the trial to comply with mandatory registration and results reporting requirements (4).
Clinical Trial Phases New investigational drugs or treatments are usually evaluated by clinical trials in phases with more people being involved as the purpose of the study becomes more inclusive (3).
Phase I Trials In these trials, researchers test an experimental drug or treatment for the first time in a small group of people (20–80) to evaluate its safety, determine a safe dosage range, and identify side effects.
Phase II Trials In these, the experimental study drug or treatment is given to a larger group of people (100–300) to see whether it is effective and to further evaluate its safety.
Phase III Trials In phase III trials, the experimental study drug or treatment is given to large groups of people (1,000–3,000) to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the experimental drug or treatment to be used safely.
Phase IV Trials These are postmarketing studies that delineate additional information, including the drug’s risks, benefits, and optimal use.
the factors that might inﬂuence outcome, such as age, stage of disease, medical history, and symptoms, are similar in patients assigned to the study protocol compared with patients assigned to placebo or traditional treatment. Published reports from the clinical trial are expected to include a table showing a comparison of the treatment groups with respect to potential confounders and to demonstrate that the groups did not differ in any important ways before the study began.
CONSORT Checklist Clearly defining the outcome or criteria for successful treatment helps ensure unbiased assessment of the outcome. A well-designed clinical trial has a sufficient number of subjects enrolled to ensure that a “negative” study (one that does not show an effect of the treatment) has enough statistical power to evaluate the predetermined (a priori), expected treatment effect. The Consolidated Standards of Reporting Trials (CONSORT) Statement is an evidence-based, minimum set of recommendations for reporting on randomized controlled trials developed by the CONSORT Group to alleviate the problems arising from inadequate reporting of randomized controlled trials. The 25-item CONSORT checklist (Table. 4.1) and ﬂow diagram
Table 4.1 CONSORT Checklist
Item Reported on Section/Topic No. Checklist Item Page No.
1a Identification as a randomized trial in the title 1b Structured summary of trial design, methods, results, and conclusions (for specific guidance see CONSORT for abstracts)∗
Background and 2a Scientific background and explanation of rationale objectives 2b Specific objectives or hypotheses
Trial design 3a Description of trial design (such as parallel, factorial) including allocation ratio 3b Important changes to methods after trial commencement (such as eligibility criteria), with reasons Participants 4a Eligibility criteria for participants 4b Settings and locations where the data were collected Interventions 5 The interventions for each group with sufficient details to allow replication, including how and when they were actually administered Outcomes 6a Completely defined prespecified primary and secondary outcome measures, including how and when they were assessed 6b Any changes to trial outcomes after the trial commenced, with reasons Sample size 7a How sample size was determined 7b When applicable, explanation of any interim analyses and stopping guidelines