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Interventional studies
Interventional studies
Clinical trials. In a randomized controlled trial, the design is experimental; the researcher has a hypothesis and participants are randomly assigned to receive an intervention versus a placebo control (whenever ethically possible). Blinding refers to whether the participant has been blinded to his or her assigned group. A double-blind study refers to one in which both the participants and the researchers are blinded to group assignment.
The outcomes and safety measured depend on the phase of the trial. Phase I trials are early, typically unblended, and may or may not include a control. These are simply a test of the tolerability and safety of the intervention in order to determine whether the
intervention is appropriate to study further. An example of a phase I trial relevant to dermatologic surgery is the study of vismodegib, a small-molecule inhibitor of smoothened (SMO) in the Hedgehog signaling pathway, for the treatment of advanced basal cell carcinoma.8 These studies may investigate the pharmacokinetics of a drug and may provide guidance for dosing during a phase II trial. A phase II study is a small controlled study where both effect and safety of intervention are measured. An example of a phase II clinical trial in dermatologic surgery involved 601 patients with superficial BCC by biopsy randomized to treatment with MAL-PDT, 5-fluorouracil, or imiquimod.9 A phase III study is similar to a phase II study, only larger. If the intervention passes through a phase III trial, then it is possible to gain FDA approval. For example, a phase III, double-blind, randomized controlled trial was used to examine the effect of oral nicotinamide (the amide of vitamin B3) on the rate of new nonmelanoma skin cancers over a 12-month period.10 Phase IV trials are utilized after the intervention has been out on market to monitor for adverse effects and define other applications for the intervention.
All of these study examples adhere to the Consolidation Standards of Reporting Trials (CONSORT) guidelines (http://www.consort-statement.org/). This group offers a 25-point checklist to follow for reporting results from a clinical trial as well as a flow diagram for an example of how to report enrollment. The checklist covers all steps from study objectives, study design, to statistical analysis.
Also, prior to submission, clinical trials that have one or more sites in the United States or that test a drug or device that is manufactured in the United States or its territories must be registered with ClinicalTrials.Gov. (http://www.clinicaltrials.gov). International trials can be registered on the Current Controlled Trials website (http://www.controlled-trials.com), which is recognized by the World Health Organization. A skin-specific resource for therapeutic trials is the Cochrane Skin Group Ongoing Trials Register (http://www.nottingham.ac.uk/ongoingskintrials/), aimed at informing the community of skin-specific therapeutic trials.
Quasi-experimental designs. In addition to clinical trials, variations on the randomized controlled trial interventional study design may increase the feasibility and efficiency of the study. For example, matched pair randomization design allows for subjects with baseline confounding variables to be balanced, while one member of the pair receives the intervention. Crossover designs involve switching the placebo and intervention groups during the study to account for confounding variables, assuming there is no lasting effect of the intervention.
Secondary data analysis: meta-analysis, systematic reviews In clinical research, systematic reviews and meta-analyses represent the highest level of clinical evidence, as they are comprised of a compilation of randomized controlled or
clinical trials (RCTs). Claims of the best treatment practices within dermatologic surgery are often based upon results from systematic reviews and meta-analyses. The simultaneous analysis of numerous RCTs helps to create a consensus answer for questions in dermatologic surgery. For example, a systematic review on the treatment of squamous cell skin cancer may include RCTs examining endpoints such as cure rates, recurrence, aesthetic and functional outcomes, or cost effectiveness in order to elucidate the best treatment. Results of systematic reviews are presented as streamlined and objective appraisals allowing the clinician to identify any potential biases.
Statistical tests may be used to mitigate heterogeneity of studies reviewed and assess potential bias in the small studies included. Methodological quality of included studies may be assessed using the Strengthening of Reporting of Observational studies in Epidemiology (STROBE) checklist.11