Clinical Trials in Chronic Diseases

Abstract

In spite of rather negative publicity on the crossover/self-controlled design for clinical trials in the early 1980s, a fair number of these studies were published in that period. Using these studies as examples, we try to give an overview of major advantages and disadvantages of crossover and parallel group studies. Strengths of the crossover versus the parallel design include: (1) elimination of between-subject variability of symptoms; (2) no need for large samples; (3) fewer ethical problems; and (4) subjects are able to express their preference for one of the compounds being given. Weaknesses include: (1) carryover effect from one treatment period into the other; and (2) time effect due to spontaneously evolving symptoms in a lengthy trial. Although routinely used for all types of therapies in phase I/II studies, the crossover/self-controlled design cannot be used in phase III/IV studies other than for symptomatic treatments of stable disease. Treatments of chronic diseases are directed primarily to the relief of persistent symptoms rather than the cure of a rapidly evolving symptomatology. These very aspects make them particularly suitable for crossover/self-controlled studies. Awareness of the weaknesses of clinical trials is especially important to clinical practitioners, who depend on reported clinical trials when making clinical decisions.

Design, Analysis, and Reporting of Crossover Trials for Inclusion in a Meta-Analysis

“…In preparing for a systematic review of medical interventions for ocular hypertension and open-angle glaucoma, we found that a large number of eligible trials are crossover trials. For some disciplines, including ophthalmology subspecialties, crossover trials may be encountered quite often in the literature [ 8 ]. We believe that data from these trials are critical to presenting summary information; and not to include them would represent a waste of research information.…”

Can keeping clinical trial participants blind to their study treatment adversely affect subsequent care?

“…In addition, where withholding information on actual treatment during the controlled phase is essential to the study's validity, subjects should understand before consenting that they will not be able to know the relationship between symptom remission or persistence and any specific treatment. In some instances, alternatives to parallel-group research, such as cross-over trials [28], may be scientifically appropriate and enable patients to indicate their preferred treatment while still masking the actual treatment they received.…”

Efficacy and Safety of Pregabalin in Patients with Fibromyalgia and Comorbid Depression Taking Concurrent Antidepressant Medication: A Randomized, Placebo-controlled Study

“…The Journal of on June 8, 2015 -Published by www.jrheum.org Downloaded from effects of study drugs from 1 treatment period to the next have been reported, including in the treatment of chronic pain 29,30 . There is the risk of unblinding when patients switch treatments, although patients in the current study were blinded to the transitions between study periods.…”

“…There is the risk of unblinding when patients switch treatments, although patients in the current study were blinded to the transitions between study periods. In addition, sample size was reduced because individual patients served as their own controls, and between-subject variability of symptoms was eliminated 15,29 . In addition, sample size was reduced because individual patients served as their own controls, and between-subject variability of symptoms was eliminated 15,29 .…”