title: Good-quality research in rare diseases: trials and tribulations.
abstract: Despite the fact that rare diseases affecting the kidney are not as uncommon as generally believed, proper clinical guidelines for guiding therapeutic management are scarce or absent owing to the overall lack of reliable scientific evidence. Although the randomized controlled trial (RCT) is the best study design for dealing with questions of intervention, RCTs under low-prevalence conditions are extremely challenging because of the limited number of patients, the variable phenotypic expression, and the long course of these disorders. In this brief review, we aimed to summarize the main alternative methods to traditional RCTs designed with the intent of minimizing the number of subjects needed for recruitment or maximizing the statistical efficiency of study analyses. Most of these approaches have not yet been extensively employed, may denote crucial limitations to wide applicability, or still lack proper validation in the field of rare diseases. Nevertheless, the growing number of proposed strategies is indicative of the perceived necessity by the scientific community to fill the quality gap between clinical guidelines for common and rare pathological conditions.
authors.affiliation: CNR - Institute of Clinical Physiology, c/o EUROLINE, Via Vallone Petrara 55-57, 89124, Reggio, Calabria, Italy. davide.bolignano@gmail.com.
authors.forename: Davide
authors.initials: D
authors.lastname: Bolignano
authors.affiliation: CNR - Institute of Clinical Physiology, c/o EUROLINE, Via Vallone Petrara 55-57, 89124, Reggio, Calabria, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Pisano
mesh_terms: D000328:Adult; D035843:Biomedical Research / Q000592:standards*; D019317:Evidence-Based Medicine / Q000592:standards*; D006801:Humans; D007674:Kidney Diseases / Q000453:epidemiology / Q000209:etiology / Q000628:therapy*; D018579:Patient Selection; D017410:Practice Guidelines as Topic; D015995:Prevalence; D016032:Randomized Controlled Trials as Topic / Q000592:standards*; D035583:Rare Diseases / Q000453:epidemiology / Q000209:etiology / Q000628:therapy*; D012107:Research Design / Q000592:standards*; D018401:Sample Size
keywords: Clinical guidelines; Clinical trials; Orphan diseases; Rare diseases
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