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Updated: Mar 26, 2026
In Vivo Functional Study of Disease-associated Rare Human Variants Using Drosophila
Published on: August 20, 2019
Good-quality research in rare diseases: trials and tribulations
Davide Bolignano1, Anna Pisano2
1CNR - Institute of Clinical Physiology, c/o EUROLINE, Via Vallone Petrara 55-57, 89124, Reggio, Calabria, Italy. davide.bolignano@gmail.com.
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.
Insights
Developing clinical guidelines for rare kidney diseases is challenging due to limited evidence. This review explores alternative study designs to randomized controlled trials (RCTs) to improve research efficiency and evidence quality for rare renal conditions.
Area of Science:
- Nephrology
- Clinical Epidemiology
- Rare Diseases Research
Background:
- Rare kidney diseases lack robust clinical guidelines due to scarce scientific evidence.
- Traditional randomized controlled trials (RCTs) are difficult to conduct for rare diseases owing to small patient populations and disease heterogeneity.
Purpose of the Study:
- To review alternative methodologies to traditional RCTs for rare kidney disease research.
- To address the challenge of insufficient evidence for developing clinical guidelines in rare renal conditions.
Main Methods:
- Literature review of alternative study designs.
- Focus on methods minimizing subject recruitment or maximizing statistical efficiency.
Main Results:
- Several alternative approaches to RCTs exist for rare disease research.
- These methods aim to overcome limitations of small sample sizes and variable disease expression.
Conclusions:
- Alternative study designs are crucial for advancing evidence-based care in rare kidney diseases.
- Further validation and application of these methods are needed to bridge the evidence gap for rare renal conditions.
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