Abstract
BackgroundRandomized controlled trials (RCTs) are the gold standard design of clinical research to assess interventions. However, RCTs cannot always be applied for practical or ethical reasons. To investigate the current practices in rare diseases, we review evaluations of therapeutic interventions in paediatric multiple sclerosis (MS) and Creutzfeldt-Jakob disease (CJD). In particular, we shed light on the endpoints used, the study designs implemented and the statistical methodologies applied.MethodsWe conducted literature searches to identify relevant primary studies. Data on study design, objectives, endpoints, patient characteristics, randomization and masking, type of intervention, control, withdrawals and statistical methodology were extracted from the selected studies. The risk of bias and the quality of the studies were assessed.ResultsTwelve (seven) primary studies on paediatric MS (CJD) were included in the qualitative synthesis. No double-blind, randomized placebo-controlled trial for evaluating interventions in paediatric MS has been published yet. Evidence from one open-label RCT is available. The observational studies are before-after studies or controlled studies. Three of the seven selected studies on CJD are RCTs, of which two received the maximum mark on the Oxford Quality Scale. Four trials are controlled observational studies.ConclusionsEvidence from double-blind RCTs on the efficacy of treatments appears to be variable between rare diseases. With regard to paediatric conditions it remains to be seen what impact regulators will have through e.g., paediatric investigation plans. Overall, there is space for improvement by using innovative trial designs and data analysis techniques.Electronic supplementary materialThe online version of this article (doi:10.1186/s13023-016-0402-6) contains supplementary material, which is available to authorized users.
Highlights
Randomized controlled trials (RCTs) are the gold standard design of clinical research to assess interventions
In contrast to [17,18,19], the purpose of the present paper is to review the methods used in the evaluations of therapeutic interventions by considering two prominent rare diseases as examples, namely paediatric multiple sclerosis (MS) and Creutzfeldt-Jakob disease (CJD)
It should be mentioned that for paediatric MS, full-text versions of two records that have been written in Russian and which may have been eligible for inclusion in the review were not available [26, 27]
Summary
Randomized controlled trials (RCTs) are the gold standard design of clinical research to assess interventions. To investigate the current practices in rare diseases, we review evaluations of therapeutic interventions in paediatric multiple sclerosis (MS) and Creutzfeldt-Jakob disease (CJD). Unkel et al Orphanet Journal of Rare Diseases (2016) 11:16 two prominent examples are paediatric multiple sclerosis (MS) and Creutzfeldt-Jakob disease (CJD). Multiple sclerosis is a disease characterized by recurrent immunemediated episodes of central nervous system demyelination [4]. Signs and symptoms such as losing the ability to walk independently vary widely, depending on the amount of damage and which areas of the brain are affected. The relapse-remitting course is the overwhelming manifestation in early-onset MS with most symptoms of MS similar to those seen in adults [7]
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