Characteristics of clinical trials in rare vs. common diseases: A register-based Latvian study.

Konstantins Logviss,Dainis Krievins,Santa Purvina,Gerd Rosenkranz

doi:10.1371/journal.pone.0194494

Abstract

BackgroundConducting clinical studies in small populations may be very challenging; therefore quality of clinical evidence may differ between rare and non-rare disease therapies.ObjectiveThis register-based study aims to evaluate the characteristics of clinical trials in rare diseases conducted in Latvia and compare them with clinical trials in more common conditions.MethodsThe EU Clinical Trials Register (clinicaltrialsregister.eu) was used to identify interventional clinical trials related to rare diseases (n = 51) and to compose a control group of clinical trials in non-rare diseases (n = 102) for further comparison of the trial characteristics.ResultsWe found no significant difference in the use of overall survival as a primary endpoint in clinical trials between rare and non-rare diseases (9.8% vs. 13.7%, respectively). However, clinical trials in rare diseases were less likely to be randomized controlled trials (62.7% vs. 83.3%). Rare and non-rare disease clinical trials varied in masking, with rare disease trials less likely to be double blind (45.1% vs. 63.7%). Active comparators were less frequently used in rare disease trials (36.4% vs. 58.8% of controlled trials). Clinical trials in rare diseases enrolled fewer participants than those in non-rare diseases: in Latvia (mean 18.3 vs. 40.2 subjects, respectively), in the European Economic Area (mean 181.0 vs. 626.9 subjects), and in the whole clinical trial (mean 335.8 vs. 1406.3 subjects). Although, we found no significant difference in trial duration between the groups (mean 38.3 vs. 36.4 months).ConclusionsThe current study confirms that clinical trials in rare diseases vary from those in non-rare conditions, with notable differences in enrollment, randomization, masking, and the use of active comparators. However, we found no significant difference in trial duration and the use of overall survival as a primary endpoint.

Highlights

Rare diseases are heterogeneous life-threatening or seriously debilitating conditions that affect less than one person in 2 000 individuals across the European Union (EU) [1]
We found no significant difference in the use of overall survival as a primary endpoint in clinical trials between rare and non-rare diseases (9.8% vs. 13.7%, respectively)
Clinical trials in rare vs. common diseases: Latvian study data and others would be able to access the data in the same manner as the authors

Summary

Introduction

Rare diseases are heterogeneous life-threatening or seriously debilitating conditions that affect less than one person in 2 000 individuals across the European Union (EU) [1]. Development of medicinal products intended for the treatment, diagnosis or prevention of rare diseases (orphan drugs) can be very challenging due to distinct rare disease features, such as small patient populations, low event rates, inadequate understanding of disease natural course, and a lack of previous clinical trials [3]. Drug approval is usually based on a phase III, double blind, randomized, controlled trial (RCT) widely regarded as the gold standard. Some orphan drugs were granted marketing approval by the FDA and the European Medicines Agency (EMA) without randomized, doubled blind, placebo controlled pivotal trials [8], but on the basis of uncontrolled phase II trial, retrospective study, or a literature analysis [9]. Conducting clinical studies in small populations may be very challenging; quality of clinical evidence may differ between rare and non-rare disease therapies

Methods

Results

Conclusion