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

Publisher Copyright: © 2018 Logviss et al. This is an open ccess article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and eproduction in any medium, provided the original author and source are credited.Background Conducting clinical studies in small populations may be very challenging; therefore quality of clinical evidence may differ between rare and non-rare disease therapies. Objective This 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. Methods The 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. Results 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). 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). Conclusions The 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.publishersversionPeer reviewe

Implementation of a population-based epidemiological rare disease registry: study protocol of the amyotrophic lateral sclerosis (ALS) - registry Swabia

BACKGROUND: The social and medical impact of rare diseases is increasingly recognized. Amyotrophic lateral sclerosis (ALS) is the most prevalent of the motor neuron diseases. It is characterized by rapidly progressive damage to the motor neurons with a survival of 2–5 years for the majority of patients. The objective of this work is to describe the study protocol and the implementation steps of the amyotrophic lateral sclerosis (ALS) registry Swabia, located in the South of Germany. METHODS/DESIGN: The ALS registry Swabia started in October 2010 with both, the retrospective (01.10.2008-30.09.2010) and prospective (from 01.10.2010) collection of ALS cases, in a target population of 8.6 million persons in Southern Germany. In addition, a population based case–control study was implemented based on the registry that also included the collection of various biological materials. Retrospectively, 420 patients (222 men and 198 women) were identified. Prospectively data of ALS patients were collected, of which about 70% agreed to participate in the population-based case–control study. All participants in the case–control study provided also a blood sample. The prospective part of the study is ongoing. DISCUSSION: The ALS registry Swabia has been implemented successfully. In rare diseases such as ALS, the collaboration of registries, the comparison with external samples and biorepositories will facilitate to identify risk factors and to further explore the potential underlying pathophysiological mechanisms

Systematic review on the evaluation criteria of orphan medicines in Central and Eastern European countries.

BACKGROUND: In case of orphan drugs applicability of the standard health technology assessment (HTA) process is limited due to scarcity of good clinical and health economic evidence. Financing these premium priced drugs is more controversial in the Central and Eastern European (CEE) region where the public funding resources are more restricted, and health economic justification should be an even more important aspect of policy decisions than in higher income European countries. OBJECTIVES: To explore and summarize the recent scientific evidence on value drivers related to the health technology assessment of ODs with a special focus on the perspective of third party payers in CEE countries. The review aims to list all potentially relevant value drivers in the reimbursement process of orphan drugs. METHODS: A systematic literature review was performed; PubMed and Scopus databases were systematically searched for relevant publications until April 2015. Extracted data were summarized along key HTA elements. RESULTS: From the 2664 identified publications, 87 contained relevant information on the evaluation criteria of orphan drugs, but only 5 had direct information from the CEE region. The presentation of good clinical evidence seems to play a key role especially since this should be the basis of cost-effectiveness analyses, which have more importance in resource-constrained economies. Due to external price referencing of pharmaceuticals, the relative budget impact of orphan drugs is expected to be higher in CEE than in Western European (WE) countries unless accessibility of patients remains more limited in poorer European regions. Equity principles based on disease prevalence and non-availability of alternative treatment options may increase the price premium, however, societies must have some control on prices and a rationale based on multiple criteria in reimbursement decisions. CONCLUSIONS: The evaluation of orphan medicines should include multiple criteria to appropriately measure the clinical added value of orphan drugs. The search found only a small number of studies coming from CEE, therefore European policies on orphan drugs may be based largely on experiences in WE countries. More research should be done in the future in CEE because financing high-priced orphan drugs involves a greater burden for these countries

The perverse impact of external reference pricing (ERP): a comparison of orphan drugs affordability in 12 European countries. A call for policy change

Objective: The study compared the relative cost differences of similar orphan drugs among high and low GDP countries in Europe: Bulgaria, France, Germany, Greece, Hungary, Italy, Norway, Poland, Romania, Spain, Sweden, UK. Methods: Annual treatment costs per patient were calculated. Relative costs were computed by dividing the costs by each economic parameter: nominal GDP per capita, GDP in PPP per capita, % GDP contributed by the government, government budget per inhabitant, % GDP spent on healthcare, % GDP spent on pharmaceuticals, and average annual salary. An international comparison of the relative costs was done using UK as the reference country and results were analysed descriptively. Results: 120 orphan drugs were included. The median annual costs of orphan drugs in all countries varied minimally (cost ratios: 0.87 to 1.08). When the costs were adjusted using GDP per capita, the EU-5 and Nordic countries maintained minimal difference in median cost. However, the lower GDP countries showed three to six times higher relative costs. The same pattern was evident when costs were adjusted using the other economic parameters. Conclusion: When the country’s ability to pay is taken into consideration, lower GDP countries pay relatively higher costs for similarly available orphan drugs in Europe