Elsevier

The Lancet

Volume 375, Issue 9719, 20–26 March 2010, Pages 1007-1013
The Lancet

Articles
Comparative demographics of the European cystic fibrosis population: a cross-sectional database analysis

https://doi.org/10.1016/S0140-6736(09)62161-9Get rights and content

Summary

Background

Country-specific patients' registries are rarely used to make international comparisons because of protocol discrepancies in data collation. We present data from a European cystic fibrosis registry that is dedicated to collection of demographic data, and assess whether the resources available in countries with and without European Union (EU) membership affects care and survival of patients.

Methods

Data for demographic indicators—age, age at diagnosis, sex, and genotype—for patients with cystic fibrosis from 35 European countries were combined, and used to establish the differences in demographic indicators between EU and non-EU countries. EU membership status in 2003 was used to divide countries. We modelled demographic indicators of EU countries on non-EU countries to estimate the size of the cystic fibrosis population if non-EU countries had had the same resources available for patients as did EU countries.

Findings

Data were gathered for 29 025 patients, who had a median age of 16·3 years (IQR 8·9–24·8), with a difference of 4·9 years (95% CI 4·4–5·1; p<0·0001) between EU (median 17·0 years, IQR 9·5–25·6) and non-EU countries (12·1 years, 6·0–19·2). The proportion of patients older than 40 years was higher in EU countries (1205 [5%]) than in non-EU countries (76 [2%]), with an odds ratio of 2·4 (95% CI 1·9–3·0, p<0·0001). We estimated that the cystic fibrosis population in non-EU countries would increase by 84% if patients had a demographic profile comparable to that of patients in EU countries.

Interpretation

Future studies need to establish the reasons for the lower proportion of patients with cystic fibrosis in non-EU countries than in EU countries, such as underdiagnosis and premature childhood mortality.

Funding

European Community's Sixth Framework Programme for Research, and Czech Ministry of Health.

Introduction

Cystic fibrosis occurs in babies of parents who are apparently healthy carriers of the defective cystic fibrosis transmembrane-conductance regulator gene (CFTR), and is one of the most common inherited disorders in populations of European descent. However, at a population level, cystic fibrosis is quite rare. Since individual hospitals do not have sufficient numbers of patients with the disorder, patients' data submitted to registries are necessary to gain an overview of the epidemiological complexities. Such registries have been running in the USA and Canada for many decades, and have been used to inform several features of cystic fibrosis, including demographic indicators,1, 2 the use of genotype to predict mortality,3 and the effect of socioeconomic status on specific outcomes.4, 5 Similar efforts have taken place worldwide—for example, country-specific databases have been used for benchmarking in Germany,6 to measure survival improvement in France,7 and to offset screening costs through a reduced treatment burden in the UK.8, 9, 10

With recognition of the limits of any national registry, we tried to begin an international comparison of disease outcomes.11 However, the conflicting evolution of national registries led to a scarcity of standardised data collection, which hampered insightful comparisons. This variance in protocol was unfortunate in view of the substantial financial and human resources that have been used for national registry data collection. For some time, geneticists have instead used CFTR mutations reported by cystic fibrosis centres to make worldwide comparisons. Such research has been published but source data were derived from several published reports rather than de novo.12

To overcome limitations with data standardisation, a new registry project was proposed in the mid-1990s, and the Epidemiologic Registry of Cystic Fibrosis was developed with sponsorship from the pharmaceutical industry until funding stopped in 2003. Around this time, the European Cystic Fibrosis Society developed a new European registry of cystic fibrosis that concentrated mainly on countries with membership of the European Union (EU) that had available cystic fibrosis registries; the registry has since yielded comparative data for 14 101 patients from ten countries.13 In 2005, funding was obtained under the European Community's Sixth Framework Programme for Research for a dedicated registry component within the European Coordination Action for Research in Cystic Fibrosis (EuroCareCF). The European Cystic Fibrosis Demographics Registry (ECFDR) now contains data from 35 EU and non-EU countries, and more than 29 000 patients.

EU and non-EU countries have populations of similar sizes (341 million vs 378 million) and similar distributions of severe genotypes of mutations causing cystic fibrosis.12 Thus, a priori, outcomes should differ little, and recorded differences would be expected to have arisen from causes primarily unrelated to CFTR. We present data from ECFDR, with specific comparison of demographic indicators in patients with cystic fibrosis, by membership of the EU in 2003—ie, preceding the expansions of EU membership in central and eastern Europe in 2004. In 2003, median gross domestic product (GDP) per person, a surrogate for health-care spending, was nine times higher in EU countries (US$30 209, IQR $28 239–33 429) than in non-EU countries ($3372, $2138–$7710).14 With the hypothesis that increased health-care spending in EU countries would correspond to improved care of patients and better survival, we sought to estimate differences in demographic indicators between populations with cystic fibrosis in EU and non-EU countries.

Section snippets

The European Cystic Fibrosis Demographics Registry

The partnership between EuroCareCF and the European Cystic Fibrosis Society aimed to obtain comprehensive demographic data, with optional clinical data, for patients with cystic fibrosis in countries across Europe. ECFDR has provided a foundation to further the cystic fibrosis registry in Europe with the support of the European Cystic Fibrosis Society. To ensure uniformity of data collection, and to account for the independent evolution of national registries, we gathered data with spreadsheets

Results

29 025 patients with cystic fibrosis were registered in 35 European countries, with 25 216 in EU countries and 3809 in non-EU countries (panel). Full data for patients' age at diagnosis and sex are presented in webappendix pp 4–7. Analysis of the age distribution of patients with cystic fibrosis showed that the population increased to a peak in the age-group of 10–14 years, with less than 2% of the population older than 45 years (figure 1). The cystic fibrosis population size increased in the

Discussion

We have shown that far fewer children and young adults have cysic fibrosis in non-EU countries than we expected. This finding is reinforced by the increased chance of patients surviving to 40 years in EU countries, even if they have the severe Phe508del mutation. This difference does not seem to be caused by an increased proportion of mild phenotypes in EU countries, which suggests that poor survival in non-EU countries could be a contributing factor. Moreover, application of demographic data

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