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Background: In times of genotype guided therapy options, a total of 3.2 % of people with CF (pwCF) in the German CF Registry[1] only have one or no CFTR-variant detected after genetic analysis. Additionally, genetic data in the Registry can be documented as free text and can therefore be prone to error. In order to allow the greatest possible amount of pwCF access to modern therapies, we conducted a re-evaluation of free text entries and established a custom-whole-CFTR-locus NGS-approach for all pwCF who remained without genetic confirmation afterwards., Methods: To this end, we assembled 731 free text variants of 655 pwCF in the German CF Registry. All variants were evaluated using ClinVar, HGMD and CFTR1/2, corrected in the Registries' database and uploaded to ClinVar. PwCF whose diagnosis remained uncertain as well as additional pwCF or pwCFTR-RD that were assembled through a nationwide call for testing of unclear cases were offered genetic analysis. Samples were analysed using a target-capture based NGS-custom-design-panel covering the entire CFTR-locus., Results: Evaluation of free text variants led to the discovery of 43 variants not formerly reported in the context of CF. The Registries' dropdown list was extended by 497 variants and over 500 pwCF were provided with their most up-to-date genotype. Samples of 47 pwCF/pwCFTR-RD were sequenced via NGS with an overall success rate of 61.7 %, resulting in implementation of entire CFTR-genotyping into routine diagnostics., Conclusion: Entire CFTR-genotyping can greatly increase the genetic diagnostic rate of pwCF/pwCFTR-RD and should be considered after inconspicuous CFTR screening panels in CFTR-diagnostics., Competing Interests: Declaration of Competing Interest The following authors declare a conflict of interest in preparing this article: SN has received grants from the CTN-ECFS, DZL and a Speaker’s fee from Vertex pharmaceuticals. LN has received institutional fees from the German Center for Lung Research, Vertex Pharmaceuticals and the Mukoviszidose Institute. He participated in the Trial Steering Committee for CF STORM and is the Medical lead of the German CF-registry and the Pharmacovigilance study manager of the ECFSPR. CS has received a Speaker’s fee from Vertex, TFF Pharma, Chiesi and Viatris and is an ECFS Board Member.All other author’s declare no conflicts of interest., (Copyright © 2023 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.)

In February 2003, the German Federal Ministry of Health presented a concept for establishing a German National Institute for Clinical Excellence. In sharp contrast to this concept, a closer look at other medical quality assurance activities in Germany shows that there is no area of responsibility in the German health care system where such an institution might prove useful. In Germany, the institutions of self-administration were the first to organise and promote medical quality assurance activities. The German Hospital Federation, the Association of Sickness Funds for salaried employees, the Association of Private Health Insurers, the professional organisations of German physicians and other organisations of self-administration entered into contracts pertaining to a medical quality partnership in order to create maximal benefit for all patients, i.e. to exactly address the patients' needs and treat their diseases with the best possible outcome. Such a framework of self-administration renders redundant the requirement for a German National Institute for Clinical Excellence.