Defining the natural history of rare genetic liver diseases: Lessons learned from the NAPPED initiative

Daan B E van Wessel; Emmanuel Gonzales; Bettina E Hansen; Henkjan J Verkade

doi:10.1016/j.ejmg.2021.104245

Defining the natural history of rare genetic liver diseases: Lessons learned from the NAPPED initiative

Eur J Med Genet. 2021 Jul;64(7):104245. doi: 10.1016/j.ejmg.2021.104245. Epub 2021 May 13.

Authors

Daan B E van Wessel¹, Emmanuel Gonzales², Bettina E Hansen³, Henkjan J Verkade⁴

Affiliations

¹ Pediatric Gastroenterology and Hepatology, University Medical Center Groningen, University of Groningen, the Netherlands.
² Pediatric Hepatology & Pediatric Liver Transplant Department, Centre de Référence de L'Atrésie des Voies Biliaires et des Cholestases Génétiques (AVB-CG), Filière de Santé des Maladies Rares Du Foie de L'enfant et de L'adulte (FILFOIE), Assistance Publique-Hôpitaux de Paris, Faculté de Médecine Paris-Saclay, CHU Bicêtre, Le Kremlin-Bicêtre, France.
³ Toronto Center for Liver Disease, University Health Network, Canada; IHPME, University of Toronto, Canada.
⁴ Pediatric Gastroenterology and Hepatology, University Medical Center Groningen, University of Groningen, the Netherlands. Electronic address: h.j.verkade@umcg.nl.

PMID: 33991701
DOI: 10.1016/j.ejmg.2021.104245

Abstract

While rare diseases collectively affect ~300 million people worldwide, the prevalence of each disease concerns a relatively small number of patients. Usually, only limited data with regard to natural history are available. Multicenter initiatives are needed to aggregate data and answer clinically relevant research questions. In 2017, we launched the NAtural course and Prognosis of PFIC and Effect of biliary Diversion (NAPPED) consortium. In three years, NAPPED created a global network focused on rare genetic liver diseases in the Progressive Familial Intrahepatic Cholestasis (PFIC) spectrum. During these years, we have learned important lessons which we feel should be taken into account when initiating and leading a global consortium. First, it is essential to 'keep it simple' from the start. Research questions, case report forms (CRFs) and data acquisition should be limited and clear to stay focused and keep the workload low for new participants. Secondly, early rewards and research output are needed to keep momentum and motivation. Quick output can only follow a clean and simple design. Thirdly, the leading team should be in touch and accessible. Ideally, an involved PhD-candidate is appointed as primary contact person. Lastly, be inclusive and actively involve all participants the consortium's course. Global consortia are critical for personalized medicine in rare diseases. Also, they are essential for setting up trials to investigate generic drugs and personalized therapies. We hope to herewith stimulate others that are starting (or are planning to start) a global consortium, ultimately to help improve the care for patients with a rare disease.

Keywords: BSEP; Consortium; FIC1; NAPPED; PFIC; Rare diseases.

MeSH terms

Cholestasis, Intrahepatic / diagnosis
Cholestasis, Intrahepatic / genetics*
Cholestasis, Intrahepatic / therapy
Consensus
Databases, Factual
Genetic Diseases, Inborn / diagnosis
Genetic Diseases, Inborn / genetics*
Genetic Diseases, Inborn / therapy
Humans
Practice Guidelines as Topic*
Rare Diseases / diagnosis
Rare Diseases / genetics*
Rare Diseases / therapy