A methodological framework for drug development in rare diseases

Orphanet Journal of Rare Diseases
Patrice NonyEpi-CRESim

Abstract

Developing orphan drugs is challenging because of their severity and the requisite for effective drugs. The small number of patients does not allow conducting adequately powered randomized controlled trials (RCTs). There is a need to develop high quality, ethically investigated, and appropriately authorized medicines, without subjecting patients to unnecessary trials. The main aim is to develop generalizable framework for choosing the best-performing drug/endpoint/design combinations in orphan drug development using an in silico modeling and trial simulation approach. The two main objectives were (i) to provide a global strategy for each disease to identify the most relevant drugs to be evaluated in specific patients during phase III RCTs, (ii) and select the best design for each drug to be used in future RCTs. In silico phase III RCT simulation will be used to find the optimal trial design and was carried out in two steps: (i) statistical analysis of available clinical databases and (ii) integrative modeling that combines mathematical models for diseases with pharmacokinetic-pharmacodynamics models for the selected drug candidates. There is a need to speed up the process of orphan drug development, develop new methods for tran...Continue Reading

References

Dec 1, 1976·American Journal of Epidemiology·O S Miettinen
Jun 1, 1991·Journal of Clinical Pharmacology·B Spilker
Dec 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·S ShakC L Baker
Feb 1, 1982·The American Journal of Medicine·H SacksH Smith
Jan 1, 1980·Bulletin of Mathematical Biology·H C Yeh, G M Schum
May 1, 1995·Epidemiology·S Suissa
Aug 1, 1993·Statistics in Medicine·P Urbach
Dec 1, 1996·Journal of Clinical Epidemiology·P PeduzziA R Feinstein
Apr 29, 1998·Trends in Pharmacological Sciences·P NonyJ P Boissel
Jun 5, 1998·Annual Review of Public Health·J P Newhouse, M McClellan
Nov 24, 1999·BMJ : British Medical Journal·I Chalmers
Jun 22, 2000·The New England Journal of Medicine·J ConcatoR I Horwitz
Jan 26, 2002·Lancet·David A Grimes, Kenneth F Schulz
Jan 29, 2002·Lancet·David A Grimes, Kenneth F Schulz
May 31, 2002·Clinical Pharmacokinetics·Patrice Nony, Jean-Pierre Boissel
Jan 10, 2003·Journal of Pharmacokinetics and Pharmacodynamics·Sylvie ChabaudUNKNOWN HERapeutic MOdeling and Simulation Group
Jul 16, 2004·Heart·P JepsenH T Sørensen
Dec 25, 2004·Journal of Clinical Epidemiology·Olaf H KlungelA de Boer
Jan 25, 2006·Clinical Pharmacokinetics·Alexia BlesiusPatrice Nony
Feb 6, 2007·Brain Research·Marie-Aimée DronneJean-Pierre Boissel
Dec 8, 2007·Progress in Biophysics and Molecular Biology·G ChapuisatJ P Boissel
Jan 18, 2008·Progress in Biophysics and Molecular Biology·Jean-Pierre BoisselMarie-Aimée Dronne
Jan 30, 2008·Journal of Clinical Epidemiology·Jean-Pierre BoisselAlain Leizorovicz
Apr 29, 2008·Respiratory Physiology & Neurobiology·D J SmithJ R Blake
May 8, 2009·Journal of Cystic Fibrosis : Official Journal of the European Cystic Fibrosis Society·R BuzzettiG Mastella
Jul 7, 2009·Contemporary Clinical Trials·Agathe BajardPatrice Nony
Dec 4, 2009·Journal of Cystic Fibrosis : Official Journal of the European Cystic Fibrosis Society·Donatello SalvatoreGianni Mastella
Mar 17, 2011·Expert Review of Molecular Diagnostics·Marc BuyseAimery de Gramont
May 3, 2011·Journal of Clinical Epidemiology·Samir GuptaAhmed M Bayoumi
Jun 19, 2012·Orphanet Journal of Rare Diseases·Nadia NathanUNKNOWN French RespiRare® Group
Aug 14, 2012·Journal of Cystic Fibrosis : Official Journal of the European Cystic Fibrosis Society·Donatello SalvatoreGianni Mastella
Mar 28, 2013·Orphanet Journal of Rare Diseases·Catherine CornuRima Nabbout

❮ Previous
Next ❯

Citations

Nov 28, 2015·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Valentina FrancoEmilio Perucca
Apr 27, 2017·The New England Journal of Medicine·Richard A Moscicki, P K Tandon
Jun 3, 2017·Briefings in Bioinformatics·Jocelyn GalEmmanuel Chamorey
Sep 12, 2017·Internal Medicine Journal·Paul LacazeAlan H Bittles
Apr 28, 2017·The New England Journal of Medicine·Nikolaos Evangelatos, Angela Brand
Aug 25, 2017·Orphanet Journal of Rare Diseases·Kojiro MaedaTeruyo Arato
Jun 3, 2020·Scientific Reports·Maryam Lotfi ShahrezaJames R Green
May 14, 2020·Experimental Biology and Medicine·Sandra H BlumenrathDanilo Tagle
Jan 14, 2017·Mathematical Medicine and Biology : a Journal of the IMA·N EymardUNKNOWN CRESim project group
Jul 25, 2019·Journal of Pharmacokinetics and Pharmacodynamics·Mariam A AhmedReena V Kartha
Mar 12, 2020·Thérapie·Patrice NonyUNKNOWN CRESim, Epi-CRESim research groups

❮ Previous
Next ❯

Methods Mentioned

BETA
rheology

Software Mentioned

CRESim )
- Simulation (

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.

Related Papers

Interventional Neuroradiology : Journal of Peritherapeutic Neuroradiology, Surgical Procedures and Related Neurosciences
U Mansmann
© 2021 Meta ULC. All rights reserved