A methodological framework for drug development in rare diseases.

Vitaly Volpert; Nathalie Eymard; Behrouz Kassai; Leon Aarons; Agathe Bajard; Clément Ballot; Yves Bertrand; Frank Bretz; Daan Caudri; Charlotte Castellan; Salma Malik; Sylvie Chabaud; Catherine Cornu; Frank Dufour; Cornelia Dunger-Baldauf; Jean-Marc Dupont; Roland Fisch; Renzo Guerrini; Behrouz Kassaï; Patrice Nony; Kayode Ogungbenro; David Pérol; Gérard Pons; Harm Tiddens; Anna Rosati; Corinne Alberti; Catherine Chiron; Polina Kurbatova; Rima Nabbout; Vincent Jullien; Pascal Benquet; Fabrice Wendling

doi:10.1186/s13023-014-0164-y

A methodological framework for drug development in rare diseases.

Vitaly Volpert, Nathalie Eymard, Behrouz Kassai, Leon Aarons (Collaborator), Agathe Bajard (Collaborator), Clément Ballot (Collaborator), Yves Bertrand (Collaborator), Frank Bretz (Collaborator), Daan Caudri (Collaborator), Charlotte Castellan (Collaborator), Salma Malik (Collaborator), Sylvie Chabaud (Collaborator), Catherine Cornu (Collaborator), Frank Dufour (Collaborator), Cornelia Dunger-Baldauf (Collaborator), Jean-Marc Dupont (Collaborator), Roland Fisch (Collaborator), Renzo Guerrini (Collaborator), Behrouz Kassaï (Collaborator), Patrice Nony (Collaborator)Kayode Ogungbenro (Collaborator), David Pérol (Collaborator), Gérard Pons (Collaborator), Harm Tiddens (Collaborator), Anna Rosati (Collaborator), Corinne Alberti (Collaborator), Catherine Chiron (Collaborator), Polina Kurbatova (Collaborator), Rima Nabbout (Collaborator), Vincent Jullien (Collaborator), Pascal Benquet (Collaborator), Fabrice Wendling (Collaborator)

Pharmacy

Research output: Contribution to journal › Article › peer-review

Abstract

INTRODUCTION: 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. AIMS AND OBJECTIVES: 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. METHODOLOGICAL APPROACH: 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. CONCLUSION: There is a need to speed up the process of orphan drug development, develop new methods for translational research and personalized medicine, and contribute to European Medicines Agency guidelines. The approach presented here offers many perspectives in clinical trial conception.

Original language	English
Journal	Orphanet Journal of Rare Diseases
Volume	9
DOIs	https://doi.org/10.1186/s13023-014-0164-y
Publication status	Published - 2014

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Volpert, V., Eymard, N., Kassai, B., Aarons, L., Bajard, A., Ballot, C., Bertrand, Y., Bretz, F., Caudri, D., Castellan, C., Malik, S., Chabaud, S., Cornu, C., Dufour, F., Dunger-Baldauf, C., Dupont, J.-M., Fisch, R., Guerrini, R., Kassaï, B., ... Wendling, F. (2014). A methodological framework for drug development in rare diseases. Orphanet Journal of Rare Diseases, 9. https://doi.org/10.1186/s13023-014-0164-y

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title = "A methodological framework for drug development in rare diseases.",

abstract = "INTRODUCTION: 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. AIMS AND OBJECTIVES: 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. METHODOLOGICAL APPROACH: 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. CONCLUSION: There is a need to speed up the process of orphan drug development, develop new methods for translational research and personalized medicine, and contribute to European Medicines Agency guidelines. The approach presented here offers many perspectives in clinical trial conception.",

author = "Vitaly Volpert and Nathalie Eymard and Behrouz Kassai and Leon Aarons and Agathe Bajard and Cl{\'e}ment Ballot and Yves Bertrand and Frank Bretz and Daan Caudri and Charlotte Castellan and Salma Malik and Sylvie Chabaud and Catherine Cornu and Frank Dufour and Cornelia Dunger-Baldauf and Jean-Marc Dupont and Roland Fisch and Renzo Guerrini and Behrouz Kassa{\"i} and Patrice Nony and Kayode Ogungbenro and David P{\'e}rol and G{\'e}rard Pons and Harm Tiddens and Anna Rosati and Corinne Alberti and Catherine Chiron and Polina Kurbatova and Rima Nabbout and Vincent Jullien and Pascal Benquet and Fabrice Wendling",

year = "2014",

doi = "10.1186/s13023-014-0164-y",

language = "English",

volume = "9",

journal = "Orphanet Journal of Rare Diseases",

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Volpert, V, Eymard, N, Kassai, B, Aarons, L, Bajard, A, Ballot, C, Bertrand, Y, Bretz, F, Caudri, D, Castellan, C, Malik, S, Chabaud, S, Cornu, C, Dufour, F, Dunger-Baldauf, C, Dupont, J-M, Fisch, R, Guerrini, R, Kassaï, B, Nony, P, Ogungbenro, K, Pérol, D, Pons, G, Tiddens, H, Rosati, A, Alberti, C, Chiron, C, Kurbatova, P, Nabbout, R, Jullien, V, Benquet, P & Wendling, F 2014, 'A methodological framework for drug development in rare diseases.', Orphanet Journal of Rare Diseases, vol. 9. https://doi.org/10.1186/s13023-014-0164-y

TY - JOUR

T1 - A methodological framework for drug development in rare diseases.

AU - Volpert, Vitaly

AU - Eymard, Nathalie

AU - Kassai, Behrouz

A2 - Aarons, Leon

A2 - Bajard, Agathe

A2 - Ballot, Clément

A2 - Bertrand, Yves

A2 - Bretz, Frank

A2 - Caudri, Daan

A2 - Castellan, Charlotte

A2 - Malik, Salma

A2 - Chabaud, Sylvie

A2 - Cornu, Catherine

A2 - Dufour, Frank

A2 - Dunger-Baldauf, Cornelia

A2 - Dupont, Jean-Marc

A2 - Fisch, Roland

A2 - Guerrini, Renzo

A2 - Kassaï, Behrouz

A2 - Nony, Patrice

A2 - Ogungbenro, Kayode

A2 - Pérol, David

A2 - Pons, Gérard

A2 - Tiddens, Harm

A2 - Rosati, Anna

A2 - Alberti, Corinne

A2 - Chiron, Catherine

A2 - Kurbatova, Polina

A2 - Nabbout, Rima

A2 - Jullien, Vincent

A2 - Benquet, Pascal

A2 - Wendling, Fabrice

PY - 2014

Y1 - 2014

N2 - INTRODUCTION: 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. AIMS AND OBJECTIVES: 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. METHODOLOGICAL APPROACH: 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. CONCLUSION: There is a need to speed up the process of orphan drug development, develop new methods for translational research and personalized medicine, and contribute to European Medicines Agency guidelines. The approach presented here offers many perspectives in clinical trial conception.

AB - INTRODUCTION: 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. AIMS AND OBJECTIVES: 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. METHODOLOGICAL APPROACH: 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. CONCLUSION: There is a need to speed up the process of orphan drug development, develop new methods for translational research and personalized medicine, and contribute to European Medicines Agency guidelines. The approach presented here offers many perspectives in clinical trial conception.

U2 - 10.1186/s13023-014-0164-y

DO - 10.1186/s13023-014-0164-y

M3 - Article

C2 - 25774598

SN - 1750-1172

VL - 9

JO - Orphanet Journal of Rare Diseases

JF - Orphanet Journal of Rare Diseases

ER -

A methodological framework for drug development in rare diseases.

Abstract

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