Towards regulatory endorsement of drug development tools to promote the application of model-informed drug development in Duchenne muscular dystrophy
Conrado DJ., Larkindale J., Berg A., Hill M., Burton J., Abrams KR., Abresch RT., Bronson A., Chapman D., Crowther M., Duong T., Gordish-Dressman H., Harnisch L., Henricson E., Kim S., McDonald CM., Schmidt S., Vong C., Wang X., Wong BL., Yong F., Romero K., Vishwanathan V., Chidambaranathan S., Douglas Biggar W., McAdam LC., Mah JK., Tulinius M., Cnaan A., Morgenroth LP., Leshner R., Tesi-Rocha C., Thangarajh M., Kornberg A., Ryan M., Nevo Y., Dubrovsky A., Clemens PR., Abdel-Hamid H., Connolly AM., Pestronk A., Teasley J., Bertorini TE., Webster R., Kolski H., Kuntz N., Driscoll S., Bodensteiner JB., Gorni K., Lotze T., Day JW., Karachunski P., Henricson EK., Joyce NC., McDonald CM., Campbell C., Torricelli RE., Finkel RS., Flanigan KM., Goemans N., Heydemann P., Kaminska A., Kirschner J., Muntoni F., Osorio AN., Schara U., Sejersen T., Shieh PB., Sweeney HL., Topaloglu H., Tulinius M., Vilchez JJ., Voit T., Wong B., Alfano LN., Eagle M., James MK., Lowes L., Mayhew A., Mazzone ES., Nelson L., Rose KJ., Abdel-Hamid HZ., Apkon SD., Barohn RJ., Bertini E., Bloetzer C., deVaud LC., Butterfield RJ., Chabrol B., Chae JH., Comi GP., Darras BT., Dastgir J., Desguerre I., Escobar RG., Finanger E., Guglieri M., Hughes I., Iannaccone ST.
© 2019, Springer Science+Business Media, LLC, part of Springer Nature. Drug development for rare diseases is challenged by small populations and limited data. This makes development of clinical trial protocols difficult and contributes to the uncertainty around whether or not a potential therapy is efficacious. The use of data standards to aggregate data from multiple sources, and the use of such integrated databases to develop statistical models can inform protocol development and reduce the risks in developing new therapies. Achieving regulatory endorsement of such models through defined pathways at the US Food and Drug Administration and European Medicines Authority allows such tools to be used by the drug development community for defined contexts of use without further need for discussion of the underlying model(s). The Duchenne Regulatory Science Consortium (D-RSC) has brought together multiple stakeholders to develop a clinical trial simulation tool for Duchenne muscular dystrophy using such an approach. Here we describe the work of D-RSC as an example of how such an approach may be effective at reducing uncertainty in drug development for rare diseases, and thus bringing effective therapies to patients faster.