Towards regulatory endorsement of drug development tools to promote the application of model-informed drug development in Duchenne muscular dystrophy.pdf
Drug development tools; Duchenne muscular dystrophy consortium (D-RSC); Model-informed drug development; Rare diseases; Regulatory endorsement
Abstract :
[en] 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.
Disciplines :
Pediatrics Neurology
Author, co-author :
Conrado, Daniela J.
Larkindale, Jane
Berg, Alexander
Hill, Micki
Burton, Jackson
Abrams, Keith R.
Abresch, Richard T.
Bronson, Abby
Chapman, Douglass
Crowther, Michael
Duong, Tina
Gordish-Dressman, Heather
Harnisch, Lutz
Henricson, Erik
Kim, Sarah
McDonald, Craig M.
Schmidt, Stephan
Vong, Camille
Wang, Xiaoxing
Wong, Brenda L.
Yong, Florence
Romero, Klaus
Servais, Laurent ; Université de Liège - ULiège > Département des sciences cliniques > Département des sciences cliniques
PDUFA Reauthorization Performance Goals and Procedures Fiscal Years 2018 through 2022. https://www.fda.gov/downloads/ForIndustry/UserFees/PrescriptionDrugUserFee/UCM511438.pdf
Conrado DJ, Karlsson MO, Romero K, Sarr C, Wilkins JJ (2017) Open innovation: towards sharing of data, models and workflows. Eur J Pharm Sci Off J Eur Fed Pharm Sci. 15(109S):S65–S71
Haas M, Stephenson D, Romero K, Gordon MF, Zach N, Geerts H, Brain Health Modeling Initiative (BHMI) (2016) Big data to smart data in Alzheimer’s disease: real-world examples of advanced modeling and simulation. Alzheimers Dement J Alzheimers Assoc. 12(9):1022–1030
Ito K, Corrigan B, Romero K, Anziano R, Neville J, Stephenson D, Lalonde R (2013) Understanding placebo responses in Alzheimer’s disease clinical trials from the literature meta-data and CAMD database. J Alzheimers Dis JAD. 37(1):173–183
Romero K, Ito K, Rogers JA, Polhamus D, Qiu R, Stephenson D, Mohs R, Lalonde R, Sinha V, Wang Y, Brown D, Isaac M, Vamvakas S, Hemmings R, Pani L, Bain LJ, Corrigan B, Alzheimer’s Disease Neuroimaging Initiative, Coalition Against Major Diseases (2015) The future is now: model-based clinical trial design for Alzheimer’s disease. Clin Pharmacol Ther 97(3):210–214
Romero K, Corrigan B, Tornoe CW, Gobburu JV, Danhof M, Gillespie WR, Gastonguay MR, Meibohm B, Derendorf H (2010) Pharmacometrics as a discipline is entering the “industrialization” phase: standards, automation, knowledge sharing, and training are critical for future success. J Clin Pharmacol 50(9 Suppl):9S–19S
Romero K, Sinha V, Allerheiligen S, Danhof M, Pinheiro J, Kruhlak N, Wang Y, Wang S-J, Sauer J-M, Marier JF, Corrigan B, Rogers J, Lambers Heerspink HJ, Gumbo T, Vis P, Watkins P, Morrison T, Gillespie W, Gordon MF, Stephenson D, Hanna D, Pfister M, Lalonde R, Colatsky T (2014) Modeling and simulation for medical product development and evaluation: highlights from the FDA-C-Path-ISOP 2013 workshop. J Pharmacokinet Pharmacodyn 41(6):545–552
FAQs About Rare Diseases|Genetic and Rare Diseases Information Center (GARD)—an NCATS Program [Internet]. [cited 2019 Jan 9]. https://rarediseases.info.nih.gov/diseases/pages/31/faqs-about-rare-diseases
Gobburu JVS, Lesko LJ (2009) Quantitative disease, drug, and trial models. Annu Rev Pharmacol Toxicol 49(1):291–301
Romitti PA, Zhu Y, Puzhankara S, James KA, Nabukera SK, Zamba GKD, Ciafaloni E, Cunniff C, Druschel CM, Mathews KD, Matthews DJ, Meaney FJ, Andrews JG, Conway KMC, Fox DJ, Street N, Adams MM, Bolen J, on behalf of the MD STARnet (2015) Prevalence of Duchenne and Becker Muscular Dystrophies in the United States. Pediatrics 135(3):513–521
Aartsma-Rus A, Ginjaar IB, Bushby K (2016) The importance of genetic diagnosis for Duchenne muscular dystrophy. J Med Genet 53(3):145–151
McDonald CM, Henricson EK, Abresch RT, Duong T, Joyce NC, Hu F, Clemens PR, Hoffman EP, Cnaan A, Gordish-Dressman H (2018) Long-term effects of glucocorticoids on function, quality of life, and survival in patients with Duchenne muscular dystrophy: a prospective cohort study. The Lancet. 391(10119):451–461
Arora H, Willcocks RJ, Lott DJ, Harrington AT, Senesac CR, Zilke KL, Daniels MJ, Xu D, Tennekoon GI, Finanger EL, Russman BS, Finkel RS, Triplett WT, Byrne BJ, Walter GA, Sweeney HL, Vandenborne K (2018) Longitudinal timed function tests in Duchenne muscular dystrophy: imagingDMD cohort natural history. Muscle Nerve 58(5):631–638
Gloss D, Moxley RT, Ashwal S, Oskoui M (2016) Practice guideline update summary: corticosteroid treatment of Duchenne muscular dystrophy: Report of the Guideline Development Subcommittee of the American Academy of Neurology. Neurology. 86(5):465–472
Bushby K, Finkel R, Birnkrant DJ, Case LE, Clemens PR, Cripe L, Kaul A, Kinnett K, McDonald C, Pandya S, Poysky J, Shapiro F, Tomezsko J, Constantin C, DMD Care Considerations Working Group (2010) Diagnosis and management of Duchenne muscular dystrophy, part 1: diagnosis, and pharmacological and psychosocial management. Lancet Neurol. 9(1):77–93
Salzberg DC, Mann JR, McDermott S (2018) Differences in race and ethnicity in muscular dystrophy mortality rates for males under 40 Years of Age, 2006–2015. Neuroepidemiology. 50(3–4):201–206
Guiraud S, Davies KE (2017) Pharmacological advances for treatment in Duchenne muscular dystrophy. Curr Opin Pharmacol 34:36–48
Drug Development Pipeline [Internet]. Parent Project Muscular Dystrophy. [cited 2019 Jan 9]. https://www.parentprojectmd.org/research/current-research/drug-development-pipeline/
McDonald CM, Henricson EK, Abresch RT, Han JJ, Escolar DM, Florence JM, Duong T, Arrieta A, Clemens PR, Hoffman EP, Cnaan A (2013) The cooperative international neuromuscular research group duchenne natural history study—a longitudinal investigation in the era of glucocorticoid therapy: design of protocol and the methods used. Muscle Nerve 48(1):32–54
Ricotti V, Ridout DA, Pane M, Main M, Mayhew A, Mercuri E, Manzur AY, Muntoni F, UK NorthStar Clinical Network (2016) The NorthStar ambulatory assessment in Duchenne muscular dystrophy: considerations for the design of clinical trials. J Neurol Neurosurg Psychiatry 87(2):149–155
Pane M, Mazzone ES, Sivo S, Sormani MP, Messina S, D’Amico A, Carlesi A, Vita G, Fanelli L, Berardinelli A, Torrente Y, Lanzillotta V, Viggiano E, Ambrosio DP, Cavallaro F, Frosini S, Barp A, Bonfiglio S, Scalise R, De Sanctis R, Rolle E, Graziano A, Magri F, Palermo C, Rossi F, Donati MA, Sacchini M, Arnoldi MT, Baranello G, Mongini T, Pini A, Battini R, Pegoraro E, Previtali S, Bruno C, Politano L, Comi GP, Bertini E, Mercuri E (2014) Long term natural history data in ambulant boys with Duchenne muscular dystrophy: 36-month changes. PLoS ONE 9(10):e108205
A study of Tadalafil for Duchenne Muscular Dystrophy—full text view—ClinicalTrials.gov [Internet]. [cited 2019 Jan 9]. https://clinicaltrials.gov/ct2/show/NCT01865084
Open label study of GSK2402968 in subjects with Duchenne muscular dystrophy—full text view—ClinicalTrials.gov [Internet]. [cited 2019 Jan 9]. https://clinicaltrials.gov/ct2/show/NCT01480245
Phase 2b study of PTC124 in Duchenne/Becker muscular dystrophy (DMD/BMD)—full text view—ClinicalTrials.gov [Internet]. [cited 2019 Jan 9]. https://clinicaltrials.gov/ct2/show/NCT00592553
A phase 2 study to evaluate the safety, efficacy, pharmacokinetics and pharmacodynamics of PF-06252616 in Duchenne muscular dystrophy—full text view—ClinicalTrials.gov [Internet]. [cited 2019 Jan 9]. https://clinicaltrials.gov/ct2/show/NCT02310763
Goemans N, Tulinius M, Kroksmark A-K, Wilson R, van den Hauwe M, Campion G (2017) Comparison of ambulatory capacity and disease progression of Duchenne muscular dystrophy subjects enrolled in the drisapersen DMD114673 study with a matched natural history cohort of subjects on daily corticosteroids. Neuromuscul Disord NMD. 27(3):203–213
Bello L, Morgenroth LP, Gordish-Dressman H, Hoffman EP, McDonald CM, Cirak S, CINRG investigators (2016) DMD genotypes and loss of ambulation in the CINRG Duchenne Natural History Study. Neurology. 87(4):401–409
Senesac CR, Lott DJ, Willcocks RJ, Duong T, Smith BK (2019) Lower extremity functional outcome measures in duchenne muscular dystrophy-a Delphi survey. J Neuromuscul Dis. 6(1):75–83
Conrado DJ, Denney WS, Chen D, Ito K (2014) An updated Alzheimer’s disease progression model: incorporating non-linearity, beta regression, and a third-level random effect in NONMEM. J Pharmacokinet Pharmacodyn 41(6):581–598
Ahn JE, Karlsson MO, Dunne A, Ludden TM (2008) Likelihood based approaches to handling data below the quantification limit using NONMEM VI. J Pharmacokinet Pharmacodyn 35(4):401–421
Bergstrand M, Karlsson MO (2009) Handling data below the limit of quantification in mixed effect models. AAPS J 11(2):371–380
Schram G, Fournier A, Leduc H, Dahdah N, Therien J, Vanasse M, Khairy P (2013) All-cause mortality and cardiovascular outcomes with prophylactic steroid therapy in Duchenne muscular dystrophy. J Am Coll Cardiol 61(9):948–954
Passamano L, Taglia A, Palladino A, Viggiano E, D’Ambrosio P, Scutifero M, Rosaria Cecio M, Torre V, Luca DE, Picillo E, Paciello O, Piluso G, Nigro G, Politano L (2012) Improvement of survival in Duchenne muscular dystrophy: retrospective analysis of 835 patients. Acta Myol 31(2):121–125
Rall S, Grimm T (2012) Survival in Duchenne muscular dystrophy. Acta Myol 31(2):117–120
Van Ruiten HJA, Marini Bettolo C, Cheetham T, Eagle M, Lochmuller H, Straub V, Bushby K, Guglieri M (2016) Why are some patients with Duchenne muscular dystrophy dying young: an analysis of causes of death in North East England. Eur J Paediatr Neurol 20(6):904–909
Kohavi R (1995) A study of cross-validation and bootstrap for accuracy estimation and model selection. Ijcai 14:1137–1145
Research C for DE and development & approval process (Drugs)—drug development tools: fit-for-purpose Initiative [Internet]. [cited 2019 Jan 10]. https://www.fda.gov/drugs/developmentapprovalprocess/ucm505485.htm