Towards regulatory endorsement of drug development tools to promote the application of model-informed drug development in Duchenne muscular dystrophy

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

Towards regulatory endorsement of drug development tools to promote the application of model-informed drug development in Duchenne muscular dystrophy.

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

Appropriateness Criteria for Ureteral Stent Omission following Ureteroscopy for Urinary Stone Disease

Introduction: To bridge the gap between evidence and clinical judgment, we defined scenarios appropriate for ureteral stent omission after uncomplicated ureteroscopy (URS) using the RAND/UCLA Appropriateness Method. We retrospectively assessed rates of appropriate stent omission, with the goal to implement these criteria in clinical practice. Methods: A panel of 15 urologists from the MUSIC (Michigan Urological Surgery Improvement Collaborative) met to define uncomplicated URS and the variables that influence stent omission decision making. Over 2 rounds, they scored clinical scenarios for appropriateness criteria (AC) for stent omission based on a combination of variables. AC were defined by median scores of 1 to 3 (inappropriate), 4 to 6 (uncertain) and 7 to 9 (appropriate). Multivariable analysis determined the association of each variable with AC scores. Uncomplicated URS cases in the MUSIC registry were assigned AC scores and stenting rates assessed. Results: Seven variables affecting stent decision making were identified. Of the 144 scenarios, 26 (18%) were appropriate, 88 (61%) inappropriate and 30 (21%) uncertain for stent omission. Most scenarios appropriate for omission were pre-stented (81%). Scenarios with ureteral access sheath or stones \u3e10 mm were only appropriate if pre-stented. Stenting rates of 5,181 URS cases correlated with AC scores. Stents were placed in 61% of cases appropriate for omission (practice range, 25% to 98%). Conclusions: We defined objective variables and AC for stent omission following uncomplicated URS. AC scores correlated with stenting rates but there was substantial practice variation. Our findings demonstrate that the appropriate use of stent omission is underutilized

Towards regulatory endorsement of drug development tools to promote the application of model-informed drug development in Duchenne muscular dystrophy

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