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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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At least 145 records · Page 8
All sourcesNASA NTRSDOE OSTI
DOE OSTI2023

Investigation of the Use of Dynamic Probabilistic Risk Assessment Methodologies for Identifying Digital I&C System Common Cause Failures

Digital Instrumentation and Control (I&C) systems have a key role in nuclear power plants in the upgrade of aging analog systems. Digital systems improve plant safety and reliability through features such as increased hardware reliability and stability and improved failure detection capability. There is no consensus on which of the current probabilistic risk assessment methods are most suitable for use in the reliability analysis of digital I&C systems. While the traditional event-tree/fault-tree (ET/FT) approach is still used for their reliability modeling, there are concerns regarding this approach in properly accounting for dynamic interactions among system components since potentially significant dependencies among failure events may not be identified and/or their likelihood may not be properly quantified. Dynamic methodologies are expected to provide a much more accurate representation of probabilistic evolution of the I&C systems in time due to their capability to more properly account for complex interactions than the static approach. The applicability of dynamic PRA methodologies for digital I&C system is investigated using the criteria presented in the NUREG/CR-6901, and the comparisons made in NUREG/CR-6901 are updated in light of the latest studies. The Dynamic Event Tree (DET) approach has been identified as one of the top dynamic methods when evaluated against the requirements for the reliability modeling of digital I&C systems. The DET method is a strong candidate for integration into existing PRA studies, as it bears many similarities to the traditional ET approach. In this study, the DET approach has been applied to the Plant Protection System of the APR1400 design, and the results are compared to results from its available traditional ET/FT analysis. Possible approaches to evaluate and quantify the effects of common cause failures on system safety using dynamic methods are also examined.

46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND ↗
DOE OSTI2024

A Proposed Evaluation Framework for New and Emerging Low Embodied-Carbon Concrete Technologies

New opportunities for carbon reductions in buildings create a strong need for a common framework and method for those who design, build and influence construction to evaluate lifecycle carbon reductions from design decisions and technology choices. These opportunities include a wide range of low-embodied-carbon concrete materials being rapidly developed and introduced to the market. How to evaluate these newer materials and technologies has become critical for both public- and private-sector actors seeking to decarbonize building constructions by leveraging the Infrastructure Investment and Jobs Act (IIJA) and Inflation Reduction Act (IRA) funds. We propose an evaluation framework to assess the lifecycle carbon reductions from adoption of these technologies, including a subset of key “must have” (1) technical criteria (embodied carbon level, technology development stage); (2) market criteria (market size, scalability); and (3) financial criteria (cost of technology implementation compared to businessas-usual) from a range of options. We discuss how to use the framework and illustrate it using a “heatmap,” rating score and short case study of a promising technology. We also propose a plan to implement this framework that includes (1) standardized measurement and validation methods for verifying emission reductions from these technologies, and (2) avenues to implement real world demonstrations. We conclude with recommendations for next steps on framework refinement and commercialization strategy development.

Singh, Reshma↗
DOE OSTI2023

Lawrence Livermore National Laboratory Livermore Site: 4200 Block Development Project Soil Sampling and Analysis Plan (June 2023)

This Soil Sampling and Analysis Plan (SAP) was prepared by the Environmental Function Area (EFA)/Technical Services Department (TSD) of the Environment, Safety & Health (ES&H) Directorate for the Project Management Office (PMO) for the proposed Maintenance Shop Facility in the 4200 Block (project). The purpose of the SAP is to describe the procedures for collection and analysis of environmental samples and evaluation of analytical data (chemical and radiological) to determine management options of excavated soil during project construction. This SAP follows criteria established in Lawrence Livermore National Laboratory’s (LLNL) Soils Screening and Management Plan (SSMP) (LLNL 2022), which was formalized in accordance with U.S. Environmental Protection Agency (EPA) guidance for developing Data Quality Objectives for environmental data (EPA 2006) and the Multi-Agency Radiation Survey and Site Investigation Manual (MARSSIM) guidance (U.S. NRC, U.S. EPA, U.S. DOE, and U.S. DOD 2000). The scope of this SAP is based on design information provided by PMO.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2020

Sample problems for Section III, Division 5 design by inelastic analysis of Grade 91 components

This report works through two sample design analyses of representative Grade 91 components using the ASME Boiler & Pressure Vessel Code Section III, Division 5, Appendix HBB-T rules for the strain and deformation and creep-fatigue design criteria using a design by inelastic analysis approach. The component geometries and loadings were selected to span a wide variety of potential applications. The sample components are an endplate geometry, which is fairly representative of typical pressure vessel construction, and a core block, representing a critical component in a heat pipe microreactor, which has a complicated geometry and complex thermal stress history. These sample problems serve several functions. First, they are complete worked examples of how to apply the current design by inelastic analysis rules. Second, they serve as test cases to evaluate the current rules and provide feedback on how they could be optimized to deal with complicated component geometries or to be better automated in modern finite element analysis software. Finally, the analysis here uses an inelastic constitutive model for Grade 91 developed by Argonne National Laboratory and proposed for inclusion in the ASME Boiler & Pressure Vessel Code Section III, Division 5 rules as a reference constitutive model. Using this constitutive model in the sample problem analyses tests the model in the context of the ASME Code rules. The final conclusions of this report are that the material model and the current Code rules are satisfactory, but that the Code rules could be optimized to simplify automation and reduce over conservatism. Future work should address the specific optimization topics discussed in this report.

22 GENERAL STUDIES OF NUCLEAR REACTORS↗
DOE OSTI2020

Pre-Commercial Scale-Up of a Gas-Fired Absorption Heat Pump

The project sought to advance the maturity of SMTI’s 80 kBTU/hr residential space and water heating GAHP from the engineering prototype stage (TRL-7) to pre-production readiness by addressing manufacturing, balance of system design and installation, cost, reliability, and field application questions. As part of this project, the project team has: (1) Matured the design package for a commercially ready product (2) Demonstrated compliance with relevant ANSI standards (3) Completed manufacturing and assembly process specifications (4) Completed total production cost estimates and capital equipment requirements (5) Initiated component and system level reliability assessments (6) Completed a small field demonstration including measured performance, installation requirements and expected costs, and customer/key stakeholder feedback. (7) Completed a Techno-economic analysis for representative applications and climate zones, including justification for utility incentive programs. (8) Completed a market intelligence report. Scope of Work: A multi-faceted project was completed that included: (a) design for manufacturing tasks for both the sealed system and balance of system, (b) development and trial of key manufacturing processes and techniques, (c) evaluation of component and system level reliability, (d) exploration of make/buy decisions including impact on cost and required capital. Additionally, (e) installation and monitoring of a small number of field test units was completed to demonstrate energy savings and collect customer/installer feedback, and (f) a focused market research task was completed to explore potential barriers and improve market introduction plans. These tasks addressed many of the remaining technical risks regarding long-term reliability, verification of manufacturing cost estimates and identification of cost concerns, identify installation and balance of system design criteria necessary to achieve energy savings and installed cost goals, and identify market barriers and strategies prior to product market introduction.

03 NATURAL GAS↗
DOE OSTI2023

Lawrence Livermore National Laboratory Experimental Test Site 300 (Site 300): Site 300 Roadway Improvements - Chem Mag Loop Soil Sampling and Analysis Plan (May 2023)

This Soil Sampling and Analysis Plan (SAP) was prepared by the Environmental Function Area (EFA)/Technical Services Department (TSD) of the Environment, Safety & Health (ES&H) Directorate for the Project Management Office (PMO) for the proposed Roadway Improvements Project at the Chem Mag Loop (project). The purpose of the SAP is to describe the procedures for collection and analysis of environmental samples and evaluation of analytical data (chemical and radiological) to determine management options of excavated soil during project construction. This SAP follows criteria established in Lawrence Livermore National Laboratory’s (LLNL) Soils Screening and Management Plan (SSMP) (LLNL 2022), which was formalized in accordance with U.S. Environmental Protection Agency (EPA) guidance for developing Data Quality Objectives for environmental data (EPA 2006) and the Multi-Agency Radiation Survey and Site Investigation Manual (MARSSIM) guidance (U.S. NRC, U.S. EPA, U.S. DOE, and U.S. DOD 2000). The scope of this SAP is based on preliminary design information provided to EFA by PMO.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2023

Lawrence Livermore National Laboratory Experimental Test Site 300 (Site 300): Site 300 Roadway Improvements - 836 Complex Soil Sampling and Analysis Plan (May 2023)

This Soil Sampling and Analysis Plan (SAP) was prepared by the Environmental Functional Area (EFA)/Technical Services Department (TSD) of the Environment, Safety & Health (ES&H) Directorate for the Project Management Office (PMO) for the proposed Roadway Improvements Project at the 836 Complex (project). The purpose of the SAP is to describe the procedures for collection and analysis of environmental samples and evaluation of analytical data (chemical and radiological) to determine management options of excavated soil during project construction. This SAP follows criteria established in Lawrence Livermore National Laboratory’s (LLNL) Soils Screening and Management Plan (SSMP) (LLNL 2022), which was formalized in accordance with U.S. Environmental Protection Agency (EPA) guidance for developing Data Quality Objectives for environmental data (EPA 2006) and the Multi-Agency Radiation Survey and Site Investigation Manual (MARSSIM) guidance (U.S. NRC, U.S. EPA, U.S. DOE, and U.S. DOD 2000). The scope of this SAP is based on preliminary design information provided by PMO.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2023

Lawrence Livermore National Laboratory Experimental Test Site, Site 300: S300 Roadway Improvements - 854 Complex Soil Sampling and Analysis Plan (June 2023)

This Soil Sampling and Analysis Plan (SAP) was prepared by the Environmental Functional Area (EFA)/Technical Services Department (TSD) of the Environment, Safety & Health (ES&H) Directorate for the Project Management Office (PMO) for the proposed Roadway Improvements Project at the Building 854 Complex (project). The purpose of the SAP was to identify chemicals of concern, describe the procedures for collection and analysis of environmental samples, and evaluation of analytical data (chemical and radiological) to determine management options of excavated soil during project construction. This SAP follows criteria established in Lawrence Livermore National Laboratory’s (LLNL) Soils Screening and Management Plan (SSMP) (LLNL 2022), which was formalized in accordance with U.S. Environmental Protection Agency (EPA) guidance for developing Data Quality Objectives for environmental data (EPA 2006) and the Multi-Agency Radiation Survey and Site Investigation Manual (MARSSIM) guidance (U.S. NRC, U.S. EPA, U.S. DOE, and U.S. DOD 2000). The scope of this SAP is based on preliminary design information provided by PMO.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2023

Site 300 Roadway Improvements - 834 Complex Soil Sampling and Analysis Plan

This Soil Sampling and Analysis Plan (SAP) was prepared by the Environmental Functional Area (EFA)/Technical Services Department (TSD) of the Environment, Safety & Health (ES&H) Directorate for the Project Management Office (PMO) for the proposed Roadway Improvements Project at the 834 Complex (project) (Figure 1). The purpose of the SAP is to describe the procedures for collection and analysis of environmental samples and evaluation of analytical data (chemical and radiological) to determine management options of excavated soil during project construction. This SAP follows criteria established in Lawrence Livermore National Laboratory’s (LLNL) Soils Screening and Management Plan (SSMP) (LLNL 2022), which was formalized in accordance with U.S. Environmental Protection Agency (EPA) guidance for developing Data Quality Objectives for environmental data (EPA 2006) and the Multi-Agency Radiation Survey and Site Investigation Manual (MARSSIM) guidance (U.S. NRC, U.S. EPA, U.S. DOE, and U.S. DOD 2000). The scope of this SAP is based on preliminary design information provided by PMO.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2023

Building 871 and 874 Retaining Wall Project Soil Sampling and Analysis Plan

This Soil Sampling and Analysis Plan (SAP) was prepared by the Environmental Functional Area (EFA)/Technical Services Department (TSD) of the Environment, Safety & Health (ES&H) Directorate for the Project Management Office (PMO) for the proposed retaining wall near Buildings 871 and 874 (project) (Figure 1). The purpose of the SAP is to describe the procedures for collection and analysis of environmental samples and evaluation of analytical data (chemical and radiological) to determine management options of excavated soil during project construction. This SAP follows criteria established in Lawrence Livermore National Laboratory’s (LLNL) Soils Screening and Management Plan (SSMP) (LLNL 2022), which was formalized in accordance with U.S. Environmental Protection Agency (EPA) guidance for developing Data Quality Objectives for environmental data (EPA 2006) and the Multi-Agency Radiation Survey and Site Investigation Manual (MARSSIM) guidance (U.S. NRC, U.S. EPA, U.S. DOE, and U.S. DOD 2000). The scope of this SAP is based on preliminary design information provided by PMO.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2024

Pop-up Langmuir probe diagnostic in the water cooled divertor of Wendelstein 7-X

The design, development, and successful implementation of pop-up Langmuir probes installed in the water-cooled divertor of W7-X are described. The probes are controlled by drive coils (actuators) installed behind the divertor plates. These drive coils make use of the magnetic field in W7-X to move the probe tips into and out of the plasma. The drive coils were installed in the vacuum vessel after extensively testing the durability of the coils and analyzing the criteria for safe operation. The probe design is carefully tailored for each of the 36 probe tips in order to be suitable for the different magnetic field configurations used in W7-X and ensure that the probes do not present leading edges to the magnetic flux tubes. An electronic bridge circuit is used for measurement to compensate for the effects of signal propagation time on the long cable lengths used. The diagnostic is integrated with the segment control of W7-X for automated operation and control of the diagnostic. The evaluation of the results from the plasma operation is presented after accounting for appropriate sheath expansion for negative bias voltage on the probes.

46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND ↗
DOE OSTI2020

Mind the Gap: Building Simulation in the Architectural Design Studio

Building modelling and simulation approaches are increasingly being utilized in architectural design studios to guide and inform the design process and offer evidence-based feedback on proposed building performance. The development of intuitive and simplified simulation interfaces has greatly contributed to achieving this integration. One aspect that is often overlooked is the workflow that governs and regulates integrated design, which can have significant impacts on final design outcomes. Currently there are numerous software packages available for building performance simulations. This makes it challenging to select an appropriate tool that provides accurate results yet allows a designer to make informed architectural decisions with a designer-friendly interface. Furthermore, workflows to incorporate simulations into the design process proved to highly impact student’s project design integration. Yet, it is not clear what type of workflows are successful to achieve this goal, under what conditions, and/or for which building and site typologies. This paper addresses these issues by first reviewing three different workflows for integrating building performance simulation processes and highlighting their strengths and weaknesses. Second, a comparative case study approach was employed to test three of the most common workflows in three different integrated design architectural studios at the senior and vertical studio levels as well as in two courses that run parallel and complementary to the design studios. The workflows, processes, and the resultant student projects were further analyzed based on criteria for better integrated design and architectural excellence as outlined in the American Institute of Architects Committee on the Environment (AIA COTE) Top 10 Student’s Competition. Third, to situate the pedagogical case studies’ results within a larger context, a survey of the AIA COTE Top 10 student competition award recipients over the last five years was conducted. The results are summarized in a pedagogical framework that outlines best strategies of the type of workflows, software, design process used, methods to achieve desired interaction between design process and analytical feedback, and metrics for educators to evaluate the success of this integration and their learning outcomes in the design studio. The goal is to help bridge the gap between the building design and simulation within the design studio’s creative process for more integrated design outcomes.

Elzeyadi, Ihab↗
DOE OSTI2025

Ammonium Looping with Membrane Absorber and Distributed Stripper for Enhanced Algae Growth

The objective of this project is to conduct a comprehensive investigation to develop and demonstrate a practical, reliable, and cost-effective integrated carbon dioxide (CO 2 ) capture and biofixation process for algae production. This process utilizes a chemical hindered ammonium solution (NH 4 OH) as both a capture reagent and an algae nutrient. The membrane absorber employed in the system ensured minimal ammonia (NH 3 ) emissions in the treated flue gas. Additionally, distributed solar-energy powered strippers located near the bioreactor modules facilitate solvent regeneration and enable just-in-time delivery of CO 2 and NH 3 to the algae, thereby minimizing the pH swing for enhanced productivity. The proposed membrane CO 2 absorber and solar-powered stripper is designed and seamlessly integrated with the existing 0.1 MWth bench-scale CO 2 capture system (CCS) and open raceway ponds (ORPs) at the University of Kentucky Center for Applied Energy (UK CAER) campus. The entire integrated process has undergone construction, operation, testing, and analysis. Furthermore, technology has been evaluated with a techno-economic analysis (TEA), technology gap analysis (TGA), life-cycle analysis (LCA), and a technology maturation plan (TMP). This project was performed within two budget periods, 54 months in duration. There are fourteen Project Tasks, twelve Milestones and four Success Criteria.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2025

Host Onboarding Tool (HObT) v1.0.0

The Host OnBoarding Tool (Hobt) is a publicly accessible, web-based software designed to organize and share information about microbial hosts under development at the Agile BioFoundry (ABF). It streamlines the assessment, tracking, and sharing of information related to microbial host development and provides a centralized platform where users can rapidly evaluate hosts' readiness for various bio processes. HObT leverages the Tier System, a standardized host development framework that organizes and assesses microbial hosts based on their readiness for biomanufacturing. Each tier outlines key targets—including genetic tools, growth conditions, omics data, and predictive models—needed to transform new or emerging microbes into established production platforms. By applying clear criteria for advancement, the Tier System helps users quickly evaluate each organism's current development status, identify gaps in available knowledge or tools, and prioritize future strain improvement efforts. Through its user-friendly interface, HObT encourages contributions of new data and insights from researchers, fostering collaboration and accelerating host development. By providing structured guidance for microbial strain advancement, HObT and the Tier System support more systematic, rapid, and cost-effective development of non-traditional microbial hosts, ultimately enhancing the efficiency and impact of biomanufacturing research and applications.

Plahar, Hector [Lawrence Berkeley National Laborat↗
DOE OSTI2024

Rapid Assessment of Sulfate Resistance in Mortar and Concrete

Extensive research has been conducted on the sulfate attack of concrete structures; however, the need to adopt the use of more sustainable materials is driving a need for a quicker test method to assess sulfate resistance. This work presents accelerated methods that can reduce the time required for assessing the sulfate resistance of mixtures by 70%. Class F fly ash has historically been used in concrete mixtures to improve sulfate resistance. However, environmental considerations and the evolving energy industry have decreased its availability, requiring the identification of economically viable and environmentally friendly alternatives to fly ash. Another challenge in addressing sulfate attack durability issues in concrete is that the standard sulfate attack test (ASTM C1012) is time-consuming and designed for only standard mortars (not concrete mixtures). To expedite the testing process, accelerated testing methods for both mortar and concrete mixtures were adopted from previous work to further the development of the accelerated tests and to assess the feasibility of testing the sulfate resistance of mortar and concrete mixtures rapidly. This study also established criteria for interpreting sulfate resistance for each of the test methods used in this work. A total of 14 mortar mixtures and four concrete mixtures using two types of Portland cement (Type I and Type I/II) and various supplementary cementitious materials (SCMs) were evaluated in this study. The accelerated testing methods significantly reduced the evaluation time from 12 months to 21 days for mortar mixtures and from 6 months to 56 days for concrete mixtures. The proposed interpretation method for mortar accelerated test results showed acceptable consistency with the ACI 318-19 interpretations for ASTM C1012 results. The interpretation methods proposed for the two concrete sulfate attack tests demonstrated excellent consistency with the ASTM C1012 results from mortar mixtures with the same cementitious materials combinations. Metakaolin was shown to improve sulfate resistance for both mortar and concrete mixtures, while silica fume and natural pozzolan had a limited impact. Using 15% metakaolin in mortar or concrete mixtures with Type I/II cement provided the best sulfate resistance.

Chemistry↗
DOE OSTI2025

PowerModel-AI: A First On-the-Fly Machine-Learning Predictor for AC Power Flow Solutions

The real-time creation of machine-learning models via active or on-the-fly learning has attracted considerable interest across various scientific and engineering disciplines. These algorithms enable machines to build models autonomously while remaining operational. Through a series of query strategies, the machine can evaluate whether newly encountered data fall outside the scope of the existing training set. In this study, we introduce PowerModel-AI, an end-to-end machine learning software designed to accurately predict AC power flow solutions. We present detailed justifications for our model design choices and demonstrate that selecting the right input features effectively captures load flow decoupling inherent in power flow equations. Our approach incorporates on-the-fly learning, where power flow calculations are initiated only when the machine detects a need to improve the dataset in regions where the model’s suboptimal performance is based on specific criteria. Otherwise, the existing model is used for power flow predictions. This study includes analyses of five Texas A&M synthetic power grid cases, encompassing the 14-, 30-, 37-, 200-, and 500-bus systems. The training and test datasets were generated using PowerModels.jl, an open-source power flow solver/optimizer developed at Los Alamos National Laboratory, NM, USA.

24 POWER TRANSMISSION AND DISTRIBUTION↗
DOE OSTI2025

Full Submersion Water Testing of SAVY-4000 Nuclear Material Storage Containers

SAVY-4000 (SAVY) containers are the primary container used at Technical Area (TA) TA-55 plutonium facility for the prevention of water ingress to mitigate against a criticality event. The basis for water resistance of these containers has long been attributed to the Polytetrafluoroethylene (PTFE) membrane that is assembled on the outermost surface of the filter assembly. On August 22nd a test of a container used inside of a glovebox was performed that brought into question this long-standing-basis. This test was performed by inverting a SAVY-lid onto a specialized piece of equipment for evaluating the integrity of the PTFE membrane. During the test water was observed passing through the filter indicating that the filter membrane was no longer preventing the ingress of water through the filter. The assumption after making this observation was that alpha-particles were rapidly degrading the membrane creating a leak path through the underlying aluminosilicate media (Fiberfrax®). The apparatus used was designed to only test the lid rather than the entire SAVY assembly. A test plan, PA-PLAN-01921, was developed to investigate whether a fully assembled container with a fully degraded PTFE membrane would be capable of meeting the criteria defined in PA-RD-1009 of not allowing more than 200 ml of water to enter the container with a water column of 6-inches applied over a 2-hour period. This report provides the results of the testing performed against PA-PLAN-01921.

36 MATERIALS SCIENCE↗
DOE OSTI2025

Pivotal trial characteristics and types of endpoints used to support Food and Drug Administration rare disease drug approvals between 2013 and 2022

Background/aims Rare disease drug development faces unique challenges, such as genotypic and phenotypic heterogeneity within small patient populations and a lack of established outcome measures for conditions without previously successful drug development programs. These challenges complicate the process of selecting the appropriate trial endpoints and conducting clinical trials in rare diseases. In this descriptive study, we examined novel drug approvals for non-oncologic rare diseases by the U.S. Food and Drug Administration’s Center for Drug Evaluation and Research over the past decade and characterized key regulatory and trial design elements with a focus on the primary efficacy endpoint utilized as the basis of approval. Methods Using the Food and Drug Administration’s Data Analysis Search Host database, we identified novel new drug applications and biologics license applications with orphan drug designation that were approved between 2013 and 2022 for non-oncologic indications. From Food and Drug Administration review documents and other external databases, we examined characteristics of pivotal trials for the included drugs, such as therapeutic area, trial design, and type of primary efficacy endpoints. Differences in trial design elements associated with primary efficacy endpoint type were assessed such as randomization and blinding. Then, we summarized the primary efficacy endpoint types utilized in pivotal trials by therapeutic area, approval pathway, and whether the disease etiology is well defined. Results One hundred and seven drugs that met our inclusion criteria were approved between 2013 and 2022. Assessment of the 107 drug development programs identified 150 pivotal trials that were subsequently analyzed. The pivotal trials were mostly randomized (80%) and blinded (69.3%). Biomarkers (41.1%) and clinical outcomes (42.1%) were commonly utilized as primary efficacy endpoints. Analysis of the use of clinical trial design elements across trials that utilized biomarkers, clinical outcomes, or composite endpoints did not reveal statistically significant differences. The choice of primary efficacy endpoint varied by the drug’s therapeutic area, approval pathway, and whether the indicated disease etiology was well defined. For example, biomarkers were commonly selected as primary efficacy endpoints in hematology drug approvals (70.6%), whereas clinical outcomes were commonly selected in neurology drug approvals (69.6%). Further, if the disease etiology was well defined, biomarkers were more commonly used as primary efficacy endpoints in pivotal trials (44.7%) than if the disease etiology was not well defined (27.3%). Discussion In the past 10 years, numerous novel drugs have been approved to treat non-oncologic rare diseases in various therapeutic areas. To demonstrate their efficacy for regulatory approval, biomarkers and clinical outcomes were commonly utilized as primary efficacy endpoints. Biomarkers were not only frequently used as surrogate efficacy endpoints in accelerated approvals, but also in traditionally approved rare disease drugs. The choice of primary efficacy endpoints varied by therapeutic area, approval pathway, and understanding of disease etiology.

Hong, Kyungwan [Rare Diseases Team, Office of New ↗