Medical related products require TRL definitions and descriptions that are appropriate to the technologies upon which they are based and that account for the statues and regulations that govern their development and use. Biomedical TRLs are further categorized into TRLs for drugs, vaccines, devices, or combined drug-devices.
- Current Research Activity Examples
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- Review of scientific literature
- Review of guidelines
- Review of screening and assessments
- Review of health information material
- Identification of relevant existing data sets
- Theoretical modeling
- Identification of conceptual frameworks
- Systematic qualitative evaluation in consultation with stakeholders (e.g., patients or providers)
- Exploratory analyses of existing data sets
- Case Reports
- Knowledge Based Tools
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KRL 1 Decision Criterion:
Initial information reviews have lead to concept of potential tool to address defined problems.
Current Activity:
Review of scientific literature and other materials to maintain scientific awareness, generate scientific knowledge base, and generate hypothesis (es). Development, peer review, and approval of research plans and/or protocols.
- Clinical Interventions
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KRL 1 Decision Criterion:
Initial literature reviews have lead to articulation of potential scientific application to defined problems.
Current Activity:
Literature reviews to maintain scientific awareness, generate scientific knowledge base, and generate hypothesis (es). Development, peer review, and approval of research plans and/or protocols.
- Drugs, Biologics, Vaccines, & Medical Devices
- Scientific literature reviews and initial market surveys are initiated and assessed. Potential scientific application to defined problems is articulated.
- Medical IM/IT & Medical Informatics
- Identification of the potential medical solution to mission need. Medical informatics data and knowledge representation issues are defined.
- Medical Simulation
- Identification of potential simulation solution to identified mission need. Data and knowledge research, with identified representation issues applied to research and development.
- Funding and Acquisition Roadmap
- Uses 6.1 and 6.2 funding used for research and discovery.
- Current Research Activity Examples
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- In vitro studies
- Animal studies
- Retrospective data analysis
- Case Reports
- Case Series
- Algorithmic modeling
- Knowledge Based Tools
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KRL 2 Decision Criterion:
Hypothesis (es) generated, research strategy and/or protocols are developed, peer reviewed, and approved.
Current Activity:
Preliminary proof-of-concept testing in computational modeling, basic laboratory experiments, or retrospective data analysis.
- Clinical Interventions
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KRL 2 Decision Criterion:
Hypothesis (es) generated, research strategy and/or protocols are developed, peer reviewed, and approved.
Current Activity:
Preliminary proof-of-concept testing in computational modeling, or basic laboratory environments.
- Drugs, Biologics, Vaccines, & Medical Devices
- Hypothesis (es) generated. Research plans and/or protocols are developed, peer reviewed, and approved.
- Medical IM/IT & Medical Informatics
- Identification of the potential medical solution to mission need. Medical informatics data and knowledge representation issues are defined.
- Medical Simulation
- Simulation concept formulated and documented. Practical applications developed. Potential data and knowledge representation issues are defined.
- Funding and Acquisition Roadmap
- Uses 6.1 and 6.2 funding used for research in preparation for a Materiel Development Decision (MDD) that is the entry point for the Decision Gate.
- Current Research Activity Examples
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- Prospective survey data collection
- Epidemiological studies
- Observational studies including surveys and questionnaire
- Cross Sectional Studies
- Computational modeling
- Knowledge Based Tools
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KRL 3 Decision Criterion:
Preliminary proof-of-concept demonstrated in laboratory studies or retrospective data analysis.
Current Activity:
Proof-of-concept and safety testing in humans under experimental conditions or observational studies.
- Clinical Interventions
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KRL 3 Decision Criterion:
Preliminary proof-of-concept demonstrated in laboratory studies.
Current Activity:
Proof-of-concept and safety testing in human studies under experimental conditions or observational studies.
- Drugs, Biologics, Vaccines, & Medical Devices
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Drugs
Documentation of the results of laboratory studies demonstrates preliminary proof-of-concept in vitro and animal studies.
Biologics & Vaccines
Documentation of the results of laboratory studies demonstrates preliminary proof-of-concept with candidate biologic/vaccine constructs in in vitro and animal studies.
Medical Devices
Documentation of the results of laboratory studies demonstrates preliminary proof-of-concept in laboratory models.
- Medical IM/IT & Medical Informatics
- Medical informatics data and knowledge representation schema are modeled.
- Medical Simulation
- Simulation data and knowledge schema are modeled in proof of concept studies. Results measure parameters of interest and comparison to analytical predictions, of separate knowledge elements.
- Funding and Acquisition Roadmap
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MDD/KP Review Point
After a successful MDD, uses 6.2 funding to complete the Materiel Solution Analysis (MSA) phase getting ready for a Milestone A.
- Current Research Activity Examples
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- Qualitative interviews
- Focus groups
- Integrated algorithmic modeling
- Knowledge Based Tools
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KRL 4 Decision Criterion:
Preliminary proof of concept shown in in vitro studies, animal studies, epidemiological studies, or by prospectively collected survey data.
Current Activity:
Preclinical evidence and observational data is translated into candidate tool (e.g., structuring and manualization of candidate tools/materials).
- Clinical Interventions
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KRL 4 Decision Criterion:
Preliminary proof of concept shown in in vitro studies, animal studies, epidemiological studies, or by prospectively collected survey data.
Current Activity:
Preclinical evidence and observational data translated into candidate therapies (e.g., structuring and manualization of candidate interventions).
- Drugs, Biologics, Vaccines, & Medical Devices
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Drugs
Proof-of-concept and safety of candidate drug formulation(s) are demonstrated in defined laboratory/animal model(s).
Biologics & Vaccines
Proof-of-concept and safety of candidate biologic/vaccine constructs are demonstrated in defined laboratory/animal model(s).
Medical Devices
Proof-of-concept and safety of candidate devices/systems are demonstrated in defined laboratory/animal models.
- Medical IM/IT & Medical Informatics
- Medical informatics data and knowledge representation models are instantiated with representative data or knowledge from applicable domain.
- Medical Simulation
- Separate knowledge elements are integrated into representative models. Computational model is validated with representative data, and preliminary integrated model is tested.
- Funding and Acquisition Roadmap
- Uses primarily 6.2 funding to prepare for a Milestone A.
- Current Research Activity Examples
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- Cognitive interviewing
- Phase 1 Randomized Controlled Clinical Trial
- Integrated algorithmic model implemented (Pilot)
- Knowledge Based Tools
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KRL 5 Decision Criterion:
Synthesis of available information and modification of candidate materials completed.
Current Activity:
Initial testing in limited controlled sample, prospective case series, cohort studies, or obtaining structured feedback on materials from stakeholders.
- Clinical Interventions
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KRL 5 Decision Criterion:
Synthesis of available information and modification of candidate intervention materials is completed.
Current Activity:
Initial testing in limited controlled sample, prospective case series, cohort studies, or obtaining structured feedback on materials from stakeholders.
- Drugs, Biologics, Vaccines, & Medical Devices
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Drugs
A decision point is reached at which it is determined that sufficient data is on the candidate drug exist in the draft technical data package to justify proceeding with reparation of an Investigational New Drug (IND) application. Testing intervention for safety in healthy volunteers.
Biologics & Vaccines
A decision point is reached at which it is determined that sufficient data is on the candidate biologic/vaccine exist in the draft technical data package to justify proceeding with preparation of an IND application.
Medical Devices
A decision point is reached at which it is determined that sufficient data is on the candidate IDE review by CDRH results to determine if the investigation can begin. For a 510(k), preliminary findings suggest the device will be substantially equivalent to a predicate device.
- Medical IM/IT & Medical Informatics
- Medical informatics data and knowledge representation models are implemented as data and/or knowledge management systems and tested in a laboratory environment.
- Medical Simulation
- Actual simulation knowledge data is introduced to the integrated computational model, which is implemented into realistic data/knowledge systems and tested in a simulated environment.
- Funding and Acquisition Roadmap
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A/KP Review Point
Uses 6.3 funding, having completed a successful Milestone A, and is working on the Technology Development (TD) phase toward Milestone B.
- Current Research Activity Examples
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- Phase 2 Randomized Controlled Clinical Trial
- Efficacy Trial
- Integrated algorithmic model tested in relevant enviroment
- Knowledge Based Tools
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KRL 6 Decision Criterion:
Clinical pilot/feasibility testing, revision of tool or material, training program development, adherence/competence measure development for invalidated tools and materials are completed.
Current Activity:
Validation study to assess whether tool meets the user’s need.
- Clinical Interventions
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KRL 6 Decision Criterion:
Clinical pilot/feasibility testing, manual revision, training program development, adherence/competence measure development for untested treatments are completed.
Current Activity:
Randomized, controlled, clinical efficacy trial.
- Drugs, Biologics, Vaccines, & Medical Devices
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Drugs
Data from Phase 1 clinical trials meet clinical safety requirements and support proceeding to Phase 2 clinical trials.
Biologics & Vaccines
Data from Phase 1 clinical trials meet clinical safety requirements and support proceeding to Phase 2 clinical trials.
Medical Devices
Data from the initial clinical investigation demonstrate that the Class III device meets safety requirements and support proceeding to clinical safety and effectiveness trials. For a 510(k), information and data demonstrate substantial equivalency to predicate device and support production of the final prototype and final testing in a military operational environment.
- Medical IM/IT & Medical Informatics
- Medical informatics data and knowledge management systems are tested with target applications in a laboratory environment. Configuration management approach developed.
- Medical Simulation
- Integrated simulation knowledge models/prototype systems are tested in target applications, in a simulated operational environment.
- Funding and Acquisition Roadmap
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B/KP Review Point
Advanced Development Decision Point
Decision based on TBD criteria, including maturity level (KRL) for transition to Advanced Development. Criteria may be specific to clinical field/domain. Uses 6.3 funding but may reach for 6.4 funding to achieve a successful Milestone B.
- Current Research Activity Examples
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- Phase Randomized Controlled Clinical Trial
- Effectiveness trial with different practitioners or settings
- Integrated algorithmic model used in limited operational environment
- Knowledge Based Tools
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KRL 7 Decision Criterion:
Validation study to assess whether knowledge tool meets the user’s identified need is completed.
Current Activity:
Further evaluation in an operational environment to determine generalizability in a large population.
- Clinical Interventions
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KRL 7 Decision Criterion:
Randomized, controlled, clinical trial is completed to determine efficacy, safety, and schedule.
Current Activity:
Randomized, controlled, clinical trial to determine generalizability in a large population, implementation strategy, cost effectiveness, dissemination.
- Drugs, Biologics, Vaccines, & Medical Devices
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Drugs
Phase 3 clinical study plan or surrogate test plan has been approved.
Biologics & Vaccines
Phase 3 clinical study plan or surrogate test plan has been approved.
Medical Devices
Clinical endpoints and test plans are agreed to by CDRH. For a 510(k), information and data demonstrate substantial equivalency to predicate device and use in a military operational environment and support preparation of 510(k).
- Medical IM/IT & Medical Informatics
- Medical informatics data and knowledge management systems are operationally integrated and tested with target applications in an operational environment.
- Medical Simulation
- Prototype of the simulation knowledge system is demonstrated and tested with target applications in an operational environment.
- Funding and Acquisition Roadmap
- Uses 6.4 and 6.5 funding to complete the Engineering & Manufacturing Development (EMD) phase heading for a Milestone C.
- Current Research Activity Examples
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- Health services research to support dissemination and adoption
- Integrated algorithmic model validated in a large population under expected conditions
- Knowledge Based Tools
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KRL 8 Decision Criterion:
Operational validation study completed to determine generalizability in a large population.
Current Activity:
Developer partners with implementer for dissemination and implementation.
- Clinical Interventions
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KRL 8 Decision Criterion:
Randomized, controlled, clinical trial completed to determine generalizability in a large population, implementation strategy, cost effectiveness, dissemination.
Current Activity:
Developer partners with implementer for dissemination, and implementation.
- Drugs, Biologics, Vaccines, & Medical Devices
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Drugs
Approval of the NDA for drug by CDER. For approval, FDA requires two pivotal proof of efficacy studies in Phase 3.
Biologics & Vaccines
Approval of the BLA for biologics/vaccines by CBER.
Medical Devices
Approval of the PMA (or, as applicable, 510(k)) for device by CDRH.
- Medical IM/IT & Medical Informatics
- Developmental test and evaluation of the HW/SW system in its intended environment demonstrates that it meets design specifications. Fully integrated and operational medical informatics data and knowledge management systems are validated in several operational environments.
- Medical Simulation
- Developmental test and evaluation (DT&E) of the final product conducted in its intended operational environment. Fully integrated and operational simulation knowledge product completed, meeting all design specifications, and operating as required.
- Funding and Acquisition Roadmap
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C/KP Review Point
Implementation Decision Point
Decision based on TBD criteria, including maturity level (KRL), LoE (including replication, generalizability, etc.) needed for implementation; will be specific to the clinical field/domain.
Using 6.5 funding to complete EMD phase and achieve Milestone C and Procurement funding after Milestone C.
- Current Research Activity Examples
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- Phase 4 Trial
- Integrated algorithmic model validation in operational environment
- Knowledge Based Tools
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KRL 9 Decision Criterion:
Dissemination and implementation complete.
Current Activity:
Continued evaluation of the tool, material, long-term effectiveness, or evaluation of adoption by users.
- Clinical Interventions
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KRL 9 Decision Criterion:
Dissemination and implementation complete.
Current Activity:
Evaluation of long-term safety and effectiveness or continued program evaluation.
- Drugs, Biologics, Vaccines, & Medical Devices
- Continued surveillance
- Medical IM/IT & Medical Informatics
- Knowledge Product successfully used during military mission as component of Initial Operational Test and Evaluation (IOT&E) phase. Logistical demonstration successfully conducted.
- Medical Simulation
- Product successfully used during Initial Operational Test and Evaluation (IOT&E). Continue surveillance, conduct successful logistical demonstration.
- Funding and Acquisition Roadmap
- May use 6.7 funding to ensure proper deployment and use of the product. Generally this requires Procurement and O&M dollars.
Sources:
- Office of the Director, Defense Research and Engineering (DDR&E) (July 2009). Appendix E. Biomedical Technology Readiness Levels (TRLs). Technology Readiness Assessment (TRA) Deskbook. Available at: https://apps.dtic.mil/docs/citations/ADA524200.