Reporting and sharing pharmacogenetic test results across clinical laboratories and electronic health records is a crucial step toward the implementation of clinical pharmacogenetics, but allele ...function and phenotype terms are not standardized. Our goal was to develop terms that can be broadly applied to characterize pharmacogenetic allele function and inferred phenotypes.
Terms currently used by genetic testing laboratories and in the literature were identified. The Clinical Pharmacogenetics Implementation Consortium (CPIC) used the Delphi method to obtain a consensus and agree on uniform terms among pharmacogenetic experts.
Experts with diverse involvement in at least one area of pharmacogenetics (clinicians, researchers, genetic testing laboratorians, pharmacogenetics implementers, and clinical informaticians; n = 58) participated. After completion of five surveys, a consensus (>70%) was reached with 90% of experts agreeing to the final sets of pharmacogenetic terms.
The proposed standardized pharmacogenetic terms will improve the understanding and interpretation of pharmacogenetic tests and reduce confusion by maintaining consistent nomenclature. These standard terms can also facilitate pharmacogenetic data sharing across diverse electronic health care record systems with clinical decision support.
This is the first in a series of essays that addresses the manifest programmatic interest in developing intelligent systems that help people make good decisions in messy, complex, and uncertain ...circumstances by exploring several questions: What is an explanation? How do people explain things? How might intelligent systems explain their workings? How might intelligent systems help humans be better understanders as well as better explainers? This article addresses the theoretical foundations.
When people make plausibility judgments about an assertion, an event, or a piece of evidence, they are gauging whether it makes sense that the event could transpire as it did. Therefore, we can treat ...plausibility judgments as a part of sensemaking. In this paper, we review the research literature, presenting the different ways that plausibility has been defined and measured. Then we describe the naturalistic research that allowed us to model how plausibility judgments are engaged during the sensemaking process. The model is based on an analysis of 23 cases in which people tried to make sense of complex situations. The model describes the user's attempts to construct a narrative as a state transition string, relying on plausibility judgments for each transition point. The model has implications for measurement and for training.
Trust in Automation Hoffman, R. R.; Johnson, M.; Bradshaw, J. M. ...
IEEE intelligent systems,
2013-Jan.-Feb., 2013, 2013-01-00, 20130101, Volume:
28, Issue:
1
Journal Article
Peer reviewed
This essay focuses on trust in the automation within macrocognitive work systems. The authors emphasize the dynamics of trust. They consider numerous different meanings or kinds of trust, and ...different modes of operation in which trust dynamics play a role. Their goal is to contribute to the development of a methodology for designing and analyzing collaborative human-centered work systems, a methodology that might promote both trust "calibration" and appropriate reliance. The analysis suggests an ontology for what the authors call "active exploration for trusting" (AET).
The Clinical Pharmacogenetics Implementation Consortium (CPIC) publishes genotype-based drug guidelines to help clinicians understand how available genetic test results could be used to optimize drug ...therapy. CPIC has focused initially on well-known examples of pharmacogenomic associations that have been implemented in selected clinical settings, publishing nine to date. Each CPIC guideline adheres to a standardized format and includes a standard system for grading levels of evidence linking genotypes to phenotypes and assigning a level of strength to each prescribing recommendation. CPIC guidelines contain the necessary information to help clinicians translate patient-specific diplotypes for each gene into clinical phenotypes or drug dosing groups. This paper reviews the development process of the CPIC guidelines and compares this process to the Institute of Medicine's Standards for Developing Trustworthy Clinical Practice Guidelines.
For pt.1 see ibid., vol.21, no.4, p. 70-73 (2006). In this paper, we have laid out a theory of sensemaking that might be useful for intelligent systems applications. It's a general, empirically ...grounded account of sensemaking that goes significantly beyond the myths and puts forward some nonobvious, testable hypotheses about the process. When people try to make sense of events, they begin with some perspective, viewpoint, or framework - however minimal. For now, let's use a metaphor and call this a frame. We can express frames in various meaningful forms, including stories, maps, organizational diagrams, or scripts, and can use them in subsequent and parallel processes. Even though frames define what count as data, they themselves actually shape the data Furthermore, frames change as we acquire data. In other words, this is a two-way street: Frames shape and define the relevant data, and data mandate that frames change in nontrivial ways. We examine five areas of empirical findings: causal reasoning, commitment to hypotheses, feedback and learning, sense-making as a skill, and confirmation bias. In each area the Data/Frame model, and the research it's based on, doesn't align with common beliefs. For that reason, the Data/Frame model cannot be considered a depiction of commonsense views
RIP1 regulates necroptosis and inflammation and may play an important role in contributing to a variety of human pathologies, including immune-mediated inflammatory diseases. Small-molecule ...inhibitors of RIP1 kinase that are suitable for advancement into the clinic have yet to be described. Herein, we report our lead optimization of a benzoxazepinone hit from a DNA-encoded library and the discovery and profile of clinical candidate GSK2982772 (compound 5), currently in phase 2a clinical studies for psoriasis, rheumatoid arthritis, and ulcerative colitis. Compound 5 potently binds to RIP1 with exquisite kinase specificity and has excellent activity in blocking many TNF-dependent cellular responses. Highlighting its potential as a novel anti-inflammatory agent, the inhibitor was also able to reduce spontaneous production of cytokines from human ulcerative colitis explants. The highly favorable physicochemical and ADMET properties of 5, combined with high potency, led to a predicted low oral dose in humans.
Active clinical decision support (CDS) delivered through an electronic health record (EHR) facilitates gene-based drug prescribing and other applications of genomics to patient care.
We describe the ...development, implementation, and evaluation of active CDS for multiple pharmacogenetic test results reported preemptively.
Clinical pharmacogenetic test results accompanied by clinical interpretations are placed into the patient's EHR, typically before a relevant drug is prescribed. Problem list entries created for high-risk phenotypes provide an unambiguous trigger for delivery of post-test alerts to clinicians when high-risk drugs are prescribed. In addition, pre-test alerts are issued if a very-high risk medication is prescribed (eg, a thiopurine), prior to the appropriate pharmacogenetic test result being entered into the EHR. Our CDS can be readily modified to incorporate new genes or high-risk drugs as they emerge.
Through November 2012, 35 customized pharmacogenetic rules have been implemented, including rules for TPMT with azathioprine, thioguanine, and mercaptopurine, and for CYP2D6 with codeine, tramadol, amitriptyline, fluoxetine, and paroxetine. Between May 2011 and November 2012, the pre-test alerts were electronically issued 1106 times (76 for thiopurines and 1030 for drugs metabolized by CYP2D6), and the post-test alerts were issued 1552 times (1521 for TPMT and 31 for CYP2D6). Analysis of alert outcomes revealed that the interruptive CDS appropriately guided prescribing in 95% of patients for whom they were issued.
Our experience illustrates the feasibility of developing computational systems that provide clinicians with actionable alerts for gene-based drug prescribing at the point of care.
Measuring Resilience Hoffman, Robert R.; Hancock, P. A.
Human factors,
06/2017, Volume:
59, Issue:
4
Journal Article
Peer reviewed
Objective:
As human factors and ergonomics (HF/E) moves to embrace a greater systems perspective concerning human–machine technologies, new and emergent properties, such as resilience, have arisen. ...Our objective here is to promote discussion as to how to measure this latter, complex phenomenon.
Background:
Resilience is now a much-referenced goal for technology and work system design. It subsumes the new movement of resilience engineering. As part of a broader systems approach to HF/E, this concept requires both a definitive specification and an associated measurement methodology. Such an effort epitomizes our present work.
Method:
Using rational analytic and synthetic methods, we offer an approach to the measurement of resilience capacity.
Results:
We explicate how our proposed approach can be employed to compare resilience across multiple systems and domains, and emphasize avenues for its future development and validation.
Conclusion:
Emerging concerns for the promise and potential of resilience and associated concepts, such as adaptability, are highlighted. Arguments skeptical of these emerging dimensions must be met with quantitative answers; we advance one approach here.
Application:
Robust and validated measures of resilience will enable coherent and rational discussions of complex emergent properties in macrocognitive system science.
As designers conceive and implement what are commonly (but mistakenly) called autonomous systems, they adhere to certain myths of autonomy that are not only damaging in their own right, but also by ...their continued propagation. This article busts such myths and gives reasons why each of these myths should be called out and cast aside.
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