Ernest T. Hawk, Lynn M. Matrisian, William G. Nelson, Gary S. Dorfman, Lisa Stevens, Jennifer Kwok, Jaye Viner, Judith Hautala, and Oren Grad for the Translational Research Working Group “The Translational Research Working Group Developmental Pathways: Introduction and Overview” Clin. Cancer Res. 2008 14: 5664-5671. [Abstract] [Full Text] [PDF] Martin A. Cheever, Jeffrey Schlom, Louis M. Weiner, H. Kim Lyerly, Mary L. Disis, Addison Greenwood, Oren Grad, and William G. Nelson for the Translational Research Working Group “Translational Research Working Group Developmental Pathway for Immune Response Modifiers” Clin. Cancer Res. 2008 14: 5692-5699. [Abstract] [Full Text] [PDF] Gary S. Dorfman, Theodore S. Lawrence, and Lynn M. Matrisian for the Translational Research Working Group “The Translational Research Working Group Developmental Pathway for Interventive Devices” Clin. Cancer Res. 2008 14: 5700-5706. [Abstract] [Full Text] [PDF] Sudhir Srivastava, Joe W. Gray, Brian J. Reid, Oren Grad, Addison Greenwood, and Ernest T. Hawk for the Translational Research Working Group “Translational Research Working Group Developmental Pathway for Biospecimen-Based Assessment Modalities” Clin. Cancer Res. 2008 14: 5672-5677. [Abstract] [Full Text] [PDF] Gary S. Dorfman, Daniel C. Sullivan, Mitchell D. Schnall, and Lynn M. Matrisian for the Translational Research Working Group The Translational Research Working Group “Developmental Pathway for Image-Based Assessment Modalities” Clin. Cancer Res. 2008 14: 5678-5684. [Abstract] [Full Text] [PDF] Richard L. Schilsky, Gary Gordon, Tona M. Gilmer, Sara A. Courtneidge, Lynn M. Matrisian, Oren Grad, and William G. Nelson on behalf of the Translational Research Working Group “The Translational Research Working Group Developmental Pathway for Anticancer Agents (Drugs or Biologics)” Clin. Cancer Res. 2008 14: 5685-5691. [Abstract] [Full Text] [PDF] Ernest T. Hawk, Addison Greenwood, Ellen R. Gritz, Anne McTiernan, Thomas Sellers, Stephen D. Hursting, Scott Leischow, and Oren Grad for the Translational Research Working Group “The Translational Research Working Group Developmental Pathway for Lifestyle Alterations” Clin. Cancer Res. 2008 14: 5707-5713. [Abstract] [Full Text] [PDF]

Fig. 1. Generic Developmental Pathway.The genericTRWG pathway is depicted as a flowchart, a schematic process representation widely used in engineering. Roundedrectangle at the top, origin of the process. Square-cornered rectangles, activity steps.Diamonds, conditional tests or decision steps.Unidirectional arrows, direction of theactivity sequence, and the direction of transfer of supporting tools from their parallel development paths to the main path of modality development.The initial steps of thepathway (blue) are required to proceed through the pathway, with the blue diamonds representing the credentialing steps of scientific validation, clinical need, and feasibility.Subsequent steps include the development of supporting tools (red), the creation of the modality (green), preclinical development (purple), and early stage clinical trials(yellow).

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Fig. 1. Biospecimen-Based AssessmentModality (BM) Pathway.The BM pathway isdepicted as a flowchart, a schematic processrepresentation widely used in engineering.Rounded rectangle at the top, the origin of theprocess. Square-cornered rectangles, activitysteps.Diamonds, conditional tests or decisionsteps.Unidirectional arrows, the direction of theactivity sequence, and the direction of transfer ofsupporting tools from their parallel developmentpaths to the main path of modality development.The three diamonds in the initial steps of thepathway (blue) are decisions required toproceed through the pathway and represent thecredentialing step. Subsequent steps include thedevelopment of supporting tools (red), thecreation of the modality (green), preclinicaldevelopment (purple), and early stage clinicaltrials (yellow). For each activity or decisionpoint, it is understood that there are many morevariations that can occur, and that not all stepsmay occur in each instance.The pathway does notaddress the ways in which insights gainedfrom late-stage clinical trials can influence thedevelopment process. Biospecimen-basedassessment devices can be used for screening,early detection, diagnosis, prediction, prognosis,or response assessment.The pathways areconceived not as comprehensive descriptions ofthe corresponding real-world processes but astools designed to serve specific purposes,including research program and projectmanagement, coordination of research efforts,and professional and lay education andcommunication.

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Fig. 1. Image-Based Assessment Modality(IM) pathway.The IM developmental pathwayis depicted as a flowchart, a schematicprocess representation widely used inengineering. Rounded rectangle (top),the origin of the process. Square-corneredrectangles, activity steps.Diamonds,conditional tests or decision steps.Unidirectional arrows, direction of theactivity sequence, and the direction of transferof supporting tools from their paralleldevelopment paths to the main path ofmodality development. Bidirectional arrows,codevelopment or concurrent, interactiverefinement.The three diamonds in the initialsteps of the pathway (blue) are decisionsrequired to proceed through the pathway andrepresent the credentialing step. Subsequentsteps include the development of supportingtools (red), the creation of the modality(green), preclinical development (purple),and early stage clinical trials (yellow). For eachactivity, decision point, parallel path, orfeedback loop, it is understood that there aremany more variations that can occur, and thatnot all steps may occur in each instance.Thepathway does not address the ways in whichinsights gained from late-stage clinical trialscan influence the development process.Image-based assessment modalities canbe used for screening, early detection,diagnosis, prediction, prognosis, or responseassessment.The pathways are conceived notas comprehensive descriptions of thecorresponding real-world processes but astools designed to serve specific purposes,including research program and projectmanagement, coordination of research efforts,and professional and lay education andcommunication.

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TRWGImage-Based AssessmentModality Pathway

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could be made that the interventive devices and the advancedimaging modalities used to provide them should be translatedas a system. Such a systems approach would often allow theinterventive device to be optimized before later-stage clinical

investigation. This is rarely done, however. In some clinicalscenarios, more than one type of imaging modality is available(and potentially appropriate) for use in treatment planning,guidance, monitoring, and end-point determination. In other

Fig. 1. Interventive Device DevelopmentalPathway.The interventive device pathwayis depicted as a flowchart, a schematicprocess representation widely used inengineering.The rounded rectangle at thetop indicates the origin of the process(point of pathway entry). Square-corneredrectangles indicate activity steps.Conditional tests, or decision steps, arerepresented as diamonds. Unidirectionalarrows indicate the direction of the activitysequence, and the direction of transferof supporting tools from their paralleldevelopment paths to the main path ofmodality development. Bidirectional arrowsare used to indicate codevelopment orconcurrent, interactive, iterative refinement.The initial steps of the pathway (blue) arerequired to proceed through the pathway,with the entry represented by eitherfundamental or applied science followed bythree blue diamonds representing thecredentialing steps of scientific validation,clinical need, and feasibility.Thereafter, thepathway includes three parallel paths,representing creation of the modality itself(green) as well as development of twodifferent classes of supporting tools (red):tools for characterizing and evaluating theeffects of the modality (i.e., responseassessment) and tools for defining thecohort for which the modality is appropriate.Parallel paths have beenmade explicitto acknowledge that some of therequired tools may not exist and theirparallel or codevelopment will beprerequisite for the viability of the newmodality.The more detailed development ofthese supporting tools, or assessmentmodalities, is represented by either thebiospecimen- or imaging-based assessmentmodality pathways. Subsequent steps tothe initial creation of the interventivedevice include preclinical development(purple), which in the case of interventivedevices may actually include limited clinicalstudies required to optimize or refinecertain aspects of the modality, and the finalstep of early-stage clinical trials (yellow),which will form the basis for later-phaseclinical studies. For each activity, decisionpoint, parallel path, or feedback loop, it isunderstood that there are many morevariations that can occur and that not allsteps may occur in each instance.Thepathway does not address the ways inwhich insights gained from late-stage clinicaltrials can influence the developmentprocess.This pathway is conceived not asa comprehensive description of thecorresponding real-world process but as atool designed to serve specific purposes,including, for example, researchprogramandproject management, coordination ofresearch efforts, and professional and layeducation and communication.

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