Perception and Cognition Research to Inform Cancer Image Interpretation (R01)

Perception and Cognition Research to Inform Cancer Image Interpretation (R01) is sponsored by National Institutes of Health (NIH). The purpose of this Funding Opportunity Announcement (FOA) is to facilitate research on the perceptual and cognitive processes underlying the performance of cancer image observers in radiology and pathology, in order to improve the accuracy of cancer detection and diagnosis.

Expired PAR-17-125: Perception and Cognition Research to Inform Cancer Image Interpretation (R01) This notice has expired. Check the NIH Guide for active opportunities and notices. Department of Health and Human Services Part 1.

Overview Information Participating Organization(s) National Institutes of Health ( NIH ) of Participating Organizations National Cancer Institute ( NCI ) National Institute of Biomedical Imaging and Funding Opportunity Title Perception and Cognition Research to Inform Cancer Image Interpretation (R01) R01 Research Project Grant February 7, 2018 - This PAR has been reissued as PAR-18-640 .

January 23, 2018 - Notice of Expiration of PAR-17-125. See Notice NOT-CA-18-043 . May 10, 2017 - New NIH "FORMS-E" Grant Application Forms and Instructions Coming for Due Dates On or After January 25, 2018.

See NOT-OD-17-062 . February 15, 2017 - Notice of Change of Key Dates for PAR-17-125. See Notice NOT-CA-17-031 .

Funding Opportunity Announcement (FOA) Number Companion Funding Opportunity PAR-17-124 , R21 Research Grant Additional Information on Eligibility .

Catalog of Federal Domestic Assistance (CFDA) Number(s) Funding Opportunity Purpose The purpose of this Funding Opportunity Announcement (FOA) is to facilitate research on the perceptual and cognitive processes underlying the performance of cancer image observers in radiology and pathology, in order to improve the accuracy of cancer detection and Open Date (Earliest Submission Date) Letter of Intent Due Date(s) 30 days before the due date May 30, 2017; September 26, 2017; May 30, 2018; September 26, 2018; May 30, 2019; September 26, 2019, by 5:00 PM local time of applicant organization.

All types of non-AIDS applications allowed for this funding opportunity announcement are due on Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date.

AIDS Application Due Date(s) New Dates October/November 2017; March/April 2018; October/November 2018; March/April 2019; October/November 2019; March/April 2020 New Dates January 2018; May 2018; January 2019; May 2019; January 2020; May 2020 New Dates April 2018; August 2018; April 2019; August 2019; April 2020; August 2020 New Date January 24, 2018 per issuance of NOT-CA-18-043 .

(Original Expiration Date: September 27, 2019 ) It is critical that applicants follow the Research (R) Instructions (R&R) Application Guide , except where instructed to do otherwise (in this FOA or in a Notice from the NIH Guide for Grants and Contracts ). Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced.

Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV . When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions. Applications that do not comply with these instructions may be delayed or not accepted for review.

Part 1. Overview Information Part 2. Full Text of the Announcement I.

Funding Opportunity Description Section II. Award Information Section III. Eligibility Information Section IV.

Application and Submission Section V. Application Review Information Section VI. Award Administration Information Section VII.

Agency Contacts Section VIII. Other Information Full Text of Announcement Section I. Funding Opportunity Description This purpose of this FOA is to facilitate research on the perceptual and cognitive processes underlying the performance of cancer image observers.

Specifically, the FOA will bring scientists with expertise in visual perception and cognition together with radiologists, pathologists, nuclear medicine physicians, and other experts in cancer image interpretation. The scientific scope of the PAR will yield insights to improve the accuracy of cancer detection and diagnosis as a result of NCI's investment in studying the underlying perceptual and cognitive processes.

This FOA runs in parallel with an FOA of similar scientific scope, PAR-17-124 , which utilizes the Exploratory/Developmental Grant (R21) in Cancer Image Interpretation Despite technical advances in many areas of diagnostic imaging, the detection and diagnosis of cancer via imaging remains fallible.

For example, data from the Breast Cancer Surveillance Consortium show false negative rates of approximately 15% and false positive rates of 10% for mammography. For lung cancer screening via computed tomography (CT) and chest radiography, false negative rates have been reported to be as high as 39% and 70% respectively, with false positive rates of 23% and 7%.

While some of these errors may be due to technical issues or limitations of contemporary imaging technologies, a large proportion are attributable limitations of the perceptual and cognitive faculties of the clinicians and other specialists wh o diagnose, stage, and treat cancer. Perceptual and cognitive errors account for 60-70% of diagnostic error in radiology, and the majority of errors in breast and lung cancer diagnosis.

The interpretation of a given case varies between different radiologists, and within the same radiologist at different times. Similar findings have been reported for cancer diagnoses in pathology and cytology, though the problem is understudied. While some sources of perceptual and cognitive errors have been identified (e.g., low prevalence, subsequent search misses).

In other words, errors in cancer image interpretation are still largely unexplained. Research in perception and cognition will uncover important factors that influence how observers perceive, remember, learn, and act upon the images they view. We are in a period of rapid technological development in medical imaging.

Conventional two-dimensional (2D) radiology is rapidly being supplanted by newer imaging techniques [e.g., computerized tomography (CT), magnetic resonance imaging (MRI), and tomosynthesis] that provide three-dimensional (3D), or volumetric information about anatomical structure. However, interpretation of 3D medical images is slower and more arduous than 2D image interpretation.

By understanding the perceptual processes that underlie how humans perceive 3D shape from 2D information, we may be able to develop and evaluate new techniques for presenting volumetric information. Similar problems are posed by a range of novel molecular imaging techniques coming into use. These techniques involve molecular probes or tracers that allow visualization of the distribution of the molecule of interest throughout the body.

For example, imaging the uptake of an androgen receptor with a combination of CT and PET can reveal the location of prostate tumors. Unfortunately, the perceptual and cognitive aspects of using molecular imaging have been largely ignored. No matter how sophisticated our imaging technologies become, we still rely on human observers to make the final decision.

It is thus critical to understand how radiologists, pathologists, and other cancer image observers process and interact with the images they are called upon to interpret. Progress in addressing these challenges will require interdisciplinary collaboration.

An effective program for solving major problems in cancer image perception will require radiologists, pathologists, cytologists, nuclear medicine physicians and other cancer image specialists to collaborate with medical image perception researchers, cognitive psychologists, computer scientists, neuroscientists, and other basic researchers with expertise in image interpretation.

In particular, a successful research program will involve a cyclic interaction between the clinical context and the basic research environment. The research program should identify a critical problem in cancer image perception, studies the underlying perceptual or cognitive mechanisms in a basic laboratory setting, and tests only the most promising hypotheses in the applied cancer imaging context.

Differences between the laboratory and clinical findings can then inform the next round. Basic research laboratories have the capacity to use highly controlled, synthetic stimuli that can be generated at will, and non-expert observers can be easily recruited at low cost, relative to professional cancer image interpretation specialist.

This allows a perceptual laboratory to test a large number of hypotheses with less cost than would be expended on a single cancer image perception study with expert clinicians. However, findings from such studies are not guaranteed to generalize to professional observers interpreting real images in the clinical contexts. Thus, research must be grounded in the realities of clinical practice.

This interactive strategy will allow an efficient winnowing of hypotheses so as to maximize the scientific impact of studies performed in in the applied cancer imaging context. Specific Research Objectives This FOA seeks to better understand the cognitive and perceptual processes underlying the interpretation of medical images, in order to improve the accuracy of cancer detection and diagnosis.

Projects suitable for this FOA will have a focus on underlying cognitive and perceptual mechanisms, rather than descriptive studies. For example, a study demonstrating the relationship between experience and interpretation accuracy would not be appropriate, but a study identifying the visual features acquired by expert observers would be appropriate.

In particular, the FOA seeks to encourage research that identifies a critical problem in cancer image perception, studies the underlying perceptual or cognitive mechanisms in a basic laboratory setting, and tests the most promising hypotheses in the applied cancer imaging context.

FOA is not appropriate for the development of new software tools or expert systems , but studies of how human observers interact with such systems would be appropriate. Projects that address international differences in cancer image interpretation performance and methods are encouraged.

This FOA encourages transdisciplinary research projects that integrate expertise from diverse disciplines such as medical image perception, cognitive psychology, vision science, neuroscience, computer science, radiology, nuclear medicine, pathology, molecular imaging, and dermatology.

Consideration and questions that might be addressed in this FOA could include (but are not limited to) the following: While computer-aided detection (CAD) systems perform well at detecting cancer in the laboratory, the technology has not improved cancer detection in the clinic. What are the perceptual and cognitive processes underlying this failure?

How can we modify the presentation of CAD information Breast density affects the detectability of cancer in mammography. Radiologists reading film find it harder to detect tumors in dense breasts than in fatty breasts. However, recent studies suggest that radiologists reading digital mammograms find it harder to detect tumors in fatty breasts.

What are the perceptual processes underlying this discrepancy? What strategies can we provide to radiologists to counteract the effects of breast density? Training of cancer image observers is largely ad hoc and varies from institution to institution based on how different instructors were themselves trained.

A more systematic approach might facilitate training and improve the performance of cancer observers. How can we leverage the principles of perceptual learning develop systematic, evidence-based techniques for training observers to interpret cancer images? Having two observers read the same case independently is known to improve the accuracy of cancer image interpretation.

In basic perceptual studies, having two observers perform the task jointly improves performance more than if they work independently. Other research has shown that dividing the perceptual labor so that different observers search for different types of targets can improve search efficiency. How can these "collaborative gains" be achieved in the cancer imaging context?

There is a robust effect of target prevalence (how often targets are encountered) in basic perception studies; rare targets are more difficult to find. This effect has now been definitively established in the cancer context as well, in both mammography and cervical cancer. Theoretical models of the effect of target prevalence on visual search performance have been developed.

How can we leverage these models to improve the sensitivity of cancer image observers in low-prevalence environments such as screening? relevant to Specific Institutes/Centers and Agencies Institute of Biomedical Imaging and Bioengineering (NIBIB) NIBIB’s Division of Health Informatics Technologies has interest in perception and cognition research, with a focus on development of new technologies and methodologies.

Specific areas of interest in perception and cognition research include, but are not limited to, Perception of multidimensional data, including in the spectral Augmented reality systems, Mobile systems within constrained environments, Optimization of images for machine learning versus for human Developing ideal observers for humans versus machine learning Image quality metrics for computers versus humans Low dose radiation and image perception (i.e. sparsity levels of image quality for image perception by computers versus humans) Advanced imaging displays (such as hololens, 4k imagers, etc.) GPU- or HPC- based algorithm implementation approaches VIII.

Other Information for award authorities and regulations. Grant: A support mechanism providing money, property, or both to an eligible entity to carry out an approved project or activity.

Application Types Allowed Glossary and the SF424 (R&R) Application Guide provide details on Funds Available and Anticipated Number of Awards The number of awards is contingent upon NIH appropriations and the submission of a sufficient number of meritorious applications. Application budgets are not limited but need to reflect the actual needs of the proposed project. The scope of the proposed project should determine the project period.

The maximum project period is 5 years.. Grants Policy Statement will apply to the applications submitted and awards made in response to this FOA.

Higher Education Institutions Public/State Controlled Institutions of Higher Education Private Institutions of Higher Education The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education: Hispanic-serving Institutions Historically Black Colleges and Universities (HBCUs) Tribally Controlled Colleges and Universities (TCCUs) Alaska Native and Native Hawaiian Serving Institutions Asian American Native American Pacific Islander Serving Nonprofits Other Than Institutions of Higher Education Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Nonprofits without 501(c)(3) IRS Status (Other than Institutions For-Profit Organizations (Other than Small Businesses) City or Township Governments Special District Governments Indian/Native American Tribal Governments (Federally Recognized) Indian/Native American Tribal Governments (Other than Federally Eligible Agencies of the Federal Government U.S. Territory or Possession Independent School Districts Public Housing Authorities/Indian Housing Authorities Native American Tribal Organizations (other than Federally recognized tribal governments) Faith-based or Community-based Organizations Non-domestic (non-U.S.) Entities (Foreign Institutions) Non-domestic (non-U.S.) Entities (Foreign Institutions) are eligible to apply.

Non-domestic (non-U.S.) components of U.S. Organizations are eligible to Foreign components, as defined in the NIH Grants Policy Statement , are allowed. Applicant organizations must complete and maintain the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted.

Registration can take 6 weeks or more, so applicants should begin the registration process as soon as Policy on Late Submission of Grant Applications states that failure to complete registrations in advance of a due date is not a valid reason for a Universal Numbering System (DUNS) - All registrations require that applicants be issued a DUNS number.

After obtaining a DUNS number, applicants can begin both SAM and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application. System for Award Management (SAM) (formerly CCR) Applicants must complete and maintain an active registration, which requires renewal at least annually .

The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code. Commercial and Government Entity (NCAGE) Code Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM.

must have an active DUNS number and SAM registration in order to complete the eRA Commons registration. Organizations can register with the eRA Commons as they are working through their SAM or Grants. gov registration.

eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to must have an active DUNS number and SAM registration in order to complete the Directors/Principal Investigators (PD(s)/PI(s)) All PD(s)/PI(s) must have an eRA Commons account.

PD(s)/PI(s) should work with their organizational officials to either create a new account or to affiliate their existing account with the applicant organization in eRA Commons. If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.

Eligible Individuals (Program Director/Principal Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization to develop an application for support.

Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.

For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF424 This FOA does not require cost sharing as defined in the NIH Grants Policy Statement . 3.

Additional Information on Eligibility Applicant organizations may submit more than one application, provided that each application is scientifically distinct. The NIH will not accept duplicate or highly overlapping applications under review at the same time.

This means that the NIH will A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.

An application that has substantial overlap with another application pending appeal of initial peer review (see NOT-OD-11-101 ). Section IV. Application and Submission Information Buttons to access the online ASSIST system or to download application forms are available in Part 1 of this FOA.

See your administrative office for instructions if you plan to use an institutional system-to-system solution. 2. Content and Form of Application Submission It is critical that applicants follow the Research (R) Instructions (R&R) Application Guide , including Supplemental Grant Application Instructions except where instructed in this funding opportunity announcement to do otherwise.

Conformance to the requirements in the Application Guide is required and strictly enforced.

Applications that are out of compliance with these instructions may be delayed or not accepted for For information on Application Submission and Receipt, visit Frequently Asked Questions Application Guide, Electronic Submission of Grant Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows IC staff to estimate the potential review workload and By the date listed in Part 1.

Overview Information , prospective applicants are asked to submit a letter of intent that includes the following information: Descriptive title of proposed activity Name(s), address(es), and telephone number(s) of the PD(s)/PI(s) Names of other key personnel Participating institution(s) Number and title of this funding opportunity The letter of intent should be sent to: All page limitations described in the SF424 Application Page Limits must be followed.

Instructions for Application Submission The following section supplements the instructions found in the SF424 (R&R) Application Guide and should be used for preparing an All instructions in the SF424 (R&R) Application Guide SF424(R&R) Project/Performance Site Locations All instructions in the SF424 (R&R) Application Guide SF424(R&R) Other Project Information All instructions in the SF424 (R&R) Application Guide SF424(R&R) Senior/Key Person Profile All instructions in the SF424 (R&R) Application Guide All instructions in the SF424 (R&R) Application Guide All instructions in the SF424 (R&R) Application Guide PHS 398 Cover Page Supplement All instructions in the SF424 (R&R) Application Guide All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions: Sharing Plan : Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.

Do not use the Appendix to circumvent page limits.

Follow all instructions for the Appendix as described in the SF424 (R&R) PHS Inclusion Enrollment Report When conducting clinical research, follow all instructions for completing PHS Inclusion Enrollment Report as described in the SF424 PHS Assignment Request Form All instructions in the SF424 (R&R) Application Guide Foreign (non-U.S.) institutions must follow policies Grants Policy Statement , and procedures for foreign institutions described throughout the SF424 (R&R) Application Guide.

3. Unique Entity Identifier and System for Award Management (SAM) See Part 1. Section III.

1 for information regarding the requirement for obtaining a unique entity identifier and for completing and maintaining active registrations in System for Award Management (SAM), NATO Commercial and Government Entity (NCAGE) Code (if applicable), eRA Commons, and Part I. Overview Information contains information about Key Dates and times.

Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission. When a submission date falls on a weekend or Federal holiday , the application deadline is automatically extended to the next Organizations must submit applications to Grants. gov (the online portal to find and apply for grants across all Federal agencies).

Applicants must then complete the submission process by tracking the status of the application in the eRA Commons , NIH’s electronic system for grants administration. NIH and Grants. gov systems check the application against many of the application instructions upon submission.

Errors must be corrected and a changed/corrected application must be submitted to Grants. gov on or before the application due date and time. If a Changed/Corrected application is submitted after the deadline, the application will be considered late.

Applications that miss the due date and time are subjected to the NIH Policy on Late Application are responsible for viewing their application before the due date in the eRA Commons to ensure accurate and successful submission. Information on the submission process and a definition of on-time submission are provided in the SF424 (R&R) Application Guide. 5.

Intergovernmental Review This initiative is not subject to intergovernmental All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement . Pre-award costs are allowable only as described in the NIH Grants Policy Statement .

Requirements and Information Applications must be submitted electronically following the instructions described in the SF424 (R&R) Application Guide. Paper applications will not be accepted. Applicants must complete all required registrations before the application due date.

Section III. Eligibility Information contains information about registration. For assistance with your electronic application or for more information on the electronic submission Electronically .

If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must for Applicants Experiencing System Issues . For assistance with application submission, contact the Application Submission Contacts in Section VII . All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile Component of the SF424(R&R) Application Package .

Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH. See Section III of this FOA for information on registration requirements.

The applicant organization must ensure that the DUNS number it provides on the application is the same number used in the organization’s profile in the eRA Commons and for the System for Award Management. Additional information may be found in the SF424 (R&R) Application Guide. See more tips for avoiding common errors.

Upon receipt, applications will be evaluated for completeness and compliance with application instructions by the Center for Scientific Review, NIH.

Applications that are incomplete or non-compliant will Requests of $500,000 or more for direct costs in any year Applicants requesting $500,000 or more in direct costs in any year (excluding consortium F&A) must contact a Scientific/ Research Contact at least 6 weeks before submitting the application and follow the Policy on the Acceptance for Review of Unsolicited Applications that Request $500,000 or More in Direct Costs as described in the SF424 Post Submission Materials Applicants are required to follow the instructions for post-submission materials, as described in the policy .

Section V. Application Review Information Only the review criteria described below will be considered in the review process.

As part of the NIH mission , all applications submitted to the NIH in support of biomedical and behavioral research are evaluated for scientific and technical merit through the NIH peer Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria and additional review criteria (as applicable for the Reviewers will consider each of the review criteria below in the determination of scientific merit, and give a separate score for each.

An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a project that by its nature is not innovative may be essential to advance a field. Does the project address an important problem or a critical barrier to progress in the field?

Is there a strong scientific premise for the project? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project?

If Early Stage Investigators those in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)?

If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project? Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions?

Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed? Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project?

Have the investigators presented strategies to ensure a robust and unbiased approach, as appropriate for the work proposed? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed?

Have the investigators presented adequate plans to address relevant biological variables, such as sex, for studies in vertebrate animals or human subjects?

If the project involves human subjects and/or NIH-defined clinical research, are the plans to address 1) the protection of human subjects from research risks, and 2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of children, justified in terms of the scientific goals and research strategy proposed?

Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements?

Additional Review Criteria As applicable for the project proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact score, but will not give separate scores for these items.

Protections for Human Subjects For research that involves human subjects but does not involve one of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.

For research that involves human subjects and meets the criteria for one or more of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials.

For additional information on review of the Human Subjects section, please refer to the Guidelines for the Review of Human Inclusion of Women, Minorities, When the proposed project involves human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for the inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion (or exclusion) of children to determine if it is justified in terms of the scientific goals and research strategy proposed.

For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following criteria: (1) description of proposed procedures involving animals, including species, strains, ages, sex, and total number to be used; (2) justifications for the use of animals versus alternative models and for the appropriateness of the species proposed; (3) interventions to minimize discomfort, distress, pain and injury; and (4) justification for euthanasia method if NOT consistent with the AVMA Guidelines for the Euthanasia of Animals.

Reviewers will assess the use of chimpanzees as they would any other application proposing the use of vertebrate animals. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section .

Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate For Resubmissions, the committee will evaluate the application as now presented, taking into consideration the responses to comments from the previous scientific review group and changes Additional Review Considerations As applicable for the project proposed, reviewers will consider each of the following items, but will not give scores for these items, and should not consider them in providing an overall impact score.

Applications from Foreign Reviewers will assess whether the project presents special opportunities for furthering research programs through the use of unusual talent, resources, populations, or environmental conditions that exist in other countries and either are not readily available in