Revised Policy: Managing Conflict of Interest in the Initial Peer Review of NIH Grant and Cooperative Agreement Applications

Notice Number: NOT-OD-11-120

Update: The following update relating to this announcement has been issued:

• February 28, 2013 - See Notice NOT-OD-13-047. Notice of Correction to Section II.B.1. "Financial Benefit".
• November 30, 2012 - See Notice NOT-OD-13-010. Advance Notice: Revised Policy for Managing Conflict of Interest in the Initial Peer Review of NIH Grant and Cooperative Agreement Applications.

Release Date: September 26, 2011

National Institutes of Health (NIH)
Office of Extramural Research (OER)

The NIH initial peer review process involves the consistent application of standards and procedures that produce fair, equitable, informed, and unbiased examinations of grant and cooperative agreement applications to the National Institutes of Health (NIH). The process, defined in regulation at 42 CFR Part 52h, is extended by policy to other types of applications submitted to the agency.

This announcement provides revised policy for managing conflict of interest (COI), the appearance of COI, prejudice, bias, or predisposition in the NIH initial peer review process. Given the increasingly multi-disciplinary and collaborative nature of biomedical and behavioral research, the revised policy is intended to facilitate reviews that involve multi-site or multi-component projects, consortia, networks, aggregate datasets, and/or multi-authored publications.

From time to time Federal employees participate in the NIH initial peer review process as part of their official duties. At all times, these Federal officials are subject to the comprehensive body of law governing the conduct of Federal employees. The applicable statutes and regulations include 18 U.S.C. 201-216, the government-wide Standards of Ethical Conduct for Employees of the Executive Branch, 5 C.F.R. Parts 2634, 2635, and 2640, and agency-specific regulations such as the Supplemental Standards of Ethical Conduct for Employees of the Department of Health and Human Services, 5 C.F.R. Part 5501. A Federal employee serving as a member of an NIH Scientific Review Group (SRG) is responsible for complying with all applicable ethical conduct rules and obtaining any clearance for his/her SRG service required by/in his/her employing institute, agency, or office.

This announcement articulates policies governing: (1) the management of conflict of interest (COI), appearance of COI, prejudice, bias, or predisposition in the NIH initial peer review process on the part of individuals who are not Federal employees participating as reviewers; and (2) the selection and use of Federal employees to participate as reviewers, in the initial peer review of:

• all applications submitted to the NIH for competing research project grants and competing revisions (formerly competing supplements); program projects; resources, including but not limited to instrumentation; center grants and cooperative agreements; institutional and individual National Research Service Awards (NRSAs); and academic, clinical investigator, and career development awards. Hereafter application refers to all these types of applications.
• such applications submitted for the September 25, 2011 due date (May 2012 Council round) and thereafter.

The revised policy does not apply to:

• the review of applications for NIH construction grants; and
• individuals serving on NIH National Advisory Councils or Boards, Boards of Scientific Counselors, or Program Advisory Committees.

Conflict of Interest: Regardless of the level of financial involvement or other interest, if a reviewer feels unable to provide objective advice, he/she is expected to recuse him/herself from the review of the application at issue. The peer review system relies on the professionalism of each reviewer to identify to the designated government official the existence of any real or apparent COI that are likely to bias the reviewer's evaluation of an application.

• Non-Federal Reviewer: COI in scientific peer review exists when a non-Federal reviewer has an interest in an application that is likely to bias his or her evaluation of it. A non-Federal reviewer who has a real or apparent COI with an application, as defined in 42 CFR Part 52h, may not participate in its review unless a deviation is granted by the NIH Deputy Director for Extramural Research (DDER).
• Federal Employee: A Federal employee has a conflict of interest (COI) when s/he participates in a particular matter, such as the review of a funding application, that will have a direct and predictable effect on his or her personal or imputed financial interests, unless a statutory or regulatory exemption or exception applies, or a waiver of the COI is granted by the individual responsible for the employee s federal employment (the appointing authority), consistent with agency delegations of authority. Imputed interests include those of the employee s spouse, dependent children, general partner, and any non-federal entity the employee serves as officer, trustee, director, or employee. See 18 U.S.C. 208; 5 C.F.R. Part 2640.

Conflict of Interest Apparent:

• Non-Federal Reviewer: The appearance of COI occurs when a reviewer or close relative or professional associate of the reviewer has a financial or other interest in an application that is known to the reviewer or the government official managing the review, and this circumstance would cause a reasonable person to question the reviewer's impartiality if he or she were to participate in the review. The Scientific Review Officer (SRO) or equivalent managing the review will evaluate the appearance of COI and determine, in accordance with the regulations at 42 CFR Part 52h, whether or not the interest would likely bias the reviewer's evaluation of the application.
• Federal employee: An appearance of a COI arises when a Federal employee is involved in a particular matter involving parties, such as the review of a grant application, and a reasonable person with knowledge of the relevant facts would question the employee’s impartiality in the matter. This may happen when the matter is likely to have a direct and predictable effect on the financial interests of a member of the employee’s household or involves a person with whom the employee is deemed to have a covered relationship as a party or the representative of a party to the matter. Federal employees have a covered relationship with, among others, the following: a person or organization with whom he or she seeks a business or financial relationship; a close relative; an entity that employs the employee’s spouse, parent, or dependent child; an organization in which the employee’s spouse serves as an officer, director, or other position; and, any organization in which the employee is an active participant. Where an appearance of a COI arises, an employee should not participate in the official matter unless he or she is authorized to do so by the appropriate designee of his or her employing agency (often the ethics official). See 5 C.F.R. 2635.502.

Criterion Scores: Before the review meeting, each reviewer assigned to an application gives a separate numerical score for each of (at least) five established review criteria. These individually scored criteria generally are those that apply to all applications for a particular program or category (e.g., Research Projects), whereas the criteria that are not scored individually generally are those that are included in the determination of the impact score only as applicable for the work proposed. For all applications, even those that are streamlined, the scores of the assigned reviewers for these criteria are reported individually on the summary statement.

Designated Federal Official (DFO): The DFO is the NIH staff member who has legal responsibility under the Federal Advisory Committee Act (FACA) for managing the peer review meeting in a manner consistent with applicable statute, regulation, and policy.

Deviation: In unusual circumstances, a deviation from established NIH policy regarding COI or appearance of COI for non-Federal reviewers, or the selection of Federal employees to serve as reviewers or the assignment of particular review responsibilities to a Federal employee, is warranted in order to facilitate the review of applications and maintain the fairness, timeliness, competitiveness, and impartiality of the review process. A request for a policy deviation must be approved by the NIH DDER in advance of the review meeting.

Fully Participating Reviewer: A fully participating reviewer is one who is formally assigned as a reviewer; is present at the SRG meeting, or for the teleconference or web-based discussion; has reviewed and evaluated the application; and has participated in the deliberation on its scientific and technical merit or in the deliberation to streamline the application at the review meeting, or during the teleconference or web-based discussion. Only fully participating reviewers are eligible to give overall impact scores for an application.

Impact Score: The impact score is the rating assigned to an individual application by an SRG, and designates the reviewers assessment of the likelihood for the research project to exert a sustained, powerful influence on the research field(s) involved, in consideration of established review criteria. For certain mechanisms (e.g., Fs and S10s), overall impact may be redefined in terms of merit for the candidate’s career or benefit for the research community. The impact score is one mechanism by which the SRG makes a recommendation to the funding component concerning the application’s scientific and technical merit. Impact scores may be numeric or alphabetical (e.g., ND).

Mail Reviewer: A Mail Reviewer provides written critique(s), criterion scores, and an initial impact score(s) on a particular application or group of applications, by some form of mail, electronic, or internet-assisted communication to the DFO, but does not attend the meeting or participate in the discussion of that application(s) and does not provide a final impact score(s).

Other Significant Contributor (OSC): An OSC is an individual who has committed to contribute to the scientific development or execution of the project, but has not committed to any specified measurable effort (in person months) to the project. These individuals are typically presented at effort of zero person months or as needed (individuals with measurable effort cannot be listed as OSCs).

Peer Reviewers: Peer reviewers are individuals who are experts qualified by training and experience in particular scientific or technical fields, or as authorities knowledgeable in the various disciplines and fields related to the applications under evaluation. These individuals provide expert advice on the scientific and technical merit of applications.

Professional Associate: A professional associate is any colleague, scientific mentor, or student with whom an individual is conducting research or other significant professional activities currently or with whom the individual has conducted such activities within three years of the date of the review. See 42 CFR Part 52h.

Request for Applications (RFA): An RFA is an initiative sponsored by one for more NIH Institutes or Centers that stimulates targeted research by requesting grant applications in a well-defined scientific area. RFAs identify funds set aside for the initiative and the number of awards likely to be made..

Scientific Review Group (SRG): An SRG is a peer review committee of primarily non-government experts (peer reviewers), qualified by training or experience in particular scientific or technical fields, or as authorities knowledgeable in the various disciplines and fields related to the applications under review, to evaluate and give expert advice on the scientific and technical merit of the applications. No more than one-fourth of the members of any SRG may be Federal employees, as noted in the Public Health Service Act and regulation at 42 CFR Part 52h. (Membership on an NIH SRG does not make an individual an employee or officer of the Federal Government.)

Special Emphasis Panel (SEP): A SEP is a chartered federal advisory committee that is authorized under FACA and may be used to perform a one-time only review of a single application or group of applications. The SRG membership of the SEP committee is designated to serve for individual meetings rather than for fixed terms of service.

SRG Member: For purposes of this policy, SRG members include all fully participating reviewers and mail reviewers unless otherwise designated. The term SRG member bears no connotation about appointments, temporary service, or assignments to particular applications.

Scientific Review Officer (SRO): The SRO is the NIH official who serves as the DFO and has responsibility for identifying individuals to serve as peer reviewers, the assignment of review responsibilities, managing the peer review meeting, and the procedures for evaluating the applications assigned to the SRG.

NIH SROs are responsible for managing COI or appearances of COI during the initial peer review process. Their responsibilities include: 1) screening potential and recruited SRG members for COI, apparent COI, and suitability for review assignment(s); 2) providing instructions for reviewers related to applicable regulations and policies regarding COI, apparent COI, and review assignment(s); and 3) managing COI, apparent COI and review assignments otherwise contrary to NIH policy.

Procedures and measures to be taken by the SRO and non-Federal SRG members in advance of, during, and after SRG meetings in relation to COI and appearance of COI are based on the peer review regulations at 42 CFR Part 52h.

NIH SROs may not assign review responsibilities to a non-Federal reviewer or Federal employee that would violate the policy set forth in section B., below, unless the DDER first grants a deviation[1].

An SRG member who is not a Federal employee and has a real COI or an appearance of a COI with an application may not participate in its review, unless a waiver has been granted consistent with the peer review regulations at 42 CFR Part 52h. As defined in regulation, several bases exist for COI for non-Federal SRG members, including employment, financial benefit, personal relationships, professional relationships or other interests. All non-Federal SRG members, including Mail Reviewers, must:

• certify that they have identified to the SRO before the SRG meeting the existence of all known COI and all situations perceived as the appearance of COI; and
• certify after the SRG meeting that they did not participate in the discussion or evaluation of any application with which they have a COI or the appearance of a COI.

An SRG member who is a Federal employee and has a COI under the criminal statute, 18 U.S.C. 208, or an apparent COI under the Standards of Ethical Conduct, 5 C.F.R. 2635.502 with an application may not participate in its review, unless a waiver or authorization, respectively, has been granted by the appropriate authority at the employing agency, consistent with agency delegations of authority. Federal employees are strongly encouraged to consult with their ethics officials regarding any questions regarding the application of the COI statute and the Standards of Ethical Conduct in the context of their service as NIH peer reviewers.

Federal employees are reminded to consider all potential sources of conflict when engaging in initial peer review, including outside activities, such as clinical practice and teaching, speaking, or writing, spousal employment, and investment interests.

All Federal SRG members and review participants must:

• certify that they will maintain the requisite confidentiality of all materials and matters associated with their participation in initial peer review; and
• certify after each SRG meeting that they have received information regarding the COI rules applicable to Federal employees and did not participate in the discussion or evaluation of any application with which they have a COI or apparent COI.

An individual considered to be participating in a project with a major professional role contributes to the scientific development or execution of the project in a substantive, measureable way, whether or not compensation is requested. Even where a Federal employee’s participation in the review would not violate government ethics rules, if s/he is identified as someone who will participate in a project with a major professional role, s/he may not serve as a fully participating member of the SRG where the application in question is reviewed (i.e., out of the SRG or "may not serve"). In addition, an individual with a primary appointment in the same component of a multi-component organization as an individual listed on the application with a major professional role may not participate in the review of that application ( out of the room or "may not review").

Individuals participating with major professional roles include:

• the Program Director/Principal Investigator (PD/PI) or one of multiple PDs/PIs;
• individuals listed on a single-project application as Senior/Key Personnel, Other Significant Contributors, collaborators[2], and consultants2;
• individuals with leadership roles in multi-site or multi-component applications or projects, such as Project/Site/Core Directors, Senior/Key Personnel, Other Significant Contributors, collaborators2, and consultants2 at the level of the overall application. Senior/Key Personnel, Other Significant Contributors, collaborators and consultants listed under individual components of multi-site or multi-component applications (e.g., research projects or cores) are not considered to be participating with leadership roles;
• a sponsor or mentor for an applicant or candidate whose application for a fellowship or career development award is undergoing review;
• members of an Advisory Board (AB) for a single project or single institution program, for a multi-component consortium or network, or for individual(s) with a leadership role in a multi-site or multi-component project. The SRO will determine whether the level of participation by the AB member is sufficient to eliminate his/her participation on the SRG.

An SRG member, including a Federal employee (where participation in the review would not violate government ethics rules), may serve on the SRG but may not participate in the review of an application ( out of the room ), in the absence of a waiver granted by the DDER if the reviewer:

• within the preceding three years, has collaborated with, co-authored a publication(s)[3] with, and/or mentored or trained the PD/PI, one of multiple PDs/PIs, or an individual named on the application as participating with a major professional role;
• is in collaboration, is negotiating collaboration, or is preparing an application(s) or publication(s) with the PD/PI, with one of multiple PDs/PIs, or with an individual named in the application as participating with a major professional role;
• writes a reference letter for an applicant or candidate to accompany a fellowship or career award application and that application is the one in question (however, other SRG members who are from the SRG member s institution, NIH IC, or agency may review the application);
• writes a letter of general support or enthusiasm for the application in question but plays no substantive role in the proposed work;
• is named as a speaker in a conference/meeting grant application;
• participates with a leadership role in another multi-site or multi-component application or project (Application "X") and the PD/PI or one of multiple PDs/PIs on the application or project in the SRG (Application "Y") also participates with a leadership role in the same multi-site or multi-component application or project (Application "X");
• serves as a member of an AB for a component within a multi-component consortium or network, or another project by the same applicant(s), unless the SRO determines that the level of participation by the AB member is sufficiently minor as to allow his/her participation in the review of the application;
• serves as a member of a DSMB for the project or investigator(s), unless the SRO determines that the level of participation by the DSMB member is sufficiently minor as to allow his/her participation in the review of the application; or
• has a primary professional appointment in the same organizational component/school of a multi-component academic institution, hospital, health center, or research institute as that of a named individual listed on the application or project as participating with a major professional role. Situations involving a secondary appointment of a named individual and an SRG member at the same component of a multi-component academic institution, hospital, health center or research institute will be assessed by the SRO on a case-by-case basis for COI.

Unless a deviation from a limitation set forth in this Section B is granted by the DDER, an investigator who participates with a major professional role on an application submitted in response to an RFA, or a Federal employee subject to one of the above-stated limitations in relation to an application submitted in response to an RFA, may not serve as a reviewer of that application or other applications submitted in response to the same RFA.

An SRG that meets regularly may not be objective as a group about evaluating the work of one of its members. In such a case, a member s application or an application that lists the member as participating with a major professional role will be reviewed by another qualified SRG to ensure a competent and objective review. In addition, an application that is from an individual who serves regularly on a recurring SEP, or lists such an individual as participating with a major professional role, may create an appearance of COI for review by that SEP. The SRO will monitor such situations for potential COI.

Multi-component Institutions. For non-Federal reviewers, the DDER has determined that separate organizational components/schools of multi-component academic institutions, hospitals, health centers, and research institutions, as well as different NIH ICs[4] and Federal agencies, are sufficiently independent that an employee of one component serving on an SRG can review an application from another component, if the reviewer has no responsibilities at the institution that would significantly affect the other component and any other real or apparent COI is resolved. For example:

• the separate campuses of the California State system are considered separate components in the same way that the separate campuses of the University of California system are so noted in 42 CFR Part 52h;
• the separate affiliates of the Harvard system are considered separate components;
• the Johns Hopkins Bayview Medical Center and the School of Arts and Sciences, Homewood Campus, are considered separate components;
• the Johns Hopkins Schools of Arts and Sciences and of Engineering, Homewood Campus, are considered separate components; but
• the Departments of Biology and Chemistry within the School of Arts and Sciences of the same academic institution are not considered separate components.

A Federal employee who has, under government ethics rules, a covered relationship with or financial interest in an applicant institution may not participate in the review of an application even if the institution is a multi-component institution.

Applicant Institution. The DDER has determined that an SRG member who is named in an application but has no other affiliation with the applicant institution may participate in the review of other applications from that applicant institution, provided that any other real or apparent COI described in Part B of this announcement is resolved. Federal reviewers must also ensure any real or apparent COI under government ethics rules is resolved by appropriate officials consistent with agency delegations of authority.

Individuals Participating with Minor Professional Roles. An individual listed in an application as participating with a minor professional role does not contribute to the scientific development or execution of the project in a substantive, measureable way and may review the application provided that any other real or apparent COI described in Part B of this announcement is resolved. Federal reviewers also must ensure that any real or apparent COI under government ethics rules is resolved by appropriate officials consistent with agency delegations of authority. Further, an SRG member from the same institution as that of an individual listed with a minor professional role may review the application, provided that any other real or apparent COI is resolved. Similarly, unless there is another unresolved real or apparent COI, an SRG member may review an application if s/he:

• supplies a resource or service to the applicant, and that resource or service is freely available to anyone in the scientific community;
• donates data, specimens or other resources to a central repository or consortium effort to which an individual(s) named on the application also donates data, specimens or other resources;
• is from the institution of the applicant, originators, planning group members, or proposed speakers for/on a conference/meeting grant application;
• co-authored a review article, position paper, professional group or conference report with the PD/PI, one of multiple PDs/PIs, or an individual listed on the application as participating with either a major or minor role;
• is from an institution that is part of a multicenter network (e.g., accrual sites for a multi-center clinical trial) or consortium (e.g., Genome Wide Association Study) that includes the applicant institution, where the SRG member is not involved in the work of the network or consortium;
• is in collaboration with an individual named in the application as a collaborator of or consultant for a PD/PI, as a collaborator of or consultant for one of multiple PDs/PIs, or as a collaborator or consultant of other individuals named in the application as participating with a major professional role2;
• participates with a minor professional role in a multi-site or multi-component application or project (Application "X") and the PD/PI or one of multiple PDs/PIs on an application or project in the SRG (Application "Y") also participates with a minor role in the other multi-site or multi-component application or project (Application "X"). Key Personnel listed on individual components of multi-site or multi-component applications are considered to participate with a minor role in that application; or
• has a primary appointment in the same organizational component/school of a multi-component academic institution, hospital, health center, or research institute as an individual listed in an application as participating with a minor professional role.

Mail Reviewers. COI or the appearance of COI for Mail Reviewers is managed only for those applications that they have been asked to evaluate, not for all applications pending review in the SRG.

Howard Hughes Medical Institute (HHMI). HHMI peer reviewers serving on SRGs may review applications from other HHMI investigators provided they do not work at the same component/school of a multi-component academic institution and no other COI or appearance of COI exists.

The NIH Peer Review Regulations at 42 CFR Part 52h.5(b)(4) specify that in the review of grant and cooperative agreement applications, the Director, NIH (or his/her designee) is authorized to waive the requirement for recusal due to a real COI, as defined in those regulations, when the Director (or his/her designee) determines that there are no other practical means for securing appropriate expert advice to provide a competent review of a grant and cooperative agreement application, and that the COI is not so substantial as to be likely to affect the integrity of the advice to be provided by the reviewer. In addition, the regulations at Part 52h.5(c) authorize the Director, NIH (or his/her designee) to waive the requirement for recusal due to the appearance of COI, when the Director (or his/her designee) determines that it would be difficult or impractical to carry out the review otherwise, and the integrity of the review process would not be impaired by the reviewer’s participation.

The authority to grant such waivers has been delegated to the DDER, NIH, and further delegation is prohibited. The DDER may waive the requirements for recusal in specific instances after review of adequate written justification submitted by an SRO or other official designated by an IC. The justification must explain fully the circumstances for the requested deviation. The SRO or other designated IC official either must exclude the reviewer or obtain advance written approval from the DDER to allow the individual to serve [e.g., 42 CFR Part 52h.5(c)].

While the NIH Peer Review Regulations do not apply to Federal employees engaged in initial peer review, the policy limitations on the selection and use of Federal employees in initial peer review are modeled on those regulations. In order to facilitate a thorough and competent review of applications, the DDER may waive the policy limitations set forth in Section B (above) in specific instances after review of adequate written justification submitted by an SRO or other official designated by an IC. The justification must explain fully the circumstances for the requested deviation. The SRO or other designated IC official either must exclude the reviewer or obtain advance written approval from the DDER to allow the individual to serve.

Situations that may be considered for deviations are of the types that exist between an individual reviewer and an individual application. Requests for deviations involving co-authorship of multi-authored publications (other than review articles, position papers, or professional group or conference reports) within the preceding three years will be considered by the DDER on a case-by-case basis. Situations that involve minor professional relationships generally can be allowed without a deviation. Situations that are disallowed by law, regulation, or designated authority cannot be waived and should never be allowed.

For Federal employees serving as NIH peer reviewers, waivers and authorizations of conflicts of financial interest and appearance concerns under government ethics rules must be obtained from appropriate ethics and agency officials prior to participation.

• Code of Federal Regulations, 5 CFR Part 2635 Office of Government Ethics Standards of Ethical Conduct for Employees of the Executive Branch (http://www.usoge.gov/laws_regs/regulations/5cfr2635.aspx)
• Code of Federal Regulations, 5 CFR Part 5501 Office of Government Ethics Supplemental Standards of Ethical Conduct for Employees of DHHS http://www.access.gpo.gov/nara/cfr/waisidx_07/5cfr5501_07.html)
• Code of Federal Regulations, 42 CFR Part 52h - Scientific Peer Review of Research Grant Applications and Research and Development Contract Projects (https://grants.nih.gov/grants/policy/fed_reg_peer_rev_20040115.pdf)
• Federal Advisory Committee Act, P. L. 92-463 (http://www.gsa.gov/portal/content/100916)

Please direct all inquiries to:

Sally A. Amero, Ph.D.
NIH Review Policy Officer
[email protected]