SOP #30 Non-Compliance with Human Subjects Research Policies/ Guide and Report Form

Owner: Vice President of Academic Affairs
Author: CSS IRB
Contact: irb@css.edu
Policy Number: 30
Effective Date: 10/8/2021

Policy

It is the policy of the CSS IRB  that all allegations of non-compliance with human subjects research must be reported promptly, each report will be investigated, and determinations made about these allegations.  Issues or events that are reported are considered possible non-compliance until a final determination is made by the convened IRB or the IRB Chair. Non-compliance that is determined to be serious or continuing must be promptly reported to the appropriate institutional officials, the Office for Human Research Protections (if applicable) and the Food and Drug Administration (if applicable).  (See, Appendix A.)

Purpose

The only mention of non-compliance in the regulations is that the organization must have “…written procedures for ensuring prompt reporting to the IRB, appropriate institutional officials; the department or agency head… of any serious or continuing noncompliance with this policy or the requirements or determinations of the IRB  and any suspension  or termination of IRB approval.”  45 CFR 46.108 (a)(4)(i) (ii) and 21 CFR 56.108 (b)(2). The purpose of this SOP is to identify the standards and responsibilities for handling reports of non-compliance related to research involving human subjects, and the actions taken when the IRB makes a finding of serious or continuing non-compliance.

Distinction – Research Misconduct / Noncompliance

The Code of Federal Regulations Policy regarding research misconduct is found at CFR Title 42 Part 93:

Public Health Services Policies on Research Misconduct. The Good Clinical Practice (GCP) training course (Good Clinical Practice (nidatraining.org) advises that Federal regulations define research misconduct as: "...fabrication, falsification, plagiarism, or other practices that seriously deviate from those that are commonly accepted within the scientific community for proposing, conducting, or reporting research." Fabrication is making up data or results and recording or reporting them. Falsification is changing research materials, equipment, or processes or altering or omitting data or results so that the research record does not accurately reflect the research findings. Plagiarism is using another person’s ideas, processes, results, or words without giving appropriate credit.  Research misconduct does not include honest error or differences of opinion. In addition, the federal policy on research misconduct does not apply to authorship disputes unless they involve plagiarism. Research misconduct has a very specific meaning in federal regulations. Noncompliance with policies and procedures for the protection of human research subjects, although reportable to an Institutional Review Board (IRB), is not considered to be research misconduct under the federal definition.

Summary of Key Points

Federal policy defines research misconduct as “fabrication, falsification, or plagiarism in proposing, performing, or reviewing research, or in reporting research results.” This definition does not include honest error or differences of opinion or authorship disputes unless they involve plagiarism. Federal policy on research misconduct applies to all federally funded research and all proposals submitted to federal agencies for research funding. The Office of Research Integrity (ORI) in the Department of Health and Human Services oversees investigations of research misconduct allegations and makes final determinations on findings of research misconduct within the U.S. Public Health Service. Federal policy places the primary responsibility for reporting and investigating allegations of research misconduct with researchers and research institutions. Generally, the response to an allegation of research misconduct has three stages:

  • Inquiry (to assess the facts of the allegation).
  • Investigation (if the inquiry provides adequate basis for one).
  • Adjudication (imposing of suitable penalties if the allegation is found to have merit). Penalties for research misconduct may include termination of employment, suspension or termination of a research grant, and suspension or debarment from receiving federal funds.

(Good Clinical Practice Course Good Clinical Practice (nidatraining.org))

The Collaborative Institutional Training Initiative (CITI) (CITI Program – Research Misconduct RCR-Basic (https://www.citiprogram.org/members/index.cfm?pageID=665&ce=1#view) includes Noncompliance as a detrimental research practice and defines noncompliance as, …conducting research in a manner that disregards or violates federal regulations or organizational policies.  Noncompliance often involves the failure to adhere to appropriate research practices when working with human or animal subjects.

Noncompliance can be associated with research misconduct if, for example, it prompts a researcher to present falsified or fabricated data.

Because allegations of research misconduct involve institutions that receives federal funding, the institution must have policies and procedures in place to handle those allegations.  A typical organizational policy will outline:

  • Definitions of research misconduct;
  • Procedures for reporting and investigating research misconduct;
  • Rights and obligations for all parties involved in the research misconduct process;
  • Provisions for protecting whistleblowers, individuals handling the misconduct process, and person accused of research misconduct.  (CITI Research Misconduct RCR-Basic Module.)

Research Misconduct is an internal CSS process of managing research misconduct allegations, as such, it is not a policy that applies to the CSS IRB or 45 CFR Part 46 (Basic HHS Policy for Protection of Human Research Subjects).  The CSS IRB Policies pertain to human subject research issues including:

  • Reporting an Unanticipated Problem Involving Risks to Subjects or Others/Adverse Event and Report Form (CSS IRB SOP #24);
  • Non-Compliance with Human Subjects Research Policies/Guide and Report Form (CSS IRB SOP #30); and
  • Suspension or Termination of IRB Approval and Report Form (CSS IRB SOP #31).

Definitions

Allegation of Non-Compliance (also “allegations”) - A disclosure of possible non-compliance through any means of communication (e.g., by written or oral statement) to the CSS IRB. This may include concerns from research participants, investigators, staff, IRB members, reports from audits, and discoveries made during review of other human subjects issues, such as protocol deviations. It does not include self-reporting by the PI/designee to the IRB, using a reportable event form (see, Appendix B) submitted to the IRB.

Non-Compliance - Failure of investigator(s) to follow the applicable laws, regulations, or institutional policies governing the protection of human subjects in research, or the requirements or determinations of the IRB, whether the failure is intentional or not.

Non-serious (minor) non-compliance - means any non-compliance that is not serious or continuing non-compliance. For example, non-serious non-compliance might include but is not limited to the following:

  • Deviating from or violating the provisions of an IRB-approved protocol in a way that does not jeopardize subjects' health or safety such as a delay in follow-up because the subject was on vacation.
  • Implementing non-substantive changes to approved procedures without IRB approval, such as:
    • Re-wording survey or interview questions where the meaning and scope of the question does not change;
    • Wording changes in recruitment materials or consent documents that do not change the meaning of the information provided or result in excluding any required element(s) of consent;
    • Changing the order in which study conditions are administered, as long as a specific order is not necessary to minimize risk;
    • Enrolling subjects who do not meet the inclusion or exclusion criteria, except in the circumstances described as serious non-compliance below;
    • Exceeding the approved number of subjects in a study.

Serious non-compliance - Non-compliance, whether intentional or not, that results in harm or otherwise materially compromises the rights, welfare and/or safety of the subject. Non-compliance that materially affects the scientific integrity or validity of the research may be considered serious non-compliance, even if it does not result in direct harm to research subjects.  For example, serious non-compliance might include but is not limited to:

  • Failure to obtain IRB approval prior to initiating research activities with human subjects;
  • Allowing unqualified or untrained individuals to perform research procedures or monitor subject safety;
  • Failure to provide participants with all information necessary to constitute meaningful “informed consent” unless a waiver has been granted by the IRB;
  • Enrolling a child in a research study without the informed permission of a parent or legally authorized representative unless parental consent was waived by the IRB;
  • Enrolling subjects from a vulnerable population (i.e., children, prisoners, cognitively impaired individuals, etc.) when their inclusion is not described in the IRB-approved protocol and appropriate protections are not in place;
  • Enrolling subjects who do not meet the approved eligibility criteria when doing so compromises the safety or well-being of the subjects;
  • Failure to follow approved measures for protecting privacy and confidentiality when the failure presents any risk of harm to the research subject (such as harm to their reputation, social or psychological harm, risks of legal or civil liability, embarrassment, harm to workplace or family relationships, etc.);
  • Implementation of changes to data collection procedures, without prior IRB approval, that increase risks to participants or adversely affect their rights, safety, or welfare (e.g., adding survey questions that collect sensitive information, substantially increasing the duration or intensity of exercise activities, adding plans to collect data from private records without subject consent, changes to confidentiality protections, etc.);
  • Failure to report serious adverse events or unanticipated problems involving risks to subjects or others as required by IRB policy (see, CSS IRB SOP #24 Unanticipated Problems and Adverse Event Reporting);
  • Instructing or knowingly allowing subordinates (e.g., research assistants, employees, etc.) to engage in activities that are contrary to IRB or institutional policies or regulatory requirements;
  • Providing false or intentionally misleading information to the IRB;
  • Multiple protocol deviations suggesting a lack of oversight, inaction, or negligence such that research subjects’ rights, safety, or welfare could be adversely affected.

Continuing non-compliance - A pattern of recurring non-compliance that either has resulted, or, if continued, may result in harm to subjects or otherwise materially compromise the rights, welfare and/or safety of subjects, affect the scientific integrity of the study or validity of the results. The pattern may comprise repetition of the same non-compliant action(s), or different non-compliant events. Such non-compliance may be unintentional (e.g., due to lack of understanding, knowledge, or commitment), or intentional (e.g., due to deliberate choice to ignore or compromise the requirements of any applicable regulation, organizational policy, or determination of the IRB). Examples include but are not limited to:

  • Repeated failure to obtain IRB approval prior to initiating human subjects research activities;
  • Continually late submissions of continuing review applications resulting in repeated lapses in approval;
  • Multiple instances of serious or minor non-compliance; this includes multiple incidents within a single project or multiple incidents by a single investigator across more than one project.

Respondent - The investigator or entity, if any, against whom an allegation of non- compliance is made.

Responsibilities and Requirements

Out of respect for all persons involved, reports of non-compliance should be made in good faith and all persons strive to maintain confidentiality and cooperate with any IRB and/or institutional review of these reports. Reports of non-compliance will be investigated by the IRB Chair.

Researchers/Investigators are required to follow all applicable laws, regulations, and CSS IRB policies governing the protection of human subjects in research. Non-CSS investigators who are under the jurisdiction of the CSS IRB, must follow applicable laws, regulations, and CSS IRB policies as they relate to governing the protection of human subjects in research.

Self-Reporting Noncompliance Researchers are responsible for self-reporting to the IRB incidences of non-compliance that involve:

(i) failure to comply with federal regulations, state laws, institutional policies, requirements or determinations of the IRB, which include provisions within the approved research study, and/or

(ii) potential or actual increased risk to the safety, rights, and welfare of research subjects. Reports of non-compliance must include a corrective action plan, which outlines the steps taken to resolve and prevent such occurrences in the future. Researchers are encouraged to work with the CSS IRB Chair in developing corrective action plans for non-compliance.

CSS IRB Chair is responsible for initially reviewing reports or allegations of non-compliance and taking appropriate action (including no action). All reports of apparent serious or continuing non-compliance reported to the CSS IRB must be reviewed at the next convened IRB meeting.

CSS IRB When allegations of non-compliance are reported to the CSS IRB, allegations must be investigated, and determinations must be given regarding whether non-compliance has occurred.  Upon receipt of an allegation of non-compliance, the CSS IRB will follow the procedures outlined below:

  • Conduct an initial (informal or extensive) inquiry for factual information;
  • Provide written correspondence to the Principal Investigator (PI), or other appropriateparty, for notification of the allegation and to grant an opportunity to respond;
  • When appropriate, the CSS IRB will work with the PI to develop an initial correctiveaction plan to present to the IRB.

Employees and Agents of The College of St. Scholastica that rely on the CSS IRB share the responsibility for reporting incidences of non-compliance with the Chair of the IRB. Allegations of non-compliance in human subjects research may come from many sources including, but not limited to, the following:

  • Investigators or investigational team members;
  • Department Chair and/or College Dean of the PI;
  • Study monitors, auditors, or sponsors;
  • Research participants or family members;
  • Individuals not directly involved in research;
  • Members of the IRB Office;
  • Any member of the CSS staff.

Procedures Addressing Allegations of Non-compliance

The CSS IRB Chair may become aware of an allegation of non-compliance or of circumstances indicating non-compliance upon the receipt of a complaint from a participant, researcher, CSS employee, or member of the public; from the interpretation of information received during a Continuation, Amendment, Unanticipated Problems Review; or from the findings of a random or for-cause audit or other quality control activities.

Once the IRB Chair has received an allegation of non-compliance, the Chair will request the alleger to submit a Non-compliance Report Form (see, Appendix B). In the case of an anonymous complaint or a request for confidentiality, the IRB Chair will fill out and submit the form.  The IRB Chair and the IRB Administrator will make the following initial determinations:

(a) whether noncompliance is alleged; and

(b) whether the allegation indicates that an immediate action such as suspension by the IRB is warranted. If it is determined that immediate action by the IRB is warranted (e.g., suspension), then the IRB Chair will initiate those proceedings in accordance with CSS IRB SOP #31 Suspension or Termination of IRB Approval and Report Form. The Chair of the IRB will then initiate an investigation of the circumstances alleged in the Non-compliance Report Form. The IRB Chair may elect to investigate informally by reading relevant documents and communicating with the affected parties. If the IRB Chair determines that the allegation is not credible or is unsubstantiated, then the inquiry ends. The IRB Chair or the IRB Administrator will document this finding in a written report and notify the IRB members of the finding on the agenda of the next available meeting. If, however, the inquiry yields evidence that non-compliance has occurred, then the IRB Chair will present this information by way of a report to the full IRB for discussion at the next available meeting.

Confirming and Resolving Non-compliance

If it is determined that the non-compliance is neither serious nor continuing (see Definitions above), the IRB Chair and IRB Administrator will devise a corrective plan, which generally will involve immediate remediation (e.g., obtaining signature of Protocol PI on submissions, providing missing documentation) and/or remedial education as defined by the IRB Chair.

If it is determined that the non-compliance is serious or continuing, the IRB Chair will conduct a for-cause audit. If it is determined that an unanticipated problem has occurred, the IRB Chair will address it in accordance with CSS IRB SOP #24 Unanticipated Problems and Adverse Event Reporting. The Principal Investigator  may request a meeting with the IRB Chair regarding the determination of serious or continuing non-compliance.  As stated in CSS IRB SOP #31 Suspension or Termination of IRB Approval and Report Form, a PI may decide voluntarily to suspend or terminate some or all of the research activities that may be under current review or investigation. The PI should inform the CSS IRB Chair of this action so that the IRB Chair can place the protocol on the agenda for the next available IRB meeting. The IRB will address the suspension or termination in accordance with CSS IRB SOP #31 as noted above.

The IRB Chair will distribute a for-cause audit report to the PI, the members of the IRB, and, if appropriate, the Institutional Official and/or VPAA. The PI may submit a response to the audit report in writing and/or may request to speak to the IRB at a convened meeting. The IRB Chair and/or IRB Administrator will place the report and any written response from the PI as discussion items on the agenda of the next available IRB meeting. The IRB will make a final determination as to whether the evidence supports a finding of serious or continuing noncompliance and, if so, will determine a corrective plan, including time frame for correction, and will, if necessary, initiate suspension or termination proceedings in accordance with CSS IRB SOP #31 Suspension or Termination of IRB Approval and Report Form.

In reviewing information to make a final determination of serious or continuing non-compliance, the IRB should consider:

  1. Whether the audit report and any other available information sufficiently supports adetermination of non-compliance.
  2. Whether the audit report and any other available information supports suspension ortermination of research in order to protect human participants or others.
  3. Additional actions to protect the rights and welfare of currently enrolled participants.
  4. Whether procedures for withdrawal of enrolled participants account for their rights and welfare.
  5. Whether participants should be informed of the non-compliance and/or any of the corrective actions.

The IRB may invite the PI to a portion of the meeting to answer questions and to discuss the issue of non-compliance. If the PI requests, or is requested, to be present at the IRB meeting, he or she may be accompanied by a faculty representative, legal counsel, or another member of his or her department. The role of these individuals is limited to providing information and support to the PI; they will not participate in the discussion between the PI and the IRB.

The PI must implement the corrective plan within the required time frame. The IRB will monitor the PI’s implementation of the corrective plan. A failure to implement the corrective plan on time will be reported to the IRB Chair for further action, including initiation of procedures for suspension or termination of IRB approval of the research protocol, in accordance with CSS IRB SOP #31 Suspension or Termination of IRB Approval and Report Form

Upon full implementation of the corrective plan, the CSS IRB Chair and/or IRB Administrator will draft a final non-compliance report for discussion by the IRB at the next available meeting. After the report is finalized it will be distributed to the following parties:

  1. Protocol PI.
  2. Institutional Official (CSS President and VPAA).
  3. Department Chair and/or College Dean of the PI.
  4. Sponsoring agency, when applicable.
  5. OHRP, when applicable.
  6. In general, these OHRP reporting requirements apply to all non-exempt human subjects research that is:
    • conducted or supported by HHS;
    • conducted or supported by any non-HHS federal department or agency that has adopted the Common Rule and is covered by a Federalwide Assurance (FWA) determined to be appropriate for such research; or
    • covered by an FWA, regardless of funding source.

While the IRB has the authority to take appropriate action concerning a research protocol, neither the IRB Chair nor the convened IRB has the authority to take disciplinary action against any individual relating to a finding of confirmed non-compliance. Instead, disciplinary action shall be the responsibility of the institution. The CSS IRB Chair shall report any termination of research to the appropriate institutional officials, and the IRB Chair will, if requested, assist in any disciplinary action process taken by the appropriate academic unit.

Corrective Actions in Response to Non-compliance

The actions taken to correct non-compliance vary and depend on the nature and seriousness of the non-compliance. The IRB may take any of the following actions:

  1. Take no action.
  2. Request a protocol and/or consent form modification.
  3. Require that all participants be re-consented.
  4. Require previous participants to be informed of any changes to the protocol and/or consent procedures.
  5. Require observation of consent procedures.
  6. Require more frequent review of the conduct of the research.
  7. Require additional training for the research team.
  8. Require follow-up audit(s).
  9. Suspend the research (See, CSS IRB SOP #31 Suspension or Termination of IRB Approval and Report Form).
  10. Terminate the research: (See, Id.).
  11. Refer issues to other institutional entities (e.g., CSS President, VPAA, Dean, Legal Counsel).
  12. Any other action deemed appropriate by the IRB to protect the rights and welfare of research participants.

Informed by any audit reports, corrective plans, and final non-compliance reports, the IRB Chair and/or IRB Administrator will develop and administer required and optional educational programs, as specified in corrective plans for the PI and for the research community generally.

Documentation Relating to Reporting and Resolution of Non-compliance

All documents relating to non-compliance will be maintained by the CSS IRB for a period of not less than 5 years. These documents include but are not limited to:

  • Noncompliance Report Forms;
  • Correspondence with the PI;
  • Documentation of implementation of corrective actions.

Resources

FDA. IRB Functions and operations.  21 CFR 56.108(b)

Public Health Service (PHS) Policies on Research Misconduct – 42 CFR Part 93 IRB EasyEd Non-Compliance: Investigation, Decision Making and Reporting.

Volume 1 Number 12 © 2017 Apex Ethical St Joseph Health

https://www.stjhs.org/documents/Clinical-Research/Noncompliance-in-Human-Subjects-Research.pdf Rutgers https://orra.rutgers.edu/research-noncompliance Cornell University

https://researchservices.cornell.edu/sites/default/files/2019-05/SOP%205%20-%20Managing%20Nonco mpliance.pdf Iowa State

https://www.compliance.iastate.edu/sites/default/files/imported/irb/guide/docs/protocol-deviation-no ncompliance.pdf

The University of Texas Health Science Center at San Antonio http://research.uthscsa.edu/ocr/policy/Institutional_Review.pdf Guidance on Reporting Incidents to OHRP (2011)

https://www.hhs.gov/ohrp/compliance-and-reporting/guidance-on-reporting-incident/index.html Purdue University

https://www.irb.purdue.edu/docs/forms/Noncompliance%20report%20form_fillable%20PDF.pdf CITI Program – Research Misconduct RCR-Basic

https://www.citiprogram.org/members/index.cfm?pageID=665&ce=1#view

Good Clinical Practice Course Good Clinical Practice (nidatraining.org)

The College of St. Scholastica Research Misconduct Policy ___________________________

This is a new policy per the 2018 Common Rule Requirements.

 

Appendix A - OHRP Reporting Guidance

 

  • Did the incident occur in non-exempt human subjects research, and is it; an unanticipated problem, or serious or continuing noncompliance, or suspension or termination of IRB approval? If no, then No need to submit an incident report to OHRP.* If yes, then:
  • Did the incident occur in research that is HHS supported or conducted? If yes, then report the incident to OHRP. If no, then:
  • Is the research conducted or supported by a Federal Agency that has adopted the Common Rule?
    • If yes; Has the Federal Agency approved a separate assurance other than the FWA for the research? If no, then report the incident to OHRP
    • If no, go to next step
  • Is the research conducted at an institution with an OHRP approved assurance? If no, then no need to submit an incident report to OHRP.* If yes:
  • Does the assurance apply to all research regardless of funding? If no, then no need to submit an incident report to OHRP.* If yes, report the incident to OHRP.*

*Other reporting requirements may apply, whether or not a report to OHRP is required.

Print Article