STANDARD OPERATING PROCEDURE ON THE HANDLING OF ALLEGATIONS OF NON COMPLIANCE

Handling Issues of Non Compliance

I. Introduction

Under institutional authority and federal regulations [Title 45 CFR 46.103(b)(5), Title 45 CFR 46.113, Title 21 CFR 56.113], Institutional Review Boards (IRBs) are responsible to oversee the safety of research participants and may suspend or terminate human research that: (1) is not being conducted in accordance with the federal, state and institutional requirements, or (2) has been associated with unexpected serious harm to participants. The IRBs are supported in this process by the Office for Research Protections (ORP) and the Human Subjects Protection Office (HSPO).

II. Applicability

The following policies apply to all research activities of faculty, staff, students and others who are involved in human research as defined by the Penn State University Policy RA14, "Protection of Human Participants in Research."

III. Definitions

A. Noncompliance is defined as failure to comply with federal regulations, IRB policy or the determinations or requirements of the IRB.

1. Nonserious and Noncontinuing noncompliance involves isolated incidents, e.g. an unintentional mistake, an oversight, or a misunderstanding. The issue is not serious or continuing in nature.
2. Serious non-compliance: An action or omission, non-compliant with Federal regulations or IRB policy, taken by an investigator that any other reasonable investigator would have foreseen as increasing risks or compromising the rights and welfare of a participant or other persons.
3. Continuing non-compliance: A pattern of repeated actions or omissions taken by an investigator that indicates a deficiency in the ability or willingness of an investigator to comply with Federal regulations, IRB policy or determinations or requirements of the IRB.

B. Protocol Deviations and Variances from the Protocol do not fall within these definitions until they meet the distinction of being serious and/or continuing.

IV. Reporting Requirements for Suspected Noncompliance

Investigators and research staff are required to report all suspected noncompliance to the IRB Administrator/Coordinator at either the ORP or the HSPO.

Additionally, information regarding noncompliance in studies that enroll human participants may come to the attention of the IRB Administrator/Coordinator or the IRB through several pathways:

• new applications
• continuing reviews
• internal audits
• FDA audit reports
• adverse event/safety reports
• reports from collaborators, employees, participants, family members, community members
• any other sources.

Each allegation is taken seriously and reviewed in a consistent, prompt, and professional manner. Additionally, care is taken to maintain confidentiality. All communications and documentations are to be factual and objective.

V. Process for Handling Suspected Noncompliance

Upon receipt of an allegation, the IRB Administrator/Coordinator will review the allegation and determine if it is valid. If the allegation is valid, then the IRB Administrator/Coordinator will undertake an inquiry.

VI. Inquiry Process

1. The IRB Administrator/Coordinator undertakes an inquiry of the allegations within 5 week days of the suspected noncompliance. The purpose of the inquiry is fact-finding, and may involve examination of study records and discussion with the research team, other personnel, research participants, witnesses, the complainant (if not anonymous), and others as appropriate.
2. The IRB Administrator/Coordinator documents and compiles the information and presents the findings to the ORP/HSPO Director.
3. The Director determines whether the allegation is (1) nonserious and noncontinuing or (2) serious or continuing noncompliance that warrants investigation by the IRB or (3) has no basis in fact.

VII. Preliminary Determination of a Temporary Hold or Non-suspension

The Director of the ORP or the Director of the HSPO determines if immediate suspension of study procedures and/or study enrollment is required for the project in question, as well as for other projects under the same investigator. This initial decision is based on preliminary review of available information, communication with the principal investigator(s) involved in alleged noncompliance activities, and the seriousness of the allegations. (See the "SOP on Suspensions or Termination of IRB Approved Research")

• The principal investigator(s) involved in the allegations and associated research staff personnel, appropriate Department Head(s), and Institutional Official (IO) are notified in writing about any suspension.
• Federal regulatory agencies are notified, if applicable.

Further fact-finding and timely review by a convened IRB determines the length of any suspension.

VIII. Resolution of Inquiry

1. Nonserious and Noncontinuing Noncompliance
   • a. If the noncompliance activity is determined to be nonserious and noncontinuing:
     • The issue is resolved among any combination of the Director, IRB Administrator/Coordinator, principal investigator(s), and student advisor, if applicable.
     • The IRB Administrator/Coordinator documents the outcome of all communications in writing. This report includes any sanctions or corrective actions required on the part of the investigator and the timelines for resolution.
   • b. A copy of this report is sent to the principal investigator(s) involved in noncompliance activities, associated research staff personnel, and others as deemed appropriate.
     • A written response from the principal investigator acknowledging the report and describing corrective actions is required within 5 week days from the date of the corrective report.
     • The complainant will be provided information as deemed appropriate by the Director.
     • All communication is documented in a restricted IRB noncompliance and confidential section within the specific IRB research study folder.
   • c. If during the inquiry of a nonserious or noncontinuing noncompliance it is determined that the noncompliance is serous or continuing, the matter will be referred to the IRB for their investigation.
2. Serious and/or Continuing Noncompliance
   • a. If the noncompliance activity is determined to be a serious or continuing, the matter is forwarded to the IRB for their investigation:
     • The ORP/HSPO Director, in conjunction with the appropriate IRB Chair(s) and IRB Administrator(s)/Coordinator(s), readdresses the possible need for suspension of study procedures and/or study enrollment for the project in question, as well as for other projects under the same investigator, pending a timely review by a convened Institutional Review Board.
     • If research activity suspension is warranted:
       • The principal investigator(s) involved in noncompliance activities and associated research staff personnel, Department Head(s), and Institutional Official are notified in writing about any suspension.
       • Federal regulatory agencies are notified, if applicable.
       • In cases of externally funded programs, notice is sent to the sponsor and to the Office of Sponsored Programs or the Office of Research Affairs.
     • Convened IRB Review
       • The issue is presented to the next appropriate convened IRB. For urgent issues, the Director may convene an emergency meeting of the IRB.
       • The IRB will receive a copy of the most recently approved consent form, any necessary sections from the IRB approved protocol and all documented communications and discussions concerning the noncompliance from the inquiry phase. The complete IRB protocol will be available at the IRB meeting.
       • The Principal Investigator will be invited to attend the IRB meeting and provided an opportunity to respond to the allegation(s).
       • The IRB may also meet with the complainant (if not anonymous), and others as needed.
       • After the IRB has completed the investigation, the IRB will determine the appropriate course of action, such as:
         • No action;
         • Modification of the research protocol;
         • Modification of the consent form or consent process;
         • Additional information provided to past participants;
         • Notification of current participants (required when such information may relate to participants' willingness to continue to take part in the research;
         • Requirement that the current participants re-consent to participation;
         • Modification of the continuing review schedule;
         • Monitoring of research;
         • Monitoring of the consent;
         • Suspension of the research;
         • Termination of the research;
         • Obtaining more information pending a final decision;
         • Referral to other organizational entities (e.g., legal counsel, risk management, institutional official, etc.);
         • Requirement of additional training or re-training;
         • Other actions appropriate for the local context.

IX. Reporting

The IRB Administrator/Coordinator will follow the IRB's Standard Operating Procedure on reporting.

X. Research Misconduct

If the noncompliance involves callous disregard for the protection of human participants or for the integrity of research, the ORP/HSPO Director will notify the Senior Vice President for Research for further action according to Penn State Policy RA10, "Handling Inquiries/Investigations into Questions of Ethics in Research and Other Scholarly Activities". This does not preclude the IRB Chair(s) or any member of the IRB from independently contacting the Senior Vice President for Research about any allegation of research misconduct. Inquiries or investigations into research misconduct do not preclude IRB review and actions.

Dates Approved:
October 21, 2004 (Social Science and Biomedical IRBs-UP)
October 07, 2004 (IRB Executive Committee - College of Medicine)