RP05 Research Quality in Human Participant Research

Contents:

• Purpose
• Policy
• Scope
• Regulatory Agencies
• Authority of Research Quality Programs
• Investigator Responsibilities
  • Reporting of Potential Noncompliance
• Further Information
• Cross References

PURPOSE:

The Pennsylvania State University (the "University") is dedicated to maintaining the ethical treatment of human participants in all research activities conducted under the auspices of this institution and assumes responsibility for safeguarding their rights and welfare (See Policy RP03 - The Use of Human Participants in Research).  The purpose of this policy is to outline the University's strategies for maintaining, improving and promoting high standards for the quality of human participant research, as well as facilitating compliance with institutional, federal, state and all other applicable regulations and laws as it relates to human participant research protections.

POLICY:

The University’s policy for maintaining the quality of human participant research is guided by ethical principles, Federal law, and institutional standards.  The Office for Research Protections and the Office for Research Affairs are responsible for coordinating and implementing quality assurance and quality improvement programs as it relates to human participant research.  These offices have established the Quality Assurance Program and the Research Quality Assurance Program. These Research Quality (RQ) programs have the responsibility to address quality assurance and quality improvement activities in conjunction with the Human Research Protections Program (HRPP) and other offices/programs, as appropriate.  

SCOPE:

Regardless of funding or funding source, this policy applies to all human participant research as defined in RP03 conducted at the University, including biomedical and social science research. 

The Quality Assurance Program primarily audits human subject research conducted by investigators from all University colleges and campuses, whereas the Research Quality Assurance Program primarily audits human participant research conducted at the College of Medicine, the Penn State Health Milton S. Hershey Medical Center and other Penn State Health locations. 

The RQ programs do not audit research conducted at the Pennsylvania College of Technology. 

REGULATORY AGENCIES:

Human participant research is regulated by the Office for Human Research Protections (OHRP) and/or the U.S. Food and Drug Administration (FDA), and the RQ programs take their direction from these governmental authorities through the Institutional Review Board (IRB).  Regulations related to audit or the review of research in 45 CFR 46 (Code of Federal Regulations. Title 45A- Department of Health and Human Services; Part 46 – Protection of Human Subjects) and 21 CFR 56 (Code of Federal Regulations. Title 21, Chapter 1 – Food and Drug Administration, DHHS; Part 56 – Institutional Review Board) are "currently interpreted as granting the institution, the IRB, and/or its representative(s) the authority and responsibility to audit research" to ensure the safety of participants. (Bankert, EA & Amdur, RJ.  2006. Institutional Review Board, Management and Function, p. 53)

AUTHORITY OF RESEARCH QUALITY PROGRAMS:

The RQ programs seek to ensure investigator and institutional compliance with federal and state regulations governing human participants research and encourage best practices to enhance the ethics, safety and quality of human participant research.  The RQ programs are independent from the HRPP Office and IRB.  The RQ programs have the authority and are mandated by this policy and the Organizational Officials (Associate Vice President for Research and Director of the Office for Research Protections) to conduct reviews of human participant research and other related activities.  Investigators have the responsibility to cooperate with RQ program requests. 

In order to verify that IRB approved procedures are being followed and to enhance the protection of human participants, the RQ programs conduct post-IRB approval reviews or audits.  Any study determined exempt or approved by the IRB may be selected for a post-IRB approval review.  Additionally, the RQ programs fulfill the regulatory and accreditation standards as an independent, third party, to audit research to ensure the safety and rights of human participants and regulatory compliance (45 CFR 46, 21 CFR 56, AAHRPP standards). Post-IRB approval reviews are conducted in an educational, pro-active, and transparent manner and are not punitive. They are an opportunity for the study team to review their procedures for consistency and quality. 

Each RQ program follows established procedures for identifying studies for post-IRB approval reviews, which can be provided by the appropriate RQ program upon request. Study selection is intended to be equitable and based on a variety of factors such as duration of the study, potential risk to participants, study population, as well as campus location among other factors. 

In addition, the RQ programs oversee compliance with clinicaltrials.gov registration and reporting as outlined in RP12. Per the Revised Common Rule, the RQ programs will require federally funded clinical trials including social, behavioral or educational (SBER) research studies (see 45 CFR 46.102(b)) to post an informed consent form to the appropriate, approved website.

Types of Audits

Routine post-IRB approval reviews or audits may include, but are not limited to, assessment of study and regulatory documentation and review of study records and participant files to ensure regulatory compliance including protocol adherence, accurate record keeping, and appropriate informed consent process. 

Directed post-IRB approval reviews or audits include the same comprehensive review as a routine audit, while focusing on specific study concerns needing further review as directed by the IRB, or the Institutional/Organizational Official or their designee. 

Routine or directed audits may also involve the following:

• Observation of the consent process
• Observation of research procedures
• Review of facilities and research personnel regarding suitability and preparedness to conduct research

The RQ program staff provides reports of any findings or observations resulting from audits to the principal investigator, who should submit as necessary to the HRPP for review.  The QA program may submit reports and observations to the HRPP in the instance that the principal investigator fails to do so or consultation is needed. 

FDA-Regulated Research

In addition to post-IRB approval reviews, the RQ programs assist in determining whether sponsor-investigator research is FDA-regulated. A sponsor-investigator is a person who both initiates and conducts an FDA-regulated study; that is, an individual who (i) holds an Investigational New Drug (IND) or Investigational Device Exemption (IDE); and (ii) serves as the principal investigator in one or more studies conducted under that IND or IDE. 

For FDA-regulated research, the RQ programs may:

• Require the investigator to provide written documentation from the FDA for Investigational New Drug (IND) exemption determinations. 
• Conduct an audit to determine if the research facilities and research personnel are aware of and able to fulfill FDA-regulations for IND and IDE holders [21 CFR 56.107(a)].

At all campuses and colleges, the ability of an investigator to serve as an IND/IDE holder is evaluated on a case-by-case basis except for the College of Medicine and Penn State Health, which requires, only a licensed physician may be an IND or IDE holder, with some limited exceptions.

INVESTIGATOR RESPONSIBILITIES (as they relate to this policy):

Investigators have general responsibilities as they relate to quality research (see Policy RP03). Investigators should:

• Cooperate with RQ program staff as they carry out their responsibilities.
• Permit study-related monitoring, audits, and inspections by the RQ programs, of all study related documents (e.g., source documents, regulatory documents, data collection instruments, study data etc.).  
• Facilitate the capability for inspections of applicable study-related facilities (e.g., pharmacy, diagnostic laboratory, etc.).
• Contact the RQ program for guidance as needed.

Additional responsibilities for sponsor-investigators conducting FDA-regulated research:

• Contact the RQ program for assistance in determining if you are a sponsor-investigator.
• Contact the RQ program staff for assistance in determining whether an IND/IDE is needed.
• Contact the RQ program prior to FDA submission of an IND/IDE application and prior to any required reporting or modifications for an existing IND/IDE.
• Contact the RQ program  prior to the time of submission to the IRB of a new study that will be FDA regulated.
• Work with the RQ program staff to arrange a review to gather information regarding research personnel qualifications and site suitability for the proposed research.
• Meet with the RQ program staff to discuss responsibilities as a sponsor-investigator prior to IRB approval.
• Provide any follow-up information requested by the RQ program staff.

REPORTING OF POTENTIAL NONCOMPLIANCE

Noncompliance is failure (intentional or unintentional) to comply with applicable federal regulations, state or local laws, the requirements or determinations of the IRB, or university policy regarding research involving human participant. Noncompliance can result from action or omission.

Determinations of noncompliance are made by the IRB. It is the responsibility of the RQ programs to document observations of potential noncompliance including any relevant information so that the IRB may follow up with the investigator as needed and make a determination. 

As relates to the RQ programs, noncompliance with this and other RQ policies may include failure to cooperate with the RQ program staff as they carry out their responsibilities, such as for assessments of FDA-regulated research or post-IRB approval reviews. Noncompliance with RQ programs will be reported to the Organizational Official. Depending on the circumstances, instances of noncompliance with RQ policies may also be reported to the HRPP. 

FURTHER INFORMATION:

For questions, additional detail, or to request changes to this policy, please contact the Office of the Associate Vice President for Research, Director of the Office for Research Protections.

CROSS REFERENCES:

RP03 - The Use of Human Participants in Research 

RP12 - Clinicaltrials.gov Registration and Results Reporting

Most recent changes:

• September 1, 2023 - Updated Subject Matter Expert to Debra Thurley, Associate Vice President for Research.  

Revision History (and effective dates):

• July 21, 2023 - Updated "Applicability" section to "Scope"; revised "Authority" section to reflect current procedures.
• March 15, 2022 - Updated name of "Quality Management" to "Quality Assurance" Program; updated to include Penn State Health; updated process change for submission of results; minor editorial changes.
• November 1, 2017 - Clarified "Authority of Research Quality Programs" section.
• June 8, 2015 - New policy.