Research Quality Assurance (RQA)

The Research Quality Assurance mission is fulfilled by working with investigators to help them identify gaps that might negatively impact their research and assist them by making recommendations to eliminate these gaps. This support is provided to aid investigators in conducting research as required by regulatory authorities, to ensure that laboratory research follows acknowledged best practices, that research fulfills promises to study volunteers and with due respect for laboratory animals.

To complete this mission, this office works directly with investigators to promote research integrity and best practices through education and mentoring of investigators and their staff.

The Research Quality Assurance team works collaboratively to develop, establish and provide training material, programs and tools (checklists) for research investigators, coordinators and research administrative and laboratory staff related to applicable federal, state, local and institutional research regulations and guidelines.

In collaboration with others at Penn State Health Milton S. Hershey Medical Center, Penn State College of Medicine and Penn State University Park, the team reviews and revises current institutional and University research policies, and drafts new policies, to maintain adherence to current regulatory guidelines and best practices.

The Manager of Research Laboratory Safety develops systems to perform laboratory site visits to assist investigators in meeting their regulatory obligations and to continually improve laboratory safety.

In addition, the team includes Research Compliance Specialist positions to provide assistance to investigators and support staff in the preparation, submission and maintenance of investigational new drug and investigational devices.

RQA also works to improve human subject research through

• personal communication and consultation;
• departmental and institutional seminars; and
• on-site and remote reviews; and
• evaluations of current research practices.

In cooperation with investigators, the Office of Research Affairs and the Office of Research Protections, the Research Quality Assurance office works to establish and maintain a contemporaneous database of clinicaltrials.gov registrations and establish mechanisms to assist investigators in compliance with statutory requirements and publication guidelines for publicly accessible clinical trial registration.

Furthermore, this office is an independent unit that oversees and directs the monitoring, auditing and evaluation of research activities.

RQA’s intent is to be a proactive unit that helps investigators successfully contribute to the advancement of medical science.

For Biosafety emergencies, contact BiosafetyOfficer@pennstatehealth.psu.edu or call 717-531-0003, ext. 289844 or 717-531-5573.

Location: The main RQA office is on the second floor of the Support Services Building.

Fax: 717-531-0995

Mailing address:

Research Quality Assurance
Penn State College of Medicine
500 University Dr., Mail Code SB36
P.O. Box 850
Hershey, PA 17033

Post-IRB approval reviews (PAR) are conducted in an effort to ensure the highest level of research participant protections. The Research Quality Assurance program is separate from the IRB, and post-approval reviews differ from IRB review. Post-IRB approval review includes an assessment of the study team’s progress in conducting a trial according the protocol while ensure all federal regulations and local regulations, as well as institutional policy, are followed. These reviews may be conducted as an onsite visit, as a remote visit, as an investigator self-assessment, or a combination of processes.
There are two different types of post-IRB approval reviews: routine and directed. In some cases, post-IRB approval reviews or audits are able to be conducted remotely. However, depending on the nature of the study and the audit, an in-person visit from the Research Quality Assurance team may be necessary.

Types of Post-IRB Review

The Quality Assurance program conducts post-IRB approval reviews or audits to enhance the protection of human subjects and verify that IRB approved procedures are being followed. Any study determined exempt or approved by the IRB may be selected for a post-IRB approval review. Post-IRB approval reviews should not be viewed as punitive. They are an opportunity for the study team and investigators to ensure that they are adequately following their IRB approved protocols and to determine if any improvements or modifications are needed for their outlined study procedures. The Research Quality Assurance team tries to provide constructive, helpful feedback on study procedures to facilitate a smoother IRB submission process for the study team in the future and to educate on IRB rules and requirements. The goal of the Research Quality Assurance team is to select a wide scope of studies to review so that investigators have a better understanding of IRB requirements and to also be prepared for outside audits from sponsors, funding agencies or other regulatory bodies.
Although not punitive in nature, failure to cooperate in the post-IRB approval review process for either onsite reviews or self-assessments is a violation of IRB policy, University policy, and IRB approved protocols. The Associate Vice President for Research and Director of the Office for Research Protections has the authority to enforce corrective action if an investigator does not cooperate with the review. The Vice Dean for Research and Graduate Education in the College of Medicine also has authority regarding corrective action.

Routine

Routine or not-for-cause reviews are reviews that occur when the Research Quality Assurance team will review study documentation to ensure regulatory compliance including but not limited to protocol adherence, accurate record keeping, and appropriate informed consent process. Studies approved at the committee-level and studies approved at the expedited-level that also are federally-funded, involve vulnerable populations, involve sensitive topics, or are FDA-regulated are most commonly selected for these reviews. Clinical trials that have no independent monitoring are also higher priority for review than those trials regularly being monitored.

Directed

Directed or for-cause reviews are conducted when the IRB directs the Research Quality Assurance Program to conduct a review. As with routine reviews, the Research Quality Assurance team may review protocol adherence, data management, and the informed consent process, as well as any study details related to the cause of concern. The most common reasons for directed reviews are to investigate a credible allegation of non-compliance and to follow up on IRB findings of non-compliance. Directed reviews are not always related to non-compliance.
The following may trigger a directed review:

• Reportable new information
• An allegation of non-compliance (perceived or confirmed)
• A suspension or termination of IRB approval
• Participant and/or employee complaint

PAR – Review Preparation

To help investigators and study team members, Research Quality Assurance will meet with the investigator and team prior to the review. Most onsite post-IRB approval reviews will take place at the investigator’s office or research office and will include a discussion with the PI or study staff about the study protocol. Most reviews also include an audit of storage procedures for maintaining research regulatory records and an audit of participant documents such as signed consent forms and eligibility screening forms. Reviews may also involve, for example, interviews with subjects and observation of study procedures or the consent process. To prepare for a post-IRB approval review PIs and study team members should have to access to and/or be knowledgeable about the following information:

• Protocol and procedures
• Enrollment numbers
• Recruitment process, including eligibility screening
• The consent process
• Data collection
• Privacy, confidentiality, and data storage
• Interaction with participants
• Study team training and roles
• Communication within the study team
• Adverse events and other reportable new information

Investigators can use the checklist and guidance document linked below to prepare for the review. These are the forms that the Research Quality Assurance team utilizes to conduct the review. A tool to determine the appropriate regulatory documents to be maintained for each type of trial is also included below for reference.

• RQA Review Checklist Guidelines
• RQA Review Checklist
• Regulatory Binder Checklist

PAR – Review Attendance

The PI can invite whomever they would like to attend. The Research Quality Assurance team may also request that particular personnel attend.
Study team personnel need not be present for the document review, but there should be at least one person readily available in-person to answer questions.

Report Summary

All post-IRB approval reviews conclude with a report that is submitted to the IRB as part of the documentation associated with the reviewed or audited study. These reports inform the actions required by the study team and IRB to address any comments or findings of the review, such as the need for additional training. Investigators will have an opportunity to review and comment on the report prior to finalization. There is no further action needed if there are no findings during the post-IRB approval review. However, if there are any findings during the post-IRB approval review or in cases of a directed PAR, the Quality Assurance team will direct the study team to submit the final report to the IRB as Reportable New Information. If the study team does not submit the report by the deadline provided, the Quality Assurance team will submit the report to the IRB citing non-compliance. In the report, the Quality Assurance program will provide recommendations to address findings and may advise that a Corrective and Preventative Actions (CAPA) plan be submitted to the IRB by the study team. The IRB will work with the study team to address findings requiring action, such as making a modification to the protocol or handling non-compliance.

Self-Assessment Reviews

Self-assessment reviews are most typically asked of studies determined exempt or approved at the expedited-level. Investigators can use the checklists linked below at any time to do a self-assessment of their study. If asked to complete a checklist, the investigator will receive an email along with a completion deadline. Depending on the answers provided, there may be additional follow-up. Investigators can find the checklists uses for the abbreviated reviews linked below:

• HRP-430 – Checklist – Investigator Quality Improvement Assessment: For studies approved at the committee or expedited review level
• HRP-439 – Checklist – Investigator Quality Improvement Assessment (Exempt Research): For studies determined exempt

Be sure to schedule enough time to complete the checklist and to ask questions as needed. The self-assessment should be completed by an investigator most familiar with the IRB approved protocol, study submission history, IRB policies, and CATS IRB.

The Data Management team in the Department of Public Health Sciences at Penn State College of Medicine offers clinical trial monitoring.

Clinical trial monitoring services provided by Data Management help the investigator ensure that:

• All clinical trial activities follow the research protocol
• Participants’ rights, welfare and safety are protected
• Quality, reliability and integrity of data collected are maintained throughout the study
• Liability risk to the institution is minimized

Learn more about Data Management’s clinical trial monitoring services

Ancillary review assists the IRB with matters related to research feasibility, risk, regulatory requirements and research compliance. When requested by the IRB, the Research Quality Assurance team conducts ancillary reviews of studies that may involve investigational new drugs (IND) and devices (IDE) as defined the FDA regulations, also referred to as IND and IDE audits. The purpose of the ancillary review is to evaluate the applicability of the FDA’s IND/IDE requirements.

Research Quality Assurance will meet with the potential sponsor investigator prior to the initial FDA submission and will discuss the submission process and provide the investigator and the study team with the documents and forms required for FDA submission. RQA must review all FDA documents prior to submission to the FDA throughout the lifecycle of the application from initial submission, modifications, annual reporting and termination.

Investigators may also seek guidance regarding the applicable FDA regulations for investigator-initiated trials early in the development process. All researchers are encouraged to complete the Research Request form in order to have Research Quality Assurance, as well as a range of support offices, included in discussions related to these projects to identify resources and pathways moving forward.

Access the Research Request form

Once an investigator has secured clearance from the FDA to proceed with the research, Research Quality Assurance will meet with the sponsor investigator to discuss their responsibilities and to obtain assurance from the investigator that they are aware of these additional responsibilities as a Sponsor Investigator. This information is provided to the IRB to complete the ancillary review process prior to IRB review.

Sponsor Investigator IND Responsibilities and Assessment Form (in Policy Portal; Penn State Health ePass login required)

Sponsor Investigator IDE Responsibilities and Assessment Form (in Policy Portal; Penn State Health ePass login required)

Research Quality Assurance will also ensure that the investigator has provided the final FDA reviewed versions of the protocol and consent form to the IRB for review. Research Quality Assurance will collaborate with the investigator and the Public Health Science Monitoring Team to arrange for routine monitoring for the trials conducted under the IND/IDE.

Additional information regarding IND and IDE clinical trials is available here.

The Research Quality Assurance program supports and monitors Penn State investigator compliance with FDA regulations, NIH policy and ORP policy regarding ClinicalTrials.gov for Penn State College of Medicine and Penn State Health investigators. ClinicalTrials.gov is a web-based resource that provides patients, health care professionals, researchers and the public with easy access to information on publicly and privately supported clinical studies conducted around the world, covering a wide range of diseases and conditions.

The site is administered by the National Library of Medicine and is meant to provide increased stewardship, transparency and access to research and research results. The Protocol Registration System (PRS) is the database system utilized to enter information and results reporting for posting to the public site at ClinicalTrials.gov.

Principal investigators (PI) conducting University research are responsible for compliance with federal requirements and with institutional policy, refer to Penn State policy RP12 – Clinicaltrials.gov Registration and Results Reporting. In most cases, the PI will be the Responsible Party identified in the PRS record.

For questions and assistance registering trials at clinicialtrials.gov, contact RQA by emailing Clinicaltrials.gov@pennstatehealth.psu.edu.

In a three-part webinar series, FDA provides a general overview of ClinicalTrials.gov and relevant definitions, laws, and regulations for complying with ClinicalTrials.gov registration and results information submission requirements. Participants will gain an understanding of CDER’s role and responsibilities with respect to ClinicalTrials.gov oversight and will hear examples of compliance and enforcement activities CDER has taken to encourage compliance.

Access the webinar series here

Services provided by Research Quality Assurance include:

• Identification of registration and results reporting requirements and related deadlines
• Assistance with establishing Protocol Registration and Results System (PRS) accounts
• Assistance with PRS login, navigation, and data entry activities
• Assistance with entry of registration data and results reporting data into the PRS database as needed
• Assistance with management of PRS queries that may occur during the registration and/or results reporting process
• Guidance regarding regulations and processes associated with annual and unscheduled updates
• Email reminders designed to ensure applicable ClinicalTrials.gov deadlines are met
• Coordinated consultations with the Office of Regulatory Affairs and IRB as needed

If you do not have a ClinicalTrials.gov account, you can have one created by emailing Clinicaltrials.gov@pennstatehealth.psu.edu. See the Clinical Trials.gov User’s Guide (Penn State Health ePass login required) for detailed guidance on how to register your study. When registering, please follow the information in the user’s guide for the details regarding registration data elements. Clinicaltrials.gov also offers a number of instructional and training materials and a guided tutorial on study registration.

The final rule for Clinical Trials Registration and Results Information Submission (42 CFR Part 11) specifies requirements for submitting clinical trial information to ClinicalTrials.gov. The “Checklist for Evaluating Whether a Clinical Trial or Study is an Applicable Clinical Trial (ACT)” (or “ACT Checklist”) and this elaboration is intended to assist users in evaluating whether a clinical trial or study is considered to meet the definition of an ACT, as specified in 42 CFR 11.22(b), and is subject to “expanded” registration requirements under the final rule.

Additionally, all NIH-funded clinical trials are expected to register and submit results information to Clinicaltrials.gov, as per the “NIH Policy on Dissemination of NIH-Funded Clinical Trial Information” for competing applications and contract proposals submitted on or after Jan. 18, 2017. The NIH website provides resources for understanding and complying with this NIH policy and the federal regulations in Section 801 of the Food and Drug Administration Amendments Act (FDAAA 801) as implemented by 42 CFR Part 11 (Final Rule).

Investigators will need to provide NIH with information regarding how registration and results reporting compliance is managed. The Penn State RP12 policy should be utilized to address this requirement.

See the “ClinicalTrials.Gov Study Registration and Results Requirements (Decision Tree)” in the Penn State Health policy portal (ePass login required) for additional assistance in determining whether your trial meets any requirements for registration and results reporting. As described earlier, the RQA office should also be contacted for assistance with this determination if investigators are unclear regarding registration requirements for their trials.

While “applicable clinical trials” (ACT) must be registered at clinicaltrials.gov, an investigator can voluntarily register any study. Many journals follow the recommendations of the International Committee of Medical Journal Editors (ICMJE) and have policies regarding clinicaltrials.gov registration. For an interventional study, the ICMJE recommends registration of the study be a requirement for publication and that the study be registered before the first subject is enrolled. Even journals that do not adopt ICMJE recommendations may still have an editorial policy for clinicaltrials.gov registration.

When the recruitment status of a study changes, the clinicaltrials.gov record must updated within 30 days. All other information in the record must be reviewed, verified, and updated as necessary and no less than every 12 months. Records must be kept free of problems. The Responsibility Party is responsible for compliance with deadlines and maintaining an accurate and complete record.

By federal law, some FDA-regulated studies voluntarily registered may be subject to further requirements.

Researchers do not have to report the results of studies they have registered voluntarily. The ICMJE does not ask that result reporting be required, but some journals following ICMJE recommendations may still require it.

Researchers must report the results of ACTs and NIH-funded studies meeting the NIH definition of a clinical trial. When required by law or NIH policy, first results and adverse events must be entered within 12 months after the “primary completion date,” the date of the last data collection for the study’s primary endpoint. All results for the primary and secondary outcomes must be reported. The results information required in clinicaltrials.gov may include more than results information in a publication. All results are entered in tabular format, not written. The government estimates a minimum of 40 hours required for results reporting but this can vary based on the complexity of a trial. Researchers should be prepared to submit results well in advance of the 12-month deadline date in order to ensure ample time in preparing the results submission and quality review checks within the PRS.

When reporting results for studies with a primary completion date on or after Jan. 18, 2017, you must upload the up-to-date study protocol and a statistical analysis plan if one is not included in the protocol.

Should any College of Medicine/Penn State Health investigator receive a “Preliminary Notice of Noncompliance (Pre-Notice) Letter” from Clinicaltrials.gov, they should immediately contact the RQA ClinicalTrials.gov Program at Clinicaltrials.gov@pennstatehealth.psu.edu.

RQA staff will report receipt of the notification to leadership and the Institutional Review Board as well as applicable departmental leadership. RQA staff will work with the investigator to review the trial(s) cited by the letter to resolve any potential violations fully and within 30 calendar days.

Should any investigator receive any notice related to ClinicalTrials.gov during an FDA inspection, they should immediately contact the RQA ClinicalTrials.gov Program at Clinicaltrials.gov@pennstatehealth.psu.edu.

In the event that the Responsible Party leaves the University or for whatever reason can no longer serve as the Responsible Party, the PI must transfer the registration and reporting obligations as directed by the Research Quality Assurance program at the College of Medicine. If a Responsible Party is leaving the University, they must notify the Research Quality Assurance program at the College of Medicine prior to departure for consultation regarding the transfer or maintenance of any active PRS records.

Penn State College of Medicine and Penn State Health have partnered with the Association of Clinical Research Professionals (ACRP) to support professional growth and development through providing membership accounts to users registered through the organizational account. User seats are currently capped at 50 members with anticipation to increase capacity based on need and utilization if funding permits.

ACRP Membership through the organizational account immediately connects users with:

• 200-plus on-demand training,  continuing education and ACRP Certification Exam preparation modules available in a Penn State College of Medicine and Penn State Health-branded learning environment
• Unlimited ACRP contact hours for ACRP certification renewal
• Breaking news and regulatory updates
• ACRP’s community and members-only discussion groups
• Plus, ACRP member pricing for ACRP certification and the ACRP annual conference

Popular Training Modules:

• Good Clinical Practice (GCP) Simulation
• Informed Consent Simulation
• Introduction to Decentralized Clinical Trials (DCTs)
• Ethics and Human Subject Protection: A Refresher Course
• Understanding Clinical Trial Protocols
• Building Quality Management Tools
• Clinical Trial Monitoring Basics
• Investigator Responsibilities

Please contact Liz Galgocy at egalgocy@pennstatehealth.psu.edu with questions, for access instructions or to be added to the waiting list for account access.

Past and upcoming RQA Lunchtime Lectures and Quarterly Workshops appear here.

Watch older presentations on Mediasite (ePass login)

Request Laboratory Equipment Service Here