Email this pageResearch Subject Advocate
The purpose of the Office of Research Subject Advocacy is to ensure the safety of research subjects involved in protocols conducted through the Clinical Research Center.
- Key Personnel
- Data & Safety Monitoring
- Protocol Deviation & Forms
- Quality Assurance Reviews
- Useful Links
Key Personnel
Introduction
The National Center for Research Resources (NCRR – the NIH Center that oversees CRCs) recently established a new position, research subject advocate (RSA) within the CRC. This position was created as part of the response to the growing concern over the safety of human research subjects in clinical trials. The Office of Research Subject Advocacy was created in 2002 at the University of Rochester. Robert Betts, M.D., and Nancy Needler, B.S., C.C.R.C., are the research subject advocates for the CRC.
Who We Are
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Roberts Betts is Professor of Medicine in the Department of Infectious Diseases, and has been involved in various clinical research projects including “Varicella Zoster Vaccine for the Prevention of Herpes Zoster and Its Complications.”
Robert_Betts@urmc.rochester.eduPhone: (585) 275-5871
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Nancy Needler has coordinated clinical trials since 1997 for the Endocrine-Metabolism Unit within the Department of Medicine, mostly recently working with Dr. Stephen Welle on his NIH Gene Expression Grant. She is a member of the Study Coordinators' Group Advisory Board here at the University of Rochester and has been involved in the quality assurance process at Monroe Community Hospital.
Nancy_Needler@urmc.rochester.edu
Phone: (585) 275-1020
What We Do
The RSAs ensure safety of human research subjects by:
- Reviewing newly submitted protocols for safety issues and making sure there is a data and safety monitoring plan in place – prior to being approved by the CRC Advisory Committee (GAC)
- Monitoring study protocols on a continual basis by reviewing CRC charts to ensure protocol adherence
- Monitoring the informed consent process through quality assurance surveys or by being an objective observer when requested by an investigator
- Reviewing adverse event and safety monitoring committee reports for studies conducted on the CRC
- Being a resource for study investigators and coordinators regarding data and safety monitoring plan requirements, regulatory issues, etc.
The RSAs are available to help investigators create the data and safety monitoring plan for a specific study.
Preparing the safety plan and consent prior to submission to the CRC and RSRB will help streamline the protocol review process. Please contact one of the RSAs if you would like assistance in writing the DSMP, or if you would like one of us to evaluate your plan prior to review.
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Data & Safety Monitoring
As currently mandated by the NIH, EVERY protocol evaluated by the CRC Advisory Committee (GAC) MUST have a Data and Safety Monitoring Plan (DSMP). To assist the Committee in completing their evaluations of this NIH-mandated requirement, please include all of the required elements. These efforts are to ensure the safety of subjects involved in clinical research conducted through the CRC.
There are two issues regarding safety:
- appropriate collection, recording, and review of data,
- recognition and recording of adverse events and general safety review as described in sections A and B below
A) Data Collection and Data Monitoring
The protocol must detail how data collection will occur and how quality will be assured, a description of the records to be maintained, and how the study is to be monitored for adherence to the protocol. The protocol should indicate how informed consent will be obtained and by whom. If the study is industry sponsored, please indicate the monitoring agency and how often monitoring will be done. If the study is investigator-initiated, then it is likely that the PI will be responsible for organizing, tracking and evaluating the data. This fact and the frequency of the monitoring should be specified. If there is a Data and Safety Monitoring Board (DSMB) or Safety Monitoring Committee (SMC), there should be a description of the general composition of the board (member names or specialties represented), its duties, and the DSMB charter if available. All studies should detail what data will be reviewed and the procedures for implementing changes as a result of the review (i.e. how deficiencies are to be resolved). The details of what will be assessed for an interim analysis should be included if this is to be done.
B) Safety Monitoring/Adverse Event Reporting
The DSMP must include an assessment of risk and the justification for the risk level (see list below). The level of risk will determine who is responsible for safety monitoring (see below). There should also be a plan for safety review, which includes when serious adverse events (SAEs) and non-serious adverse events (AEs) are reported and to whom (i.e., RSRB, DSMB, and CRC), and an AE grading and attribution scale.
(1) PI monitoring only: PI monitors study, with prompt reporting of adverse events and other study related safety information to the RSRB, CRC, sponsor, or other agencies, as needed. Protocol deviations and protocol amendments also need to be reported.
Example: This level of monitoring would be appropriate for studies with minimal to low risk that can be effectively monitored by the PI.
(2) PI monitoring and safety monitor: PI monitors study as noted above, with oversight by a safety monitor. This individual should have appropriate clinical and research expertise and should have no conflicts in monitoring the study.
Example: This level of monitoring would be appropriate for moderate to high risk studies that may require independent safety monitoring, such as a relatively small investigator-initiated study involving a vulnerable population.
(3) PI monitoring and DSMB: PI monitors study as noted above, with oversight by a Data and Safety Monitoring Board. DSMB members typically include scientists, clinicians, statisticians, and others who periodically review the safety and integrity of a study and evaluate accumulating data to consider a need for early stopping due to significant evidence of benefit, harm, or futility. DSMB members should have appropriate clinical and research expertise and should have no conflicts in monitoring the study. The description of the DSMB should include the composition of the DSMB (the names of the DSMB chair and its members- if known), how frequently it will meet, and its responsibilities.
Example: This level of monitoring would be appropriate for studies which: (1) are multicenter; (2) use high risk interventions; (3) trials testing an agent for which little or no toxicity data in humans is available; (4) are blinded to the investigator; or (5) include vulnerable populations (e.g., children, pregnant women, psychiatric patients, prisoners, etc.). All NIH-funded multicenter Phase III clinical trials must have a DSMB.
Please submit copies of adverse event reports to the CRC as they are submitted to the RSRB/WIRB (i.e. send SAE reports as detailed in the protocol, and if applicable, send a copy of the RSRB progress report which lists all other AEs, upon re-approval of the study). Please also send copies of any DSMB or safety committee reports to the CRC as well.
Please contact Nancy Needler at (585) 275-1020, if you have any questions regarding the DSMP requirements or would like assistance in writing a plan.
Examples for Risk Assessment
| Minimal |
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| Low |
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| Moderate |
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| High |
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Download these instructions (the information is the same as that in the CRC application):
CRC DSMP Requirements (MS Word Document)
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Protocol Deviation & Forms
Significant protocol deviations that occur in CRC studies are to be reported to the RSA office as soon as possible using the form that can be downloaded below. Significant protocol deviations are those that involve consent form issues or those that affect the safety of subjects or the integrity of the study data. Corrective actions must also be described which include measures taken to ensure that similar deviations do not occur in the future. If you have any questions, please call Nancy Needler at (585) 275-1020.
Examples:
- The subject dates the consent form incorrectly, and the error is not noticed at a time when the subject can make the correction.
- The wrong consent form is used (i.e., the most recent approved version of the consent was not given to the subject).
- Lab tests for safety to be done at each study visit were not done as indicated in the protocol.
- A subject did not take medication or took prohibited medication during a study.
- A subject was included in a study even though the inclusion/exclusion criteria was not met.
To download form in Microsoft Word, click on this link: Protocol Deviation Report Form 030906.
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Quality Assurance Reviews
The RSAs will periodically review protocols using the CRC to ensure that the research is being conducted according to the protocol, and that the approved data and safety monitoring plan is being followed. The RSAs will randomly select protocols to be reviewed, usually those that are moderate to high risk, or those that have limited monitoring.
The CRC research subject files will be reviewed for:
- Consistency between the physician orders and the labs tests and procedures listed in the protocol
- Eligibility criteria
- Adherence to study procedures and schedules
- Reporting of adverse events
- Informed consent issues
A written Quality Assurance report will be submitted to the PI of the study at the completion of the review. The report will list the findings and recommendations from the RSAs. If concerns arise during a continuing protocol, the investigator may be contacted before the final report is completed.
The confidentiality of all research subjects will be maintained during the review, and the QA reports will be kept confidential by keeping copies in a locked file cabinet in the RSA’s office. The reports will only be shared with the PI and the CRC Advisory Committee.
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Useful Links
Data and Safety Monitoring (e.g., DSMPs):
- Updated guidance on data and safety monitoring for Phase I and Phase II trials (June 5, 2000)
- Recommendations to Clinical Research Centers (CRCs) for Patient Safety in Clinical Research
- National Cancer Institute DSMP (essential elements applicable to many trials)
- A Downloadable Template (by Duke CRC) to Create a Safety and Data Monitoring Plan
Food and Drug Administration:
- The Food and Drug Administration (FDA): The FDA is responsible for protecting the public health by assuring the safety, efficacy, and security of human and veterinary drugs, biological products, medical devices, our nation’s food supply, cosmetics, and products that emit radiation. The FDA is also responsible for advancing the public health by helping to speed innovations that make medicines and foods more effective, safer, and more affordable; and helping the public get the accurate, science-based information they need to use medicines and foods to improve their health.
- FDA Operations: FDA inspections of institutional review boards, clinical investigators, and clinical investigator regulatory sanctions. This site also includes information on audits/inspections.
National Institutes of Health:
- National Institutes of Health: Health information (resources, clinical trials, drug information); grant and funding opportunities; scientific resources; and NIH institutions, centers, and offices.
- NIH Guidance on Adverse Events Reporting: NIH guidance on reporting adverse events to institutional review boards for NIH-supported multicenter clinical trials. Release date: June 11, 1999
- Original NIH guidelines on inclusion of women and minorities as subjects in clinical research (Notice: OD-00-048, August 2, 2000)
- National Library of Medicine: The National Library of Medicine (NLM), on the campus of the National Institutes of Health in Bethesda, Maryland, is the world's largest medical library. The Library collects materials in all areas of biomedicine and health care, as well as works on biomedical aspects of technology, the humanities, and the physical, life, and social sciences. The collections stand at more than 7 million items – books, journals, technical reports, manuscripts, microfilms, photographs, and images.
Other sites listed in the Internal/External Links page.
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