1. Topics discussed at HSRAC and the number of meetings at which each topic was raised;
2. The top 20 topics raised by HSRAC because of an internal NIH IRP issue and what concurrent national event contributed to the discussion, and
3. Some concurrent national events related to the protection of human subjects documented in HSRAC minutes.

Results
Fifty-seven HSRAC meetings took place from 1992 through 2002. The 20 most commonly discussed topics will be presented. Informed consent was the most frequently discussed topic; it was mentioned 44 times in 29 meetings, and 3 working groups were established to study various aspects of informed consent. HSRAC discussion items referred to concurrent national events or activities 26% of the time. Overall, national events or activities were incorporated into HSRAC discussions 30% of the time. The poster will give an overview of the concurrent national events or activities mentioned by HSRAC.

1. From 1992 through 2002, HSRAC discussed 61 different topics related to the protection of human subjects in the NIH's IRP. The 3 most frequently raised topics were informed consent, NIH's assurance of compliance with DHHS regulations and IRB performance and procedures.
2. HSRAC has been instrumental in the standardizing of processes and procedures across NIH's 14 IRBs, in increasing understanding and compliance with HHS federal regulations and in promoting the training of IRB members and clinical investigators on the protection of human subjects,
3. Many HSRAC discussions about the conduct of research in the NIH's IRP were informed and influenced by concurrent national events,
4. In a diverse and multi-faceted clinical research program, HSRAC has managed to foster an institution wide perspective on the protection of human subjects,
5. HRPPs, particularly those with multiple IRBs, are well served by having regular meetings of IRB chairs and others with responsibilities for the protection of human subjects.

Results
Following a successful pilot course for faculty in July 2002, the first offering of CORE was held on June 12, 2003. Registrants included 74 faculty and 40 fellows or research personnel, with a total of 111 (97%) attending the course. Thirteen faculty learners (18%) opted to attend the whole day course. For workshops, attendees were divided into 6 small groups, with group sizes ranging from 10-30 participants (mean=19). Based on the research interests of the learners, workshops focused on different types of protocols: clinical investigation, research on stored tissue samples, research involving vulnerable populations, and behavioral and social science research. Evaluations were received from 76 (68%) of attendees: 46 (62%) faculty and 30 (75%) fellows or research personnel. The majority of evaluators (79%) had submitted a protocol to the IRB previously. All respondents felt the course was a useful experience and 97% respondents would recommend the course apart from the SOM requirement. Most agreed the course improved their ability to conduct human subjects research (72%), obtain informed consent (82%), and interact with the IRB (83%). The course was highly rated (Likert scale of 1=poor and 5=excellent): overall evaluation 4.4, course organization 4.2, course content 4.2, quality of presentations 4.2, conference facilities 4.2, syllabus materials 4.1, usefulness 4.1, and audiovisual aids 4.0. Small group sessions were the most valued feature: overall evaluation 4.4, facilitation skills of leaders 4.5, and liveliness of discussion 4.5. Written comments echoed the benefit of the workshops, especially the practical discussion of issues from researchers in other disciplines and the opportunity to have access to IRB members.

With the implementation of BRAIN the quality and completeness of protocols and IRB reviews have noticeably improved. To further assist the research community and the IRB members, the human research assurances staff has developed a web-based on-line educational help system that provides guidance to the research community on how to write a protocol and/or consent form that is compliant with federal regulations/guidance and Baylor College of Medicine's policies and procedures. A similar system has also been created for IRB members to enhance the review of protocols.

The educational on-line materials are a combination of the federal regulations/guidance and Baylor College of Medicine's policies and procedures. The educational materials provided have been interpreted by the human research assurances staff to assist the research community and IRB members to understand what is needed and why. On-line help has been developed for each section of the standard template provided in BRAIN, applicable to the protocol summary, and informed consent, renewal, amendment and adverse event reporting forms. For IRB members the on-line help exists within the review application. Appropriate links to the federal regulations/guidance and Baylor College of Medicine policies and procedures are provided as an explanation for each section, applicable to the submission of a protocol and IRB review application. The on-line help can be easily revised/updated by the IRB Administrator therefore the information will always be current.

Baylor College of Medicine hopes to benefit from the creation and use of the new on-line help system in the following ways:

• Improve the quality of the submission of the protocol summary, and informed consent, renewal, amendment, and adverse event reporting forms;
• Improve the completeness of forms submitted to the IRB;
• Facilitate the review of protocols, continuing review, amendments and adverse events;
• Educate and help the research community and IRB members to understand the regulations/guidance and institutional policies and procedures;
• Assist IRB members in making determinations when a concern is encountered during the review of a protocol;
• To provide continuation education to the IRB members concerns encountered and researched are presented at IRB; and
• Enhance the review of the IRB.

To enhance the community's understanding, the human research assurances with the assistance of Baylor College of Medicine Center for Collaborative and Interactive Technologies has created written materials and a video that define clinical research and what Baylor College of Medicine and other institutions do to assure the safe and ethical conduct of research. The materials and video will explain the concept of the Institutional Review Board (IRB) and other protections for human subjects, as well as the need for community input into the process.

The written materials will be distributed to all Baylor College of Medicine personnel and students, regardless of their involvement in clinical research. The community will be able to access the information via Baylor College of Medicine's public website, written materials will be distributed at clinics and a six minute video will continuously play at those clinics. The video can also be viewed via the Baylor College of Medicine public website.

Baylor College of Medicine hopes to benefit from the media and written educational tools in the following ways:

• Educate the broader community about research protection programs;
• Educate the community about the informed consent form;
• Educate the community about the importance of clinical research and their participation;
• Provide the community a fair chance to access research conducted at Baylor College of Medicine; and
• Encourage community input.

With the implementation of BRAIN, the coordinator positions were upgraded to Analyst positions. The Analyst position requires staff to be knowledgeable of federal, state and local regulations, institutional policies and ethical guidance, to understand concepts and be able to interpret and apply regulations and policy, and to provide assurance guidance to Board members, IRB staff and the research community.

The Human Research Assurances section at BCM comprises of a total of eight staff members: the Administrator, a Senior Analyst, five Analysts and an Administrative Assistant.

The Administrator, with the assistance of the Senior Analyst, directs the day-to-day operations of the IRB. The Administrator also functions as the system administrator for the electronic protocol routing system (BRAIN) to ensure compliance.

The main function of the Analyst is to act as a liaison between the Board members and the investigators. Each Analyst also functions as a primary Analyst for each Board (includes the Senior Analyst).

The Administrative Assistant's main function is to be the primary point of contact for the IRB (the first to receive calls and emails) decreasing the number of calls the Analyst and Administrator receives.

Baylor College of Medicine has benefited from the upgrade of the positions in the following ways. The IRB staff can:

• Make systematic comparisons between two or more alternatives;
• Notice discrepancies and inconsistencies in available information;
• Weigh the benefits, risks and chances for success in making a decision;
• Identify causes for problems and provide suggestions for preventing the problem therefore assisting investigators to navigate through the IRB process efficiently while maintaining compliance;
• Educate Board members, the research community, IRB staff and BCM affiliates with respect to the conduct of human research;
• Review and provide feedback for protocols allowing staff members to be part of the meeting discussion;
• Provide and present guidance/regulation/policy to IRB members regarding issues of concern for protocols during a meeting to help IRB member make decisions;
• Provide Board members with a better understanding of individual protocols; and
• Provide investigators with a better understanding of the Board's review.

In 2001 Family Health International (FHI) developed the Research Ethics Training Curriculum (RETC) for use by its own staff as well as by its international collaborators. The Curriculum was reviewed by international experts and field tested in four developing countries. In addition, FHI has dedicated a portion of its NIH Human Subjects Research Enhancement Grant to strengthening the research ethics infrastructure in Sub-Saharan Africa and South East Asia.

The participants included bioethicists, researchers, IRB members, administrators and government representatives from 20 countries (11 in Asia, 9 in Africa). Topics covered by the RETC include the principles of research ethics, informed consent, and responsibility in research. Following the workshops, all participants are invited to participate in a moderated email listserv to continue the discussions that were raised during the workshop.

Results
Data were remarkably useful and reveal an unexpectedly high level of satisfaction with, and understanding of, the IRB. For example, nearly 80% of respondents stated they had confidence in IRB reviews, almost 90% indicated they understood the IRB review process, 57% thought IRB reviews were consistent and added value, and 83% indicated that the IRB staff were helpful. On the other hand, nearly 20% of respondents were uncertain whether or not research ethics were clearly explained and nearly 35% were uncertain if regulatory requirements were clearly explained. Our questionnaire and statistical analyses - including breakdowns by faculty or not, PI or not, frequent submitters or not - of responses will be presented in our poster.

The goals of the CIRB Initiative are to reduce the administrative burden on local IRBs and investigators, while maintaining a high level of protection of research participants. Additionally, the CIRB model may enable local sites to open trials faster and have more trials available to a greater number of research participants. Established in late 2000, the CIRB has reviewed 60 phase 3 protocols in a variety of cancer types. These reviews are available to 168 currently participating local IRBs. As of October 15, 2003, facilitated review has occurred 328 times for 40 protocols at 69 sites. The number of participating IRBs has increased significantly since last year's annual ARENA meeting. Updated information about these local IRBs and the overall Initiative will be presented at the meeting.

1. Informed Consent Process and Document,
2. Third Party Rights,
3. Data and Safety Monitoring, and
4. Subject Participation in Clinical Research.

1. Evaluate the existing procedures for human subjects protection in non-therapeutic clinical research, and
2. Establish new policies and procedures to address the issues while
3. Improving the overall protection of the human subjects participants and producing the highest quality clinical research.

Results
Informed Consent Process and Document - In an effort to improve this process for participants, the Informed Consent working group evaluated and revised the consent process for non-therapeutic research studies. The working group developed three new MSKCC informed consent templates for non-therapeutic research: one for questionnaire studies; one for questionnaire studies with biological sample collection, but no transmission of individual results; and one for studies with collection of biological samples and transmission of individual test results.

Third Party Rights - The Third Party Rights working group completed a critical review of the limited published literature, reviewed policies and procedures at other institutions and proposed several recommendations intended to evaluate and protect the rights of third parties. We have prepared a manuscript to be submitted for publication which includes decisional algorithms intended to assist IRB reviewers and suggested protocol and consent form templates intended to assist investigators in addressing these issues.

Data and Safety Monitoring - The Data and Safety Monitoring (DSM) working group assessed the need for revisions and/or additions to the existing MSKCC DSM Plans in order to appropriately incorporate the data and safety monitoring of participants on non-therapeutic clinical trials. The evaluation resulted in a revised MSKCC Data and Safety Monitoring form that includes questions for monitoring non-therapeutic studies and utilizes a "Risk Assessment Tool" to determine the necessary frequency of review.

Subject Participation in Clinical Research - In an effort to improve the process for recruiting non-MSKCC patients into our clinical research program, the Subject Participation in Clinical Research working group assessed the many challenges faced by these investigators. Areas of focus included: recruiting potential subjects by mail and the informed consent process, assessing protected health information required for research purposes, and maintaining up-to-date contact information. New procedures were developed.

The main goal of our on-going project is to develop and implement a comprehensive human subjects information system. After exploring numerous options to buy or build software, UW-Madison licensed the IRBWebKit software of Traversent, LLC for its new IRB office management system. The IRBWebKit provides a comprehensive web-based protocol administration system that consolidates operations into a single IRB database, streamlines processes, and increases efficiency. The IRBWebKit software also provides web-based submission of protocols and linkage of data for use by other compliance offices and campus research units. The web-based submission of protocols has several features that will help investigators improve the quality and completeness of protocol applications.

With such wide-ranging objectives, UW-Madison divided the transition from existing computer systems to the IRBWebKit into several phases. The first phase, now complete, provided the IRB Offices a web-based database system that streamlines and automates administrative process. This phase also moved the work of all IRB offices on campus to a single computer system. The second phase will allow the IRBs to provide information to and receive it from other offices on campus, such as the Office of Clinical Trials, the General Clinical Research Center, the Office of Biological Safety, animal care and use committees, the Office of Research and Sponsored Programs, and the UW-Madison Hospital and Clinics. Of particular importance in the second phase, will be integration with the Conflict of Interest Committee, which provides information on potential conflicts of interests of clinical investigators to the IRBs. The final phase of our project will be to implement an on-line protocol application process.

The phased implementation of the IRBWebKit has already demonstrated distinct advantages. It allows us to build acceptance, and even enthusiasm, among users for the diverse abilities of the new software and changes in business processes that have been facilitated by the computer system. It has also mitigated the risks of conversion to a new system.

Phase one, conversion of all IRB offices to a single information management system, has also been a huge success. Improvements include:

• Sending continuing review notices, which formerly took a day or more, automatically overnight
• Automatically tracking whether PIs have responded to requests for modifications and, if not, emailing reminders
• Allow IRB office staff to enter information about a protocol once and have it appear in Meeting Minutes, letters, and other documents without manual cutting and pasting

We are looking forward to equally beneficial results as we integrate IRB data systems with other offices on campus and move to on-line submission of protocols in the next year.

1. Improve the Principal Investigator's (PI) research protocol submission,
2. Facilitate the IRB's review process,
3. Assure compliance with federal regulations, and
4. Educate the research community on human research subject protections.

1. Individuals responsible for reviewing the research and safety data,
2. Types of adverse events (AE) considered to be serious, unexpected, and attributable to the intervention;
3. The manner in which AE will be reported to the IRB and funding and regulatory agencies;
4. Interim analyses of main safety and efficacy data and their relationship to changes in study design or continuation, and
5. A summary of recent literature that may be relevant to the research.

Assessments of AE constitute an essential element of DSMP for drug and device protocols. The BCM Human Research Assurances Staff developed an algorithm for reporting AE to the IRB based on:

1. The site at which the AE occurred,
2. The type of AE that occurred,
3. The seriousness of the AE, and
4. Whether the AE was expected or not.

Future Directions
The BCM Human Research Assurances Staff plans to:

• Develop a key word index using common medical terms found in MedDRA or SNOMED to characterize adverse events that are reported in BRAIN;
• Expand the use of third party databases created by pharmacology vigilance groups and data and safety monitoring boards to supplement decision making by the IRB;
• Conduct an analysis of the educational program linked to BRAIN based on the information provided by the PI to validate the BRAIN process.

The software is 100% web-based and electronically handles routing the protocol from desktop to desktop, providing email notifications with hyperlinks to the web site. The workflow rules are designed so that they can be easily modified within the software. In addition, this software is linked with other electronic research administration software so that funding initiation cannot occur without IRB protocol approval. Each entity in the system - the PI, IRB board member, IRB Co-Chair, IRB Coordinator, and the Office of Sponsored Research –has a unique view of the protocol database and each can track the progress of a protocol through the system. User identification is tied into the university system and automatic notices are sent to PIs concerning the status of protocols, required or missing information, and renewal dates.

The software supports the uploading of supporting documentation to a protocol, helping move towards a more paperless workflow. Any electronic file (Word, etc.) can be "attached" to a protocol. The Documents can be viewed on-line or printed out from the web. The software converts documents to PDF, reducing the headaches of not having the right viewer installed to open documents on-line. While this software is helpful for all protocols, we feel it will be particularly efficient for those that fall into the exempt and expedited categories. These two categories of protocols make up the bulk of the work in a large public university without a medical school. [Work supported by NIH]