Volume I, Issue 4 August, 2001	Research and Sponsored Programs

NIH Clarifies Stem Cell Funding
That is, an investigator may derive human pluripotent stem cells from embryos in a university laboratory only if no NIH funds are used in support of the laboratory, its equipment, personnel working on the project, and/or building infrastructure costs usually charged to indirect costs. In order to meet this requirement, universities seeking to derive human pluripotent stem cells from human embryos may have to establish separate research facilities for such work.

However, unlike pluripotent stem cells derived from human embryos, DHHS funds may be used to derive pluripotent stem cells from fetal tissue as well as for research utilizing such cells. Such research is governed by Federal statutory restrictions regarding fetal tissue research at 42 U.S.C. _ 289g-2(a) and the Federal regulations at 45 CFR _ 46.210. In addition, because human pluripotent stem cells derived from fetal tissue may, at a later date, be used in human fetal tissue transplantation research, it is the policy of NIH to require that all NIH-funded research involving the derivation or utilization of pluripotent stem cells from human fetal tissue also comply with the fetal tissue transplantation research statute at 42 U.S.C. _ 289g-1 and with 42 U.S.C. _ 289g-2(b).

Research-AAMC

New Task Force to Focus on IUPUI/Clarian Operational Procedures
Human Subject Research Awareness Message #1 This message is the first in a series that you will be receiving describing a new emphasis of IUPUI/Clarian in the area of research with human subjects. These messages will be focused on human subject protection in research and what IUPUI/Clarian is doing and will be doing to assure that subjects are treated with respect and that everything is done to assure their well being during their participation in research.

These messages will apply to those involved with any type of research with human subjects, be that clinical investigations in the School of Medicine studying new drugs, devices or therapies, human behavior experiments or observation in the Departments of Sociology or Psychology, and also academic classroom assignments that involve human subjects with students as the investigators.

So, what is this all about? Why this increased focus on human subject research.and why a "Human Subject Projection Awareness Campaign" at IUPUI/Clarian? This introductory section from a recent article published in Applied Clinical Trials sets a background.

"Human Safety in Clinical Research" Applied Clinical Trials - July 2001
By Michael Schmidt, Ph.D.
Much has been written recently about clinical research involving human subjects. Unfortunately, much of the "news" has been "bad news": fraudulent investigators in academia exposed, fined and sent to prison1-2; institutional review boards, (the watchdog groups for ethics and safety in institutions) examined and restrained or shutdown by the U.S. government due to inappropriate practices3-6; a physician not following regulatory guidelines and treating cancer patients with vaccine manufactured with a "lack of control"7; the death of a young man in a university clinical trial testing a gene therapy. The FDA reports that complaints filed against clinical investigators were markedly increased in 19998.

Reports and recommendations have been issued from government agencies. The Office of Inspector General of the U.S. Department of Health and Human Services published a report on recruiting of patients into clinical trials that pointed to some possible reasons for problems and suggested some changes9-10. Editorials have been written11. Academia, as represented by a task force on research accountability sponsored by the Association of American Universities, has also investigated and analyzed the current state of clinical research practices. Very clear "conclusions and calls to action" are stated in their report12. Some private focus groups, such as PRIM&R (Public Responsibility in Medicine and Research) are coming forth with performance standards, self-assessment tools and peer-based accreditation of Institutional Review Boards (IRBs) and institutions engaged in human research13. Education, testing and accreditation for clinical research physicians and staff are being considered, and new regulations or guidelines for oversight of clinical research seem imminent14.

Speaking from the highest levels, Dr. Donna Shalala, former Secretary of Health and Human Services, voiced her opinion as to the reasons for recent problems in the execution of clinical research and also provided specified recommendations for change16, as did Dr. Jane Henney, Commissioner of the FDA17.

And now another tragic event has recently occurred as a healthy student volunteer died in a study at Johns Hopkins. Major investigations were undertaken to understand the details of this event and to seek "lessons to be learned". Both the judgment and action by the office of Human Research Protections (OHRP) was severe: all research involving human subjects was stopped until adequate improvements in processes and assurances for subject safety are put in place.

Thus, in light of all of the events highlighted above, it is important for us to assess and revise, when appropriate, the standards under which IUPUI/Clarian currently conducts research with human subjects, and to put in place, if needed, appropriate new practices for all who are involved in research with humans.

IUPUI/Clarian is committed to do everything possible to avoid "an event" within its research programs. A number of things are taking place, all of which you will be hearing more about in greater detail subsequently. A brief listing of the initiatives so far is as follows:

• Formation of an IUPUI compliance committee composed of senior administration from the compliance groups across the University; e.g., Radiation Safety, Environmental Health and Safety, Animal Care and Use, human subject research, etc.
• The hiring of an outside consultant to overview the IUPUI/Clarian human subject research program, make assessments as to strengths and weaknesses, and to assist administration by providing an "outsider" view. This individual is Dr. Michael J. Schmidt who recently retired from Eli Lilly as their Global Director of Quality Assurance for Clinical, Toxicology and Drug Disposition, and Animal Science Research.
• The formation of the Human Subject Research Oversight Task Force composed of clinical investigators, study coordinators, and others representing various operational units within IUPUI/Clarian human subject research programs. The first objective of this group is to assess existing standard operating procedures across the organizations, to benchmark these against "best practices" at other institutions, and then to compile a first rate compendium of succinct and relevant SOPs for human subject research at IUPUI/Clarian.
• Participation on national task forces and symposia focused on the areas of human subject research and institutional processes. Dr. Mark Brenner, Vice Chancellor for Research and Graduate Education, represents IUPUI/Clarian on the Big 10 Assembly and the Association of American Medical Colleges. His presence will help keep us abreast of current developments in academia, and new regulations or guidelines from regulatory agencies. He will also hear the opinions and philosophies of agency members.
• The completion of formal compliance risk assessments in numerous areas within our organization.

Our next message will describe in detail the membership, objectives, and activities to date of the Human Subject Research Oversight Task Force.

Michael J. Schmidt, Ph.D.
Research Compliance Advisor

References:

1. Sandy Hodson, "Ex-MCG Doctors Face Suit Over Drug Study", The Augusta Chronicle, Web posted January 30, 2001.
2. Kurt Eichenwald and Gina Kolata, "A Doctor's Drug Studies Turn Into Fraud", New York Times, May 17, 2000.
3. Dr. David C. Broski and Dr. Elizabeth Hoffman, "Text of the letter from the NIH Office for Protection from Research Risks to UIC Chancellor David Broski and Provost Elizabeth Hoffman", Department of Health and Human Services Public Health Service, August 27, 1999.
4. Eric A. Gislason, Ph.D. and Brenda Russell, Ph.D., "UIC Priorities and Processes Immediate and Short Term Plans", University of Illinois at Chicago Human Subjects Protection Bulletin, September 8, 1999.
5. Letter of March 22, 1999: From OPRR to VA Greater Los Angeles Healthcare System Office of Protection from Research Risks.
6. Department of Health and Human Services, Institutional Review Boards: A time for reform, (Washington D.C., June 1998).
7. David Malakoff, "Flawed Cancer Study Leads to Shake-Up at University of Oklahoma", Science, (Vol. 289) 706-707 (August 4, 2000).
8. Allen Spera, "Blowing the Whistle on Investigative Sites", CenterWatch, (Vol. 7, Issue 8) pages 1,5-9 (August 2000).
9. Department of Health and Human Services Office of Inspector General, June Gibbs Brown, Protecting Human Research Subjects: Status of Recommendations, (Washington, D.C., April 2000 (OEI-01-97-00197)).
10. Department of Health and Human Services Office of Inspector General, June Gibbs Brown, Recruiting Human Subjects: Pressures in Industry-Sponsored Clinical Research, (Washington, D.C., June 2000 (OEI-01-97-00195)).
11. Adil E. Shamoo, "Future Challenges To Human Subject Protection", The Scientist, June 26, 2000, 35.
12. Associate of American Universities, Report on University Protections of Human Beings Who Are the Subjects of Research, (Washington, D.C., 2000).
13. F-D-C Reports, Inc., "FDA May Request 'Intermediate' Enforcement Authority For Clinical Trials", The Pink Sheet, May8, 2000 (16-17).
14. Jill Wechsler, "Clinical Trial Safety and Oversight Top Policy Agenda", Applied Clinical Trials, January 2001, 18-21.
15. Shalala, D., "Protecting Research Subjects - What must Be Done", The New England Journal of Medicine, November 14, 2000, 808-810.
16. Association of American Medical Colleges, Henney, J.E., Remarks Presented at the Council of Teaching Hospitals Spring Meeting, 2000.
17. Ganter, Jane, "Responding to Industry Critics: If the industry doesn't address concerns raised by the consumer press, who will?", Applied Clinical Trials, November 1999.

NIH Proposal Issues
Announcement #1
Following the June 1 and July 1 deadlines, Research and Sponsored Programs was notified by NIH that several proposals did not comply with the format requirements. While project directors were allowed to correct and resubmit their applications, the time allowed to do so was very short, sometimes only a few days. If the appropriate corrections were not made or the deadline was not met, NIH stated that the proposals would not be reviewed.

The full text of the NIH announcement was sent to the members of this list in January and an update can be found at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-01-037.html. Please share this information with faculty and administrators in your school and emphasize the importance of complying with the NIH format requirements.

Announcement #2
R&SP immediately sends each principal investigator a memo informing them of the deadline, along with a pre-printed face page and a blank application packet. A copy of the list is also sent to the appropriate dean's office. Despite these reminders, several investigators have failed to submit their non-competing renewals by the required date. This is becoming an increasing problem and recently one NIH institute indicated that if the application was not received by a certain date the funds would be reallocated to other projects. Please remind your investigators of the importance of meeting the specified deadlines.

Expedited Review Process
The term "expedited" does not refer to how quickly a study can be reviewed by the IRB. Generally, expedited studies take 2-3 weeks for processing once the investigator has provided all of the appropriate information. Additionally, an "exempt" review can be approved in approximately 5-10 working days. To decrease processing time, the investigator should ensure that all relevant paperwork is appropriately signed and submitted to the R&SP office as soon as possible. For additional information regarding the Protocol Review Process refer to the online PI Guidelines at http://www.iupui.edu/~resgrad/spon/piguide.pdf.

Imaging Funding Opportunities Available
For additional information regarding IN-CEBI visit: http://www.indyrad.iupui.edu/in-cebi/ .

Research Courses/Seminars Planned

Instructional Courses/Seminars for Research 2001-2002 Academic Year

September 12-14: RESEARCH COORDINATOR EDUCATION COURSE
A three day hands on course for coordinators or faculty/fellows who want to have a full understanding of the research resources and regulatory requirements for clinical research here at IU. Fee is $300 and registration can be made through School of Nursing CME: jward@iupui.edu or Marta Sears at msears@iupui.edu

September 28: FACULTY CLINICAL RESEARCH TRAINING SEMINAR
A one day course designed for Faculty and fellows interested in clinical research. The goal is to demonstrate the resources available and help the investigator understand the "nuts and bolts" of research. Fee is $25 and reservations can be made through SOM Medical Education Office, AFTER AUGUST 1st. For information contact: The Medical Educational Resources Program http://iumeded.med.iupui.edu/ or 317.274.8353.

October 6: ASSOCIATION CLINICAL RESEARCH PROFESSIONALS:
Circle City Chapter Meeting. Ritz Charles in Carmel. This is a National organization focused on clinical research. This meeting is an all day symposium for both industry and academics focusing on important and current issues affecting us all. Fee is estimated to be $100 for the entire day. A reservation form can be e-mailed to you. E-mail Liz Pertile at liz.pertile@roche.com.

October 8 and 9: GRANT WRITING WORKSHOP:
This is a 1-1/2 day course taught by a professional organization focusing on how to write a grant. The grant format will utilize the NIH PHS 398 form, and focus on how to develop a fundable idea, preparation before you write the grant, how to write for reviewers, tips and strategies for writing the specific aims, how much and what kind of preliminary data to have, how detailed and how to format the research design and methods section, budgets, and other pearls on how to get funded. The second day will focus on finding a funding source. The fee will be $25-50 (TBD), and registration will be through School of Medicine Continuing Education office AFTER September 1. For information contact: The Medical Educational Resources Program http://iumeded.med.iupui.edu/ or 317.274.8353.

March 20-22: RESEARCH COORDINATOR EDUCATION COURSE
Same course as above.

~March (Final date TBA):
Clinical Research and Regulatory Affairs A 1 day symposium focusing on the regulatory requirements for conducting human subjects research for the IUPUI campus. The final part of the day will highlight the newly developed IUPUI Standard Operating Procedures.

~April (Final date TBA):
Annenberg Patient Safety Symposium, preceded by a 2 day symposium on Patient Safety in Clinical Research The Annenberg conference is dedicated to examining patient safety. The two day long preceding symposium on clinical research will be an open discussion by leaders in the field on the issues surrounding clinical research.

Utility Tunnels to Close in August
Complete Details Although originally meant to provide easy access to repair utilities, use of the hallway-sized tunnels as pedestrian ways has grown over the years, including transporting patients from one campus hospital to another rather than moving them above ground.

A pedestrian tunnel between Riley Hospital and University Hospital will remain open, as will an underground connection between the Medical Research/Library Building and the Van Nuys Medical Science Building. Water, electrical, and communication lines run through the utility tunnels, as do steam pipes. Safety concerns associated with aging infrastructure, including steam joints that could develop leaks, prompted restricting the use of the tunnels to the purpose for which they were originally designed, officials said.

Trucks, vans, and other vehicles will be purchased and drivers hired to transport equipment, supplies, items used in experiments, and other material that is now routinely moved through the tunnels.

Surface ambulances will be used to move patients who have been transported through the tunnels between Riley/ IU Hospitals and Wishard Hospital.

Persons with safety questions or questions about why the tunnels are being closed may contact Emily Wren, Assistant Vice Chancellor for Facilities. Operations questions should be directed to the appropriate supervisor. Zone maintenance trouble lines are available to report tunnel emergencies 24 hours a day.

You're Invited…
Dr. Donna Dean, Interim Director of the new NIH Institute of Biomedical Imaging and Bioengineering (NIBIB), will be the guest of honor. She will introduce us to the objectives of the new Institute, its likely evolution, and role vis a vis the other Institutes.

In addition, Dr. George Wodicka, Professor and Head of Biomedical Engineering at Purdue University, West Lafayette, will speak on "Biomedical Engineering in Indiana"; and Dr. Shuming Nie, Associate Professor of Chemistry, Indiana University, Bloomington, will speak on "Genomic and Proteomic Technologies for Medical Diagnostics and Drug Discovery".

There is no registration fee. Lunch will be provided, as will parking in the Adam's Mark garage. Please RSVP to jmauro@21fund.org so we can be certain to provide both enough food and adequate seating for this interesting meeting.

In the longer-run we hope this luncheon will encourage members of the dynamic Indiana Biomedical Imaging and Engineering communities to develop state and federal proposals addressing the large-scale developmental needs of both the academic and commercial sectors in these areas.

Dr. Dean's itinerary includes stops at IUPUI (on the 6th) and Purdue, West Lafayette (on the 7th).

Research and Sponsored Programs UN 618 General - 274-8285 Research Compliance - 274-8289 Sponsored Program Development - 278-0249

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