Conflict of interest

Workshop Summary

Lister Hill Auditorium

National Institutes of Health

Bethesda, Maryland

September 30, 2002

Prepared by:

Analytical Sciences, Inc.

# Conflict of Interest Workshop

**National Institutes of Health, Bethesda, MD**

**September 30, 2002**

# Executive Summary

Objectivity of researchers is an essential value in scientific research
and the basis for public trust. Any research links with industry, while
not intrinsically unacceptable raise the prospect that scientific
advances will bring financial gain for the research scientist and his or
her institution. Concerns arise when financial considerations may
compromise---or have the appearance of compromising---the professional
judgment of the investigator or the institutional official, independence
in the design, conduct, publication of research, and/or the welfare of
human subjects. As the major sponsor of biomedical research, the
National Institutes of Health (NIH) seeks to work in partnership with
research institutions and university groups to harmonize approaches to
conflict of interest (COI) issues and to address these issues in a
reasonable way without hindering scientific innovation and discovery.
Although a specific outcome was not the goal of this workshop, the
meeting elicited wide-ranging discussion from diverse viewpoints to
inform officials involved in developing, implementing, and monitoring
policies to disclose, assess, and manage conflicts of interest. Meeting
attendees included research scientists; university administrators;
representatives from professional organizations that have taken
leadership roles in drafting guidelines for their members, such as the
Association of American Medical Colleges (AAMC) and the Association of
American Universities (AAU); and senior staff from the individual
Institutes and Offices of the NIH. Although raising the bar on oversight
in managing financial interests helps to underscore principled
relationships that withstand public scrutiny, it is important not to
over-react and over-regulate, which can limit patient opportunities and
exact unintended and significant transaction costs in the conduct of
research.

The issues associated with *individual* COI have already received a
great deal of deliberation, with current attention now focused largely
on developing and improving existing systems for managing such
conflicts, as well as on sharing best practices and lessons learned. The
understanding of Public Health Service (PHS) reporting requirements and
individual COI policies and procedures varies widely at institutions
across the country. These variations include management and monitoring
practices, how and when the Institutional Review Board (IRB) is
involved, and limits on equity holdings and company participation \[1,
2\]. Meeting participants generally agreed with the core principles the
AAMC and the AAU have articulated to guide policy development in this
area. These core principles include disallowing individuals who hold
significant financial interest in research involving human subjects from
conducting the research except under compelling circumstances;
coordinating COI and IRB processes with adherence to a more stringent
determination; and promoting disclosure and transparency of financial
interests. The American Society for Gene Therapy (ASGT) has put forth a
simple but rigorous policy disallowing investigators who have stock in a
company that sponsors a trial to have any patient contact during that
trial. Some participants emphasized that COI are highly situational and
should be evaluated on a case-by-case basis, while others argued
vehemently for standard rules, particularly in non-clinical research to
keep at a minimum the number of exceptions that will become precedents.

Guidelines associated with managing *institutional* COI are less
developed but of increasing concern. This concern arises from the
increase in equity holdings and royalties by universities in non-public
companies that have spun off from university-based research findings,
particularly in the decade following the Bayh-Dole legislation. Current
efforts focus on developing *new* policies and principles since no
regulations govern this area. In addition, workshop participants'
reactions to the suggested guidelines and procedures often varied. The
AAU issued general recommendations on managing institutional conflicts
of interest in October 2001 \[3\] and the AAMC issued complementary
recommendations in October 2002 \[4\] that apply specifically to
institutional financial interests in human subjects research. The AAU
concluded that a university's institutional financial COI process should
follow a 3-fold approach: 1) *Disclose* always, 2) *manage* the conflict
in most cases, and 3) *prohibit* the activity when necessary to protect
the public interest or the interest of the university.

The recommendation to segregate research endeavors from financial and
technology transfer activities generated lively discussion. Most
participants, including those from the Department of Health and Human
Services (HHS), were highly supportive. Others expressed skepticism that
separating out technology transfer will foster clearer focus on COI
issues. Even though the appearance of a conflict might exist, some
institutions view technology transfer as an integral part of the
academic function with reporting properly handled through academic
research channels. Some expressed particular concern about talk of a
"firewall" between research and technology transfer offices because they
place enormous value on the technology transfer office as a frontline
player in ensuring compliance and in promoting institutional values of
scientific integrity. Participants acknowledged that the role of
university officials is increasingly complex, particularly if they
oversee IRBs and grants administration. They also underscored the
importance of rigorous, effective, and disinterested monitoring of
research protections for human subjects. In some cases, reciprocal IRBs
may be a good approach for managing institutional COI. Participants
articulated a key principle of separating lines of management and
governance of protection for human subjects, technology transfer, and
research management. They also acknowledged that oversight for all such
issues must ultimately converge at a higher and appropriate level. There
is need to further elaborate how institutions might generate firewalls
between financial interests and oversight of research.

The role of the IRB in COI issues also generated significant discussion.
Some expressed strong sentiments that potential conflicts of interest
should be a material consideration in IRB deliberations. The overriding
opinion, however, was that IRBs would adopt an increasingly adversarial
tone, that IRBs are already burdened by a heavy workload and not
competent to address COI issues, and that review of financial conflicts
of interest should more properly be the purview of a separate committee
dedicated to this purpose, as some universities have already done. On a
related issue, participants noted that IRB members should report certain
financial interests annually and should adhere to federal policies
governing recusal from protocol review when necessary.

A proper balance between federal regulation and self-regulation is
needed, with the primary onus on research institutions to develop
guidelines and mechanisms to ensure and enhance research integrity. The
research community understands that serious action on their part in
demonstrating compliance can help to mitigate increasing public pressure
for government regulation. As institutions strive to balance risks,
public perception, and patient safety, their development of COI policies
and procedures, including clear assignment of institutional
responsibility, must occur in tandem with the education of researchers
and the public about proper disclosure and management of potential and
real conflicts of interest, both individual and institutional. Next
steps for the NIH will likely include further discussion about involving
students in COI issues to foster an understanding of the issues
underlying these topics, linking human subject protections with COI
guidelines, creating a shared knowledge base with data on the volume and
type of COI issues, and developing best practices on how conflicts are
resolved, including effective auditing and sanctions once an infraction
has occurred.

# Conflict of Interest Workshop

**National Institutes of Health, Bethesda, MD**

**September 30, 2002**

# Meeting Summary

# Opening Remarks

Dr. Elias Zerhouni, M.D., Director of the NIH, opened the workshop by
thanking the participants and organizers, Dr. Wendy Baldwin, Dr. Tony
Demsey, and Dr. Steven Hausman. Dr. Zerhouni recognized the research
community for working hard to address COI issues and noted that the NIH
was pivotal in establishing regulations by the Department of Health and
Human Services (HHS) in 1995 regarding this topic. He viewed this
workshop as fundamental to NIH efforts at maintaining public trust and
confidence in biomedical enterprises.

Having addressed conflict of interest issues both personally and at the
institutional level as an extramural scientist, Dr. Zerhouni
acknowledged how difficult it can be to implement policies and
procedures. Government institutions and universities must be partners
and deal with this issue in a realistic way. However, he cautioned
against too much diversity in regulations and expressed his expectation
that the workshop would help identify a proper balance by providing
views on how regulations have been lived "on the ground." Ultimately,
the workshop sponsors hoped to discern best practices and to harmonize
the way academic institutions approach conflict of interest issues.

Dr. Zerhouni then focused on the subject of institutional conflicts of
interest, noting the increased attention to this topic and how it has
evolved since the enactment of the Bayh-Dole Act in 1980. Beyond science
and translation, he emphasized that the American public has gained from
this investment in science through the development of new products,
drugs, and research tools. He shared his personal concerns that if
further regulation were ever to become necessary, it should not impose
unduly high "transaction costs" on the enterprise of science such that
innovation and discovery are hindered. Dr. Zerhouni added that while NIH
makes awards to institutions, it entrusts most of the oversight of
research to partner institutions. Therefore, he was pleased to see
strong representation from universities and from organizations, such as
the AAMC and AAU, which have taken a leadership role on this topic. Dr.
Zerhouni concluded by emphasizing the need to understand the differences
between government regulations and underscored the important
responsibility of universities to maintain their image as fair and
objective arbiters of scientific knowledge.

Before introducing the first panel, Dr. Wendy Baldwin, Deputy Director
for Extramural Research, NIH, described the goals for the workshop as
2-fold. The first half of the workshop addressed problems and solutions
concerning *individual* conflicts of interest. The second part of the
workshop focused on *institutional* conflicts of interest. No specific
outcome was expected on these topics, other than a synthesis of the
discussion. Dr. Baldwin acknowledged that these are very complicated
issues and will require considerable discussion if the academic
community is to move toward a consolidated view. The workshop was
intended to be an interactive process that would allow participants to
share experiences and to inform officials involved in writing,
implementing, and monitoring regulations.

## Current Climate and Visions for the Future

##### Nils Hasselmo, Ph.D., Association of American Universities

After thanking senior NIH officials and the meeting organizers, Dr.
Hasselmo spoke briefly about the perspective of the AAU on COI. He gave
an overview of the AAU October 2001 report \[3\], noting that a task
force addressed both individual and institutional COI in an effort to
sustain public confidence and to assist members in reviewing and
strengthening their policies. As a result of these activities, the AAU
found that developing reliable systems to manage COI was a major
challenge. Therefore, in regard to individual COI, they looked at
improving existing systems. Dr. Hasselmo considered institutional COI to
be more like an "unplowed field," and the AAU is focused on developing
*new* policies and principles, since no regulations govern this area.

Dr. Hasselmo discussed AAU's approach to this topic in a broad way,
noting the formation of a task force, workshops, and coordination with
the AAMC. In terms of individual COI, the task force identified
extraordinary complexities so case-by-case review is often necessary for
specific situations. However, because universities still need guidance,
the AAU developed 10 operating guidelines. One major recommendation is
that related financial interests in human subjects research should
generally not be allowable, absent compelling circumstances. Their
guidelines also address the need to coordinate IRB and COI processes,
since both are required by different government regulations, but need to
be connected by campuses so that neither system operates in isolation
from the other.

Turning to institutional COI, Dr. Hasselmo said it is important to focus
on this topic because there has been a dramatic increase in start-up
firms coming out of universities. Universities are receiving equity in
non-public companies, as well as royalties. This means control of equity
is sometimes managed by those who have research responsibility, thereby
increasing the potential for conflict. The AAU task force came up with a
"mantra" that illustrates a strategy for addressing potential
institutional COI. First, institutions should always disclose potential
conflicts. Second, if a conflict is identified, there should be a
strategy for managing the conflict, and if necessary, the activity that
caused the conflict should be prohibited. Most importantly, however,
decision-making about financial activities and research activities
should be segregated, so they are independently managed.

The AAU report has been distributed widely to its members and the
science policy community. Although no comprehensive evaluation of the
report has been done, the AAU has convened campus experts, consulted
with government colleagues, and contacted some of their member
organizations to discuss the implications of the report. The association
has also helped to establish a new accrediting body, the Association for
the Accreditation of Human Research Protections Programs, and has
encouraged member universities to undergo such evaluation. Dr. Hasselmo
expressed the AAU's hope that these activities have helped universities
tighten their COI policies and have demonstrated that the research
community is serious about these issues. Dr. Hasselmo also discussed
some future challenges for the academic community, which include
monitoring research collaborations, educating researchers and
administrative officials about COI issues, and fostering an ethic of
accountability and responsibility. He concluded by emphasizing that the
research community *must* act with integrity in addressing these
important matters.

##### Janet Heinrich, Dr.P.H., R.N., U.S. General Accounting Office

Dr. Heinrich gave an overview of the November 2001 General Accounting
Office (GAO) report, *Biomedical Research: HHS Directions Needed to
Address Financial Conflicts of Interest* \[1\], which was prepared at
the request of Senator Bill Frist (R-TN). As discussed in the report,
she noted that there has been an increase in research collaborations
since the 1980 Bayh-Dole legislation, which has led to new products and
innovations. However, recent allegations of investigators with improper
financial interests threaten to compromise research integrity and to
jeopardize the safety of human subjects in research.

Turning to the methodology of the study, Dr. Heinrich reported that the
GAO conducted interviews with many HHS officials, including those from
the NIH, the Food and Drug Administration (FDA), and the Office for
Human Research Protections, as well as case studies from five
universities: UCLA; University of North Carolina (UNC), Chapel Hill;
University of Washington, Seattle; Washington University, St. Louis; and
Yale University. These five universities are among the top 20
institutions receiving NIH support and conducting major technology
transfer activity.

As a result of the investigation, GAO evaluators found that universities
had in place individual COI policies that covered both private and
publicly funded research, but that these policies and procedures varied
greatly. For instance, there were differences in how and when the IRB
was involved in COI matters. GAO also noted that all of the universities
allowed self-certification of compliance. However, research and COI
information were kept in multiple locations and formats, making it a
challenge to ensure that COI issues were managed properly.

Institutional COI is a more recent focus of attention, and Dr. Heinrich
reported that the five universities GAO visited tended to manage
institutional investments separately from academic affairs. In some
cases, technology transfer activities were separated from academic
affairs, but this practice varied. The five universities had, or were
developing, policies on accepting equity in start-up companies, but they
placed varying limits on equity holdings and their role in start-ups.
For example, equity limits ranged from 2 to 49 percent, and roles in the
company ranged from "no involvement" to having a seat at the table.

Overall, the GAO found no direct link in the federal regulations between
oversight of financial interests and protection of human subjects. In
addition, they noted that PHS and FDA financial interest regulations are
not uniform in timing or disclosure thresholds. They also noted that the
universities in the GAO study were confused about PHS reporting
requirements.

As a result of its investigation, the GAO identified a number of future
challenges. First, they found that institutions need and want
information on best practices. The GAO considered the draft interim
guidance on financial relationships in clinical research by HHS to be
promising but in need of revision, especially in addressing
institutional COI. In addition, HHS needs to link the protection of
human subjects and the financial interest regulations. Finally, the GAO
stated that as more biomedical research becomes privately funded, it
will be important to address potential financial conflicts of interest
in settings that may not be operating under broad financial COI policies
and procedures. The GAO recommended that HHS develop and communicate
information on best practices for managing both individual and
institutional COI. In addition, HHS should develop specific guidance or
regulations concerning institutional financial COI.

##### David Korn, M.D., Association of American Medical Colleges

Dr. Korn gave a history of the AAMC's interest in this topic, noting
that they were aware of AAU's efforts, and, as a result, decided to
focus on financial COI and human subjects research. The AAMC undertook
this effort in the context of a confluence of issues, including growing
public concerns about potential conflicts of interest in research,
increasing laxness in federal legislation and regulations, and the
dramatically changing "ecology of biomedical research." In general, this
includes the astonishing progress of biomedical science itself and,
specifically, the advent of recombinant DNA technology, the 1980 Supreme
Court ruling that living organisms can be patented, and the 1980
Bayh-Dole Act. Dr. Korn observed that there is a public sense that the
national biomedical research enterprise is beset by a "virtual pandemic"
of financial conflicts of interest.

Dr. Korn then provided a brief overview of the efforts the AAMC task
force has undertaken to address this topic, noting that the AAMC was
pleased that this diverse group of scientists, patient advocates, and
industry leaders reached consensus. The core principles the task force
developed are outlined in the AAMC December 2001 publication,
*Protecting Subjects, Preserving Trust, Promoting Progress: Policy and
Guidelines or the Oversight of Individual Financial Interests in Human
Subjects Research* \[5\]. The five principles establish: 1) The
"rebuttable presumption" that research in which there are financial
interests should not be conducted by the affected individual or
institution; 2) that institutions should ensure that administrative
practices related to research administration are separate from
investment management and technology transfer activities; 3) that
separate COI committees should be established to review individual and
institutional COI, and that they, especially the latter, should have
public representatives; 4) that institutional COI policies and
procedures should be comprehensive, unambiguous, well-publicized,
consistently applied, and effectively enforced; and 5) that in the
presence of financial interests, approved research must be managed
through rigorous, effective, and disinterested monitoring, and that
mandatory disclosure should be provided to prospective subjects and in
all communications.

Importantly, the AAMC report did not contain language banning any
activity. Rather, it emphasized that conflicts of interest are highly
situational, and evaluations of conflicts should be on a case-by-case
basis, considering the nature of the financial interest, as well as a
host of other factors. Universities and their medical centers will
establish their own standards for how compelling the circumstances must
be to support rebuttal, although the task force intended highly rigorous
standards.

The AAMC plans to promote the adoption of their principles, evaluate the
influence of the reports, and ensure that practices do not exact
unreasonable transaction costs. It is expected that widespread adoption
of the stringent principles in these reports would significantly raise
the bar of oversight in management of financial interests, reduce the
disturbing variability in institutional policies and procedures that has
recently been documented, and help sustain principled relationships
between academia and industry that withstand public scrutiny. Quoting
from the first report from the AAMC task force, Dr. Korn concluded by
emphasizing that the Task Force did not intend that its reports should
interfere with healthy academic/industry relationships or with the
continued development of products from academic biomedical inventions
that will benefit the public.

##### Lawrence Rudolph, J.D., National Science Foundation (NSF)

Mr. Rudolph began his presentation by emphasizing that the research
community should neither do nothing, nor over-react to the issue of
conflict of interest. He commended NIH's work on financial disclosure
policies in the 1990s and described how the NIH and the NSF worked
collectively to enact a joint individual financial disclosure policy for
investigators. The real question will be how well institutions can
self-regulate. Referring to an OER survey of 300 institutions, he said
he endorses federal institutions such as the NIH to gather information
on best practices, but believes organizations like the AAMC and AAU
should provide leadership and take ultimate responsibility for these
issues, noting that perfect behavior cannot be regulated. However, he
warned that if something is not done, the public and Congress will
pressure federal agencies to act.

Mr. Rudolph said his work with the NSF has shown that the "one size fits
all" approach is not necessarily optimal. For instance, there are
important differences between the research that NIH supports and the
research that NSF supports, so policies will not be the same. He
questioned whether even a government-wide policy was possible given the
complexities and difficulties inherent in auditing and ensuring
compliance. Mr. Rudolph stressed that the most practical policy is one
that works for most, addresses real issues rather than paper issues, and
separates management of institutional conflicts from research activity.

In conclusion, Mr. Rudolph cautioned against over-regulating. It is easy
to create elaborate mechanisms to give an appearance that issues are
being addressed, he noted, but it is more important to clearly identify
what needs to be addressed and make sure those concerns are met.

##### Eve Slater, M.D., Office of the Assistant Secretary for Health, HHS

Dr. Slater said that HHS recognizes the presence of conflicts related to
the protection of human research subjects and emphasized that the
research community and governing agencies must promote an "exquisite and
implicit" trust in clinical studies through openness, honesty,
integrity, and responsibility. She applauded the group's efforts in
trying to strengthen the infrastructure for the protection of human
subjects and increase participation in clinical trials.

Dr. Slater then briefly discussed the evolution of the HHS guidelines on
this issue. In 2000, HHS requested that experts comment on their
experiences, ideas, and suggestions regarding HHS guidelines for
protecting human subjects when financial interests are involved. In
January 2001, draft interim guidance on this topic was published. Since
then, HHS has obtained input through conferences and from organizations
such as the AAMC, American Medical Association (AMA), and AAU. The
guidance will soon be finalized. Dr. Slater said that HHS strongly
supports suggestions to separate responsibility for institutional
development and licensing from the actual conduct of research. HHS also
supports recommendations that an investigator be recused from research
when conflicts are identified.

## Participant Discussion

Dr. Baldwin reiterated the importance of having flexible policies and
firm principles in place. She also noted that NIH's recent survey of
institutions captured the diversity of practices and level of
understanding in the research community. She called for participants to
contribute their ideas about the best ways to share "best practices" and
reach out for help.

Participants expressed concern about the concept of separating
technology transfer activities from research endeavors because there is
no evidence that separating out technology transfer will foster a better
focus on COI issues. At MIT for instance, the technology transfer office
reports through the academic function because they do not view this as
purely a business activity---although some money is made---but as an
integral part of the academic function. Some participants felt this
decision should be made on a case-by-case basis. Respondents agreed that
these matters are complex, but suggested the key factor is how to
develop a functioning system that separates research from financial
decision-making. Dr. Korn added that the AAMC task force did not feel
separating out technology transfer was a controversial idea, since the
"appearance" of a conflict is clearly evident.

Another participant asked whether it would be a conflict of interest for
a pharmaceutical company to reimburse an investigator based on patient
accrual levels. Dr. Korn responded that the AAMC task force came out
strongly against bonus payments for patient accrual, but payment of
costs, such as staffing for recruitment, is reasonable, even if broken
out on a per patient basis. Others echoed this sentiment, saying that it
is acceptable if it does not impede objectivity or the payments are not
outlandish, and that it was similar to receiving money from a grant.
Participants also emphasized that skepticism should not automatically be
triggered simply because a pharmaceutical company is providing financial
support. The focus should not be on the dollars themselves but on the
conditions that accompany the funds. One participant said their
institution considered payments to enroll human subjects to be a clear
financial conflict, although manageable, and disclosed this as part of
the informed consent process. Participants also pointed out that as a
result of university uneasiness about financial relationships,
pharmaceutical companies are increasingly turning to the commercial
sector to manage clinical trials.

Discussion also addressed the best administrative lines of management to
avoid conflicts of interest. Participants acknowledged that the role of
university officials is difficult, especially when they oversee IRBs and
grant administration. Participants also asked AAMC and AAU
representatives how they see the role of the university official. Dr.
Kelch said that key principles from both documents, especially the
newest document, have separate lines of management and governance for
things as disparate as protection for human subjects, technology
transfer and research management. While the report was not prescriptive,
it indicated consensus on the belief that functions can be separated,
but can also come together at the level of the Board of Trustees.
Dr. Korn added that the AAMC recognizes the processes have to come
together, but they should not be too far down in the hierarchy, such as
at the laboratory chief level; the "rule of reasonableness" should
apply. Others suggested that Offices of Research Integrity, under the
auspices of the president, should govern IRBs. Another alternative is to
have a compliance officer provide independent verification to the
president. Every organization should be able to identify appropriate
senior officials to govern, and it is impractical to eliminate their
interaction with researchers.

## Case Study Presentations

##### Lisa Bero, Ph.D., University of California, San Francisco (UCSF)

Representing the perspective of a medical school, Dr. Bero gave an
overview of UCSF's financial disclosure policies. She noted there are
different courses of action depending on whether the funding source is
private or public. She then discussed the extensive information
gathering process undertaken when investigating a financial disclosure
that exceeds certain thresholds. Dr. Bero explained that, in reviewing
financial disclosures related to federal grants, the COI committee's
main concern is whether the financial relationship could have a direct
and significant effect on the NIH-funded research, and if so, how the
relationship should be managed. Dr. Bero then presented two conflict of
interest scenarios and discussed UCSF's response. These hypothetical
case studies arose from an ORI-funded study, conducted by Dr. Bero and
colleague Elizabeth Boyd, of how decisions are made at the institutional
level to manage COI.

> **Case 1:** Case 1 involved an investigator, Dr. Toe, who had a \$1.2M
> NIH grant to conduct a comparative evaluation of toe cancer diagnostic
> techniques. At the same time, Dr. Toe had a relationship with a
> company that manufactured her toe cancer detection device. She was
> named on the company's patent application as inventor and served on
> the scientific advisory board. Dr. Toe also received consulting fees
> to help train people to use the diagnostic test and to review samples
> to assess the technique and had stock options, of unknown value, in
> this privately owned company.
>
> ***Resolution:*** UCSF determined that Dr. Toe's conflict was likely
> to have a direct and significant effect on her NIH research. The
> testing of the cancer devices overlapped with the NIH research. UCSF
> decided that Dr. Toe *should not participate* in the research portion
> of the grant, and she should disclose financial ties to the company in
> all publications and presentations. However, Dr. Toe participation in
> the training activities related to her consulting for the company did
> not pose a conflict with the NIH grant because they involved training
> and not research.
>
> **Case 2:** Case 2 involved Dr. Fountain, the Principal Investigator
> (PI) of a large NIH grant in its 25^th^ year of funding. Dr. Fountain
> is chairman of the board, founder, and owner of a biotechnology
> company, which he started in January 2000 to commercialize discoveries
> from his research. The company licensed the patent rights to Dr.
> Fountain's invention when a previous licensee failed to commercialize
> the invention. The company is not currently selling or manufacturing a
> product, but intends to do so someday.
>
> ***Resolution:*** UCSF's COI committee found that the disclosed
> conflict could have a direct and significant effect on the NIH grant,
> but also that the NIH grant activities were adequately separate from
> the company's activities. The committee agreed the Dr. Fountain
> *should* continue to receive the funding, but must also disclose his
> financial ties to the company in all publications and presentations.

## Participant Discussion

In elaboration of the first case, Dr. Bero clarified that the university
had not patented Dr. Toe's work because she conducted the research
before coming to the university. Dr. Bero said this highlights the
differences between junior and senior faculty when conducting COI
reviews. There was also discussion about how UCSF handles "conflicts of
commitment" (e.g., the investigator's time is compromised due to
multiple commitments). Dr. Bero noted that the COI committee does not
address this issue, but they can refer it to the department chairperson
who handles these matters.

In reference to Dr. Toe's case study, participants also discussed
approaches to the valuation of privately held stock. One participant
suggested that since Dr. Toe's stock had an unknown value on the
disclosure form, the university could assign a value based on what the
venture capitalist paid. Dr. Bero responded that the assigned value can
be irrelevant if the investigator has a large management role in the
company and suggested that the better alternative might be for the
investigator/inventor, rather than the university, to declare a
valuation range. Another participant suggested that having a stock that
is not (yet) worth anything could create a further conflict and impair
the investigator's judgment. For instance, the investigator may be
motivated to do certain things because he or she wants to see the stock
value increase.

Participants also inquired how UCSF handles research that involves
testing an Investigational New Device (IND) for FDA approval. Dr. Bero
responded that it depends on whether the investigator is an expert in
working with the device or procedure. If the investigator is so expert
that they must be involved in the research, the PI normally has to
eliminate conflict, either by divesting the financial interests or
refusing the funding. A suggestion was made to remove chairpersons from
COI decision-making because they are too close to the faculty.

Dr. Bero also explained that the UCSF campus' clinical trial policy does
not allow an investigator to accept income from a company during the
course of a trial if that company is funding the trial. Furthermore,
state law governs conflict thresholds for private donations. She also
noted that clinical trials are not treated as basic science when
evaluating possible financial conflicts.

##### Mark Brenner, Ph.D., Indiana University-Purdue University, Indianapolis

Dr. Brenner represented the perspective of an institution that has
parallel systems of COI review. He first gave an overview of the
structure of the university system, noting that a large portion of its
sponsored research goes toward the medical school. Dr. Brenner noted
that Indiana University's COI committees are moving from a diversified,
decentralized system toward a single, more functional COI committee.
Existing policies address individual COI, conflict of commitment, and
state laws regarding receiving contracts. A separate requirement
addresses disclosure of financial interests for senior administrators,
but this does not apply to deans or department heads. The university is
also working to implement new policies on administrative conflict of
interest, institutional conflict of interest, and potentially, ownership
rights for textbooks.

Dr. Brenner said that at his institution, low-risk issues are managed
locally, but higher-risk cases are referred to the COI committee. The
university's COI committee categorizes the range of severity of
financial relationships from normally acceptable to not allowable unless
there is a compelling case. The severity of the financial relationships
determines the level and extent of review the situation receives and the
disclosure required. Dr. Brenner noted, however, the university's COI
committee does not develop a plan for managing COI, it only validates
the plan.

Dr. Brenner then presented examples of several draft case studies
developed by the Council on Governmental Relations (COGR). The COGR
series of case studies address consulting, licensing, clinical studies
involving human subjects, procurement, mentoring relationships, and
institutional conflicts. These case studies and resolutions are
described in more detail on the COGR Web site, <http://www.cogr.edu/>.

> **Case 1:** Case 1 is an example of a low-level scenario. It involves
> Dr. Maple, a highly regarded oncologist at university medical college
> (UMC). A major pharmaceutical company, Blue Drug, wants to sponsor a
> clinical study testing whether its existing soft-tumor drug is
> effective in treating certain atypical forms of solid tumors. Dr.
> Maple has an existing relationship with Blue Drug that involves travel
> to company-sponsored conferences at no charge and receipt of
> honorariums that totaled \$5000 the previous year. COGR suggested a
> number of questions to assess the scenario and then suggested an
> appropriate response.
>
> ***Resolution:*** The recommended strategy for this particular
> scenario was to disclose all financial ties in publications and
> presentations and in informed consent for clinical trials.
>
> **Case 2:** Case 2 is an example of a more complex scenario. It
> involves Dr. Teak, who is the inventor of a new drug that has been
> patented and licensed to a pharmaceutical company, Gray
> Pharmaceuticals. However, Gray misses some key development milestones
> that are part of the licensing agreement. Meanwhile, Dr. Spruce, the
> department chair, devotes resources to conduct phase II testing of the
> drug. The university's technology transfer office helps Dr. Spruce
> create a start-up company (Pink Drugs) to sublicense the drug from
> Gray Pharmaceuticals. Dr. Spruce solicits start-up funds from a friend
> who is the wife of Dr. Hickory, the IRB chairman. Dr. Hickory's
> research is unrelated to this study. His wife invests the money in
> exchange for company equity and stock. Dr. Spruce persuades the
> university president to approve this with the promise that the
> department can recoup sunk costs from future revenues. Dr. Teak serves
> as consultant to Pink Drugs and is asked to help with phase III
> trials. He receives generous compensation and insists the phase III
> studies be conducted at the university because of his unique
> expertise.
>
> ***Resolution:*** In this example, COGR suggests a number of
> management strategies. First, many universities might conclude that a
> UMC should not be involved as a performance site for clinical studies
> given the complexity of the relationship, while still allowing Dr.
> Teak to assist Pink Drugs in developing the drug through a consulting
> relationship. Alternatively, Dr. Teak, if he serves as the PI, should,
> with UMC approval, divest himself of his stock options and modify the
> scope of his consulting activities. COGR also recommends full
> disclosure to human volunteers and all involved in the study.

Dr. Brenner concluded his presentation by issuing a general caution and
reminders for addressing conflict of interest issues, including the need
for full disclosure and the use of a higher standard when human subjects
are involved. The greater the risk or complexity of the activity, the
more likely the university will limit activity. Furthermore, when
institutional and individual COI occurs, it is prudent for the clinical
research to be conducted at other sites.

## Participant Discussion

One participant noted that with the complexity of cases, the COGR
management strategies are not as broad as they should be. Dr. Brenner
explained that these management strategies are not meant to be a
complete compendium, and COGR will eventually enrich what is listed in
these case studies. These case studies seek to highlight items that need
attention but do not prescribe solutions. Others noted that recusal from
IRB *should* be mandatory where a conflict is present. Another
participant suggested that reciprocal IRBs for clinical research might
be a good approach for managing institutional conflicts of interests.

There was also significant discussion about the role of the IRB in COI
issues. One participant thought it would be inappropriate to have the
IRB responsible for investigating scholarly misconduct, adding that
researchers should be made to feel they are working with the IRB, not
investigated by it. Another participant urged that the IRB focus solely
on human subject issues, otherwise, it would require the creation of a
whole new skill set. Instead, the institution should have a separate
entity focus on financial interests. Many other participants echoed this
sentiment and said that IRBs have a heavy workload and are not competent
to address COI issues. Others countered that IRBs *do* have a
significant role in protecting the right of the patient to be free from
coercion and undue influence, and to be recruited in a fair, objective
manner. While the IRB may not have the expertise to conduct the
financial review, coordination between the two committees needs to
occur. Another participant said it would be helpful for the IRB to have
a checklist of standard criteria and conditions to help facilitate the
process.

Dr. Faye Austin also cautioned that in our zeal to protect subjects and
the study's integrity, we must take care in determining which site
should be part of a multicenter trial. Multisite studies are beneficial
to patients, and we should lean more toward management strategies rather
than prohibitions. In protecting patients, it is important not to be
paternalistic and take away their opportunities.

##### Gerald Gotterer, M.D., Ph.D., Vanderbilt University School of Medicine

Dr. Gotterer spoke from the perspective of an institution with a single,
unified process for addressing COI issues. He noted that the publication
of guidelines in 1989/90 by the NIH, the AMA, and the AAMC stimulated
review of COI policies at Vanderbilt University. A Vanderbilt dean's
committee recommended in the early 1990s that the Medical School develop
a system for annual disclosure by all faculty, operational standards for
faculty addressing COI issues, and a COI committee. The committee
assigned categories of risk to faculty activities, ranging from
routinely allowable to not allowable, and also now has a process for
annual disclosure and review. Dr. Gotterer then presented Vanderbilt
University itself as a case study.

> **Lessons Learned (Disclosure Forms):** A simple one-page screening
> document with checklist for initial screening yields good compliance.
> A supplemental form can obtain the needed information from those with
> something significant to disclose. The use of "nested" questions
> minimizes the need for follow-up inquiries. The disclosure forms
> should also contain brief statements that serve to educate faculty.
>
> **Lessons Learned (Process of Review):** Centralized review assures
> uniformity in application of criteria, while the use of subcommittees
> supports efficient gathering of needed information and developing
> management plans without overburdening committee members. Since the
> issues are complex and there will be a learning curve for committee
> members, it is important to include members who have a history of
> working with industry and to maintain a stable membership. A number of
> factors, most especially patient risk, should be considered when
> assessing COI in human investigations. Additional factors that
> committees must examine include the implications of a phase I versus
> phase II trial, a single versus multicenter trial, a double-blind
> versus open-label study, and independent data analysis compared to
> analysis by the investigator.
>
> **Lessons Learned (Oversight Committees):** Oversight provides the
> opportunity to have continuing review of a conflict situation. Three
> individual oversight committees took time to understand and reach
> comfort with their roles. The faculty members found it difficult to
> monitor their peers' data. Individual committees were combined into a
> single committee. This approach takes advantage of the members'
> cumulative experience and facilitates efforts to ensure a firewall
> between financial conflicts and research efforts.
>
> **Additional Lessons.** Furthermore, if conflicts are managed
> appropriately, oversight may not be necessary. IRBs are responsible
> for ensuring patients' awareness of financial conflicts of interests,
> whereas the COI committee assures that COI situations are managed in a
> manner that avoids inappropriate influence of conflicts on research
> design and outcome. IRB approval is contingent upon satisfactory
> clearance from the COI committee.

In conclusion, Dr. Gotterer noted that the faculty truly wants to do the
right thing. Therefore, assessment of COI and education of scientists by
COI committees need to occur simultaneously.

# Responder Panel

##### Michael Corn, J.D., University of Washington School of Medicine

Mr. Corn, who has experience in industry as well as in higher education,
emphasized that policy should not be based on random, rarely occurring
events. He too receives a range of responses from others about the
impact of potential conflicts of interest in research, ranging from
"what's the problem" to "the sky is falling." He emphasized that
Bayh-Dole is still the prevailing public policy and expressed concern
that over-reaction could lead to future policies that create significant
and excessive transaction costs while at the same time denying patient
opportunities and delaying important research advances.

He also noted that earlier presentations had featured a number of
comments about COI becoming pandemic, some of which were accompanied by
complex charts depicting multiple organizational and review schemes. He
cautioned that the research community needs balance in this area and
must remain rational. He also said that we needed to be sensitive about
protecting the morale of researchers. He expressed the view that COI
must be taken in context, that not all research difficulties are caused
by COI, and that every problem does not require an ethics/COI analysis.

Timely reviews as well as standards to guide investigators' behavior are
needed if a policy is to be effective and useful. Some degree of
predictability and certainty are necessary in order that investigators
can know what is and what is not allowable. Mr. Corn said "appearance of
a conflict" is being applied in a very unclear manner. While taxpayer
support and public confidence for the research enterprise is important,
appearance of conflict should not be equated with bad publicity and
unfavorable media coverage. He said that the legal test should not be
"the front of the newspaper test" but instead should be whether the
purported "appearance" interferes with the discharge of a professional
duty by a researcher or the institution.

Mr. Corn also called for an improved theoretical framework in which to
analyze research-related COI issues and suggested that policy
development would benefit from more legal expertise. He agreed that
committees have a role in COI reviews but suggested that overuse of
committees be guarded against because of time constraints, expenses,
need for uniformity of decision, and other issues.

Mr. Corn commented that the "compelling circumstances" test in the AAMC
and AAU reports might be interpreted by some in an excessively high
manner and suggested that there could have been a better choice of words
to indicate when research could proceed. Although portions of the actual
text from the AAMC and AAU reports suggest that "compelling
circumstances" means something less stringent, a court or others may
interpret it to mean "rare or never." In addition, the "compelling
circumstances" test may fail to adequately consider those types of human
subjects research that present little or no risk to human subjects, such
as minimal risk or exempt human subjects research.

Finally, Mr. Corn expressed concern that increased attention to
institutional COI may jeopardize contributions of gifts and endowments.
He also noted that, due to recent news articles, attention to
non-financial conflicts might spiral out of control.

##### Susan Ehringhaus, J.D., University of North Carolina (UNC) at Chapel Hill

Ms. Ehringhaus spoke about conflict of interest from the perspective of
a university general counsel and as one of five institutions reviewed by
the GAO audit team on conflicts of interest. She commended both the GAO
audit team, as well as the workshop organizers, for their efforts. Ms.
Ehringhaus first outlined a number of issues that are currently at
stake, including integrity of research and the university, fiscal
responsibility, independence of IRB and Institutional Animal Care and
Use Committee (IACUC) review, research compliance, primacy of interests
of human subjects, and external credibility.

She then discussed the current status of universities' activities,
describing first what they have done well. Universities have developed
comprehensive policy statements; clear definitions of what triggers a
review. Universities have work to do in terms of explicit delineation
(e.g., clear scripts) of review criteria for researchers and reviewers,
such as documenting institutional management of COI, education to
correct errors, and disciplinary action to correct wrongs. Critical
areas that need more work also include establishing external credibility
by involving those outside the institution and maintaining transparency.

Ms. Ehringhaus continued by outlining some of the key processes
universities need to implement. These processes include a clear
assignment of institutional responsibility, interactive searchable
databases to help research COI issues, separation of responsibility for
research from entities such as finance and technology transfer, workable
review mechanisms, training programs for researchers and reviewers, and
public education efforts. In particular, universities should consider
implementing review mechanisms that are risk-based and that minimize
unnecessary burdens.

Ms. Ehringhaus also addressed the question of whether the work of the
AAMC, the AAU, and from various professional associations constituted
"standards of care" for research on human subjects. Whatever
characterization is used, the standards articulated by the national
organizations will help to reduce problematic variability of operating
principles across institutions and organize processes along common
themes yet preserve necessary self-determination for individual
institutional responses to instances of financial conflict of interest.

##### Christina Hansen, University of California, Irvine

Ms. Hansen spoke from the perspective of a senior official in research
administration. As Assistant Vice Chancellor for Research, she oversees
staff responsible for sponsored projects and the regulatory committees
such as the IRB and IACUC, and she serves as staff to the COI and
research conduct policy committees.

Ms. Hansen first discussed the organizational issues related to conflict
of interest. Earlier in the conference, support was registered for new
protections for the IRB from institutional pressures related to
conflicts of interest in clinical situations. Ms. Hansen noted that the
IRB is established under federal regulations as an independent body.
Thus, her experience at two campuses of the University of California is
that the IRB would not be swayed by these external forces. With respect
to other organizational issues, she then pointed out that other
university offices are involved in COI issues and these were not
mentioned at this workshop, such as personnel and academic affairs,
purchasing, and the graduate schools. These offices deal with conflicts
of commitment, procurement for research activities, and protection of
students from coercion, respectively, and should be considered in
discussions of COI.

In terms of policy, Ms. Hansen stressed the importance of conveying the
institutional message and fostering a culture of compliance. It is also
important to define terminology since many terms are used
interchangeably. For instance, words such as technology transfer,
equity, consulting, patents, and licensing have very different meanings
and should be recognized for varying levels of concerns related to
potential risks in conflict of interest situations. .

In developing policies and procedures, it is important to address the
real question: What is the value added? That is, are policies and
procedures being developed to manage serious conflicts, and then pulling
in situations that are only minimal risk? And, do these policies
ultimately protect subjects or hinder important research? AAMC and AAU
guidance can help us refine the task but, ultimately, policies should be
tailored to the type of research that is occurring on the campus.

Lastly, Ms. Hansen emphasized that communication is the key in
developing processes, whether it be through electronic media, shared
databases, or handwritten methods. This information can and should be
shared among IRBs, COI committees, and grant and contract staff. IRBs,
in particular, need feedback from the COI committee, and the COI
committee can obtain valuable information from the protocol review.

##### Debra Lappin, J.D., NIH Council of Public Representatives

As a member of the NIH Council of Public Representatives, Ms. Lappin
said it was a tough challenge to represent the public. She said she was
here because of her concerns about maintaining public trust and
partnering with the American public and suggested that these goals were
often easier to espouse than to implement. COI issues and human research
protections *do* intersect---it is not just about objectivity in
science.

She described the public's relationship with science as having evolved
from a relationship comfortable with paternalism to one respecting of
autonomy and to one demanding equality and partnership. This
transformation has occurred in part because of media headlines
announcing clinical trial deaths (e.g., research subjects Jesse
Gelsinger and Ellen Roche) and depicting humans as guinea pigs (e.g.,
*Time Magazine*'*s* cover story "Human Guinea Pigs," which depicted a
woman trapped in a cage). Given the events of the past few years, it is
little wonder that the public trust in institutions of science is at
risk. Much is at stake if public trust is diminished: this is the same
public that funds endowments, gives their tax dollars to support federal
appropriations, heroically offers to participate in clinical trials, and
ultimately "owns" the magnificent enterprise of the NIH.

In sharing her perspective on both individual and institutional COI, Ms.
Lappin said institutions must develop a new "culture of conscience"
created through examples set by the most senior leaders at the
institution. Institutions should expect intense scrutiny as trust is no
longer free and is increasingly viewed as a business commodity. In terms
of individual COI, the patient weighs the risks and benefits of
participating in clinical trials. Patients should also be allowed to
consider the impact of an investigator's financial interests when
deciding to participate. Not revealing this information to the patient
is paternalistic, reinforces the disparity between individuals and
institutions, and contributes to a further misunderstanding of research.
Ms. Lappin added that IRBs *must know* about conflict of interest
issues. Keeping this information from IRBs takes away critical pieces of
knowledge about safety, welfare, and objectivity in research on human
subjects.

##### Christine Maziar, Ph.D., University of Minnesota

Although she recently became Provost, Dr. Maziar also comes to this
workshop with the perspective of a Vice President of Research who had
oversight responsibility for technology transfer, sponsored projects
administration, and supporting IRB and biosafety committees. She also
spoke from the perspective of a land-grant institution, which has Board
of Regent meetings that are open to the public.

Dr. Maziar stressed the importance of being clear that punishing
investigators for their commercial success is *not* the goal of COI
policies. She also emphasized the importance of considering the language
that is used when talking about COI issues. She expressed particular
concern about talk of a "firewall" between research and the technology
transfer office. The technology transfer office can promote
institutional values in this regard and can be enormously valuable as a
front-line player in ensuring and promoting compliance.

In discussing institutional COI, Dr. Maziar noted that many university
vice presidents feel "on the edge" of these conflicts because many
institutions have been promoted as the "economic engines" of their
state. However, many state legislators do not fully comprehend the
intricacies of the research enterprise. She concluded by emphasizing her
pleasure that associations are dealing with this and that guidance from
the federal government is needed to help universities proceed.

##### Lita Nelsen, M.S., M.B.A., Massachusetts Institute of Technology (MIT)

Ms. Nelsen commented from the perspective of an institution that
conducts no clinical research, but is active in technology transfer
activities. With this in mind, Ms. Nelsen asserted that clinical
research versus other types of research should have different rules.
Since many institutions such as MIT handle a massive caseload, it is
important that oversight use simple, but strict, rules on COI. She
denounced the idea of weighing conflict of interest issues on a
case-by-case basis because exceptions set precedents, and because it is
impossible to manage large numbers of cases by oversight committees and
still have these committees do their oversight with any degree of
thoroughness.

Ms. Nelsen also strongly advocated that technology transfer offices
should remain part of the academic process. She said that technology
transfer is a byproduct of the academic mission and that it should be
integrated within the academic process so that conflict of interest
decisions are made primarily with the academic mission in mind. There
are very positive benefits in addition to technology development from
technology transfer; it allows investigators to see their research used
for practical purposes, and teaches students to foresee practical
applications. Ms. Nelsen concluded by emphasizing that the implications
of separating technology transfer from the academic environment could
cause more problems than it solves by making the technology transfer
function an "outside, money-making function" that is adversarial to COI
rules rather than proponents and enforcers. (She noted that her staff is
not on any sort of bonus or commission system and sees itself as part of
the university research process rather than a separate business.) She
concluded by thanking the AAMC for their clear firm guidelines, even if
she disagreed with some of them.

##### Savio Woo, Ph.D., Mount Sinai School of Medicine

Dr. Woo opened his presentation with an anecdote of a tragic gene
transfer clinical trial in 1999 that led to much negative publicity,
while he was serving as president of the ASGT. He said this traumatic
experience has given him strong opinions on financial conflict of
interest issues. Three years ago, the ASGT adopted a "just say no"
policy---that is, society members who own stock in a company that
sponsors a trial should not have any patient contact during that trial.
This simple but rigorous policy demonstrates the intent that most
investigators try to do the right thing. But is it sufficient to simply
try to do things right from the investigator's and institution's
perspectives, or should the focus also be on earning and winning back
the public trust? Dr. Woo urged the participants to keep the public and
academic community in mind when developing policy.

The topic of equity is a serious issue, and Dr. Woo reiterated the ASGT
policy on equity. Royalties have a different connotation, however, since
the product must have undergone numerous clinical trials, been subjected
to rigorous FDA reviews, and licensed for sale. The influence that a
single investigator or institution can exert on a product's ultimate
success is rather limited. Dr. Woo described the most potentially
corruptive situation as occurring when an investigator conducting
clinical trials also has equity in non-publicly traded biotechnology
companies that sponsor the trial. When an investigator announces the
successful completion of an early phase single-site clinical trial,
equity prices can escalate significantly without a product.

Dr. Woo then addressed some of the case studies that were presented
earlier. In the case of Dr. Toe, he said the situation is fine if
nothing adverse happens to a patient. However, a misdiagnosis can lead
to widespread publicity. Moreover, the press may present the facts in a
way that implicates conflict of interest when an investigator has a
financial stake in the product. This will be viewed negatively by the
public and can lead to escalating negative publicity. In the case of Dr.
Oak, the situation as presented is full of conflicts and that any
adverse event will lead to not one, but a series of news articles that
question the roles of the investigators and the academic institution.
Therefore, if the goal is to win back the public trust, academic medical
institutions must not consider the investigator's and institution's
conflicts of interest in isolation, but also view the impact of public
perception.

# 

# Participant Discussion

Several questions were directed to Dr. Woo. One participant asked
whether a clinical trial should be conducted at an institution if the
institution has equity in that trial. Dr. Woo responded that the
institution has to make that decision, considering a number of factors,
including the impact of potential adverse effects on the institution and
the academic medical community. Another participant asked Dr. Woo his
opinion on the case study where a PI could not participate in the NIH
research. Dr. Woo explained that the investigator actually has two
options, either to divest or not participate. He added that, in general,
the investigator should not put his/her personal interests ahead of the
institution's and more importantly, the patients who volunteer to
participate in the trial. Another participant said this response would
be appropriate for clinical research, but not basic research, since many
inventions stem from an investigator's long history with a research
study. Therefore, telling an investigator he cannot accept NIH funding
or work in his given field is a strong message that could potentially
hinder technology transfer activities. Dr. Woo indicated that the ASGT
policy is indeed applicable in clinical trials only.

Dr. Koski of the Office for Human Research Protections (OHRP) stimulated
significant discussion on the "rebuttable presumption" provision. Dr.
Koski expressed concern that some provisions in Dr. Gotterer's case
studies seemed to be inconsistent with the "rebuttable presumption"
against doing research when conflicts are identified. Dr. Koski posited
that if compelling circumstances allow the vast majority of human
research to go forward in the presence of conflicts, it will undermine
the credibility of the public in these efforts, will be of little value,
and will be destructive. He asserted that the "rebuttable presumption"
should mean that the vast majority of cases would not go forward. Dr.
Koski also commended the AAMC for its stated intention to begin auditing
Academic Medical Centers to determine the level of self-imposed
compliance with the AAMC guidelines. He suggested that without a
demonstration of compliance, in the near rather than extended term,
government regulation might ensue.

Several participants responded to Dr. Koski's discussion. Dr. Gotterer
stated that the case studies simply provide an overview of the
situation, not a precise response. In addition, many projects that are
approved with disclosure are actually low-risk situations. Dr. Maziar
noted that it is important to communicate clearly that a situation was
"managed" and not just tolerated. Another participant claimed there are
legitimate and compelling cases, especially in the early stages of
clinical testing when only one researcher can do the work safely and
effectively because the technology is too new. One participant suggested
that the group should marshal its efforts to inform the public that
while a high standard relates to conflicts of interest, the problem is
not insurmountable.

Participants turned next to strategies for assessing risk. Institutions
need to look at risks when setting the bar for what is an acceptable
compelling situation. If risk is considered minimal, a committee might
accept a compelling argument; if the risk is large, the committee might
not, but it must have criteria on which to base that judgment. Other
participants sought to broaden the discussion of risk, suggesting that
health policy studies, for instance, may have minimal individual risk
but major implications for public policy.

The issue of intellectual property rights for graduate and postdoctoral
students was also raised. For example, in some cases, a company may want
to support a student's work and retain the intellectual property rights.
Institutions must consider issues such as "intellectual capital" and
work to preserve this. Other institutions consider whether students are
involved when weighing conflict of interest issues. However, students
tend to take their concerns to the Academic Freedom Committee rather
than other committees.

Participants also discussed the advantages and disadvantages of public
involvement in the conflict of interest review process. The majority of
respondents felt public representatives were extremely useful in these
discussions, and their institutions either currently involve the public
or plan to integrate them in the future. Many provided anecdotal
evidence and emphasized that institutions need the public perspective,
especially in developing language for informed consent documents. Others
expressed reservations, however, about involving the public before the
conflict of interest process was fully implemented and working well.

Finally, the ethics of weighing basic research differently from clinical
research was discussed. One participant said the standard of trust
should be uniform for all, and objectivity is important. Guidance
specific to clinical research is needed but does not imply that basic
research scientists do not have to be held to the same standard. Some
emphasized that while such distinctions are important, clinical research
generally attracts a great deal more public and congressional attention
if a patient is harmed in the course of research.

# Institutional Conflicts of Interest

##### Joseph Martin, M.D., Ph.D., Harvard Medical School

Dr. Martin provided an overview of the AAMC Task Force Report on
Institutional Conflicts of Interest in Research. The three councils of
the AAMC---which represent teaching hospitals, medical school deans, and
professional societies---unanimously approved the guidelines this task
force developed. Dr. Martin discussed the AAMC framework for assessing
institutional conflicts, which essentially states that an institution
may have a conflict of interest in research involving human subjects
whenever the financial interests of the institution appear to affect
institutional processes for conducting, reviewing, and overseeing such
research.

Dr. Martin went on to discuss some of the key points of the framework.
He noted that institutions should ensure that administrative
responsibilities related to human subjects research are separated from
investment management and technology licensing activities. The
guidelines also state that an institutional official's financial
interests may at times be in conflict with his or her position of
authority. At these times, options include being recused from official
responsibilities, managing the conflict, or not performing the research
at all. Ultimately, there should be a "culture of conscience" at the
institution whereby senior officials lead by example and rigorously
enforce COI policies.

Dr. Martin also discussed a number of circumstances that may create or
appear to create an institutional COI and thus require intense scrutiny.
Generally, these situations may occur when the institution or a
responsible official receives royalties or has a significant role or
ownership interest in a company. Officials that engage in major
purchases or managing and soliciting gifts may also have a financial
relationship that warrants close scrutiny.

Dr. Martin outlined the AAMC guidelines for the specific organizational
structure of institutional COI reporting and review processes. Specific
recommendations for IRB members include reporting certain financial
interests annually and adhering to federal policies governing recusal
from protocol review, when necessary. Overall, the AAMC urged that
disclosure to the IRB of record, to research subjects, and in
publications, should be *required* whenever the institution holds a
financial interest that could *reasonably* present a conflict to
research involving human subjects.

Dr. Martin also reported on an AAMC-AAU survey, which sampled the
opinions of seventy people over the past 9 months. He presented the
following seven recommendations:

1.  Use an open, informed, transparent, and timely process to prevent
    COI and other threats to academic independence.

2.  Make flexible arrangements to accommodate certain research
    collaborations with industry; however, each approach should be
    considered experimental and subject to periodic scrutiny.

3.  For faculty who wish to found or play an active role in a company,
    increased latitude might be best obtained through part-time
    appointments or leaves of absence.

4.  Adopt very specific working definitions of allowable activity under
    basic research, clinical research, and research on devices.

5.  Adopt the same standards for both devices and drugs by precluding
    the physician or inventor from evaluating the device or compound.
    However, in special cases, the inventor may be allowed, under
    objective supervision, to perform *initial* clinical use of a
    device.

6.  Apply the same standard for commercially sponsored research and
    government-funded research.

7.  Adopt the AAMC framework for *deciding* whether a conflict of
    interest exists; if one arises, manage the conflict by a separate,
    objective party.

Panel members echoed these sentiments, agreeing that one overarching
theme is absolute transparency and allowing patients to make informed
decisions. They also emphasized that maintaining public image is most
important and that decisions to commercialize should be driven by public
good, not institutional or individual good.

##### Faye Austin, Ph.D., Dana-Farber Cancer Institute

Dr. Austin noted that Dana-Farber Cancer Institute is a teaching
hospital of Harvard Medical School, and as such, its investigators are
Harvard faculty and must adhere to the COI rules of both Harvard Medical
School and Dana-Farber. She described how the culture of her institution
changed in the wake of a fatal overdose seven years ago and emphasized
the importance of a "culture of conscience." Even though financial
arrangements may not have been a factor in some of the more recent
tragic episodes at other institutions, the press may still frame it that
way. Therefore, her institution has tried very hard to learn from those
unfortunate circumstances by continually assessing their systems when
others' are criticized to determine if Dana-Farber has any systems or
policy gaps, and if so, how to remedy them.

While COI policies for individual investigators are very clear at
Dana-Farber, she acknowledged the complexities of trying to develop
reasonable institutional COI policies. Dr. Austin explained that
Dana-Farber conducts many early stage clinical trials. Technologies
owned by Dana-Farber could be licensed to companies that, in some cases,
would want to sponsor early phase clinical trials of these technologies
at the place with the most experience with it. She said it would be
difficult not to be the performance site for a clinical trial solely
because of institutional financial interest. For instance, if their
institution has the expertise for a technology, it is probably the
safest environment for the patients to participate in the clinical
trial. Thus, it will be very important for institutions to examine how
they balance risks, public perception, and patient safety. Dr. Austin
stressed that for science to move forward, complex technologies must be
given a chance to be tested in the environment where they have been
developed, when warranted, to allow for the best chance of success for
the technology as well as the best and safest patient outcome. Financial
conflicts must be disclosed to all involved parties and must be managed
in a meaningful way.

##### Robert P. Kelch, M.D., University of Iowa College of Medicine

Dr. Kelch commented that his work on the AAMC's conflict of interest
task forces was educational and has made his job easier. He noted that
the AAMC report contains wonderful guidelines for managing complex
institutions but emphasized that these guidelines are not prescriptive.
Dr. Kelch also underscored the difficulties medical schools face in
achieving their missions while managing the additional challenge of
developing ideas in an entrepreneurial manner. He suggested that the
academic community balance the societal good of commercializing research
discoveries with business aspects. This approach will help medical
schools stay true to their "core missions" of creating and sharing
knowledge.

##### Cornelius Sullivan, Ph.D., University of Southern California

Dr. Sullivan summarized some of the questions and major observations
that arose from an AAU workshop on institutional COI in May 2002. Dr.
Sullivan said that one of the overall themes was that participants did
not want to build a system that is impossible to administer. They also
recommended separate procedures for reviewing personal, financial, and
institutional COI. It is also important to develop guiding principles
and to establish a code of conduct that meshes with the campus conduct
principles. Recognizing that one size does not fit all, the workgroup
also recommended the use of risk-based response. The group also
suggested local control of institutional COI management that does not
preclude public comment, as well as reliable, cross-linked information
technology systems.

Dr. Sullivan said the workshop participants responded to 13 key
questions that dealt with how to grapple with this formidable task. To
facilitate risk-based analysis, they also developed a graph depicting a
non-linear relationship with potential for conflict correlated to the
degree of scrutiny warranted. The risk factors are additive---the more
factors, the more scrutiny. At low levels of risk, certain activities
are acceptable; at higher levels of risk, more resources are devoted to
reviewing the situation.

Dr. Sullivan concluded by complimenting the AAU, AAMC, and COGR for
their work on this topic, and for not reinventing the wheel. He said it
was gratifying to be part of an academic research enterprise and
emphasized that when institutional leadership is on board, everything
falls into place.

***Carl Gulbrandsen, Ph.D., J.D., Wisconsin Alumni Research Foundation
(WARF)***

Mr. Gulbrandsen discussed WARF as an alternative method for managing
institutional conflicts of interest. WARF is the university's patent
management organization. He said that the University of
Wisconsin-Madison does not require assignment of intellectual property
as a condition of employment unless the federal government or private
industry funded the invention. This increases the potential for personal
COI but decreases the potential for institutional COI.

In a brief history on WARF, Mr. Gulbrandsen explained that it was
established in 1925 by Professor Harry Steenbock to commercialize his
discovery that UV radiation produces vitamin D in food and prevents
rickets. WARF is a nonprofit foundation that supports research at the
university, protects technology, and licenses it to industry. It has an
18-member Board of Trustees, all alumni, which is self-perpetuating. The
only university employee on the board is the Chancellor. The foundation
has sole discretion regarding what will be patented and licensed. It
also gives an annual grant to the university, but allows the university
to determine how the funds will be used. WARF also consults daily with
university personnel regarding grant-making and intellectual property
policy.

Mr. Gulbrandsen then outlined the separation of functions between WARF
and the university. He explained that the university focuses on its
roles as educator, grant recipient, and recipient of research materials,
but does not take title in intellectual property. By contrast, WARF can
hold title to intellectual property, manage patent and license
activities, provide research materials, and have stock in faculty
start-up companies. Mr. Gulbrandsen said the advantage of this structure
is that the university does not have a direct commercial interest in the
research activities, and researchers at the university are not employed
by WARF. However, the university still assesses and manages COI issues
and benefits from WARF grants.

# Participant Discussion

Participants talked briefly about Mr. Gulbrandsen's presentation on
WARF, and whether or not it solves the problem of institutional
conflict. The AAMC documents also were discussed. Many participants felt
that they were excellent and a good tool for planning and assessment.
Others questioned to what extent the AAMC was promoting or discouraging
commercialization of technologies. Dr. Martin said that he is personally
in favor of Bayh-Dole, but the universities vary greatly in the extent
of their technology transfer activities. He emphasized that it is
important to sustain interest in these activities while managing them in
a realistic way.

Mr. Roumel from the NIH Office of Technology Transfer (OTT) informed the
audience that NIH has a new, Web-based training module to educate
scientists about technology transfer and related COI issues. It is
located at:
[http://tttraining.od.nih.gov](http://tttraining.od.nih.gov/) and can be
viewed by the public. In addition, NIH has internal COI policies related
to technology transfer that will be posted on the OTT public Web site
([http://ott.od.nih.gov](http://ott.od.nih.gov/)) under "Current
Issues." While these policies deal with intramural research and federal
regulations, they may still be helpful to the academic community. In
response to an earlier suggestion that the AAMC and AAU educate the
media about financial interest issues, Mr. Roumel said that, like the
Centers for Disease Control and Prevention (CDC), the NIH has
Knight-Ridder fellowships to educate members of the media about
research. This may be a model for universities and associations that
want to conduct similar outreach efforts.

A representative from the Center for Science in the Public Interest
asked whether disclosure to research subjects and the public is simply a
management strategy, or whether it is done in good faith. Dr. Austin
responded that disclosure is a minimum requirement at her institution.
However, IRBs have discretion about what kind of information to disclose
to patients. Dr. Austin stressed the importance of providing information
in the appropriate context and to not overwhelm patients with
information. Dr. Kelch echoed these sentiments, saying there must be a
balance. It may seem paternalistic, but too much information can be
harmful as well.

# Where Do We Go from Here?

Dr. Baldwin summarized the day's discussions by suggesting a slogan for
the workshop: "Public Funds, Public Trust, and Public Benefit." She said
the meeting was valuable, particularly the discussion on institutional
COI. She then outlined issues that need to be addressed more fully. For
instance, very little discussion focused on involving students in COI
issues; we cannot wait until students are full-fledged investigators to
educate them about these issues. We also need more data and cannot rely
solely on anecdotal evidence. She called for more systematic data on the
volume and type of COI issues and how they are being resolved. In
addition, little discussion addressed auditing and sanctions once an
infraction has occurred.

Next steps will involve institutionalizing how the research and academic
community can tap into shared experiences. She asked participants to
provide suggestions on how to do this in the best way possible. However,
she expressed caution about using listservs for this purpose and
suggested that more structure may be needed. Dr. Baldwin concluded by
thanking the workshop participants and fellow sponsors for their
participation.

Dr. Korn of the AAMC added that the meeting was wonderful and thanked
Dr. Baldwin and colleagues. He reiterated that the treatment of
conflicts of interest has a lot to do with institutional culture and
requested that federal agencies limit their involvement to allow
institutions time to work these issues out internally.

# References 

1\. General Accounting Office (GAO), *Biomedical Research: HHS
Directions Needed to Address Financial Conflict of Interest,* November
2001.

2\. National Institutes of Health (NIH) Office of Extramural Research,
*Financial Conflict of Interest: Objectivity in Research,* July 18,
2002. \[http://grants1.nih.gov/grants/policy/coi/nih_review.htm\].

3\. Association of American Universities, *Task Force on Research
Accountability. Report on Individual and Institutional Financial
Conflict of Interest*, October 2001.

4\. Association of American Medical Colleges, *Task Force on Financial
Conflicts of Interest in Clinical Research. Protecting Subjects,
Preserving Trust, Promoting Progress II -- Principles and
Recommendations for Oversight of an Institution's Financial Interests in
Human Subjects*

*Research,* October 2002.

5\. Association of American Medical Colleges, *Task Force on Financial
Conflicts of Interest in Clinical Research. Protecting Subjects,
Preserving Trust, Promoting Progress -- Policy and Guidelines for the
Oversight of Individual Financial Interests in Human Subjects Research*,
December 2001.