in this issue:

915 15th Street, NW Suite 400 Washington, DC 20005 Phone: (202) 783-1112 Fax: (202) 783-1113 www.aahrpp.org accredit@aahrpp.org

• list of accredited organizations grows, 3

• HRPP Innovations, 4

• AAHRPP Answers, 5

Strengthening the clinical research enterpriseAccredited teaching hospitals respond

Spring 2005, Vol. 2, No. 1

AAHRPPAAHRPPAdvanceadvancing human protection in research.

continued on Page 6 ...

In this article, three accredited teaching hospitals respond to questions about the value of accreditation in their unique settings, with an introduction by David Korn, M.D., Senior Vice President, Division of Biomedical and Health Sciences Research, Association of American Medical Colleges (AAMC).

A s a result of both the remarkable pace of biomedical research and the doubling of the NIH budget, there is

growing impatience with the rate at which the heavily publicized scientifi c fruits of this unparalleled public investment are being translated into tangible public benefi ts: diagnostics, therapeutics, and preventives that will mitigate the prevalence and severity of human disease.

To accelerate the desired translation will require three things. First, unfl agging investment in biomedical research, because in spite of the prodigious advancements of recent decades, we still lack the comprehensive and detailed understanding of the mechanisms of complex diseases required for predicting the most effective and safe therapeutic and preventive strategies.

Second, enhancement of the nation’s clinical research workforce and especially of physician clinical investigators, who are uniquely capable of building and traversing the bridges that link scientifi c discovery with clinical medicine. More effective institutional systems of support, greater educational exposure, and attractive pathways for initiating and sustaining productive clinical research careers must all be in place to encourage medical students and residents to choose to become clinical investigators.

Third, strengthening of our nation’s clinical research capability, not only within

academic medical centers but also in our communities in order to be able to test more rapidly in appropriate populations new interventions for safety and effi cacy, as well as medical and cost effectiveness. To create such an expanded clinical research enterprise poses large challenges, among them establishing the necessary organizational and administrative systems,

fi nancing and implementing the requisite electronic information networks, and enlisting practicing physicians for education and credentialing in clinical research.

Critical to the success of this bold endeavor is ensuring that the national clinical research enterprise is committed from its inception to the highest ethical standards of human research experimentation. Why is this so critical? Because human experimentation in our society

depends on the voluntary participation of research subjects, and such a system of voluntarism can only work when there is confi dence that at every level of the research enterprise, protecting the rights and welfare of human research participants is the highest priority.

AAMC believes that voluntary, peer-driven, educationally focused accreditation of human research protection programs is the most effective tool available to promote adoption of uniformly high ethical standards of human research experimentation, to inculcate an institutional commitment to continuous quality improvement, and to spur organizations to rise beyond a

David Korn, M.D.

AAHRPPAdvance

2 3

Spring 2005

Executive Director

&

Human Research Protection Accreditation: Three Years Later

From the

News notes

Marjorie A. Speers, Ph.D.

A AHRPP’s fundamental premise is that ensuring protection of research participants is an institutional responsibility that will best be accomplished

through voluntary accreditation. The goal is nothing less than effecting institutional change, moving from a culture of compliance to one of conscience and responsibility.

In an environment of grave concern about human research protections, AAHRPP launched its accreditation program on Feb. 26, 2002. Suspensions of prestigious university research programs had occurred, and talk on Capitol Hill was running toward a legislative response, perhaps more stringent than ever before. Many organizations made commitments to seek accreditation early on and confi rmed those commitments; however, the majority discovered that more time was needed to prepare and apply.

Organizations reported a lack of readiness to apply for accreditation. They had to take numerous corrective actions internally, such as developing and strengthening policies and procedures; setting up additional institutional review boards; hiring staff, particularly in the compliance area; implementing educational programs for investigators, IRB members and staff, and organizational offi cials; and establishing internal tracking or auditing activities.

In the past three years, other factors affected accreditation of human research protection programs. Unprecedented cuts in state budgets for colleges and universities directly affected discretionary spending, as did poor returns on investments. Organizations had to comply with new privacy and medical information security regulations in the Health Insurance Portability and Accountability Act. These regulations became effective in April 2003; becoming compliant proved to be a large and costly burden for affected institutions.

And though it was a positive step that recognized the need for greater research infrastructure support, the NIH Human Subjects Research Enhancement Program was

rolled out. In the past two years, universities have twice competed for these grant awards and used them to support key activities that will put them in good form when they apply for accreditation.

Perhaps most disconcerting is a recent trend in which institutional offi cials are questioning accreditation’s necessity in demonstrating public accountability. No horrifi c research problems have occurred in the past three-

and-a-half years, they argue, and consequently no research programs have been suspended, giving institutional offi cials a false sense of security.

Nonetheless, despite these numerous obstacles, AAHRPP has moved forward with its accreditation program and, to date, has announced accreditation of 18 organizations of various types. Over 200 organizations are in the accreditation pipeline.

A number of factors contributed to this success. In 2004, AAHRPP introduced tools to help organizations prepare for accreditation, recognizing the need for education and assistance in a process that, for the majority, is truly novel. These tools include orientation workshops, individualized consultations, a streamlined application process, an enhanced evaluation instrument that removed uncertainties in standards interpretation, and educational materials in the form of Tip Sheets and AAHRPP Advance, this quarterly newsletter.

AAHRPP also launched the preliminary applicant option, which allows organizations to receive written feedback on their self-assessment and make changes prior to submitting a formal accreditation application.

In keeping with its educational mission, AAHRPP will host its fi rst annual accreditation conference in 2005. The conference will highlight common challenges and help organizations prepare for accreditation, with the express purpose of reducing application delay times.

Government support for accreditation is also evident. The Offi ce for Human Research Protections (OHRP) and

the Food and Drug Administration (FDA) plan to launch a single, online registration system for all IRBs that review research conducted or supported by DHHS or for clinical investigations regulated by FDA. Notably, OHRP and FDA propose that the registration system capture information on accreditation status: whether the IRB is part of an accredited organization and, if so, the accreditation date and the accrediting body that conferred the status.

And industry support for accreditation is emerging. The Pharmaceutical Research and Manufacturers of America (PhRMA) Science and Regulatory Executive Committee reviewed the matter of accreditation recently and adopted the position that it supports the movement toward the voluntary accreditation of human research protection programs.

Reports from accredited organizations are that industry sponsors have pre-approved organizations for research studies based on their AAHRPP accreditation status and that sponsors have canceled routine site inspections when they learned that an organization is accredited.

Finally, AAHRPP has a growing reputation in the research community for offering a high-quality accreditation program. We are particularly known for the quality of our site visitors, a focus on outcomes rather than documentation, and our educational approach. The overall image of the program is strong—AAHRPP adds value to organizations’ human research protection programs. §

“The Organization and Management of the Research Enterprise: Vice Presidents for Research,” a report from the Association of Academic Health Centers, highlights a trend to consolidate research administration at academic health centers through the creation of vice presidents of research positions. To order, visit http://shop.store.yahoo.com/ahcnetpubs/orandmaofree.html.

A nationwide survey by the Center for Information and Study on Clinical Research Participation and Opinion Dynamics Corporation show that two-thirds of respondents think clinical research studies are safe for those who participate. More than half of respondents would have greater trust in clinical research information if results were made available on a public Web site or registry. Detailed survey results are available at www.ciscrp.org.

List of Accredited Organizations GrowsOrganizations of diverse types continue to achieve AAHRPP accreditation. Hospitals constituted the December announcement of accredited organizations, which brought the total number to 18.

AAHRPP’s Council on Accreditation meets quarterly, with its next meeting scheduled for early March. Since October 2004, Full AAHRPP Accreditation has been awarded to these organizations:

• Iowa Health-Des Moines, Des Moines, Iowa

• Massachusetts General Hospital and Brigham & Women’s Hospital as part of Partners Healthcare System, Boston, Mass.

• Saint Francis Hospital and Medical Center, Hartford, Conn.

• Vanderbilt University, Nashville, Tenn.

See the list of accredited organizations on the Web site at www.aahrpp.org.

‘‘

‘‘

In 2004, AAHRPP

introduced tools to help

organizations prepare for

accreditation, recognizing the need for

education and assistance

in a process that, for the majority, is truly novel.

AAHRPPAdvance

4 5

Spring 2005

HRPP Noncompliance Reporting Policy at Iowa Health-Des Moines

Academic/Industry Interactions at Partners HealthCare System

AnswersAAHRPP

The accreditable entityAs part of its educational mission, AAHRPP periodically disseminates information on innovations encountered in accredited organizations.

Innovations

Iowa Health-Des Moines

The identifi cation and reporting of noncompliance represents a critical component of a high-quality human research protection program.

Iowa Health-Des Moines (awarded Full AAHRPP Accreditation in December) has a well-designed policy and procedure for responding to concerns about non-compliance. The defi nition and spectrum of noncompliance are stated explicitly, and who can make such reports is clearly articulated:

“Reports of noncompliance in human subjects research may come from many sources including, but not limited to, an investigator (as a self-report); a study monitor, auditor or sponsor; a research subject; or a person not directly involved with the research.” The policy goes on to list which organizational offi cials would receive such reports for the Iowa Health-Des Moines IRB and the Des Moines City Wide IRB, which were both included in the accreditation review.

Further, the policy and procedure lay out how concerns will be responded to and addressed under these additional sections: Responding to concerns; Evaluation; Notifi cations; Protection for whistleblowers; and Actions that the IRB may take in responding to concerns or allegations of noncompliance.

The policy is notable for its wide breadth, that is, concerns can be reported to a range of individuals at high levels; explicit protection from retaliation is provided for those making reports; and transparent direction is given about what will occur when a complaint is lodged.

Robert Bienkowski, Ph.D., executive director of the Offi ce of Research at Iowa Health-Des Moines, worked with IRB leadership and institutional compliance offi cers to develop the policy and to harmonize it with other institutional compliance policies. He said that it has been successful in practice. “The policy has been tested a few times. My folks have always had my support, and I, in turn,

Partners HealthCare System

A well-developed system for handling issues that arise in the interchange with industry is in place at Partners HealthCare System in Boston. Massachusetts General Hospital and Brigham and Women’s Hospital as part of Partners HealthCare System were awarded Full AAHRPP Accreditation in December.

The Professional and Institutional Confl ict Committee (PICC) comprises Partners trustees, faculty members,

internal counsel, and, in an ex-offi cio capacity, system executives who play a role in relating to industry, such as the vice president who negotiates industry agreements, and Senior Vice President for Research and Technology Ron Newbower, Ph.D.

Newbower said the precursor to PICC was a board subcommittee formed about 25 years ago at Massachusetts General Hospital that dealt with industry issues as they related to major academic-industrial research agreements. “Some of the concerns in negotiating with industry—freedom of investigators to publish, the integrity of the academic enterprise—are the same as what we see now, but no models existed for managing them,” Newbower said.

Newbower said the nature of research constantly evolves and that PICC now sees a greater number of issues regarding clinical research and human research protections. The committee has recently dealt with issues of confi dentiality of research results and the material transfer of tissue samples. “PICC gives backbone to what offi cers need to do as we negotiate with industry,” Newbower said. The committee sets policy in terms of the “drop dead” items that must be present in contract negotiations and also reviews specifi c cases in the “gray areas” where new policy direction must be provided.

For example, when MGH’s confl ict-of-interest policies were fi rst drawn up, and even when Partners policies were developed nearly a decade ago, royalties channeled through institutional mechanisms to investigators were

continued on Page 8 ... continued on Page 8 ...

1. What entity within an organization does AAHRPP accredit?AAHRPP operates on the premise that accreditation is an organization-wide process: the responsibility to protect research participants is shared among the IRB, investigators, and the organization. Therefore, AAHRPP accredits what is known as a human research protection program (HRPP). An HRPP comprises all the activities that an organization undertakes to protect research participants. Thus, accreditation occurs at the organizational level, rather than the individual component level, such as IRBs or investigators. Any public or private, non-profi t or for-profi t entity engaged in human research and that has an HRPP is eligible for accreditation.

2. In an organization that provides medical or teaching services, does AAHRPP evaluate these functions?No. AAHRPP is interested only in the human research protection program and not ancillary activities such as patient care, service, or teaching.

3. Who defi nes the accreditable entity—AAHRPP or the organization?The decision is generally made by the organization. However, for complex organizations, the decision is often made jointly. Organizations are encouraged to contact AAHRPP to discuss the accreditable entity as soon as a decision to seek accreditation is reached. Discussing the options at an early stage can often help an organization in conducting the self-assessment and in economizing resources.

4. What is the accreditable entity that AAHRPP is looking for?Generally, the organization seeking accreditation is a functionally separate entity with a single director. Its HRPP may be composed of internal organizational units, external units that contribute to the human research protection program, or both. For example, some organizations arrange for research review by an independent review board, and some entities share resources to form a single, comprehensive human research protection program.

Some large organizations may have multiple HRPPs. For example, within a university or large hospital system, individual departments or hospitals may have their own HRPPs. On the other hand, human research protection might be centralized with the parent corporation of a hospital system, providing an HRPP for several hospitals, or a state university system that might provide an HRPP for several campuses. There is no one way to defi ne an HRPP.

More detailed information about the defi nition of accreditable entities as it applies to academic institutions, hospitals, government agencies, private corporations, independent review boards, international, and other entities is available at www.aahrpp.org.

5. Can you provide an example of an accredited entity that shares resources to make up a single program?Massachusetts General Hospital and Brigham & Women’s Hospital as part of Partners HealthCare System; this entity was accredited in December 2004. Although each hospital has its own Federalwide assurance (FWA) and IRBs are registered to each institution, since 1996 the hospitals have combined the operation and management of their respective IRBs into a single, integrated IRB system, known as the Partners IRBs (Human Research Committees). The six Partners IRBs use a common set of policies, procedures, and operations. In addition, other functions, such as confl ict-of-interest management, post-review monitoring, and management of noncompliance, are handled centrally. The integrated protection program is managed by Partners Research Management, a centralized department that provides investigators from both institutions with a variety of research-related support services.

6. What is the rationale for this broad-defi nition approach? AAHRPP’s goal is to improve participant protections as defi ned by the organization—not to change the organizational structure, but to work within it. The defi ned accreditable entity—what research is covered and what is not—must be clear to all involved in the research process, including the public and those who participate in research as subjects.

7. How does AAHRPP determine the name of the accreditable entity?AAHRPP defers to the applicant organization; the name should refl ect the entity that is being accredited. AAHRPP also recommends using a name that is descriptive of the entity or entities being accredited. §

‘‘The lesson might be that people have ‘faith’ in the

system if they have seen it work as the

policy says it should.

‘‘

—Robert Bienkowski

AAHRPPAdvance

6 7

Spring 2005

(from Page 1 ...) culture of compliance to a culture of concern and respect for human subjects. In short, accreditation can help organizations dependent on public trust to demonstrate that they are trustworthy.

Widespread participation in accreditation by medical schools, teaching hospitals, and community health care systems will directly contribute to the goal of enhancing the nation’s clinical research enterprise by inspiring confi dence in patients and other research volunteers, and by ensuring that the educational experiences of health professions students are grounded in sound ethical principles and practices. By so doing, accreditation will help to facilitate the translation of biomedical research discoveries into public benefi t.

As one of the founding members* of AAHRPP, the Association of American Medical Colleges is gratifi ed to see the nation’s most respected teaching hospitals and health care systems achieve accreditation.

Why did your hospital seek AAHRPP accreditation?

Susan L. Freeman, M.D., Senior Vice President for Medical Affairs, Saint Francis Hospital and Medical Center: Saint Francis Hospital and Medical Center (SFHMC) sought accreditation because the institution works to excel and be a leader in its human research protection program (HRPP). Institutional offi cers were aware that the process of accreditation encouraged a critical analysis of the HRPP, serving as a basis for improvement of the program. The proactive leadership of SFHMC decided to seek accreditation, even though this is a voluntary process. The institution embraced the concept of accreditation, particularly because it would lead to the standardization of the protection of human subjects across institutions. SFHMC found that this would be benefi cial not only to its patients but to all subjects involved in research. AAHRPP’s Accreditation Standards embody the values of institutions seeking to excel in their policies on human subjects protection. We were familiar with AAHRPP through our association with Public Responsibility in Medicine and Research (PRIM&R) and the Applied Research Ethics National Association (ARENA).

P. Pearl O’Rourke, M.D., Director, Human Research Affairs, Offi ce of Research Management, Partners HealthCare System (accredited entities are Massachusetts General Hospital and Brigham & Women’s Hospital as

part of Partners HealthCare System): We are fully committed to providing fi rst-rate protection for all persons who participate in our human research program. While we felt that our program for the oversight of human research was excellent, we truly believed that our program, like any program, could benefi t not only from aggressive self-assessment but also from a review by external experts. The AAHRPP program provides both. In addition, we felt that AAHRPP’s focus on the entire “research protection program” gave us the opportunity to evaluate and strengthen individual component parts as well as maintain the intricate collaboration and communication that supports the system as a whole.

It is a privilege, not a right, to conduct research with human participants—and to that end, activities that provide an opportunity for improvement are invaluable.

Shlomo Melmed, M.D., Senior Vice President, Academic Affairs, and Eifaang Li, D.V.M., M.P.H., Director of Research and Compliance, Cedars-Sinai Medical Center:Cedars-Sinai Medical Center has a long-standing commitment to rigorous protection of patients participating in clinical research. Since 2000, we have embarked upon several initiatives to further improve our human research protection program (HRPP). Core to this commitment is an institutional desire to follow the highest standards and so provide the utmost protection to research participants and thereby enhance the quality of our research.

We decided to seek AAHRPP accreditation because having an independent expert panel review our HRPP would enable us to validate

the quality of our program as well as to strengthen our continuous process improvement efforts. Additionally, because AAHRPP’s Accreditation Standards include all elements of an institutional HRPP, the accreditation process required us to bring all of the stakeholders together to conduct an intense self-assessment of our HRPP. This process created many new organizational opportunities for sharing the responsibilities and understanding the values associated with conducting research with human subjects.

For your particular hospital environment, how does accreditation add value to your mission?

Dr. Freeman: The mission of Saint Francis Care is to improve and enrich the lives of individuals and families in our region. Compassionate care, superior technology, and prevention-oriented education will combine in centers of clinical excellence. Dedication to our founding core values

will create a spiritual and healing environment. Our core values are:• Respect for the dignity of every individual • Caring, compassion, and support for patients and families

at the most critical times • A focus on health enhancement as well as patient care,

teaching, and research • A level of service that exceeds expectations • An acknowledgement of spirituality as a dimension

of well-beingAccreditation enhances each one of these values by

ensuring that the institution has met the highest standards possible. The process of accreditation has connected various departments and research staff throughout the institution, and will provide research participants with confi dence in our medical care and research programs.

Dr. O’Rourke: I think that the process of seeking and achieving accreditation has added value to the way that we conduct the activities that support our mission, as opposed to adding value to our mission directly. Investing the time and energy into the accreditation process was a visible endorsement of the importance that we assign to our HRPP. Research is a key component within the Partners system, and achieving accreditation has made clear to a variety of stakeholders—including the public—that human research protections is a clear, demonstrable priority.

Drs. Melmed and Li: Research is one of our institution’s key missions. At the most basic level, becoming accredited ensures that our HRPP is in compliance with state and federal regulations, which serves to build the public’s trust and to increase the credibility and transparency of the research program at Cedars-Sinai. Further, we believe it helps us to more readily achieve our goal of promoting excellence in cutting-edge medical care through the pursuit of research. The Accreditation Standards help to build the pathway for meeting this objective. First, the establishment of ongoing quality improvement processes ensures excellence in the processes we employ to ensure that clinical research is thoroughly reviewed and, ultimately, conducted at Cedars-Sinai with the paramount goal of protecting patient safety.

Secondly, the accreditation process promotes awareness of the critical importance of human research protection principles among all involved parties and at all levels of our organization, including faculty and physicians, nurses, research staff, administration, and our public volunteers. Above all, our patients and community are assured that we adhere to the highest values inherent in human subjects

protection, while striving to bring to our patients cutting-edge cures.

How do you think accreditation will improve the training of residents, if at all?

Dr. Freeman: The announcement of our accreditation with AAHRPP was publicized within the institution, which initiated a campaign to educate and inform residents of the importance of this accomplishment. As new residents arrive at SFHMC for training, an effort is made to educate them on the value of well-conducted research endeavors. The announcement of our accreditation was followed by a widespread mailing of a new “Pocket Guide for Human Subjects Research at Saint Francis Hospital and Medical Center” summarizing the responsibilities of investigators

conducting human research studies. The publicity surrounding accreditation has highlighted the importance of the HRPP and the commitment of SFHMC to the care and protection of its patients.

Dr. O’Rourke: Resident education takes many forms—among others, didactic sessions and observation of real-life situations. Accreditation forces the entire institution to focus on and strengthen the component pieces that make up an HRPP. Residents interact with a number of the components of an HRPP. and clearly will benefi t from being able to work with and observe people and committees that maintain the highest standards.

Accreditation has helped strengthen the entire HRPP and provide better models, education, and

mentoring for the entire system, although I’m not sure that accreditation has a specifi c focus on the residents and their training.

Drs. Melmed and Li: Often a young investigator’s fi rst exposure to the research arena occurs during medical residency. Introducing young scientists to an institutional culture that promotes respect for the dignity of research participants is an incredible educational opportunity. We think residents benefi t through enhanced education for the research community as a whole. Cedars-Sinai has established a comprehensive initial and continuing education program on human research protection principles. Through the ongoing educational efforts, we strive to enhance collaboration among physicians, nurses, residents, administrators, investigators, staff, and the IRB to create an institutional culture of respect for the dignity and welfare of individuals volunteering as research participants.

Ultimately, this kind of environment is conducive to fostering creative scholarship in residency, in which top-quality patient care is provided in a research setting, while high-quality research is conducted in a patient care setting. §

‘‘

‘‘Introducing young scientists

to an institutional culture that

promotes respect for the dignity

of research participants is an incredible educational opportunity.

*AAHRPP founding members: Association of American Medical Colleges, Association of American Universities, Consortium of Social Science Associations, Federation of American Societies for Experimental Biology, National Association of State Universities and Land-Grant Colleges, National Health Council, Public Responsibility in Medicine and Research

Susan L. Freeman, M.D.

Shlomo Melmed, M.D.

P. Pearl O’Rourke, M.D.

—Drs. Melmed and Li

AAHRPPAdvance

915 15th Street, NW, Suite 400 Washington, DC 20005

Phone: (202) 783-1112 Fax: (202) 783-1113www.aahrpp.org accredit@aahrpp.org

Non-Profi t Org.U.S. Postage

PAIDWashington, DC

Permit No. 96

AAHRPPAdvance

888

AAHRPPAdvanceAAHRPP Advance is published

quarterly by the Association for the Accreditation of Human Research

Protection Programs, Inc.® (AAHRPP®)

Executive DirectorMarjorie A. Speers, Ph.D.

EditorTodd P. Bentsen

Assistant Director, Marketing& Communications

DesignWieder Communications

PrintingFederation of American Societies

for Experimental Biology(FASEB)

www.aahrpp.org

not considered a concern, either locally or nationally. Academic royalties were considered income derived after completion of trials, completion of commercialization and external validation, and

have always had support from my superiors,” Bienkowski said.

“I have personally assured each member of my staff that I will support any action they take to protect the rights and welfare of an individual research participant or maintain the integrity of the research program, regardless of whom they

might have to confront,” Bienkowski added. “The lesson might be that people have ‘faith’ in the system if they have seen it work as the policy says it should.”

The policy is available on the Iowa Health Web site at www.ihsdesmoines.org/irb. §

Information: Robert Bienkowski, bienkors@ihs.org.

Iowa Health-Des Moines, from Page 4 ...

Partners HealthCare System, from Page 4 ...

after success in the marketplace. Royalties were so new that no examples existed of investigators’ conducting clinical research on products that were already generating royalties for them. That is no longer the case. PICC has dealt with the complex issues of handling the perception or reality of unacceptable confl icts that may now exist simply because of a legitimate inventor’s share of academic royalties, with no direct fi nancial connection to a company. And from cases adjudicated by PICC, policies for managing those confl icts have been developed.

PICC is independent of the Partners IRB and regards its ongoing deliberations in almost a legal sense: the decisions that result from meeting discussions—which are recorded in detailed minutes—are added to the body of “case law,” Newbower said, and then become the basis for responding to similar cases in the future.

The committee meets as needed, generally about every two months, and also deliberates “offl ine” for more urgent matters, Newbower said. Members of the research management team and general counsel generally frame issues in the form of memoranda, which are then vigorously debated and discussed, and then moved toward resolution.

“The deliberative atmosphere is like an IRB meeting,” Newbower said. “The members of PICC include committed trustees who are very engaged in these issues.” §

Information: Ron Newbower, rnewbower@partners.org.