The Association for the Accreditationof Human Research ProtectionPrograms (AAHRPP) is steadilyextending its reach — and its higherstandards — throughout the researchenterprise, shaping research practicesin academic institutions, independentinstitutional review boards (IRBs), con-tract research organizations (CROs),and U.S. and international medicalcenters.AAHRPP standards are now in

place in 45 organizations with 127entities — in 24 U.S. states, Canada,and South Korea. Each of these organ-izations has demonstrated that it fol-lows research requirements even morestringent than those set by the UnitedStates or the organization’s own gov-ernment. Each is setting an examplefor research institutions worldwideand, in its own way, exerting pressureon others to follow suit.A prime example is ethica Clinical

Research, a Canadian research organ-ization that recently became the firstCRO to attain AAHRPP accreditation.Janice E. Parente, Ph.D., ethica founderand President, announced the accredi-tation in January and took the oppor-tunity to call on other organizations tojoin ethica in adhering to AAHRPP’shigher standards.“We encourage our government

and organizations involved in clinicalresearch to embrace AAHRPP’s stan-

dards for accreditation and implementa transparent system of oversight,”she said. “Our industry has an excel-lent opportunity to lead the world ininstituting clinical trial regulationsand guidelines not born of tragedy,but simply out of a desire to protectthe rights and well-being of ourclinical trial participants.”Even those organizations that have

not yet committed to accreditation arefeeling its impact, in part because theresearch enterprise has evolved into acomplex, interdependent system ofindividuals and entities. In thisincreasingly collaborative environ-ment, those engaged in researchinvolving human participants mustinteract with other institutions and,therefore, must rely on one anotherfor compliance and to ensure theintegrity of the research process.Furthermore, they must accept com-mon standards and practices.As a result, as AAHRPP continues to

make inroads across the researchenterprise, entities that interact withaccredited organizations more andmore are being held to AAHRPP’shigher standards. If, for example, amultiple-site research study is overseenby an IRB of an AAHRPP-accreditedorganization, all participating sites arerequired to adhere to AAHRPP stan-dards — even those sites that have notyet attained accreditation. The same

holds true in studies managed byAAHRPP-accredited CROs.Market forces also are advancing

accreditation. As sponsors becomeaware of accreditation’s benefits —the assurances of compliance, quality,and greater protections for researchparticipants — increasingly they willselect AAHRPP-accredited researchpartners. Research participants willmake a similar choice. As they

Research Enterprise Feeling Positive Impact ofAAHRPP, Accredited OrganizationsAcademic and medical institutions, IRBs, CROs commit to higher standards

VOLUME 4 • NUMBER 1

3 BRANY — An EffectiveModel for Oversight

4 Insights into IRBs

6 HRPP Innovations—Continuous QualityImprovement

CONTINUED ON PAGE 3

SPRING 2007

The past few months have beenmarked by a series of “firsts” forAAHRPP:

� The first Department of VeteransAffairs (VA) Medical Centers to earnaccreditation since we were award-ed the $4.9 million VA contract ayear ago.

� The first contract research organiza-tion (CRO) to attain accreditation.

� The first AAHRPP-accredited entitiesin Canada, New Jersey, New York,North Dakota and, not too longago, in South Korea.

All of these are noteworthy achieve-ments. However, their significance liesnot in the fact that they are “firsts”but in that they underscore anincreased commitment to humanresearch protections — and a growingrecognition of the role accreditationplays in fulfilling that commitment.As we point out in Research

Enterprise Feeling Positive Impact ofAAHRPP, Accredited Organizations(page 1), an organization’s decisionto seek accreditation affects not justthe organization itself but the entireresearch enterprise. Each accreditationraises the bar yet another notch andgives the public yet another reason tohave confidence — and to participate— in research.Because one requirement for

accreditation is continuous qualityimprovement, this issue’s HRPPInnovations (page 6) highlights twonewly accredited organizations —Biomedical Research Alliance of NewYork (BRANY) and the Department of

Veterans Affairs, New Jersey HealthCare System (VA NJHCS) — whosequality assurance efforts were recog-nized with distinction by the Councilon Accreditation. Both programs arecomprehensive, systematic, flexible,ever-evolving, and both emphasizeeducation. We also profile BRANY(A Unique Model for Oversight,Protection, page 3) for its singularapproach to providing IRB services.In Insights into IRBs (page 4),

J. Andrew Bertolatus, M.D., addressessome of the issues surroundinginformed consent and the heightenedsensitivity that is required for researchinvolving vulnerable individuals, suchas organ recipients. Dr. Bertolatus isone of five new members of ourCouncil on Accreditation. We welcomethem (News & Notes, page 8), alongwith four new appointees to our Boardof Directors, and we thank all of themfor agreeing to share their time andtalents with us.

On page 7, we recognize twoAAHRPP-accredited organizations —Children’s Hospital Boston andWashington University in St. Louis —that recently were selected as recipi-ents of the prestigious 2006 Awardfor Excellence in Human ResearchProtection. We are gratified, butcertainly not surprised, that AAHRPP-

accredited entities took two of thethree top honors for “best practices.”Congratulations!Finally, I’d like to acknowledge the

dedication and extraordinary effort ofall of you who have earned accredita-tion or who are in the middle of theaccreditation process. We know thatobtaining accreditation isn’t easy, butthat’s true of anything worthwhile.Time and again, organizations thatcomplete the accreditation process tellus that they are better for it — that theendeavor has resulted in system-wideimprovements that enhance

the safety of participants and ensurethe integrity of research.I thank all of you who have joined

AAHRPP in committing to the highestprinciples and practices for research,and I look forward to continuing towork together to strengthen protec-tions for participants and to advanceethical research.

2 AAHRPP ADVANCE

Fulfilling Our Commitmentto Participants and Research

MAR JOR I E A . S P E ER S , Ph.D.

“Each accreditation raises the bar yet another notch and

gives the public yet another reason to have confidence —

and to participate — in research.”

AAHRPP ADVANCE 3

become more familiar with accredita-tion, it will influence their decisions,especially if participants have anopportunity to choose from more thanone research organization conductinga trial. Given the option, most wouldprefer an organization that has vol-untarily committed to increased safe-guards for research participants. With

an estimated 400 more organizationsworking on accreditation, those thathave yet to consider accreditation runthe risk of being perceived either asless concerned about human researchprotections or operating programsthat cannot meet AAHRPP’s more rig-orous requirements.All of this is good news for research

participants and for the research

enterprise, both of which benefitwhen research practices are safe,ethical, and of the highest quality.Such practices not only reduce riskbut also result in more efficientprocesses and more reliable data. Inaddition, they help restore and main-tain the public confidence that is criti-cal to long-term support for research.

Research Enterprise Feeling Positive Impact of AAHRPP, Accredited Organizations

FROM PAGE 1

In 1998, six prominent New York insti-tutions — the Council on BiomedicalResearch and Development at the NewYork Academy of Medicine, MontefioreMedical Center, Mount Sinai School ofMedicine, NYU Medical Center, NorthShore-Long Island Jewish HealthSystem, and Saint Vincent CatholicMedical Centers — joined forces tocreate the nation’s first combined IRBowned and operated by medical cen-ters. In the years since then, BRANYhas emerged as the world’s largestalliance of research sites, with morethan 200 affiliated centers. It alsoremains the only IRB of its kind.According to Eileen Hilton, M.D.,

BRANY President and CEO, the IRBis unique not just for its ownershipmodel and structure but also for theexperience, efficiency, and qualitythat it provides.

“We took the chairs, vice chairs, andmembers of the collaborating institu-tions and formed a single IRB thatdraws on the expertise of individualsfrommany organizations,” sheexplains. “They bring an incredibledepth of knowledge to the table — ofthe review process, their own organiza-tions and communities, and the localresearch context.”Dr. Hilton cites the convenience and

efficiency of dealing with one IRB, onecontract, and one budget, as well asthe advantages of objective review byexternal IRB members who are freefrom the prejudices and politics thatcan unintentionally influence discus-sions of internal IRBs. She points toBRANY’s rigorous quality assuranceprogram (see Continuous QualityImprovement at BRANY, VA NJHCS,page 6) and accreditation as indicators

of the IRB’s unwavering commitmentto compliance and human researchprotections. She also emphasizes thatBRANY supports the work of theinternal IRBs by freeing staff time tofocus efforts where they can be mosteffective.“Typically, the studies that present

the greatest risk to institutional IRBsare those initiated by individual inves-tigators, some of whommay not havethe necessary experience to make surethe appropriate controls are in place,”Dr. Hilton says. “By outsourcing thereview of industry-sponsored protocols,the institutional IRB can concentrateits resources where they’re needed mostand, in the process, providethe greatest protections for researchparticipants.”

A Unique Model for Oversight, Protection

For nearly a decade, the Biomedical Research Alliance of New

York (BRANY) has served as a successful, unique IRB model,

providing comprehensive, centralized administration and IRB

services for research sponsors and institutions. BRANY is profiled here, in part, because of interest

in alternative IRB models, as evidenced by the recent 2006 National Conference on Alternative IRB

Models: Optimizing Human Subject Protection.

4 AAHRPP ADVANCE

J . ANDREW BERTOLATUS, M.D.

Insights into IRBsOne purpose of the consent process and the regulatory requirement to seek

informed consent is to ensure that any decision to participate in research

receives the consideration it deserves. Part of the consent process is

straightforward: making sure the participant understands how the study

will be conducted, the risks it entails, and its potential benefits. More

complicated — and more difficult to assess — are the emotional issues

that can affect the consent decision.

In the questions and answers below, J. Andrew Bertolatus, M.D., discusses

the challenges of the consent process, particularly with participants who,

because of their medical conditions, might feel that their options are lim-

ited. A transplant nephrologist, Dr. Bertolatus is an associate professor of

internal medicine and co-chair of the biomedical IRB at the University of

Iowa. He is a member of the AAHRPP Council on Accreditation.

Q.What are some of the consentissues that you face duringtransplant research?

A.One of the biggest challenges isthat decisions often must be madevery quickly, especially if we’re dealingwith an organ from a deceased donor.In that type of transplant, the organtypically comes in at the last minute,from a donor who has serious braininjuries and is not going to recover.We would like to have the organ andthe recipient get to the operating roomas quickly as possible — for example,within 12 to 24 hours of the removalof the kidney from the donor. So muchis happening, clinically, and on top ofthat we’re adding a research compo-nent that involves obtaining informedconsent. We don’t have the option ofapproaching the prospective researchparticipant under calm, stable circum-stances. We can’t solve this problemby speaking in advance to people onthe waiting list because waiting timesare so long.We also can’t speak to people aboutresearch projects underway today,because the research will probably be

completed by the time they get calledin for a transplant.The situation is further complicated

by the fact that the recipients typicallyhave waited years for a transplant.Many feel very grateful and almostobligated to participate in research.Some will even come right out andsay so. I’ve had patients tell me, “I’mgetting this chance for a better life. Ithink I owe it to people.” In someways, this situation is no differentfrom obtaining consent before anytype of surgery. There are always con-cerns about the potentially coercivenature of seeking consent in a surgicalsetting. Our IRB is very sensitive to theimplications of being asked — bysomeone who’s about to administeranesthesia or operate on you — ifyou’ll agree to participate in aresearch study.The best we can do is keep prospec-

tive participants informed, be upfrontabout the risks and the value andimportance of the research. This is notunique to the transplant situation. It’strue of any research. It’s just that thoseof us involved in transplant researchhave a heightened awareness of theseissues.

Q. Under these circumstances,how do you ensure that con-sent is given freely?

A.We do everything we can to sepa-rate the consent issue from the trans-plant procedure. We make it a point,for example, to choose someone out-side the fray of the clinical prepara-tions to explain the research studyand ask for consent. That way, therecipient might feel more comfortablesaying no. If I’m the one speaking tothe patient — especially if I get a sensethat he or she feels obligated to partic-ipate — I make it very clear that it’soptional. I’ll say something like, “Thisis research, and you don’t have to doit. You will still get the transplant, andwe will still do everything according toplan.”We’re also very aware that we’re

dealing with a somewhat vulnerablepopulation, so we’re extra careful notto place them at risk of undue influ-ence or coercion. Most transplantstudies deal with different anti-rejec-tion or immunosuppressant drugcombinations. Some use investigation-al drugs, but not all. Some use alreadymarketed drugs but in different doses

AAHRPP ADVANCE 5

or combinations. Regardless, we tryto design studies in which we knowenough so that it’s highly unlikelythat we’ll place anyone at higher risk.

Q.What is the role of the IRBin the consent process?

A.We pay particular attention to thedetails to make sure — not just thatconsent is given willingly — but alsothat participants understand what theresearch involves. We want to ensurethat the individual voluntarily andfreely participates in the research. Oneof our concerns, as investigators andIRB members, is that transplant recip-ients are able to separate the risks andmethods of the research from the risksand methods of the transplant proce-dure. For instance, all transplantpatients — regardless of whether theyare involved in a research study —must take anti-rejection drugs thatweaken their immune system andexpose them to unusual infectionsand malignancies. These are not therisks of research; they are the risks ofthe transplant procedure. The sameholds true for post-operative care: It iscomplex, even for those not involvedin research. Patients are asked tocome in for a lot of lab work as part oftheir routine care. Then, on top ofthat, a research protocol might add totheir inconvenience. It can be difficultfor them to understand which proce-dures are part of the research andwhich are part of standard care. AsIRB members, we have to appreciatethe realities of the transplant situa-tion. We rely on the investigators toeducate the participants/patients and

present the information in a waythat’s not confusing.

Q. Can you give an example of aparticularly complex consentissue?

A.One of the more difficult issuesrevolves around donor management.Consent for donation involves obtain-ing permission from amember of thedonor’s family to use the organs forgeneral research purposes if one ormore organs end up not being suitablefor transplantation. That’s fairlystraightforward. But what happenswhen a donor has been declared brain-dead, and an investigator wants to con-duct research onmaintaining theorgans until they can be removed?Essentially, you want to change the wayyou treat the donor to discover if

that could better preserve the organsfor transplantation. How do you deter-mine whether the donor is a “humansubject” (as defined in regulation) andyou need consent? These are the typesof questions that the IRB would dis-cuss at some length. It would reviewthe regulations and guidance andconsult with legal counsel. In thiscase, the regulations define humansubjects as living human beings. Sothe question becomes, “Is a brain-dead organ donor alive?” We havenever found official guidance on this,but in the state of Iowa, brain-deadorgan donors are legally dead. In theopinion of legal counsel, if the studyinvolves only the donor after the pointof declaration of brain death, the reg-ulations do not apply. Therefore, con-sent is not necessary because theresearch does not involve a humansubject.The IRB recognizes that, although

the law might be clear, family mem-bers and the community may feel dif-ferently. This, too, is considered duringthe IRB discussions — and is weighedagainst the potential benefits of theresearch.

“The best we can do is keep prospective participants

informed, be upfront about the risks and the value and

importance of the research. This is not unique to the

transplant situation. It’s true of any research.”

Successful AAHRPP ConferenceApproximately 500 individuals representing all segments of the researchenterprise turned out for the 2007 AAHRPP Conference: Quality HumanResearch Protection Programs, which was held in February in Baltimore.Conference presentations covered topics ranging from the history and

future of accreditation to the role of the institutional official to industryperspectives on accreditation. Breakout sessions were targeted for specificaudiences, with separate sessions for organizations that are already accred-ited, those who are new to the accreditation process, hospitals, foreigninstitutions, institutional officials, and behavioral and social programs.

Save the date: February 24-26, 2008The 2008 conference will be held February 24-26 in Minneapolis. Based onthis year’s attendance, interest is expected to be high. Mark your calendar,and be sure to register early.

At Biomedical Research Alliance ofNew York (BRANY) and the Depart-ment of Veterans Affairs, New JerseyHealth Care System (VA NJHCS) —both awarded full AAHRPP accredita-tion on December 14, 2006 — qualityimprovement efforts are effectivebecause they are systematic andcomprehensive yet have just theright degree of flexibility. Both organi-zations take an uncompromisingview of compliance and standardsof human research protections. Bothalso acknowledge that there’s alwaysroom for improvement — even inquality improvement processes.“Our quality improvement process

has allowed us to identify ourstrengths and weaknesses and makeour processes more efficient,” explainsRaffaella Hart, C.I.P., BRANY IRBDirector. “As a result, we’ve taken ourmonitoring program to the next level.We have streamlined the paperwork sowe can spend more time focusing onglobal issues.”Both BRANY and VA NJHCS have

developed processes that target certainelements for routine audits and othersfor periodic spot-checks. Some of thelatter are part of random, comprehen-sive reviews designed to ensure thatstandard operating procedures arefollowed in the field. Others are inresponse to questions that arise duringinspections of documents, such as IRBminutes, consent forms, and protocolapplications. Still others are promptedby specific concerns or complaints.Results are shared with the audited

parties, the IRB, various committees,and individuals throughout the organ-ization who either could benefit fromknowledge of the findings or could

provide insight into possibleimprovements.“Our process is evolving, flexible,

and inclusive,” says Orval Gautier,M.Ed., C.I.P., VA NJHCS ResearchCompliance Officer. “We’re not justchecking for individual compliance,although that certainly is important.We’re also looking for trends, for waysto continually improve the process.”In fact, Mr. Gautier says it’s com-

mon during audits for investigatorsto suggest changes that streamlineprocedures while ensuring maximumprotection for research participants.For BRANY, quality improvement is

as much about education as evalua-tion. “We look at it as a learningexperience,” says Portia Rindos, R.N.,C.C.R.C., C.C.R.A., BRANY Manager ofQuality Improvement and Auditing.“At a research site, we serve as aresource, assisting investigators inmeeting the requirements, explainingwhy certain documentation is required,sharing best practices, andmaking surethe research is of the highest quality.Once they realize we’re here to help,

investigators understand and evenappreciate the process.”Both BRANY and VA NJHCS apply

their quality improvement efforts notjust to research studies but to the work-ings of their organization as a whole.The result is a corporate culture thatvalues ongoing self-assessment andthe positive change that can occur.At VA NJHCS, “we examine every

aspect of our human research protec-tion program, starting with the infra-structure, to confirm that we consis-tently meet our obligations to everyoneinvolved, particularly research partici-pants,” Mr. Gautier says.At BRANY, “we’ve developed a self-

critical culture, one which recognizesthat in the research enterprise, changehappens every day,” Ms. Hart says.“Our quality improvement program—as well as our decision to seek accredi-tation — assures research participants,sponsors, and investigators that wekeep up with the regulations and guid-ance, that we’re constantly seeking abetter way, and that we adhere to thehighest standards and practices.”

Information: Raffaella Hart (BRANY),rhart@brany.com, 516-470-6909;Orval Gautier (VA NJHCS),orval.gautier@med.va.gov,973-676-1000, ext. 2024

6 AAHRPP ADVANCE

Continuous Quality Improvement at BRANY, VA NJHCS

AAHRPP ADVANCE 7

Scientific advances, changing demo-graphics, and the global economyhave combined to create unparalleleddemand for research involvinghuman participants. Consider thefollowing:

� In 2005, U.S. investment in health-related research totaled $111 bil-lion.1 Fully 58 percent of Americanssay that increasing funding formedical and health research isessential to the nation’s futurehealth and economic prosperity.2

� Federal support for aging researchhas more than tripled in the pasttwo decades, and private researchand development in aging-relatedhealth has reached an all timehigh.3

� The completion of the HumanGenome Project has transformedthe study of life processes andopened the door for unprecedentedresearch advances. At the sametime, it has raised serious questionsabout the ethical, legal, and socialramifications of such research.4

� Pharmaceutical companies andothers engaged in clinical trialsincreasingly are looking beyondtraditional Western markets.Turkey, for example, is emerging asa global market for clinical trials.5

In India, global clinical trials nearlyquintupled between 2001 and2005, with clinical research out-sourcing reaching $70.5 million in2005.6

As the number and scope ofresearch studies increase, so will thedemand for accountability, commonstandards, and objective assessment ofthe quality of human research protec-tion programs. In such an environ-ment, accreditation is expected to playa heightened, pivotal role in ensuringthat the rights and welfare of researchparticipants remain paramount.

1. “2005 Investment in U.S. Health Research,”Research!America

2. 2006 Research!America public polling

3. Alliance for Aging Research

4. National Human Genome ResearchInstitute

5. CenterWatch, Volume 13, Issue 7

6. CenterWatch,Volume 13, Issue 3

Trends Point to Increased Demand for Accreditation

Award forExcellence WinnersTwo AAHRPP-accredited organiza-tions — Children’s Hospital BostonandWashington University in St.Louis — are among the winners ofthe Health Improvement Institute’s2006 Award for Excellence inHuman Research Protection. Theawards recognize excellence inpromoting the well-being of peoplewho participate in research.Children’s Hospital Boston

received the highest award, theAnnual Award, for the hospital’sbest practice, “An education pro-gram designed to increaseparental knowledge aboutthe nature of medical research.”Washington University’s HumanResearch Protection Office earnedthe Award of Excellence for its bestpractice, “Merger of WashingtonUniversity’s multiple IRBs.”

Six Join List of Accredited OrganizationsThe following organizations were awarded accreditation at theDecember 14, 2006 meeting of the AAHRPP Council on Accreditation.

Full Accreditation� Biomedical Research Alliance of New York,

LLC, Great Neck, New York

� Department of Veterans Affairs, New JerseyHealth Care System, Orange, New Jersey

� ethica Clinical Research, Inc.,Montreal, Canada

� The Pennsylvania State University,University Park, Pennsylvania

Qualified Accreditation� Department of Veterans Affairs Black Hills

Health Care Center, Black Hills, South Dakota

� University of North Dakota,Grand Forks, North Dakota

Focus Conference

The Forum for Institutional ReviewBoards (IRBs)/Research EthicsBoards (REBs) in Canada and theUnited States (FOCUS) will holdits Fifth Annual InternationalConference — Public Trust andResearch in Humans — at theOttawaMarriott Hotel, Ottawa,Ontario, on May 31–June 1, 2007.The conference is held in collabora-tion with the Department of Healthand Human Services USA, HealthCanada, Canadian Institutes ofHealth Research, InteragencyAdvisory Panel on ResearchEthics, Canada’s Research-BasedPharmaceutical Companies, andthe National Council on Ethics inHuman Research. For programdetails and registration, please goto http://www.ncehr-cnerh.org/english/events/ncehr_events.php.

New AAHRPP DirectorsWe are pleased to welcome thefollowing to the AAHRPP Boardof Directors:

Elizabeth H. Cothran, M.S., C.I.P.Director, Office of Research SubjectProtectionBaylor Research Institute

Gordon R. Gray, Ph.D.Associate ProfessorDepartment of Plant SciencesUniversity of Saskatchewan

Christopher C. Houston, Esq.Director of Real Estate Developmentand General CounselRedevelopment Authority of theCounty of Cumberland

Brent Miller, Ph.D.Vice President for ResearchDirector of Federal RelationsProfessor of Family andHuman DevelopmentUtah State University

Additions to Council onAccreditation

The following individuals havebeen appointed to our Councilon Accreditation:

J. Andrew Bertolatus, M.D.Associate Professor ofInternal MedicineThe University of Iowa

Leslie I. Katzel, M.D., Ph.D.Associate Professor of MedicineUniversity of Maryland, BaltimoreChair, Research and DevelopmentCommitteeVAMaryland Health Care System

Lisa KorcuskaDirector, Office of HumanSubjects ProtectionsThe University of South Dakota

Lisa Leiden, Ph.D.Director, Office of ResearchSupport and ComplianceThe University of Texas at Austin

Peter Vasilenko, Ph.D.Director, Human ResearchProtection ProgramMichigan State University

AAHRPP ADVANCEis published quarterly by the Association forthe Accreditation of Human ResearchProtection Programs, Inc.

Executive Director:Marjorie A. Speers, Ph.D.

Editor:Elisa GallaroClifton Park, NY

Design: Levine & Associates, Inc.Washington, DC

Printing: Federation of American Societies forExperimental Biology (FASEB)

Non-Profit Org.U.S. PostageP A I D

Washington, DCPermit No. 96