Strengthening Researchers’ Role in the HRPP

One of the most significant improvements in the research enterprise is the now widespread acceptance that responsibility for protecting participants rests not just with the institutional review board (IRB) but with the organization as a whole—including its researchers.

This shift in perspective is often attributed to AAHRPP’s emphasis on comprehensive human research protection programs (HRPPs). Even organizations highly respected for their research have educated researchers and underscored their role in strengthening protections while preparing for AAHRPP accreditation.

For example, at Connecticut Children’s Medical Center (AAHRPP accredited since 2009), the accreditation process included education on research ethics, federal regulations, hospital policies and procedures, the role of investigators and the HRPP, and interacting with the IRB.

As a result, “the level of awareness and responsibility for subject protection is always in the forefront,” says Francis J. DiMario Jr., M.D., HRPP Medical Director and IRB chair at Connecticut Children’s. “Researchers feel they have a role to play and a stake in the entire process.”

Organizations cite the following benefits of increased researcher involvement:

• Better understanding of researchers’ responsibilities.
• Improved communication.
• Increased collaboration.
• Greater likelihood that research proposals will meet federal and organizational requirements and, therefore, will face fewer hurdles for approval.
• Fewer protocol deviations and incidents of noncompliance.
• Higher-quality research.
• Stronger research protections.

James Hagadorn, M.D., M.S., has seen the value of AAHRPP accreditation firsthand, both at Connecticut Children’s Medical Center and at other organizations that pursue AAHRPP accreditation. In addition to serving as a member of the Medical Center’s IRB and as Director of its Fellowship Program in Neonatal-Perinatal Medicine, Dr. Hagadorn is an AAHRPP site visitor.

“We see the teamwork that develops as a natural part of going through the accreditation process,” he says. “Ten years ago, investigators often viewed the IRB as an obstacle. Today that’s unusual―and definitely considered obsolete.”

Instead, the AAHRPP team members are “consistently impressed that all the different components of the HRPP are working toward the same goal,” Dr. Hagadorn says. “They consider it a partnership, and that’s much better for the researchers, the organization, and research participants.”

Organizations Cite Positive Changes After Completing AAHRPP Process

Organizations that complete the AAHRPP accreditation process say they see fundamental, positive changes throughout their human research protection programs (HRPPs) and across their institutions. Many of the changes, such as stronger research and standardized procedures, were expected. Others, such as a more customer-focused approach, have come as a pleasant surprise.

At first, the effect of these changes was noticeable only within a small group of organizations. But over the past decade, as AAHRPP accreditation has become the gold standard nationwide, the research enterprise as a whole has undergone a transformation.

Following are some of the most common changes noted by AAHRPP-accredited organizations:

• Shared responsibility, from the top down, for research protections. Senior officials are more aware of and involved in research protections. This involvement has a ripple effect, setting the stage for a culture of compliance across the organization. In addition, researchers, IRB staff, and others cite the improved communication and collegiality that result when everyone has a common goal.
• More knowledgeable researchers and IRB members. Because researchers have a better understanding of the federal regulations, organizations are seeing fewer protocol deviations and incidents of noncompliance. In addition, as IRB members and staff become more confident in their own knowledge of the regulations, they also feel more comfortable when they apply the regulations—and take advantage of the flexibility that the regulations allow.
• Increased emphasis on customer service. Many say the AAHRPP accreditation process gives them a different perspective not just on research protections but also on their relationship with their colleagues. As a result, although they continue to require compliance, IRBs tend to stress their role as a resource, focused on meeting the needs of their customers, including researchers and research participants.
• Emphasis on quality improvement and metrics. AAHRPP standards require organizations to “measure and improve, when necessary, the quality, effectiveness, and efficiency” of the HRPP. AAHRPP-accredited organizations lead the way in using metrics to assess and report on progress and to guide quality improvement efforts. As organizations find new ways to streamline the research review process, they report shorter turnaround times and increased customer satisfaction.
• Greater visibility and respect for the HRPP. AAHRPP was instrumental in promoting the concept of a comprehensive, systematic HRPP. At AAHRPP-accredited institutions, administrators, faculty, and students have a greater awareness of the importance of the HRPP and their own responsibility to protect research participants.

Organizations realize that to succeed in today’s research enterprise, they must demonstrate quality, improve efficiency, and increase collaboration. For many, AAHRPP accreditation provides the means to accomplish these objectives. Through its combination of in-depth self-assessment, external peer review, and one-on-one engagement with applicants, the AAHRPP accreditation process has played a singular role in strengthening research protections and improving the quality of research.

Responding to Globalization

A framework for protecting participants worldwide

International markets are now home to more than half the world’s clinical trials, including 40 to 65 percent of studies investigating U.S. Food and Drug Administration (FDA)-regulated products. Bioethicists and others have expressed concerns that monitoring has not kept pace with global growth. At the same time, they recognize that the trend toward global research will only continue. The goal, then, is not to reduce the number of global trials but to find ways to ensure adequate safeguards for research participants and, ultimately, for patients who use the resulting products.

• Why sponsors turn to global markets
• Oversight and other challenges
• AAHRPP’s role

Why sponsors turn to global markets
Many attribute the increase in conducting clinical trials in global markets to reduced costs. However, according to Albert J. Allen, M.D., Ph.D., Senior Medical Fellow for Bioethics and Pediatric Capabilities at Eli Lilly and Company, “when you factor in the work required to get multiple international sites up to speed and increasing costs in some regions such as Asia, there’s not as big a difference in costs as many think.”

Instead, two other factors draw sponsors to international markets:

• Access to larger numbers of participants for phase 3 trials. U.S. investigative sites simply do not enroll enough patient-participants to receive FDA approval in a timely, cost-effective manner. To meet FDA requirements for study enrollment and minimize delays in bringing medicines to market, research sponsors increasingly look to countries where more people are available and willing to volunteer.
• Changing requirements for international approval. Many countries now have their own regulatory agencies and require that medicines be approved by those agencies—even if the medicines have already been approved in the U.S. or in European countries. Therefore, to make medicines available to patients worldwide, pharmaceutical companies often must conduct trials in specific global markets.

Oversight and other challenges
One of the greatest concerns of those involved in protecting research participants is the challenge of monitoring multiple global sites. In its June 2010 report, “Challenges to FDA’s Ability to Monitor and Inspect Foreign Clinical Trials,” the Department of Health and Human Services Office of Inspector General (OIG) noted that the “FDA inspected clinical investigators at less than 1 percent of foreign sites.” The same report found that “80 percent of approved marketing applications for drugs and biologics contained data from foreign clinical trials.”

Other challenges of globalization include bridging language and cultural differences; meeting regulatory requirements of all nations involved; assessing skills and qualifications of the research team; evaluating the strength of the institutional review board or ethics committee; monitoring the quality of the data; and, above all, ensuring the strongest possible protections for research participants.

The OIG report acknowledged that the FDA has taken steps to improve its oversight of foreign clinical data. Even so, the report called on the FDA to make additional changes, including expanding its oversight of foreign clinical trials in three ways:

• Continuing to develop inspection agreements with foreign regulatory bodies.
• Inspecting clinical trials in more countries.
• Looking to new models of oversight.

AAHRPP’s role
AAHRPP is a natural partner in this effort. Applying AAHRPP’s rigorous standards around the globe can duplicate the positive results achieved in the U.S. in the decade since AAHRPP was founded.

In fact, AAHRPP has set an ambitious goal of establishing one standard for research protections worldwide. In keeping with that goal, AAHRPP has developed standards that acknowledge and account for the variations in research regulations from country to country. In general:

• AAHRPP accreditation standards are based on the International Conference on Harmonisation-Good Clinical Practice (E6) guideline and on FDA and DHHS regulations.
• All organizations are evaluated according to the same set of AAHRPP accreditation standards. In addition, organizations based outside the U.S. must comply either with their own nation’s regulations or those of the U.S.—whichever are more stringent.

Already, organizations in Canada, China, India, Korea, and Singapore have earned AAHRPP accreditation, delivering the message—to sponsors, participants, and the general public—that they offer an assurance of quality that others cannot claim. AAHRPP’s influence will grow overseas, just as in the U.S. Increasingly, international organizations that earn AAHRPP accreditation will become the research partners of choice for sponsors and research organizations in the U.S. and around the globe.

From De Minimis to Gold Standard

Case Study: Lehigh Valley Health Network Accredited Since 2009

The Situation
Lehigh Valley Health Network routinely oversees approximately 400 research protocols. Most involve Phase 3 clinical trials designed to provide patients with treatment alternatives for chronic or life-threatening conditions. Back when Lehigh Valley Health Network began looking at accreditation, the organization had a single institutional review board (IRB) and was in compliance with federal regulations, but “was operating at a relatively de minimis level,” says Scott Lipkin, DPM, Chief, Network Office of Research and Innovation.

The Challenge
To meet AAHRPP’s accreditation standards, Lehigh Valley Health Network had to create a comprehensive, integrated human research protection program (HRPP). As part of that effort, the organization was required to develop policies and procedures, establish training programs, and professionalize and strengthen the IRB.

The Solution
Lehigh Valley Health Network reorganized and revamped its research protection efforts, including:

• Changing the reporting structure for the IRB to establish it as an independent committee.
• Adding a second IRB to ensure that research protocols receive the necessary, thorough review.
• Creating scientific review committees to ensure departmental review before research is submitted to the IRB.
• Developing an education program.
• Establishing a quality improvement/quality assurance program.
• Creating a community outreach program.
• Integrating the work of the IRB with other departments, including pharmacy, materials management, and legal services.
• Strengthening conflict-of-interest reporting requirements and integrating them with corporate compliance efforts. 
• Hiring additional staff.

In essence, Lehigh Valley Health Network built an HRPP that emphasized that the responsibility for research protections is borne not just by the IRB but by the entire organization. Change of that magnitude would not have been possible, Lipkin says, without “an unyielding financial and political commitment from the institutional official and the rest of the senior leadership team.”

The Results
Lehigh Valley Health Network’s efforts were officially recognized March 27, 2009, when the organization was awarded AAHRPP accreditation. That distinction boosted Lehigh Valley Health Network’s standing with researchers, with regulators, and among its peers. Accreditation also acknowledged that “we were doing a better job,” Lipkin says. “We didn’t just strengthen protections; we created a comprehensive, sustainable HRPP to ensure enhanced protections for the long term.”

A greater emphasis on education helped IRB chairs, members, and staff gain a better understanding of the federal regulations. That, in turn, bolstered confidence and increased the IRB’s willingness to take advantage of the flexibility in the regulations―to lessen the regulatory burden while providing equivalent protections.

The bottom line, according to Lipkin, is that Lehigh Valley Health Network transformed its research operation for the good of patients, researchers, and the organization as a whole. “We were a big success story,” he says. “In 2 ½ years, we went from functioning at a low level to achieving the gold standard of accreditation.”

   

Accreditation Then and Now

When we issued the first AAHRPP-accreditation standards, our goal was to strengthen human research protections and, in the process, improve the quality of research. A decade later, AAHRPP has succeeded beyond expectations. Equally important, with support from AAHRPP-accredited organizations around the globe, we continue to find new ways to advance research while raising the bar for ethics and quality.

The most obvious measures of AAHRPP’s success can be found in the numbers:

• All major U.S. independent institutional review boards (IRBs) are AAHRPP accredited.
• 53% of U.S. research-intensive universities are AAHRPP accredited, and an additional 10% have begun the AAHRPP-accreditation process.
• 52% of U.S. medical schools are AAHRPP accredited, and an additional 10% have begun the AAHRPP-accreditation process.

Perhaps even more impressive, however, are the fundamental changes that AAHRPP and AAHRPP-accredited organizations have spurred across the research enterprise. Following are just a few examples:

• Before AAHRPP, efforts to strengthen research protections focused primarily on IRBs. Today, largely in response to AAHRPP’s accreditation requirements, IRBs typically represent just one component of an organization’s comprehensive human research protection program (HRPP). Furthermore, organizations recognize that the responsibility for research protections is shared across the HRPP—and that the entire HRPP must meet AAHRPP standards to earn the AAHRPP gold seal.
• The first independent IRBs to pursue AAHRPP accreditation did so as a way to differentiate themselves from their peers. For today’s independent IRBs, AAHRPP accreditation is a must. In fact, independent IRBs tell us that clients often ask about AAHRPP accreditation before contracting for IRB services.
• A decade ago, quality was considered important but not quantifiable. Today, AAHRPP and AAHRPP-accredited  HRPPs, routinely use metrics to assess quality improvement efforts and set higher goals.
• AAHRPP-accredited organizations have embraced and often exceed our standards, and the result has been significant gains in knowledge, competence, and professionalism. AAHRPP site visitors say they are struck by how far HRPPs have come in the past decade—and by the differences between AAHRPP-accredited and non-accredited organizations.
• Now that AAHRPP is firmly established as the gold standard for accreditation within the U.S., we are looking to extend our influence overseas. With AAHRPP-accredited organizations in Canada, China, India, Korea, and Singapore, we are determined to achieve our goal of one standard worldwide for research protections.

The Evolution of AAHRPP’s Accreditation Standards

The research enterprise has seen significant changes in the decade since we introduced AAHRPP’s first accreditation standards, yet today the standards are more relevant than ever.

One reason is that the original standards were on the mark. They were rooted in ethical principles and sound research practices. Equally important, the original standards recognized the activities and controls that are at the heart of quality research protections.

Like our accredited organizations, AAHRPP is committed to continuous quality improvement. By 2009, we had identified opportunities to update the AAHRPP Accreditation Standards to keep pace with the more global research landscape. We also had listened to accredited organizations and responded to their concerns about the need for more flexibility and less burdensome processes.

After a fairly lengthy public comment period, we launched a new and streamlined set of standards that strengthened human research protection programs (HRPPs) by accomplishing the following:

• Addressing new, pressing issues such as conflicts of interest, community-based participatory research, data monitoring, and transnational research.
• Organizing the AAHRPP Accreditation Standards in a more logical framework in three domains instead of the earlier five.
• Better defining the roles and responsibilities of the entities within an HRPP.
• Consolidating the numbers of standards and elements.
• Giving organizations more flexibility to develop their own approach to complying with the AAHRPP Accreditation Standards.

We understand the challenges that organizations face when pursuing AAHRPP accreditation, so we are determined not to make it a moving target. At the same time, our overriding commitment is to strong research protections.

Today’s AAHRPP Accreditation Standards reflect both of these positions, and the resulting benefits extend to all of us: accredited organizations, research participants, and the research enterprise as a whole.

Celebrating Our Successes Together

Our 2012 AAHRPP Conference was a reminder of how far we’ve come together since AAHRPP introduced its accreditation standards in 2002. Three years later, we hosted our first conference and drew a respectable crowd of nearly 300 participants. This year, approximately 450 individuals attended. That says a great deal about both the educational value of the conference and the support for accreditation and research protections.

AAHRPP’s early conferences focused almost exclusively on building human research protection programs (HRPPs) and on the accreditation process. This year, as in the past, we offered pre-conference sessions to help organizations that are new to accreditation or in the midst of the accreditation process. For the main conference, we took a different approach and concentrated on protecting vulnerable participants. This issue is central to human research protections but often is misunderstood. It also relates directly to our accreditation standards.

Why the shift? Primarily because AAHRPP and the research enterprise have matured considerably in the past decade, and our conference and other education efforts reflect this changing landscape. Once a rarity, HRPPs are now firmly entrenched in research organizations around the world. Furthermore, more than 240 organizations have demonstrated their commitment to research protections by achieving accreditation.

If your organization is among them, we commend you for your continued commitment to high-quality, ethical research. If you have yet to apply for accreditation, we invite you to learn more about AAHRPP and the accreditation process—and to join us and our accredited organizations as we pursue our goal of one standard worldwide.

AAHRPP’s Accomplishments Help Transform the Research Landscape

From the beginning, AAHRPP recognized that each accreditation would have a ripple effect throughout the research enterprise. Yet as we look back on the progress of the past decade, even we are surprised at the stature accreditation has gained and its positive ramifications.

From aspiration to expectation. At first, accreditation was perceived as a way for organizations to distinguish themselves from their peers—to demonstrate that they are part of an elite group with standards exceeding those set by the federal government. As more and more organizations attained accreditation, the perception began to change. Accreditation no longer is something that only a few can strive for. Instead, it has become a must.

AAHRPP’s standards remain the most rigorous in the world, and more than 240 organizations have demonstrated that they can meet these requirements. Increasingly, others are being asked, “Why not you?” Many organizations now include accreditation in their criteria for research partners. And IRBs report that their clients will not consider an unaccredited IRB.

An unwavering commitment to quality. Accreditation has value because, despite outside pressures, AAHRPP has consistently refused to yield on quality. In the early years, that position appeared to place AAHRPP at a disadvantage. Yet AAHRPP stood firm, convinced that enough organizations would make a commitment to AAHRPP’s higher standards. Ultimately, AAHRPP became the sole accrediting body for HRPPs.

Together, AAHRPP and its accredited organizations have raised the bar—for both accredited and non-accredited organizations―and have created a culture of continuous quality improvement. Consequently, in the years since AAHRPP accreditation took hold, the research enterprise has seen a dramatic decrease in major research abuses. Equally telling, accredited organizations are significantly less likely to receive determination letters from the Office of Human Research Protections identifying major deficiencies.

Measurable progress. AAHRPP has led the way in using metrics to evaluate the progress of HRPPs. Perhaps even more important, AAHRPP makes the data available to research organizations, researchers, sponsors, government agencies, and research participants. Detailed information—from types of research conducted and regulatory oversight to IRB resources and review times, to audits, deviations, and complaints—is available on the AAHRPP website.

A comprehensive, integrated approach. To attain accreditation, organizations must demonstrate that they have a systematic, comprehensive program that affords protections for all research participants. This requirement spreads the responsibility for research protections over the entire organization, not just the IRB. As a result, and in large measure because of AAHRPP, the past decade has witnessed the rise of the HRPP. In accredited organizations and, to a lesser extent, throughout the research enterprise, AAHRPP’s standards have helped improve communications, increase efficiency, and strengthen research protections.

One standard worldwide. Increasingly, AAHRPP’s standards are becoming the world’s standards. With accredited organizations in Canada, China, India, Korea, and Singapore, AAHRPP is earning an exemplary reputation in nations that are expected to see the most dramatic growth in clinical trials. That’s good news for researchers, sponsors, and participants, who benefit from accreditation’s assurances of higher quality and enhanced protections.

Acknowledging Accreditation’s Leaders

This month marks 10 years since AAHRPP issued its first accreditation standards, challenging organizations to voluntarily adopt more stringent criteria for human research and research protections.

Today, more than 240 organizations worldwide have demonstrated that they comply with what is now considered “the gold standard” for the research enterprise. But back in 2002, it required leadership and vision to invest time and resources in what was then an unproven process.

Six organizations rose to the challenge and, almost as soon as the standards were released, signaled their intent to pursue accreditation:

• The University of Iowa, Iowa City, IA
• Western Institutional Review Board, Olympia, WA
• New England Institutional Review Board, Newton, MA
• Hunter Holmes McGuire Veterans Affairs Medical Center, Richmond, VA
• Baylor Research Institute, Dallas, TX
• Catholic Medical Center, Manchester, NH

These six organizations were the first to conduct the comprehensive self-assessments that AAHRPP requires, the first to submit the extensive accreditation application, and the first to undergo the rigorous AAHRPP site visit.

Ultimately, their foresight earned them a place in history. They are, and always will be, the first organizations to demonstrate their commitment to research participants by earning AAHRPP accreditation.

As AAHRPP celebrates our tenth anniversary, we salute those who had the courage to support accreditation in its earliest days. These six organizations led by example. In the process, they laid the foundation for stronger protections and better research—for decades to come.

A Decade of Accomplishments in Helping Organizations to Promote Research Participants and Promote Research

2001
Founding Members incorporate AAHRPP
Chief Executive Officer takes helm
Interim standards and procedures published for comment

2002
Accreditation program launched
First applications accepted
Council on Accreditation established
Site visits begin

2003
First organizations attain accreditation

2004
OHRP and PHRMA announce support for accreditation
AAHRPP published newsletter, AAHRPP Advance

2005
First annual accreditation conference
First supporting members join AAHRPP
Department of Veterans Affairs awards accreditation contract to AAHRPP

2006
First international accreditation in Korea announced
Reaccreditations begin

2007
Getting Started workshops offered
First accreditations in Canada and Singapore

2008
100 organizations accredited
Revised procedures (Step1/Step2) implemented

2009
Revised accreditation standards published
World Health Organization approaches AAHRPP to consult on developing standards for IRBs
Fellowship program formed with Korean Association of IRBs
Educational webinars offered
Industry sponsors require independent IRBs to be accredited

2010
200 organizations accredited
Published first report on metrics of HRPPs

2011
241 organizations accredited
First accreditations in China and India
National Institute of Neurological Disorders and Stroke funds an institution’s IRB to serve as central IRB for all awardees of a multi-site clinical trial grant
AAHRPP Advance goes electronic

HRPPs: A Concept That’s Come of Age

For decades, the responsibility for protecting human research participants rested squarely with the IRB. Today, while it still plays a pivotal role, the IRB is part of a comprehensive human research protection program (HRPP) designed to spread responsibility and accountability across the research enterprise.

Some have expressed concerns that the rise and acceptance of HRPPs have ushered in a more rigorous review process. But that was the intent: to hold researchers and IRBs, among others, to high standards and, in the process, improve the quality of research and strengthen research protections.

The concept of an HRPP was officially introduced in 2001 by the Institute of Medicine (IOM) and its Committee on Assessing the System for Protecting Human Research Subjects. Yet it is AAHRPP that is widely credited with moving HRPPs from concept to reality.

“AAHRPP’s contributions have been substantial,” says James A. Weyhenmeyer, Ph.D., Vice President for Research and Economic Development at Georgia State University and Chair of AAHRPP’s Board of Directors. Because of AAHRPP and its accreditation standards, “now there’s an infrastructure in place and agreement on the ground rules. The research is better, and so are the protections,” he says.

Marking 10 Years of Accreditation

As AAHRPP prepares to mark the 10th anniversary of the release of our first accreditation standards, we will look back on some of the changes and accomplishments of the past decade--for AAHRPP, for research participants, and for the research enterprise as a whole. The first article in this series, to be posted December 15, will focus on how HRPPs have come of age in the years since AAHRPP was founded.