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.

Promoting Community-Based Participatory Research

When the AAHRPP Accreditation Standards were revised in 2009, Element I.4.C. was added, that requires organizations to promote the involvement of community members, when appropriate, in the design and implementation of research and the dissemination of results. An organization can conduct community-based participatory research to meet the new Element. This methodology involves community members in the research process, but it presents unique ethical challenges to IRBs.

Educate your IRB about the ethical issues related to community-based participatory research:

• Consider the risks to the community, as well as the individual participants.
• Evaluate the working relationships between the researchers and community members, including the possibility for undue influence on the community members when they are prospective participants.
• Obtain consent from community members who are both research participants and representatives of the research team (e.g., conducting surveys).
• Approve the use of interview tools that evolve and change from one interview to the next.
• Provide research results to the community.

Experts in your organization might serve as consultants, IRB members, or teachers. Literature reviews show that community-based participatory research is increasing in the scientific community and is being sponsored by both public and private funders. Organizations should encourage researchers to conduct this type of research and train IRBs to review it. Working together can benefit all—researchers, the organization, the IRB, and the community—while still protecting participants in the research.

Representative publications on community-based participatory research and IRBs:

Brugge, D. Institutional review boards need to increase their understanding of community-based participatory research: commentary on a case study in the ethics of mental health research. J Nerv Ment Dis. 2012 Mar;200(3):242.

Brown P, Morello-Frosch R, Brody JG, Altman RG, Rudel RA, Senier L, Pérez C, Simpson R. Institutional review board challenges related to community-based participatory research on human exposure to environmental toxins: A case study. Environ Health. 2010 Jul 16;9:39.

Hyatt RR, Gute DM, Pirie A, Page H, Vasquez I, Dalembert F. Transferring knowledge about human subjects protections and the role of institutional review boards in a community-based participatory research project. Am J Public Health. 2009 Nov;99 Suppl 3:S526-31.

Flicker S, Travers R, Guta A, McDonald S, Meagher A. Ethical dilemmas in community-based participatory research: recommendations for institutional review boards. J Urban Health. 2007 Jul;84(4):478-93.

http://depts.washington.edu/ccph/commbas.html Accessed 4/23/2012.

AAHRPP Releases Updated Evaluation Instrument

On January 3, AAHRPP released an updated version of the Evaluation Instrument for Accreditation. The latest version includes some minor edits and the addition of changes in the Department of Defense requirements according to DOD Instruction 3216.02. Also, the requirements on financial conflict of interest in the new DHHS rule were added to Element 1.6.B. The new rule goes into effect on August 24, 2012, and will need to be addressed in initial and reaccreditation applications received in 2012.

Revised versions of the application forms, instructions and guidances have also been published on the Web site. These application forms must be used for all applications submitted in 2012.

IRBs Must Review and Approve Plans for Data and Safety Monitoring

The regulatory criteria for approval of research includes the requirement that, when appropriate, the research plan makes adequate provisions for monitoring the data collected to ensure the safety of participants. The researchers and the IRB must “satisfy” this criterion before the research can be approved and conducted. The National Institutes of Health (NIH) require all clinical trials to have data and safety monitoring, with the method and degree of monitoring commensurate with the risks.¹ Every NIH institute offers guidance on data and safety monitoring plans. The Food and Drug Administration (FDA) provides guidance for the establishment and operation of clinical trial data monitoring committees and in August released draft guidance for oversight of clinical investigations with a risk-based approach to monitoring.^2-3  AAHRPP has incorporated this requirement into Element II.3.B.: The IRB or EC has and follows written policies and procedures for reviewing the plan for data and safety monitoring, when applicable, and determines that the data and safety monitoring plan provides adequate protection for participants. In general, data and safety monitoring plans should be required for research that involves greater than minimal risk, but in some instances the IRB may find such plans important for a particular research project that is considered no greater than minimal risk.

Contract Provisions Help Protect Research Participants

Sponsors play an important role in protecting participants in research. AAHRPP Standard I-8 describes the working relationship that organizations and sponsors must have in order to protect participants. Organizations and sponsors can exert flexibility in negotiating contracts and funding agreements to meet these requirements. Standard I-8 deals with five required provisions for contracts and funding agreements that are designed to contribute to the protection of research participants in sponsored research. The five Elements are described below with explanations for why they are important.

Element I.8.A. The Organization has a written agreement with the Sponsor that addresses medical care for research participants with a research-related injury, when appropriate.

When there is a risk of physical injury from participating in a research study, organizations should work with sponsors to determine who is responsible for paying for care following research-related injury. When agreeing to participate in a research project, participants should be made aware of whether care will be provided when they are injured because of the research project, and who will be responsible for paying for such care. This information should be in the consent document and should be consistent with the terms of the contract or funding agreement with the sponsor.