Development and progression of a model: prospective research compliance monitoring.

Introduction

More than a decade ago, Weijer (Weijer et al., 1995) called for institutional research compliance monitoring programs for several purposes: education of researchers; prevention of problems; and avoidance of financial loss due to fraudulent research. In 2001, the FDA monitoring program revealed that 70% of human subject protection deficiencies are the result of investigator noncompliance (Wolfe & O'Rourke, 2002). Following the 1999 death of a healthy volunteer, the University of Pennsylvania developed the Office for Human Research (OHR) to assume internal compliance monitoring responsibilities. The focus of OHR was on investigator-initiated studies and moderate- to high-risk research whose mission was "not only to discover possible noncompliance but also to provide the education, tools, and resources to correct noncompliance" (Sherwin & Fromell, 2002). The UHCMC CCRT implemented a comparable approach, emphasizing post-IRB approval monitoring in unison with research education to promote research integrity.

Prior to the development of a prospective compliance monitoring program, investigation of allegations of noncompliance was a burdensome task requiring extensive resources by the UHCMC IRB office. Rather than compromising the effectiveness of the IRB and compliance program by exhausting shared personnel, the CCRT recognized that separate staff with compliance expertise would ensure efficiency of the monitoring program. The CCRT's prior experience also demonstrated that directed monitoring, or monitoring required by the IRB in response to a noncompliance issue, was not an effective or proactive means by which to manage noncompliance. As a result, the Office of Research Compliance (ORC) was created under the quality improvement initiatives for the Human Research Protection Program (HRPP), and was introduced to the research community as research-support services. The ORC applied the Association for the Accreditation of Human Research Protection Programs (AAHRPP) requirements as the foundation for the ORC's Standard Operating Procedures (SOPs). The initial SOP manual summarized the monitoring process, including the categories listed in Table 1.

The following factors are considered when identifying priorities for monitoring of clinical research protocols: risk level; study population; whether the study involves treatment or intervention; and whether the study is investigator-initiated, industry or foundation originated, or federally funded. These categories represent factors to classify research conduct that poses greater than minimal risk to participants and may have a lesser amount of oversight by external regulatory monitors.

Congruently, with the development of the prospective compliance monitoring program, research education resources were being dedicated to establish a consistent offering of individualized and interactive education sessions. Beginning in September 2000, institutional programs were developed in preparation for the NIH mandate for investigator certification requirements in Human Subject Protections. Along with the initial core training utilizing the text "Protecting Human Subjects in Research" (Dunn & Chadwick, 1999) and subsequent adoption of the Collaborative Institutional Training Initiative (CITI) core curriculum, institutional seminar series, panel discussions, and workshops were developed, marketed and conducted monthly. The following categories of individuals from the research community were targeted for the research education and training (Table 2).

These extensive efforts have successfully culminated in improving the conduct and oversight of research and establishing a program that transformed compliance monitoring into research integrity through principles of research conduct.

Background

The diverse roles of research administrators have become progressively more comprehensive as this discipline moves toward continued professionalization and the conceptualization of research expands to an all-encompassing Human Research Protection Program (HRPP) (Cola, Fedor, & Haffke, 2005). Research administrators are responsible for the legal, fiscal, ethical, and scientific and compliance reviews of protocols from their initiation through completion. In the past, research administrators were regarded primarily as grant or IRB administrators (Cola, Fedor, & Haffke, 2005). In response to recent trends in clinical research and growth of regulatory oversight requirements, the profession has become more encompassing, and research administrators have assumed the roles of grant writers, clinical research coordinators, human subject protection and compliance specialists, and research billing professionals. This professional evolution has lead to increased awareness and understanding of the vital roles that research administrators serve in the conduct of both basic science and clinical research.

A distinct area that has recently gained considerable momentum has been the role of the clinical research compliance monitor. Similar to other academic or business specialties, the process of conducting clinical research is closely monitored. Historically, this monitoring has been performed by external sources (i.e., the sponsor, contract research organization(s), or federal agencies). During the past decade, given the remarkable growth in clinical research, it has become evident that relying solely on external monitoring is inadequate to preserve the responsible conduct of research. Slater (2002) noted that, not only has federal funding for research doubled in the past decade, but from 1997 to 2000, the estimated number of participants in federally funded research increased from 7 million to 12 million. Non-federally sponsored research has grown at a similar pace (Slater).

These trends have driven the desire and need to create internal research compliance monitoring functions in an effort to improve research programs and to provide supportive services to investigators that allow them to conduct clinical research effectively. Some institutions have developed these programs in response to specific compliance findings discovered by external monitoring activities (Steinbrook, 2002). Such shortcomings in human subject protection programs at major institutions should serve as a catalyst for all institutions, researchers and IRBs that are charged not only with promoting clinical advances, but first and foremost, protecting the human subjects involved in the process (Shalala, 2000).

Additionally, the continuing education of research administrators and institutional officials makes it apparent that internal compliance monitoring programs that proactively review the conduct of clinical research at the institution are essential. Research institutions must commit to regular and routine internal monitoring of all research activities. Critical self-examination can bring to light weaknesses and other issues before significant errors occur (Icenogle, 2003).

It is believed that, to be effectively connected to the other critical components areas of an HRPP (i.e., the administrative functions of an IRB and grant accounting), compliance monitoring programs should be established within Offices of Sponsored Projects at Universities and Research

Administration of hospitals based in Academic Medical Centers (AMCs) (Speers & Cooper, 2003, Institute of Medicine, 2001). Research compliance monitoring and education programs are not only a routine function of these types of institutions, but rather specialized functions that enhance the overall research administration effort.

In June 1998, the Office of Inspector General of the Department of Health and Human Services issued four investigative reports, which indicated that IRBs have excessive workloads and inadequate resources (Shalala, 2000). The inadequate resources included insufficient staff, expertise, space, and equipment such as databases.

It is difficult to absolutely ascertain the accuracy and impact of these reports on the behavior of AMCs, however, the information provided has prompted research institutions to define the role of the IRB in greater detail and to expand the scope of programs better designed to ensure the protection of human subjects in research. These programs have been developed by institutions through research administrative offices to provide assurances of their compliance with regulations (Sherwin & Fromell, 2002). Out of these developments, the focus has shifted from traditional research administration toward a prospective compliance and education focused approach.

The fusion of internal monitoring programs and research administration activities into central research offices has also led to the creation of external accrediting bodies for Human Research Protection Programs (HRPPs) (Cola, Fedor, & Haffke, 2005). This may be attributed to the concept that preparation for voluntary accreditation includes a self-assessment of the overall research protection programs, including compliance and safety (Burke, 2005). These programs are often construed as being synonymous with IRB accreditation, however the scope and purpose of such programs goes beyond the operational matters of an IRB and its corresponding administrative office and assesses many more components (i.e., institutional support and understanding; congruence with grant administration; research educational programs for investigators, clinical research coordinators, research administrators, research participants; and research compliance programs). Accreditation must approach the HRPPs broadly from an organizational perspective that is beyond a focus of IRB operations to examine whether policies and procedures of the organization as a whole result in a coherent, effective scheme for the protection of human research participants (Speers & Cooper, 2003).

Efforts aimed at improving HRPPs would be remiss if comprehensive education was not an integral component of the approach. As Shalala (2000) notes, "The never-ending challenge for academic institutions and other organizations participating in research is to make sure that researchers and other personnel have up-to-date training and a thorough knowledge of their responsibilities. Those responsibilities include communicating with IRBs, ensuring that procedures for informed consent are followed, monitoring compliance with protocols, and reporting on safety issues." Comprehensive education efforts for the entire research program at AMCs should be focused not only on facilitating the understanding of federal regulations and institutional policies and procedures, but also on the results of their own compliance activities.

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