The National Institutes of Health Clinical Center — one of the most prestigious research institutions in the world — has been rocked by an independent panel report that found glaring errors in research oversight and safety.

Among the panel’s recommendations in a recent report1 was for the NIH to establish an Office of Research Support and Compliance (ORSC) and “evaluate institutional review board activities and other human subjects protections activities and ensure consistent standards are met.”

IRB Advisor asked the Clinical Center in Bethesda, MD, for comment on this aspect of the report, and after repeated inquiries over several weeks was emailed a statement that was attributed to the NIH rather than a specific individual.

“In developing its report and recommendations, the working group of the Advisory Committee to the Director did not identify any documented problems with the NIH Human Research Protection Program, i.e., with IRB review and oversight of clinical trials at NIH, nor did it identify areas of oversight inconsistency or lapses in common issues like informed consent and conflict of interest,” according to the statement. “[The report] directs NIH to refine its approach to regulatory support services and compliance quality assurance so that there is a greater uniformity and transparency across the 20 NIH Institutes and Centers that conduct human participant research. NIH agrees with this recommendation and is grateful for the fresh, independent, and outside perspective of the committee. We are currently working hard to stand up a new office at NIH, the ORSC.”

The problems at the NIH center began in May 2015, when an FDA inspection found drug-processing problems in the pharmacy department and the Intravenous Admixture Unit (IVAU). In the preceding month, two vials of drugs used in research were found to have fungal contamination. Moreover, some of the contaminated drugs were administered to patients, though no infections resulted.

As the center looked into the causes of the problem, it became evident that they reflected larger, troubling issues within the institution and the work culture. Thus, NIH Director Francis Collins, MD, PhD, charged an independent panel to conduct an investigation.

“It was deeply disturbing to me when I learned last May of serious deficiencies in the hospital Pharmaceutical Development Section identified by the FDA,” Collins said in a statement posted on the NIH Clinical Center website. “Fortunately, there was no evidence then, and there is no evidence to this date, that any patients were harmed by these problems, but it was incumbent on NIH to act swiftly. While the immediate deficiencies identified by FDA have since been addressed, it became clear to me while addressing these issues that a broader review of hospital operations was needed by outside experts in hospital management and administration, patient safety, and clinical laboratory quality and safety regulations.”

The recently released1 working group’s findings included the following:

  • absence of a readily apparent and anonymous avenue to escalate concerns within NIH beyond immediate supervisors,
  • failure of supervisors to appropriately address and escalate important deficiencies that were reported by staff,
  • evolution of a culture and practice in which patient safety gradually, and unintentionally, became subservient to research demands,
  • insufficient expertise in regulatory affairs, compounded by misunderstandings about how to comply with regulations for a federal research institution conducting clinical operations,
  • fragmentation of authority and responsibility for clinical operations, driven by a unique decentralized structure, authority, and funding for intramural clinical research, resulting in accountability and quality assurance gaps that could compromise patient safety,
  • inadequate independent oversight of safety and regulatory compliance within NIH, and
  • insufficient regular monitoring and metrics for identifying and tracking needed steps for improvement.

Patient Safety Failure

Among the most damning findings in the working group report was a “failure to prioritize patient safety,” which should be the prime directive of any research activity.

“[P]atient safety was occasionally put at risk, perhaps as a result of a well-intended, single-minded focus on research with an unintended but concerning concomitant inattention to safety,” the working group report concluded. “In some instances, regulatory compliance and quality assurance was not viewed as a principal priority of the [Clinical Center]. NIH should ensure that the staff views the needs of research participants rather than researchers as their ultimate priority, and commensurately consider patient safety in all activities. Promotion of patient safety and adherence to the highest standards of practice must be viewed as an essential, non-negotiable mandate, not simply an exercise to satisfy internal and external regulators.”

The panel also found a surprising “dearth of regulatory expertise,” saying the NIH lacks knowledge on regulations that apply to research facilities.

“There is no central source of information about the regulatory requirements that pertain to intramural clinical activities,” the panel found. “Because the Clinical Center is a federal facility, some formal requirements for oversight and regulation that are in place at typical research hospitals are not mandatory for the [center] — and were not instituted.”

Moreover, the investigation “brought to light serious failures in reporting and addressing known problems. Until the FDA intervened, leadership at the center and the NIH were not aware of issues in compliance, quality, and safety that spanned many years,” the independent panel found.

The Clinical Center needs a sweeping culture change, one that would encourage information-sharing and reporting any concerns, the group recommended.

“Staff should feel safe reporting concerns, and information-sharing, including near-misses, should not in itself be an indication for a need for reprimand or any negative consequences,” they noted. “Staff in the [pharmacy] raised concerns regularly, but these concerns apparently were never reported beyond the department, and there was no formal mechanism at the [Clinical Center] for staff to report concerns outside their chain of authority.”

New Human Research Approach

In recommending the Clinical Center create the ORSC oversight branch, the panel advised the NIH to incorporate its existing Office of Human Subjects Research Protections (OHSRP) into this new office. The working group recommended that this new combined research support and compliance office should do the following:

  • serve in a coordinating role for existing compliance activities (including but not limited to human subjects protections, lab safety, and FDA compliance), and it should be equipped to efficiently respond to data calls about compliance,
  • ensure that all institutes have sufficient compliance support, including training, auditing, and compliance tracking that feeds into a common, NIH-wide system,
  • report directly to NIH senior leadership to ensure that there are no barriers to identifying or remediating compliance gaps,
  • establish improved systems to reduce burden and increase research quality and safety, so that compliance creates better results for research participants and researchers,
  • establish overarching systems, and serve as a repository for documentation of best practices and checklists that are robust and do not rely on the initiative of specific individuals,
  • increase tracking and evaluation of both standard hospital metrics and metrics that are germane to a research hospital,
  • evaluate IRB activities and other human subjects protections activities and ensure consistent standards are met,
  • be attentive to regulatory responsibilities for scientists, clinicians, and staff and seek mechanisms that promote standards, accountability, and performance without unduly increasing staff workload, and
  • improve training programs and implement a centralized learning management system to track training for regulatory compliance and patient safety, and share training resources across units.

The NIH Clinical Center is in the process of considering and implementing the recommendations.

REFERENCE

  1. The Clinical Center Working Group Report to the Advisory Committee to the Director, NIH. Reducing Risk and Promoting Patient Safety for NIH Intramural Clinical Research. Draft Report. April, 2016: http://bit.ly/29Qjm9a.