History and Common Challenges of Human Subject Research Compliance

Authors:
Frank McAneny, MS, MBA, CCRP, CHRC, CCEP, CSSGB – Director of Research Compliance
Sarah Ziegler, Ph.D., SM(NRCM), RBP, CBSP – VP of Research Compliance

Research compliance encompasses adhering to regulations, guidelines, and ethical standards governing the conduct of research activities, whether human subjects, benchtop, or animal research. It ensures that research is conducted ethically, transparently, and in accordance with legal requirements to safeguard participants’ rights and maintain integrity in scientific inquiry.

Engaging in research within a healthcare organization is inherently distinct from other operational endeavors and can sometimes pose significant challenges. The landscape of research compliance and regulatory frameworks governing research activities in healthcare settings has become increasingly intricate. To fully understand the challenges and issues unique to research compliance for Institutional Review Boards (IRB), it is essential first to understand the history of human subject research protection and regulations.

The Nuremberg Code of 1947 was established as an initial response to the egregious experiments conducted in Nazi concentration camps during World War II. In 1976, the International Conference on Harmonization and Good Clinical Practice set international ethical and scientific standards for clinical trials involving human subjects. Additional documents such as the Declaration of Helsinki (1964) and The Belmont Report (1979) further fortified protections for human subjects, outlining three fundamental ethical principles:

• Respect for persons
• Beneficence
• Justice

The U.S. Department of Health and Human Services (HHS) regulates human research supported by federal funds, investigational drugs, biologics, and devices. The HHS Office of Human Research Protection, established in 2000, oversees the “Common Rule,” which consolidates human research protection principles. Adherence to these standards ensures the protection of trial subjects’ rights, safety, and well-being and upholds the credibility of clinical trial data.

Evolving alongside human subject protections, FDA regulations, established in 1906, aim to enforce protections for the U.S. public in food, drugs, and cosmetics. Ethical and regulatory challenges continue to surface as scientific and clinical trial advancements occur.

The Kefauver–Harris Amendments of 1962 enhanced FDA controls over drug trials, altering the approval and regulation of new drugs. In 1980, the FDA came under the purview of HHS, expanding its oversight to include human subjects, IRBs, investigational drugs, devices, biologics, food safety, cosmetics, and radiation-emitting products.

The HHS Office of Laboratory Animal Welfare (OLAW) supervises the care and use of animals in research across various settings. Due to their biological similarities to humans, especially in terms of genetic makeup, animals are indispensable in testing potential drugs and medical treatments. The three Rs—Replacement, Reduction, and Refinement—serve as guiding principles for ethical and practical animal research.

Navigating the landscape of research compliance presents many challenges for individuals involved in scientific inquiry and institutional oversight. From grappling with complex regulatory frameworks to addressing emerging ethical dilemmas, ensuring adherence to compliance standards is multifaceted. Some of the common challenges faced by researchers, compliance officers, IRBs, and institutions alike including:

• Federal Awards and Grant Expenditures
• Foreign Influence
• Export Control Regulations
• Research Integrity and Misconduct
• Conflicts of Interest

Federal awards and grant expenditures are crucial in funding research initiatives across various fields. These grants provide financial support to institutions and researchers, driving innovation and advancement in scientific endeavors. Managing a research portfolio with federally sponsored awards necessitates additional oversight due to the complexity of regulations.

Institutions grapple with intricate regulations dictating allowable costs, requiring meticulous attention to budget allocation and expenditure tracking. Additionally, accurate time and effort reporting ensures compliance with federal mandates, warranting thorough documentation of personnel contributions to grant-funded projects.

Cost transfers between budget categories or periods necessitate meticulous justification to mitigate risks of audit findings or allegations of financial mismanagement. Navigating these complexities mandates a robust compliance framework supported by clear policies, rigorous training, and proactive oversight, safeguarding the integrity of federally sponsored research endeavors.

Growing concerns about inappropriate foreign influence on federally funded research led to investigations by the National Institutes of Health (NIH) in 2018. These investigations targeted faculty engagement in research outside the U.S., particularly in China, resulting in terminations, False Claims Act (FCA) allegations, and legal actions. Institutions face increasing pressure to implement stringent compliance measures, including robust due diligence processes for assessing foreign partnerships and collaborations.

Researchers must diligently disclose foreign affiliations or financial interests to funding agencies and IRBs, ensuring transparency and integrity in research activities. Proactive measures, such as comprehensive training on foreign influence policies and mechanisms for monitoring and reporting conflicts of interest, are essential for safeguarding research integrity and upholding national security interests.

Research integrity, guiding ethical principles in professional behavior, intersects with research misconduct involving fabrication, falsification, or plagiarism in HHS-funded research. A robust research compliance program, including responsible conduct of research education, helps prevent, identify, and address research misconduct and ethical issues.

Conflicts of interest (COIs) may compromise a researcher’s professional judgment. COIs within the realm of research pose a significant risk to the integrity of scientific inquiry and the welfare of research participants. These conflicts can sway a researcher’s professional judgment, leading to biased outcomes or compromised ethical standards. Therefore, it is imperative that any significant financial interests or other potential conflicts are disclosed transparently and managed effectively. This transparency enables stakeholders, including IRBs, to assess the possible risks and take appropriate steps to mitigate them.

Managing conflicts of interest involves employing various strategies tailored to each case’s specific circumstances. These strategies may include independent monitoring by impartial parties, adjusting research protocols to minimize bias, or implementing safeguards to protect the interests of research participants.

In conclusion, understanding the history and adhering to the intricate landscape of research compliance are paramount for organizations engaged in healthcare research and administering IRBs. A comprehensive compliance program is vital, from protecting human subjects and animals to managing federal awards, addressing foreign influence concerns, and ensuring ethical integrity. Noncompliance can lead to severe consequences, emphasizing the importance of navigating these challenges with diligence and expertise.

Sitero is committed to supporting organizations in navigating the complexities of research compliance and IRB approvals. Our expertise and tailored solutions empower institutions to proactively address compliance challenges and ensure the ethical conduct of research. Contact us today to learn more about how we can assist you in achieving your compliance goals.