Clinical Researcher—June 2025 (Volume 39, Issue 3)

ETHICS IN ACTION

Scott W. Ward, BS, CCRP, CT-C, ACRP-CP

 

 

 

This article explores the evolution of ethical standards in clinical research, emphasizing historical violations and contemporary challenges. With a focus on maintaining participant safety, autonomy, and trust, the article provides clinical research professionals with insights into the foundational principles of ethical conduct, regulatory frameworks, and strategies for safeguarding human subjects in modern research environments.

Background

Ethical conduct in clinical research is essential to ensure the rights, safety, and well-being of participants. While ethical standards have evolved significantly, past violations have left lasting scars, and new challenges continue to emerge. Clinical research professionals play a crucial role in upholding these standards amidst technological advancements and global expansion of trials. This article examines key ethical violations—both historical and contemporary—alongside the ethical frameworks and oversight mechanisms that guide research practices today.

Historical Cases of Ethical Violations

The Tuskegee Syphilis Study—Conducted between 1932 and 1972 by the U.S. Public Health Service, this study involved misleading African American men diagnosed with syphilis by withholding treatment to study disease progression. Participants were denied informed consent and life-saving penicillin, even after it became the standard treatment in the 1940s. The study’s legacy includes widespread mistrust of medical research within Black communities and served as a catalyst for stricter regulatory policies.{1}

Nazi Medical Experiments—During World War II, Nazi physicians conducted non-consensual and often fatal experiments on concentration camp prisoners. These atrocities, which included exposure to extreme temperatures, infection with diseases, and forced sterilizations, led to the development of the Nuremberg Code in 1947—establishing voluntary consent as a cornerstone of ethical research.

Willowbrook Hepatitis Study—Between 1956 and 1970, researchers at the Willowbrook State School in New York intentionally infected children with intellectual disabilities with hepatitis. Although some form of consent was obtained from parents, the coercive nature of enrollment and the vulnerability of the population highlighted serious ethical breaches.

Core Ethical Principles in Clinical Research

Ethical research practices are built upon widely accepted principles, including:

• Respect for Persons: Upholding informed consent and respecting individual autonomy.
• Beneficence: Maximizing potential benefits while minimizing harm.
• Non-maleficence: Avoiding actions that cause harm.
• Justice: Ensuring equitable distribution of research burdens and benefits.
• Confidentiality: Safeguarding participants’ personal information and data.

These principles are embedded in global ethical codes and are essential to maintaining integrity and participant trust.

Contemporary Ethical Challenges

Despite improved regulations and oversight, modern clinical research presents new ethical challenges:

• Globalization of clinical trials: Research conducted in low- and middle-income countries raises concerns about informed consent, standard of care, and potential exploitation.
• Inclusion of vulnerable populations: Individuals with diminished autonomy—such as children, incarcerated persons, or economically disadvantaged populations—require special protections to ensure voluntary participation.
• Conflicts of interest: Financial relationships between investigators and sponsors can compromise objectivity and lead to biased outcomes.
• Data integrity and transparency: Selective reporting, data manipulation, and lack of reproducibility erode public trust and compromise patient safety.
• Emerging technologies: The use of artificial intelligence, genomic data, and digital health tools poses new challenges around consent, data privacy, and algorithmic fairness.

Regulatory and Oversight Mechanisms

Ethical oversight has become more robust, with multiple institutions and guidelines working to enforce compliance:

• Institutional review boards: Review protocols to ensure participant safety and ethical conduct.
• Declaration of Helsinki: Provides internationally recognized ethical guidance for biomedical research.
• Good Clinical Practice: Offers standardized practices for the design, conduct, and reporting of clinical trials.
• Regulatory agencies: Organizations such as the U.S. Food and Drug Administration, European Medicines Agency, and World Health Organization play critical roles in ensuring ethical standards and protocol adherence.

Case Study: COVID-19 Vaccine Trials and Ethics

The urgency of COVID-19 vaccine development tested ethical boundaries. For example, while Moderna’s Phase III trial complied with regulatory expectations, critiques arose around the representativeness of trial populations and informed consent in a high-stakes environment. This highlighted the delicate balance between speed and ethical rigor in public health emergencies.

Moving Forward: Best Practices for Clinical Research Professionals

To prevent ethical violations and promote responsible research conduct, clinical research professionals should:

• Engage in ongoing ethics education and training.
• Foster transparency in funding, design, and results dissemination.
• Prioritize community engagement in protocol development.
• Advocate for equitable access to research and benefits.
• Strengthen global partnerships to harmonize ethical standards.

Conclusion

Past ethical failures in clinical research have taught us invaluable lessons. As stewards of ethical conduct, clinical research professionals must remain vigilant and proactive. By embedding ethical principles into every aspect of clinical research—from design to implementation—we can ensure scientific advancement that respects human dignity and promotes public trust.

Resources

The Belmont Report. 1979. U.S. Department of Health and Human Services.

Emanuel EJ, Wendler D, Grady C. 2000. What Makes Clinical Research Ethical? JAMA 283(20):2701–11.

Lurie P, Wolfe SM. 1997. Unethical Trials of Interventions to Reduce Perinatal Transmission of the Human Immunodeficiency Virus in Developing Countries. NEJM 337:853–6.

National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research. 1973. The Tuskegee Syphilis Study: Ethical Implications.

U.S. Food and Drug Administration. 2023. Code of Federal Regulations – Title 21.

World Medical Association. 2013. Declaration of Helsinki: Ethical Principles for Medical Research Involving Human Subjects. JAMA 310(20):2191–4.

Scott W. Ward, BS, CCRP, CT-C, ACRP-CP, has worked in the clinical research profession for more than 25 years, primarily in oncology Phase I–IV clinical trials. His experience also includes involvement in COVID-19 vaccine trials and, more recently, gastrointestinal Phase II–IV studies. He began his career in data management before moving into clinical research coordinator duties and his current focus on clinical trials management. He serves on the ACRP Ethics Committee, the ACRP-CP Exam Committee, and the Job Analysis Committee, and has been certified through ACRP since 2020.