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CHAPTER OBJECTIVES

  • Explain the clinical phases of the drug approval process

  • Understand the guiding ethical principles in clinical research

  • Understand the regulatory framework governing clinical research including informed consent and data confidentiality

  • Explore key ethical challenges involved in clinical research

KEY TERMINOLOGY

  • Belmont Report

  • Beneficence

  • Common Rule

  • Conflicts of interest

  • Data and Safety Monitoring Board

  • Ethical principles

  • Human subjects research

  • Informed consent

  • Institutional Review Board

  • Justice

  • Phase I trials

  • Phase II trials

  • Phase III trials

  • Phase IV trials or post-marketing study

  • Respect for persons

  • Therapeutic misconception

INTRODUCTION

Clinical research, which involves testing interventions in humans to establish their effectiveness and safety, must involve careful design and implementation to ensure the protection of the human subjects. When applied to drug development, the focus of clinical research is on establishing the efficacy and safety of the new drug. Clinical research trials are tightly controlled for both inclusion and exclusion of the participants and design of the protocol, with strict control over study procedures and interventions. It is important to recognize that the overall goal of clinical research is to develop or contribute to generalizable knowledge, which is hoped to be useful to future patients and providers. Clinical research involves actual patients with a disease; consequently, actual effects in terms of benefits and risks to these individuals also become relevant. In clinical practice, the clinician has an obligation to always act in the best interest of the patient. In clinical research, conflicts may arise as the clinician/researcher may have dual goals: to protect the patient/subject and to maintain research integrity.

A case example may help illustrate some of the conflicts that can arise in the conduct of clinical research.1 In the late 1990s, researchers at the University of Pennsylvania were developing a gene-transfer intervention that was intended to target the underlying pathology causing ornithine transcarbamylase (OTC) deficiency syndrome, which is a rare metabolic disorder that leads to the accumulation of ammonia in the blood. An 18-year-old man with partial OTC deficiency was recruited and consented to research. He received an infusion of the study agent and, after a short course, died. His family was distraught, claiming that they were never informed of the possibility of death from the study. A variety of very disturbing facts came to light as part of investigating the death, including issues involving study design, consent, and conflict of interest. It was uncovered that the researcher held patents on the technology being tested, and he had founded and held significant equity in the biotech company that stood to benefit from the clinical trial. The university also held very significant equity in the company. Troubling questions were raised about the researcher’s conflicting interests and whether the young man had been inappropriately enrolled in the trial. In addition to the death of this young man, this tragedy has been a devastating blow to the gene transfer ...

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