ENFORCING ETHICAL INFORMED CONSENT PRACTICES TO PROTECT HUMAN RIGHTS IN THE PURSUIT OF CLINICAL RESEARCH GLOBALIZATION.

• Author: Farhat, Chena

1. INTRODUCTION

   The evolution of clinical research dates back thousands of years. (1) From the earliest clinical trials, medical research has advanced into the complex globally tested trials performed today. (2)

   With advancements in trial design, it became increasingly vital to ensure strong ethical standards were not only driving research, but also protecting human life, rights, and dignity. (3) Informed consent is one of the most important mechanisms for ensuring ethical execution of clinical trials. (4) As the pharmaceutical industry and practice of conducting clinical trials has grown in complexity and created a more substantial global footprint over time, the risk of neglecting adequate informed consent provisions is a growing concern, particularly in less developed areas. (5)

   This Note discusses the critical need for ensuring ethical informed consent is carried out across global clinical trials, regardless of the regulatory standards, or lack thereof. (6) Part II of this Note highlights the significant history behind the development of the informed consent process, which poignantly illustrates the potential threat of historical atrocities repeating themselves. (7) Part III explains the growth of clinical trials over the years and the ensuing regulatory complexities to starting, monitoring, and executing international clinical trials while ensuring adequate ethical standards and voluntary informed consent. (8) Part IV explains the need to implement stronger provisions on an international level for ethical clinical trials and informed consent regulations that will enforce compliance by pharmaceutical companies worldwide. (9) Finally, Part V concludes with a summary of this critical issue and a call to the global community to unite against this humanitarian issue to ensure human rights are preserved and further atrocities against human lives are not committed. (10)

2. HISTORY

   1. The Evolution of Ethical Clinical Research

      The evolution of clinical research transcended a variety of challenges over the years, from scientific to regulatory to ethical. (11) The industry has made significant strides in developing and progressing the standards for quality research and development. (12) Although science and technology are essential to clinical research, it is still important to remember the critical role of human rights in the progression of this field. (13) Science and human rights are not mutually exclusive topics; in fact, they intertwine at their very core. (14) Sadly, in the pursuit of clinical research, human rights have historically been abused. (15) Despite the advancements in regulation, as clinical research globally expands and clinical trials trickle down into developing nations, an increased awareness of informed consent regulations is necessary to ensure human rights are not abused and ethical lines are not blurred. (16)

   2. The Nuremburg Code

      Following the end of World War II, the International Military Tribunal held a trial of doctors charged with overseeing and executing inhumane medical testing against innocent prisoners of war on behalf of the Nazi regime. (17) The defendant doctors were charged and convicted of conspiracy to commit war crimes against humanity, war crimes, crimes against humanity, and membership in a criminal organization. (18) Their crimes included carrying out medical experiments against the will of the prisoners to study various diseases and anatomical processes, including testing of malaria vaccines, sterilization, and bone, muscle and nerve transplantation surgery. (19) Following the convictions of these criminals, the Nuremberg Trials laid out a new and improved standard of medical ethics focusing on respecting human rights, which would be recognized as, The Nuremberg Code. (20)

      The Nuremberg Code was a pivotal ethical development that established ten requirements to be followed in the pursuit of medical research. (21)

   3. The Declaration of Helsinki

      The Declaration of Helsinki was instituted in 1964 and is rooted in ensuring the priority of clinical research focuses on the health and safety of the humans participating. (22) The Declaration of Helsinki echoes many of the principles outlined in the Nuremberg Code, while further building upon the requirements and standards for obtaining voluntary informed consent. (23) The Declaration of Helsinki was premised on the notion that the need for knowledge and information cannot take precedent over respecting human life and human rights. (24) The Declaration of Helsinki was curated to focus on what would be considered as indisputable human rights, nevertheless, reaching a consensus among the global community was extremely challenging, which further underscored the alarming need to continuously enforce respect for human rights in clinical research. (25)

   4. The Belmont Report

      The Belmont Report was first published in 1979 by the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research. (26) In response to the 1974 National Research Act, the National Commission was charged with developing the Belmont Report. (27) The 1974 National Research Act and subsequent Belmont Report emphasized the need for respecting humans and limiting any restrictions upon their autonomy, with the goal of ensuring that benefits outweighed the risks and that all individuals would be treated equitably without discrimination. (28) In addition to the development of the Belmont Report, the 1974 National Research Act created one of the most pivotal and fundamental ethics enforcers in clinical research: the Institutional Review Boards (IRBs). (29) The U.S. Food and Drug Agency (FDA) outlines the provisions of IRBs in the Code of Federal Regulations Title 21. (30) Furthermore, the development of the Belmont Report provided vital clarification for understanding and applying informed consent in clinical research. (31)

3. FACTS

   There are over 400,000 registered clinical trials spanning across the globe. (32) The United States, as well as a number of countries in Europe, tend to have the highest number of clinical trials per country; however, Africa, the Middle East, South America, Eastern Europe, and Asia, together, register a significant number of trials as well. (33) The increasing globalization of clinical trials presents complicated challenges in managing differing legal and ethical standards among nations. (34) Ensuring adequate informed consent is particularly challenging as there are numerous language and cultural differences to overcome. (35)

   Obtaining informed consent is more than simply getting an individual to sign off on participating in a clinical trial. (36) Per FDA standards, informed consent requires ensuring that the informed consent form comprehensively covers the risks and benefits of participating in the trial while at the same time being written in lay terms which can be fully understood by an individual of at least an elementary school reading and writing level. (37) The informed consent process also requires that the participant is given adequate time to consider their potential participation, have all of their questions answered, and must be free from any coercion or persuasion inducing participation. (38) Similar to the United States and the FDA, the European Union has also developed and implemented a sophisticated informed consent process. (39) The European Union further strengthened its informed consent regulations by requiring comprehensive data protection guidance and language. (40) Considering that clinical trials involve human subjects who inherently handle significant quantities of sensitive data, the European Union General Data Protection Regulation (GDPR) significantly impacts the clinical research and corresponding informed consent process. (41) The GDPR underwent a serious update as recently as May 2018, where the framework maintained many of the foundational protections, but also enhanced regulations by initiating several new requirements and amplifying the consequences for noncompliance. (42)

   The EU is a global trailblazer in comprehensive data protection regulations and, therefore, any clinical trial (EU based or not) that wishes to operate in the EU must ensure its informed consent forms comply with the GDPR standards. (43)

   In an effort to harmonize clinical research standards for participant protection, the Office for Human Research Protection developed an international program to compile a list of human research standards among nations throughout the world. (44) The 2020 edition of the International Compilation of Human Research Standards outlines over 1,000 global standards from 133 countries with the purpose of protecting human research participants. (45) The stark disparities among nations with regards to informed consent standards are apparent, and there is serious concern that less developed countries may be ill-equipped to adhere to the necessary protection safeguards. (46) Some countries lack strong regulations that promote full transparency to patients. (47) Furthermore, many countries are largely guided by cultural norms, some of which contrast with disclosure requirements outlined by informed consent standards. (48)

   Despite the apparent threats to informed consent integrity, clinical trials are still rapidly shifting into less developed countries. (49) As the pharmaceutical industry grows, corporate executives have increasingly been analyzing which aspects of the pipeline can shift to lower cost areas. (50) Recognizing the shift in the clinical trial landscape, some countries are working towards engaging pharmaceutical companies to run their clinical trials. (51) Although at first glance such countries present a promising future, on a deeper level, they present complicated issues compromising clinical trial and patient protection standards. (52)

4. ANALYSIS

   1. Responsibility of Drug Development Leaders

      Beyond science, innovation, and technology, the fundamental...