Published online Mar 20, 2024.
https://doi.org/10.3346/jkms.2024.39.e116
Government Initiatives for Research Ethics During COVID-19 Pandemic in Korea
Abstract
Background
Despite the growing necessity for government-led policy changes on clinical research ethics during pandemic, the scope of previous literature is limited to Korean government’s pandemic response strategies or reflections of research ethics at the level of institutions and academic societies. This paper examines the proactive policy changes and responses by the South Korean government in addressing the challenges and issues of research ethics against the backdrop of the urgency of rapid development and emergency supply of medical products during the coronavirus disease 2019 (COVID-19) pandemic.
Methods
We conducted searches of various government documents, using predetermined keywords related to research ethics and integrity during the COVID-19 pandemic. Only documents issued by governments or public institutions were included. A total of 24 documents were selected for analysis. They were divided into two phases: the first phase for urgent response (January 2020–February 2021) and the second phase (March 2021–February 2023) for long-term preparedness.
Results
The Korean government recommended several measures of research governance to accelerate the ethical review of COVID-related research to be shortened less than one week: the joint operation of Institutional Review Boards (IRBs), exempted or expedited review by a special review committee, guidelines for urgent reviews, and designation of the Korean Academy of Medical Sciences as the supervising agency for the Clinical Trial Safety Support Institution as well as the Central IRB. It allowed temporary non-face-to-face methods for informed consent process (telephone explanations and a photo of the original signed consent) and clinical trials (telephone counselling and prescription, proxy prescription, and drug delivery and supply to clinical trial participants, and online ethics training).
Conclusion
As a result of South Korea’s commitment to ethical principles in their pandemic response, the medical system did not experience collapses due to the pandemic, and pandemic research was conducted with careful ethical considerations. The pandemic ethics immunization during the Middle East respiratory syndrome epidemic in 2015 laid the foundation for prompt government initiatives that ensured both pandemic research ethics and pandemic response ethics.
Graphical Abstract
INTRODUCTION
The coronavirus disease 2019 (COVID-19) pandemic has brought about an unprecedented and challenging crisis for Korean society. The Korean government has actively promoted rapid research and development to control the COVID-19 outbreak while facing unforeseen medical risks. In response to the disruption and hindrance of existing clinical research due to the pandemic, the efforts of Korean society, including accelerated research and development to combat COVID-19, have posed significant practical difficulties and challenges to the established research ethics framework based on regulations and ethical principles. In this context, a proactive government-led response in Korea has been noticeably present, drawing attention for its significance.
The global research community has highlighted the substantial impact of the COVID-19 pandemic on biomedical and research ethics,1, 2 underscoring the necessity for government-led policy changes and national coordination.3, 4, 5 However, there is limited research examining the government’s specific measures in the realm of clinical research ethics. Several studies have explored the Korean government’s response and strategies for COVID-19, but research focusing on research ethics is scarce. The Korean government’s pandemic response ethics are sufficiently extensive beyond the scope of this paper. Instead, this paper focuses on pandemic research ethics and examines the policy changes and responses by the Korean government in addressing the challenges and issues of research ethics in light of the unexpected crisis of the COVID-19 pandemic. It aims to analyze how the Korean government, with a brief overview of the history of clinical research ethics and research integrity governance prior to COVID-19, has taken proactive measures and responses to address the issues of research ethics and research integrity in the face of the crisis.
Disruptions of studies by COVID-19 called for alternative strategies and fundamental shifts in research ethics and methodologies while maintaining safety and ethical standards.6 Regarding potential modifications of research ethics during a pandemic, ethicists proposed expedited administrative process via changes in paperwork, regulations or policies without loosening ethical principles.7, 8 For instance, an Institutional Review Board (IRB) can increase the frequency of ethical reviews from monthly to weekly, providing initial review decisions within 2.13 days.9 COVID-19 pandemic brought substantial challenges in the informed consent process, including uncertainties about new treatments and comorbidities, isolation from family for shared decision making, and limited patient-doctor interactions, while enabling novel mode of communication and electronic informed consent if provided with constant transparent access to information.5, 10, 11, 12 Ethical questions has been raised for exceptional allowances during a pandemic such as delayed consent or consent by a proxy, waiver of informed consent for studies using electronic medical charts or surveys under public health emergencies.13, 14, 15, 16 Despite growing scholarly reflections on pandemic responses for research ethics at the level of institutions and academic communities, government responses for research ethics have been left as lacuna in the literature. Although previous studies called for government policy changes on research ethics, what governments actually implemented those measures during the COVID-19 pandemic have been less explored comprehensively. The Korean government responded proactively to the research ethics challenges that arose due to the COVID-19 pandemic by providing pre-emptive guidelines through a cross-government support team including the Korea Ministry of Food and Drug Safety (MFDS), the Centers for Disease Control and Prevention, and the Ministry of Health and Welfare (MOHW). Subsequently, laws and regulations were established to prepare for potential pandemics and global crisis in the future.
As indicated in Table 1, Korea entered the field of clinical research ethics relatively later but has made significant progress within a short period. It has developed a comprehensive regulatory framework in this area. The regulation of human research ethics in South Korea began with the introduction of the Korean Good Clinical Practice (KGCP) in December 1987 (Table 1). However, the KGCP was not fully enforced at that time. Only when it was implemented on October 1st, 1995, did the regulations become effective in adopting an ethical process to protect the participants and the integrity of clinical trials.17 This included obtaining informed consent from the participants and establishing IRBs for the review, approval, and continuing oversight of the trials. Research ethics committee is an independent autonomous body comprised of a diverse group of members from both the scientific and non-scientific communities that functions on basic principles of autonomy, justice, beneficence, nonmaleficence, confidentiality, and honesty.18
Table 1
Research governance and oversight timeline in Korea
In April 1998, the Korean Food and Drug Administration (KFDA) issued regulations to facilitate a designation system for clinical trial institutions in Korea. Since then, clinical trials can only be conducted in institutions designated by the KFDA. To be designated as a clinical trial institution, the hospital must apply to the KFDA with appropriate facilities, personnel, and an IRB. In January 2000, the KGCP was revised to the level of the International Conference on Harmonisation–Good Clinical Practice, thereby harmonizing ethical requirements for clinical trials in Korea with international regulations.19
In Korea, guidelines and regulations regarding research integrity at the national level were established in 2007, in response to the research misconduct case of Hwang Woo-Suk at the end of 2005.20 In the aftermath of the Hwang Woo-Suk scandal, the Bioethics and Safety Act, which had previously been primarily focused on genes and embryos, was revised in 2013 to expand its regulation to include research involving human materials and human subjects. With the enforcement of the National Research and Development Innovation Act in January 2021, Korea unified the research ethics guidelines that had been differently established by each ministry into a national law, enabling consistent enforcement of research misconduct policies for all research funded by national research budgets.21
Within a relatively short period, Korea has established well-structured regulations and governance related to research ethics and research integrity at the national level. However, the healthcare crisis caused by the COVID-19 pandemic has posed significant challenges in the realm of research ethics, leveraging substantial impact on the trends in biomedical publication and citation frequencies of COVID-19 related studies.2 The Korean government has responded swiftly not only in the field of COVID-19 response but also in the domain of research ethics. This study aimed to examine how the Korean government has addressed the challenges in the areas of research ethics and research integrity after the sudden onset of the COVID-19 pandemic. By analyzing and reflecting on the measures taken by the Korean government in the field of research ethics during the COVID-19 pandemic, this research will provide valuable insights for future crises such as pandemics, climate emergencies, natural disasters, and artificial disasters, which pose significant threats to public health, offering important implications.
METHODS
The Korean government has released hundreds of documents related to COVID-19 from February 2020 to February 2023 (Table 2). In order to examine the challenges and guidance related to research ethics and integrity during the COVID-19 pandemic in Korea, various searches were undertaken of government documents using predetermined keywords: “Research ethics COVID-19,” “Research ethics challenges COVID-19,” “Research integrity COVID-19,” “Research misconduct COVID-19,” “Research governance COVID-19,” “Research ethics oversight COVID-19,” “Ethics guidance COVID-19,” “Research ethics committees COVID-19,” “Scientific integrity COVID-19,” and “Research ethics and clinical trials COVID-19.” For the purpose of this review, only documents related to research ethics and integrity were selected, excluding those related to pandemic response per se. We included only documents issued by governments or public institutions such as Korean Academy of Medical Sciences (KAMS), excluding documents produced by non-governmental organizations or private sectors.
Table 2
Government documents source information
The Korean government’s initiatives for research ethics during the COVID-19 pandemic can be divided into two phases according to its temporal nature. The first phase (January 2020–February 2021) characterized the urgent national response to the pandemic crisis that facilitated research for development of therapeutics while maintaining ethical principles. The second phase (March 2021–February 2023) is centered on long-term preparedness for future crises by establishing legal and institutional frameworks at the national level such as the Central IRB and the Clinical Trial Safety Support Institution. A total of 24 documents were selected for analysis that address themes emerged from the two phases (Table 3). Table 3 shows the documents of Korean government initiatives for research ethics during the COVID-19 pandemic in chronological order.
Table 3
Korean government documents on COVID-19 research ethics
RESULTS
The first phase (January 2020–February 2021)
In the first phase of Korean government’s administrative measures for research ethics, there have been urgent needs to develop pharmaceuticals and vaccines to prevent further morbidities and mortalities during early days of COVID-19 pandemic via research prioritization and modification of clinical trial processes.
Research prioritization
The Korean government established research priorities for the development of diagnostic tools, vaccines, and treatments for COVID-19 (Korea Ministry of the Interior and Safety [MOIS], Korea Ministry of Science and ICT, Korea Disease Control and Prevention Agency 2020.02.06). As part of these efforts, a series of documents, including press releases and public notices, were issued and regularly updated by the Pan-Governmental Support Group (PGSG) on Development of COVID-19 Vaccine and Treatments. This group was launched on April 24, 2020, following the Industry-Academia-Institute Joint Meeting held by the President on April 9th (MFDS 2020.03.27, PGSG 2020.04.24). Given the absence of any effective treatments or vaccines for COVID-19 worldwide, the Korean government recognized the importance of developing these measures in order to overcome the pandemic. To achieve this goal, the government implemented a support system that aimed to facilitate strong and intensive policy measures for effective collaboration among industry, academia, research institutes, hospitals, and the government.
Ethical principles for the COVID-19 research
Since its inception on April 20, 2020, the PGSG has formulated ethical principles to guide the prioritization of clinical trial support. The COVID-19 pandemic has led to an unprecedented surge in demand for clinical trials on therapeutics and vaccines. But there were challenges presented by the limited time available before the end of the epidemic and the restricted number of eligible patients. To address these issues, the PGSG adopted a strategic approach to concentrate national support by establishing priority criteria based on ethical principles.
• First is Safety: Since patients can recover from COVID-19 without treatment, national support should be given to candidate materials with a proven safety record.
• Second is Research Ethics: It is against research ethics to administer a candidate substance that has not completed preclinical studies on animals and phase 1 clinical trials (safety studies on healthy subjects).
• Third is Public Value: Vaccines and treatments are public goods in a pandemic situation, so research that prioritizes public interests should be supported.
• Fourth is International Standard: To ensure global competitiveness, research that meets international standards should be prioritized for national support.
On May 25, 2020, the Chairperson of the National Bioethics Committee (NBC) of Korea issued a statement regarding the COVID-19 situation (NBC Chair 2020.05.25). The Chairperson emphasized that it is the public responsibility of both the government and businesses to lead necessary efforts and cooperate in the development of vaccines and treatments. Furthermore, domestic and international cooperation should be followed in accordance with global standards for research. The safety of research participants must be prioritized in clinical research, regardless of the urgency and importance of the research. All clinical research must adhere to the basic norms of bioethics, with scientific and ethical judgment determining whether the risk is acceptable to the research participant.
Prompt and efficient IRB review
On March 20, 2020, the MFDS issued a document entitled “Considerations for COVID-19 Related Clinical Trial,” which was distributed to Clinical Trial Institutions, IRBs, and the Korean Association of IRBs (MFDS 2020.03.20) This document addressed the key features of changes necessary to adapt to the radically altered situation due to the COVID-19 pandemic. The MFDS requested that all IRBs in Korea prioritize the review of COVID-related research. Normally, IRB review takes one to two months, but due to the urgent pandemic situation, the government requested that the review process be shortened to less than one week. To facilitate prompt and efficient IRB review, the MFDS recommended the joint operation of IRBs and the designation of a review committee for consignment review. The MFDS also provided guidance on the deliberation procedure of IRBs. Each IRB can conduct non-face-to-face meetings, such as video conferences, to prevent the spread of infectious diseases, provided that appropriate methods for deliberation are prepared, operated, and documented in compliance with the Pharmaceutical Affairs Act.
The PGSG assigned the Public Institutional Bioethics Committee (IRB) to swiftly deliberate on COVID-19-related research on April 20, 2020 (PGSG 2020.04.24). Starting from April 29, 2020, the Public IRB established at the National Institute of Bioethics Policy has begun to operate an expeditious review process for COVID-19-related studies that can be exempted from IRB review based on the exemption criteria outlined in the Bioethics and Safety Act.
According to the Bioethics and Safety Act, research that is commissioned directly by national and local governments during a public health emergency and research that uses COVID-19-related data owned by the Health Insurance Review and Assessment Service can be exempted from review. In May 2020, the National Institute of Bioethics Policy established a special review committee dedicated to reviewing COVID-19 research, so that the review process for COVID-19 research that is not subject to review exemption can be expedited (Korea National Institute for Bioethics Policy [NIBP] 2020.04.28; MOHW, NIBP 2020.04.29).
The MFDS issued comprehensive guidelines on November 30, 2020, which were swiftly reviewed by the IRBs (MFDS 2020.11.30). This was in response to the urgent need to develop drugs for the COVID-19 pandemic, which had caused over 50 million infections and 1 million deaths worldwide by that date. Regulatory agencies in various countries had been working diligently to shorten the timeline for clinical trials of COVID-19 candidates through prior consultation, rapid review, and approval. The guidelines provide detailed procedures for the urgent review of protocols, including whether or not to use an urgent review, the composition of the urgent review IRB, and the process and notification of urgent review results.
The examples of urgent review cases include clinical trials related to current or future national disasters, critical safety, or life-related issues, as well as situations where a serious hazard to bioethics or safety is present, or clinical trials utilizing life science technology that could have a significant ethical and social impact. In cases requiring urgent review, an emergency meeting must be held promptly, regardless of the regular review schedule. For multicenter trials, a joint review committee or an external designated review committee is strongly recommended. On December 30, 2020, the MFDS issued Joint Review Committee Operation Guidelines, which detailed the procedures and principles of the joint IRB for multicenter clinical trials (MFDS 2020.12.30).
In cases where COVID-19 patients are in serious or imminent danger, the IRB is requested to expedite their deliberation process to ensure that the use of investigational drugs for therapeutic purposes is not delayed. The MFDS issued this guidance on January 12, 2021, which facilitates the availability of potentially life-saving investigational drugs for COVID-19 patients who urgently require them (MFDS 2021.01.12).
Adaptation of informed consent process
From the early phase of the COVID-19 pandemic, MFDS gave guidelines on the informed consent process adapted to the changed situation (MFDS 2020.03.20). In the case of participants (including their legal representatives) of clinical trials for COVID-19 treatment, it is possible to proceed with the consent process through telephone explanations, etc., considering the isolated situation. If it is necessary to destroy the consent/explanatory note (signed original) provided to the subject during the process of consent to participation to minimize infection through the paper, the testing institution may replace the original paper with a photo of the original signed consent of the subject for documentation. When the participant (including their legal representative) is released from the quarantine, consent and explanation form should be given to the clinical trial subject again.
Adjustment of clinical trial conduct process
The MFDS has issued guidelines to adjust clinical trial processes, including drug prescription and management, remote clinical trial visits, and other logistical considerations, to account for the unique challenges posed by the COVID-19 pandemic. These guidelines were developed to facilitate clinical trial operations while ensuring participant safety and data reliability throughout all stages of the trials. Notably, the MFDS provided early guidance on how to adjust investigational drug prescription management in response to the pandemic. Overall, these guidelines represent an important effort to ensure that clinical trials can continue to operate effectively in the face of disruptive external factors (MFDS 2020.03.20).
While disruptions and deviations are inevitable due to COVID-19, the MFDS has emphasized the importance of developing pre-emptive measures and promptly seeking approval from the IRB for each subject to ensure ethical acceptability. The MFDS has temporarily permitted measures such as telephone counselling and prescription, proxy prescription, and drug delivery and supply to clinical trial participants under the same standards as commercially available drugs. The MFDS has provided guidance on specific aspects to be reviewed in advance, including individual safety factors, continuous or repeated prescription of the same medicine, omission of pre-prescription and laboratory tests for severe diseases, reliability of laboratory test results from other testing institutions, and stable delivery through a pre-determined delivery company. The MFDS has recommended assigning responsibility for COVID-19 related measures in individual clinical trials to both the principal investigator and sponsor in accordance with the Pharmaceutical Affairs Act. Given the varying characteristics of each trial, pre-emptive measures to address potential protocol deviations arising from COVID-19 should be established and approved by the IRB. Overall, these measures aim to ensure the safety and ethical acceptability of clinical trials during the ongoing pandemic.
On January 12, 2021, the MFDS issued guidelines for conducting temporary non-face-to-face clinical trials in response to the COVID-19 crisis. These guidelines can be applied during a period when national crisis level of the COVID-19 response is escalated to the heightened alert stage, “Warning.” The Medical Act and the Infectious Disease Prevention and Management Act temporarily permit non-face-to-face patient treatment and care, and medical treatment during the clinical trials can also go on with non-contact measures. The MFDS provided detailed instructions on the procedures and criteria for conducting these trials, including who can conduct them, when they can be conducted, and what needs to be done (MFDS 2021.01.12).
Flexible training for clinical trial workers
In January 2015, the Pharmaceutical Affairs Act was revised to mandate education for clinical trial personnel. The Ordinances of the Pharmaceutical Affairs Act set mandatory training hours and required methods and contents for each group of clinical trial investigators, monitors, research coordinators, IRB members, and auditors. Due to the COVID-19 pandemic, research institutions have faced difficulties in conducting in-person training sessions, prompting the MFDS to issue a notice in April 2021, allowing for online and non-face-to-face education to fulfil mandatory legal education requirements for clinical trial practitioners (MFDS 2021.04.01). On January 12, 2021, the MFDS provided more detailed policy for mandatory education for clinical trials, recognizing real-time remote video education as on-site training, and encouraging hands-on practical training, case-based workshops, and other approaches that enable actual job training (MFDS 2021.01.12).
As clinical trials for COVID-19 treatments and vaccines have become increasingly active, the MFDS has implemented special measures to ensure that clinical trial practitioners can receive rapid education and participate in COVID-19 clinical trials. In cases where practitioners are unable to participate in COVID-19 clinical trials due to a lack of certified mandatory training within a short period of time, the MFDS has allowed the sponsor and the head of the clinical trial institution (including principal investigators) to replace mandatory training with their own education, provided it covers sufficient ethical considerations such as protection of clinical trial subjects, vulnerable populations, and conflicts of interest, as well as safety reporting and other necessary contents for GCP and implementation of clinical trial plans. The MFDS has also instructed that such self-education content and attendance signatures be documented. To aid in self-education, the MFDS has provided online educational materials such as the ‘Program for the Protection of Clinical Trial Subjects and Ethics Reinforcement,’ developed by the MFDS and Korea Institutional Review Board (MFDS 2021.01.12).
Mobilization of COVID-19 patients and institutions for clinical trials
To expedite the development of treatments and vaccines for COVID-19, the Korean government has mobilized COVID-19 patients and designated hospitals to participate in clinical trials. To accomplish this, the existing system for designating clinical trial institutions, which has been in place since 1998, has been relaxed and modified. However, as the number of COVID-19 patients and severe cases decreased in Korea in September 2020, conducting clinical trials for COVID-19 treatments and vaccines became difficult. To address this issue, the MOHW established the “National Infectious Disease Clinical Trial Center,” which consists of consortia between designated hospitals capable of conducting clinical trials and COVID-19 designated hospitals with a high number of hospitalized patients (PGSG 2020.09).
To ensure a smooth process for securing COVID-19 clinical trial participants and supporting multi-site clinical trials, the MOHW has arranged for COVID-19 patients who have agreed to participate in clinical trials to be transferred to hospitals conducting clinical trials, based on the medical judgment of the attending physician. The MFDS has also provided guidelines on participation procedures, as well as the entities responsible for clinical trial management and supervision, in order to enable medical institutions that have not been designated as clinical trial institutions to participate in COVID-19 clinical trials (MFDS 2021.01.12).
The second phase (March 2021–February 2023)
The second phase of the research ethics-related initiative of the Korean government’s COVID-19 pandemic response aimed to establish legal and institutional frameworks for future public health crisis responses.
Emergency supply of public health crisis response medical products
As South Korea experienced consecutive outbreaks of infectious diseases such as severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and COVID-19 in the 21st century, the development and stable supply of vaccines and therapeutics for infectious disease prevention have been recognized as core issues for national security and competitiveness. Consequently, on March 9, 2021, “The Special Act on Promotion of Development and Emergency Supply of Public Health Crisis Response Medical Products” was enacted at the peak of the COVID-19 pandemic. The primary objective of this legislation is to facilitate prompt responses to a wide range of public health crises, including infectious disease outbreaks such as pandemics, as well as incidents involving biological and chemical weapons, nuclear power plants, radiation emergencies, and radioactive disasters.
The COVID-19 pandemic has highlighted the urgent need for a supply system that can manage the production, import, and distribution of necessary medical products to respond quickly to public health emergencies. However, the current individual laws, such as the Pharmaceutical Affairs Act and the Medical Device Act, lack institutional mechanisms to support the development and emergency supply of pharmaceuticals and medical devices.
As a result, it has become imperative to establish a distinct legal framework that oversees the entire spectrum of medical products, encompassing pharmaceuticals (such as vaccines and therapeutics), non-pharmaceuticals (like masks and hand sanitizers), and medical devices (including diagnostic kits and artificial cardiopulmonary devices), with the capacity to rapidly research, develop, and supply emergency products in a consistent manner during public health crises. Consequently, there has been an increasing societal demand for a system that can accelerate the development and market entry of essential medical products by providing expedited approval and development support for products that can effectively respond to public health emergencies.
To achieve this aim, it is essential to allocate increased resources and people power, and to foster collaboration between the government and private sector entities. To facilitate the swift development of medical products for public health emergency response, a comprehensive system has been established which includes the designation of medical products for preliminary approval, priority review, rolling review, expedited review with conditional approval, and urgent production and import orders, as well as the implementation of measures to improve distribution. The law provides a legal basis for emergency use authorization, conditional approval, and review of crisis response medical products, such as vaccines, therapeutics, masks, and diagnostic kits, to ensure their rapid deployment and stable supply in crisis situations.
As a critical provision of this law, the Emergency Medical Products Safety and Supply Committee has been established within the MFDS to oversee the safety and supply of medical products for emergency public health crisis response. The Committee brings together experts and relevant government agencies responsible for medical product management, including the MOHW and the Korea Centers for Disease Control and Prevention, as well as other agencies such as the Office of the Prime Minister, the Ministry of Economy and Finance, the Ministry of Foreign Affairs, the MOIS, and the Ministry of National Defense, to establish a legal framework for an integrated national system that can allocate budgets and resources during times of crisis. In practice, the Committee has played a critical role in decision-making regarding the introduction of vaccines and therapeutic agents, as well as enhancing the distribution of diagnostic kits during the COVID-19 pandemic.
This law empowers the Commissioner of the MFDS to provide support for planning, subject recruitment, conducting international joint clinical trials, and providing relevant information for clinical trials of designated emergency medical products, for which plans have been submitted by the parties seeking to conduct such trials. Furthermore, for emergency medical products or devices that cannot undergo human clinical trials for ethical reasons, or for which the effects can only be partially predicted through clinical trials, the law provides a provision for submitting certain documents separately within a specified period when applying for approval, enabling the approval of such products. The MFDS has also issued various guidelines to facilitate clinical trials under this law (MFDS 2021.04.02; MFDS 2021.11.26; MFDS 2022. 05; MFDS 2022.05; MFDS 2022.09.30).
Clinical trial safety support institution and Central IRB
On July 20, 2021, the Pharmaceutical Affairs Act’s fifth clause was established to designate a Clinical Trial Safety Support Institution and a Central IRB. The MFDS established a Central IRB to review clinical trials for drugs such as COVID-19 vaccines, treatments, and anti-cancer drugs required by the public. On January 20, 2022, the KAMS was designated as the supervising agency for the Clinical Trial Safety Support Institution and Central IRB (MFDS 2022.07.29). Regulations governing the designation and operation of the Clinical Trial Safety Support Institution and Central IRBs were put into effect, and the Central IRB’s review scope was expanded to include all diseases. The Central IRB conducts comprehensive reviews of multicenter clinical trials from various perspectives, including ethical, scientific, and medical aspects, to protect the rights, safety, and welfare of clinical trial participants and ensure the validity and reliability of clinical trials. Its objectives include reducing the burden on IRBs of individual institutes, promoting the rapid entry of new drugs into clinical use, and streamlining administrative procedures in multicenter clinical trials. The board also strengthens the safety net for trial participants and expands treatment options by supporting the rapid introduction of new drugs developed by the pharmaceutical industry (KAMS 2023.02).
DISCUSSION
When the first COVID-19 patient came to Korea from China on January 20, 2020, the Korean government set the infectious disease crisis alert to ‘caution.’ On February 23, the COVID-19 infectious disease crisis alert was raised to ‘serious.’ On March 11, 2020, the World Health Organization declared COVID-19 a pandemic, the third after the Hong Kong flu in 1968 and swine flu in 2009. In the early stages of the COVID-19 outbreak, when there were no vaccines or treatments available, Korea focused on building its Testing-Tracing-Treatment (3T) capacity with the goal of “suppressing the emergence of confirmed cases.” Despite being one of the countries that suffered the most damage during the early stages of the pandemic, Korea managed to quickly flatten the curve after late March 2020 and has been praised for its response compared to other countries.22, 23 The official response of the Korean government to COVID-19 is based on the three principles of transparency, openness, and democracy, and adopts the 3T strategy.24, 25, 26 The 3T strategy involves identifying and isolating confirmed cases early through mass and rapid testing and tracing and providing treatment. Within this context, the South Korean government deployed several measures to promote research for rapid development and emergency supply of medical products to control COVID-19 pandemic, while maintaining ethical principles of research.
The success of South Korea’s pandemic response and research was rooted in its experience with the 2015 MERS outbreak.27, 28, 29 At that time, South Korea had the second-highest number of MERS patients and deaths after the Middle East. In the early stages of the outbreak, the government did not disclose information about disease occurrence and transmission due to concerns about patient privacy and hospital reputational damage, despite the high uncertainty regarding the nature of the disease.30 However, as the number of patients increased and deaths surged, public distrust, anxiety, and fear grew significantly, leading to stigma and discrimination against MERS patients and their families. Moreover, the disease’s spread within hospitals resulted in further stigmatization and discrimination against healthcare workers and their children. Similar to Hong Kong and Singapore’s experiences with SARS, Korea suffered severe economic damage from MERS. The Korean response to MERS was not based on ethical principles, or more accurately, lacked ethical and effective pandemic response preparedness, leading to the spread of an unknown infectious disease, fear, significant confusion, and public distrust.31 After experiencing MERS, Korea thoroughly reflected on its lack of overall preparedness for emerging infectious diseases and subsequently established various legal and systemic frameworks, as well as strengthened its infrastructure and capacity, which produced effective governance and coordination between government, market, and civil society.32, 33 This resulted in an effective response to the COVID-19 pandemic when it occurred. One of the measures taken was the revision of the Infectious Disease Control and Prevention Acts.
Since 1998, only institutions designated by the MFDS are allowed to conduct clinical trials in Korea. These institutions must meet certain requirements such as having appropriate facilities, equipment, personnel, and IRBs to conduct clinical trials. In this unique system in Korea, the regulatory authority, the MFDS assigns the responsibility for ethical oversight of clinical trials to clinical trial institutions. During the COVID-19 pandemic, this system was temporarily relaxed and modified to allow clinical trials related to COVID-19 to be conducted at institutions that were not designated as clinical trial institutions. Some COVID-19 patients received treatment isolated in medical institutions that were not designated as a clinical trial institution. In these cases, the MFDS allowed a consortium to be formed between designated and non-designated institutions, with the designated institution’s IRB providing ethical review and oversight for clinical trials conducted at the non-designated institution. Additionally, the MFDS issued guidelines allowing for online training of clinical trial practitioners, as alternatives to mandatory face-to-face education for those conducting clinical trials. This flexible and efficient government response to the COVID-19 pandemic can be evaluated as a means of promoting research while ensuring safety and ethical standards in clinical trials.
In Korea, there were no incidents of clinical trial institutions, such as hospitals, closing their doors due to the successful response to the COVID-19 pandemic. In the initial phase of the pandemic in February and March 2020, 12% of clinical project managers reported that COVID-19 hindered subjects’ scheduled study visits.34 Contrary to initial concerns from the government and academia, seriously ill patients receiving medication through clinical trials, such as cancer patients, rarely experienced delays in receiving testing or medication in the outpatient care and hospitalizations due to the pandemic, unlike in the United States or some European countries.35 There have been no instances of border closure or city lockdowns, and hospitals have not closed their doors, although there were cases where patients with COVID-19 could not receive timely treatment for being unable to attend scheduled appointments. However, there were hardly any cases where medication or testing were unable to be administered. Yet the MFDS has not actively participated in global data standardization collaboration efforts, which should be seriously considered in the future. On the whole, both the government and academic community in Korea have consistently emphasized the importance of protecting research participants and research ethics principles in discussions and practices related to pandemic research and development.
There is a close relationship between pandemic response and pandemic research that reinforces each other (Fig. 1). To effectively respond to a pandemic, prompt and high-value pandemic research must be conducted, and its results play a crucial role in enhancing the pandemic response. In the early stages of the pandemic, research on the characteristics of the coronavirus and the resulting pandemic, as well as research and development of infection diagnostic methods, made significant contributions to Korea’s rapid response to COVID-19.
Fig. 1
A model for the relationship between pandemic research ethics and pandemic response ethics.
The success of the South Korean government’s pandemic response can be attributed to its adherence to ethical principles of transparency, openness, and democracy.36, 37, 38, 39, 40 Thus, pandemic response and ethics have an integrated relationship that cannot be separated. Various ethical discussions have taken place regarding pandemic response, including considerations of the ethical implications of restricting freedoms for the greater public good,41 vaccine distribution ethics,42 and mandatory vaccination.43 Adhering to ethical principles, prioritization for COVID-19 patient testing, treatment, and vaccination supply was determined and provided for without cost through government funding. As a result of Korea’s commitment to ethical principles in their pandemic response, the medical system did not experience collapses due to the pandemic, and pandemic research was conducted with careful ethical considerations.
The experience of MERS in Korea can be metaphorically likened to a vaccination.28 In terms of Korea’s ethical response to infectious diseases, the MERS outbreak served as a “pandemic ethics immunization.” The experience with MERS taught the Korean people that it is better to cooperate and control infectious diseases early on, rather than waiting until it becomes uncontrollable. Korea used advanced technology and implemented the 3T strategy to control MERS within three months. Based on this experience, the government revised its infectious disease prevention measures to allow for the collection of information without individual consent for disease control purposes. The government also actively communicated with the public, ensuring transparency and openness by networking with various stakeholders and involving them in decision-making. To prevent the spread of COVID-19, the Korean government emphasizes providing prompt, accurate information and encouraging voluntary participation. From the perspective of Western countries, pandemic response methods such as internet-based disclosing of information involving the location and movement of confirmed cases and implementing self-quarantine measures for contacts may appear to have elements of human rights infringement. However, the Korean public has reached social consensus on these measures through the experience of MERS, and they have been legislated as future pandemic response policies. During the pandemic, the voluntary participation of citizens in wearing masks, disinfecting their hands, and practicing social distancing has been emphasized. As a result, certain activities have been transitioned to non-face-to-face methods, but there has been no need for a complete shutdown as the measures were able to be sustained.
The practical implications of this study's findings are as follows: during the COVID-19 pandemic, the Korean government implemented institutional and practical changes regarding research ethics to overcome the pandemic. These changes, such as the establishment of the Central IRB and the Clinical Trial Safety Support Institution based on the revised Pharmaceutical Affairs Act, need to be further developed to ensure their efficiency and suitability even after the pandemic ends.
In conclusion, the COVID-19 pandemic in Korea advanced not only population-based bioethics, but also deepened and developed individual-based bioethics, which respects the rights and autonomy of individuals, both in pandemic research ethics as well as in pandemic response ethics, largely due to pandemic ethics immunization during the MERS epidemic in 2015.
Funding:This research was supported by the Pro-active Pandemic Crisis Ethics and Integrity Framework (PREPARED) project through the European Commission (grant No. 101058094).
Disclosure:The authors have no potential conflicts of interest to disclose.
Author Contributions:
Conceptualization: Park YS, Kim OJ.
Data curation: Kim OJ.
Formal analysis: Kim OJ.
Funding acquisition: Kim OJ.
Investigation: Kim OJ.
Methodology: Kim OJ, Park YS.
Validation: Park YS.
Writing - original draft: Kim OJ, Park YS.
Writing - review & editing: Park YS, Kim OJ.
ACKNOWLEDGMENTS
The authors give thanks to Doris Schroeder, Professor at the Centre for Professional Ethics, University of Central Lancashire, Preston, England, who secured the research fund, reviewed and commented this manuscript.
References
-
Ten Have H. In: The COVID-19 Pandemic and Global Bioethics. Cham, Switzerland: Springer; 2022.
-
-
Zhang H, Shao F, Gu J, Li L, Wang Y. Ethics committee reviews of applications for research studies at 1 hospital in China during the 2019 novel coronavirus epidemic. JAMA 2020;323(18):1844–1846.
-
-
Yang JH. Korean Good Clinical Practice. J Korean Soc Clin Pharmacol Ther 1996;4(1):35–48.
-
-
Kim OJ. The National Academy of Medicine of Korea. Bioethics and research ethics in Korea after Hwang Woo-Suk Scandal. In: The Hwang Woo-Suk Scandal 10 Years Ago From the Present Perspective. Seoul, Korea: Park Young-Sa; 2018. pp. 37-49.
-
-
Lee MJ, Kim OJ, Cho EH, Jeon JH, Lee DH, Lee S, et al. Introduction of the National R&D Innovation Act and research ethics in Korea. Asia Pac J Health Law Ethics 2021;14(2):155–192.
-
-
Choi JY, Lee SH, Jamal T. Smart Korea: governance for smart justice during a global pandemic. J Sustain Tour 2021;29(2-3):541–550.
-
-
You K, Kim D, Kim OJ. Application and expansion of the harm principle to the restrictions of liberty in the COVID-19 public health crisis: focusing on the revised bill of the March 2020 ｢Infectious Disease Control and Prevention Act｣. Korean Soc Law Med 2020;21(2):105–162.
-
-
Fang Y, Kim OJ. The ethics of COVID-19 vaccine allocation. Korean J Med Ethics 2021;24(2):121–137.
-
-
You K, Kim OJ. A review of the justifications for mandatory vaccination policies in response to the COVID-19 public health crisis. Korean J Med Ethics 2022;25(1):1–20.
-
