Challenges and strategies to research ethics in conducting COVID‐19 research

Abstract The number of research involving human subjects on coronavirus disease 2019 (COVID‐19) is surging, bringing challenges to the ethical review committee (ERC) in terms of reviewing speed and special ethical considerations under the pandemic. However, the existing ethical review system and regulations have their limitations to meet the demand for a prompt and efficient epidemic control. Since the research under the public health emergency is different from that carried out in familiar situations to design and implementation, the strategy for a satisfactory ERC response should balance the duty of protecting individual participants as well as the special public needs derived from the disease control. It is suggested that the ethical review‐related regulations need to be updated, and a unified supervision system to the overall ERC is required. ERC collaboration, capacity‐improving and efficiency‐improving measures need to be taken. With respect to the reviewing guidelines, it is suggested that the international norms should be explained with more consideration of the local condition and the exceptional circumstances in this public health emergency. A joint effort needs to be taken for better research conduction.


INTRODUCTION
In December 2019, an epidemic with pneumonia as the major manifestation of the 2019 novel coronal virus infection first broke out in Wuhan, China, imposing massive impact on China and the world. 1,2 This new coronavirus is highly infective, threatening public health and safety. The disease was so severe that as early as 30 January 2020, Widely recognized by the international community, ethical review plays an important role in protecting the rights, safety, and well-being of the research participants and ensuring the scientific correctness.
In the current grim situation of the epidemic, the authors believe that in the COVID-19 emergency condition, the exceptional circumstances of the pandemic should justify the use of unproven interventions just like the WHO panel considered in 2014 for the Ebola disease. 3 Therefore, the ethical review committee (ERC) should explain the general ethical principles more flexibly, streamline the work, and facilitate its procedure as a response if it allows. The priority to the protection of life and the pursuit of effectiveness should always be kept in mind. Therefore, the research during an unusual period can be reviewed, and informed consent can be obtained in a timely and reasonable manner.

CHARACTERISTICS OF RESEARCHES ON COVID-2019
Scientific research is of great significance to quickly understand the COVID-19 when there is no definitive treatment for it, thus promoting the emergency response. On 30 January 2020, the WHO issued temporary recommendations that we should enhance public health measures for containment of the current outbreak, continue to identify the zoonotic source of the outbreak, and particularly the potential for circulation, and conduct investigations to understand

ETHICAL REVIEW OF RESEARCH UNDER COVID-19 EPIDEMIC
It's widely known that an ethical review is required before the launch of any biomedical research involving human subjects. The ethical review for researches of COVID-19 at this time is at "exceptional circumstances" for a series of special considerations, such as the magnitude of the epidemic, its contagiousness, additional burdens on health

Case
Is informed consent necessary for epidemiological investigation of COVID-19 using electronic medical record?

Paragraph 32 in Declaration of Helsinki (2013)
For medical research using identifiable human material or data, such as research on material or data contained in biobanks or similar repositories, physicians must seek informed consent for its collection, storage, and/or reuse. There may be exceptional situations where consent would be impossible or impracticable to obtain for such research. In such circumstances, the research may be done only after consideration and approval of a research ethics committee.

Research in disasters and disease outbreaks in International Ethical
Guidelines

Claim
The investigation uses the medical history, and the identifiable human data are involved, so the ethical review is mandatory. Informed consent obtaining is not impossible in the epidemic. CIOMS also claims that an ethics committee should not approve a waiver of informed consent because of obtaining difficulties. To get the informed consent and signature, if possible, it is required to ensure that the interests of these subjects are being served.

The counter claim
All researches in the epidemic are racing against time. Risks involved in investigations with electronic history are minimal; the arrangement of informed consent and the signature seems to be burdensome; medical personnel as the researchers will be more likely to be infected, entailing more risks than benefits.

Reflection: ethical review in a public health emergency should take special circumstances into account
Ethical review is an institutional tool recognized for the safe conduc-

Suggestion
With the above-mentioned principles of seeking substantial results and giving priority to life, the ethical committee can decide to streamline the review algorithm by removing temporarily the informed con-sent procedure or just the signature of the consent. In the specific conduction of an investigation, oral informed consent can be employed first, and the written consent can be signed after the subject is recovered from the disease and released from quarantine, if possible. In addition, if one changes his or her mind and refuses to sign the informed consent, then his or her data can be excluded from the research. Hence, the informed consent right of the potential subjects is respected. Signature obtained afterward can also minimize the infection risk during research, protecting the life security of the researchers and the public.

REFLECTIONS ON THE ETHICAL REVIEW IN THE BACKGROUND OF COVID-19
The ethical review for researches on COVID-19 involving biological specimens or data should abide by relevant laws and regulations in China. However, the demand for a timely ERC respond contradicts with that of the current ethical regulations in China with regard to procedure specifically. Moreover, the ERC in China is lacking a unified supervision system and the ERC capacity is not evaluated in due time, which may cause undue delay of a potential scientific protocol.

Special considerations to research ethics in the epidemic
In the epidemic, front-line medical personnel are shouldering responsibilities for both everyday diagnosis and treatment and scientific research. It is difficult for them to balance the life-saving obligation with scientific observation, informed notification, and records keeping. 6 Thus, ERC is suggested to assess the risk/benefit ratio and the way of informed consent in this occasion by comparing the individual interest and collective interest besides general ethical considerations. 12 Different kinds of researches may be conducted during the epidemic, including randomized controlled trials (RCTs) bearing the highest evidence-based level, prospective observational studies, crosssectional studies, real-world studies, and retrospective studies using human specimen or data from electronic medical records. Therefore, the risks are different. The risk of RCT is generally high, and therefore informed consent should be mandatory even on this occasion.
Since the demand for a qualified RCT is extremely high, the RCT design should not be encouraged in this limited resource condition, unless it is of great importance and is in real need just like the scientists called for recently. Therefore, ERC has to evaluate the local situation of the research site to human resources, sample size, and so on, besides the general ethical considerations. 13 However, other observational studies can be considered to review with an expedited procedure with informed consent and/or signature waived. This can be justified from the ethical aspect with comparisons of individual needs and collective interest.

The ethical review regulation needs to be updated, and ERC cooperation should be strengthened
According to the current guidelines in China, meeting review is the major reviewing method for researches with more than minimal risks and a valid meeting review requires approval from more than half of the present committee members. In the face of COVID-19 research, teleconference and videoconference review have already been widely applied by ERC; yet, many issues, such as sign-in form, validity of electronic signature, and archiving of the ERC, need to be recognized by the regulations.
It's criticized that the lengthy ethical review procedures and communication between ERCs were important reasons for the delay in the commencement of research in the Ebola virus disease outbreak stage. 12 Hence, the importance of efficient ERC collaboration and the quick response from the local ERCs are much emphasized to mitigate the disease harm especially in front of public health emergencies. [14][15][16] Models for coordination and communication between ERCs and templates for expediting review of research protocols in epidemic and emergency conditions are being developed, 17 providing useful infor-mation for the followers to learn. Additionally, the quality or capacity of the local ERC is crucial for the initiation of a pragmatic clinical trial which may adopt innovative and nontraditional methods other than traditional RCT design that goes beyond the ability of most ERC and may delay the research opportunities. 18 In China, no consensus has been reached on the ethical cooperation of multi-center clinical trials and there's no unified system to supervise the quality of single ERC. Therefore, China is in great need for an ethical review emergency response mechanism especially with regard to ERC collaboration in multisite clinical trials to contain the current and future possible public health emergencies. 18