Is written informed consent ‘cast in iron’ even during a pandemic?

Clinical research and ethics during infectious disease pandemic

Coronavirus disease 2019 (COVID-19) pandemic is the latest in a series of viral respiratory outbreaks such as severe acute respiratory syndrome, (2003–04), H1N1 (2009), Middle East respiratory syndrome (2011–12), and Ebola (2014–16).^{1, 2, 3, 4} Having infected more than 38 million individuals and having claimed more than a million lives globally, COVID-19 has been declared a “Public Health Emergency of International Concern” by the World Health Organization (WHO).^{5, 6} As a natural fallout, there has been a huge spike in COVID-19–related research with a whopping 5875 clinical trials registered at the International Clinical Trials Registry Platform of the WHO, by the end of September 2020.⁷

In a dynamic and fast changing environment of a pandemic, research surge may step on the very core of the ethical principles, that is, informed consent. The dilemma for ethics committees may also be heightened, and counting all the marbles of informed consent process may not always be viable. While undoubtedly safeguarding the participants’ autonomy, taking informed consent is a time- and resource-intensive process. However, as per the WHO, ethics remains a cornerstone, notwithstanding the imperativeness or urgency of research.⁸ Whether to peruse rigorous written informed consent in an infectious pandemic OR to relook at the consent process during such times is an international holy grail. In the following paragraphs, we try to submit the arguments on both side of the logic followed by our own comprehensive take.

The eternal research dilemma: consent or waiver

The most intuitive argument in favor of robust informed consent is that it forms one of the most important pillars of ethics that helps avoid scientific misadventures.^9,10 It acts as a bulwark against reckless institution of experimental modalities and provides an individual the control over his therapeutic choices. There may be a cogent argument for waiving informed consent process when a pandemic threatens the very existence of mankind and the research needs to be nimble. Absence of a cure makes a good case of “implied consent” for the experimental treatment. There may also be situations where a seriously ill patient cannot give consent and legally authorized representatives (LARs) are inflicted themselves. The sheer stress of suffering from an unknown, potentially fatal and as yet incurable infection could be too overwhelming for the lay public.

From dilemma to direction: bespoke consent process

Waiver of consent is a difficult choice to make for any ethics committee or institutional review board. Instead of being an ‘All or None’ option, informed consent in the pandemic can take many shapes depending upon the situation and needs a case-by-case approach. We have divided the informed consent process based on three likely situations in an outbreak and propose derivatives of consent process that may help the investigator and ethics committee (Fig. 1).

Fig. 1.

Suggested derivatives of informed consent process during a pandemic.

The first situation pertains to research in healthy volunteers, such as vaccine trials, drug prophylaxis trial, or a phase I clinical trial. The safety of healthy volunteers is paramount, and the issue of complete informed consent should be a must and nonnegotiable.

In situations where patients are research subjects, it is to be noted that pandemics happen only when the pathogen is highly contagious. This puts the study team at risk of exposure during informed consent process, either due to direct transmission from the patient or from fomites through the informed consent documents. To facilitate consent process, some modifications can be considered.¹¹ First, electronic devises such as tablet computers secured in transparent protective bags may be given to the participants with a prerecorded video with frequently asked questions (FAQs) for the participants. Any biometric marker (physical signature, finger print, or iris features) can be used as an electronic signature of the patient, thereby decreasing the time of exposure to investigators (virtual consent). Similarly, the participants can be shown introductory messages of the study followed by a consenting process in a “question-answer” format, and the whole process including verbal consent of the patient can be video recorded (video-verbal consent). The ethics committee may also approve a shorter version of informed consent process for the study by allowing only brief description of study and intervention to the study participants (abbreviated consent). During pandemics/epidemics, a large number of studies (both interventional and observational) usually go hand in hand, sometimes recruiting same patients. In these situations, the consent process of multiple projects may be combined and a common minimum process may be evolved (composite consent) which addresses ethical imperatives without compromising the alacrity of research. Although bordering on the ethical practices, another method may also be considered where consent from multiple participants present in a common hospital area can be taken together by using some form of public address system (collective consent).

The third situation is likely to be the most challenging. It includes research in patients with severe disease who cannot give consent while their LARs are untraceable. It is relatively a common occurrence in pandemics where whole household is either infected or quarantined in a separate facility. Ethics committee may consider a complete waiver of consent, if the patient is severely ill and study intervention is being tried as a last option. If the ethics committee is not comfortable with a complete waiver, modified consent may be tried. The ethics committee may appoint a person of repute (social worker or priest) or form a committee to give a surrogate consent on behalf of the patient (appointee's consent). This will help continue scientific research with a good degree of ethical cover. Similarly, in case the patient has no LAR, then the treating physician may take a call for enrollment in the trial. If the patient recovers, the consent can then be taken from him to continue the trial (deferred consent).¹² Seeking consent from LAR itself is laden with ethical issues as there may be some conflict of interest therein. In case, multiple individuals from the same family are infected, how many individuals can a single LAR give consent for? These are some issues that may require case-to-case deliberation by investigators and ethics committees.

The global village phenomenon has ensured that no one exclusively owns his own backyard. It is also appreciated that we are not seeing the last of pandemics. Our response to next pandemic will depend on lessons that we learn today and response that we articulate. Aforementioned is a parsimonious list of situations pertaining only to the informed consent process, not the whole nine yards of bioethics. The proposed consent processes may not be ideal but, alone or in combination with one another, they provide a tool to balance research rigor and ethical challenges without compromising the functional utility of these processes for special situations including, but not limited to, pandemics.