Waived or deferred consentSeptember 5, 2020
Clinical research investigators conducting trials of investigational therapies face challenges of obtaining consent from COVID-19 patients who may seem incapable to do so or whose family members or legally acceptable representatives (LARs) are not available. Hence, they may consider the option of waiving the consent before screening a patient. The consent process may be deferred till the patient improves or a LAR is available. However, such waiver and deferral of consent requires strong justification from the clinical researcher and approval from the ethics committee (EC).
Council for International Organizations of Medical Sciences International Ethical Guidelines allow EC to consider waiver of informed consent in the following situations:
1) If the research would not be feasible or practicable to carry out without the waiver; and
2) The research has important social value; and
3) The research poses no more than minimal risks to participants.
The waiver or deferral of consent is acceptable in a clinical trial in emergency-care settings when patients are not capable of giving informed consent; e.g. in case of seizures, sepsis, shock, severe traumatic brain injuries. However, in emergency-care settings where the ability of vulnerable patients to understand the information – nature, purpose, risks, potential benefits, methods, randomization and placebo-controlled designs and alternative treatments — and provide voluntary informed consent — may appear diminished, e.g. respiratory distress or myocardial infarction, the waiver of consent is debatable.
In the Oxford RECOVERY clinical trial, COVID-19 patients who lacked the capacity to consent due to severe disease requiring ventilation and for whom an LAR was not immediately available, randomization was done with the consent provided by a treating physician who was independent of the investigator and who would act as the LAR. The consent would be obtained from the patient’s LAR, or directly from the patient if they recover promptly. This may not be practically possible if the treating physician is unlikely to be available during a pandemic.
It is important to document refusal or withdrawal of consent in a clinical trial in emergency settings. In the remdesivir trial, out of 1063 patients, 10 participants or LAR withdrew consent before randomization,
and 28 withdrew after randomization. If a waiver is applied, there will not be any consent refusals. If the patient or LAR refuses deferred consent or the patient does not recover from the disease, there would be major ethical issues.
Any proposed waiver of informed consent in COVID-19 clinical trial is not ethically acceptable, as 1) the participants are conscious and 2) not incapable of giving consent and 3) the potential benefits of potent investigational drugs such as hydroxychloroquine, lopinavir, remdesivir, tocilizumab, dexamethasone are uncertain, but the risks of severe and serious adverse drug reactions are real.
Violations in obtaining voluntary consent from socio-economically-educationally disadvantaged Indians have been the major reason for clinical trials falling in disrepute. In a pandemic situation, it is ethically and legally prudent for the investigator to complete and document the consent process from all potential participants.