ICH harmonised guideline integrated addendum to ICH E6(R1): Guideline for Good Clinical Practice ICH E6(R2) ICH Consensus Guideline. https://ichgcp.net/es Accessed 18 May 2021
]. Third, all large placebo-controlled RCTs with COVID-19 vaccine candidates have long (12-27 months) follow-up periods []. And fourth, it is the investigator responsibility to inform participants in a timely manner if information becomes available that may be relevant to the subject's willingness to continue participation in the trial [10ICH harmonised guideline integrated addendum to ICH E6(R1): Guideline for Good Clinical Practice ICH E6(R2) ICH Consensus Guideline. https://ichgcp.net/es Accessed 18 May 2021
]. The availability of a TUA vaccine for the prioritization group to which the participant belongs, is likely the most relevant (positive) information that could be communicated to trial subjects. These latter must know whether they have received a placebo or the vaccine candidate to make an informed decision about whether to withdraw from the RCT to be vaccinated with a TUA vaccine, as well as the risks of remaining unblinded in the trial for many more months.Regarding the availability of TUA vaccines, four are the critical elements to consider. First, several TUA vaccines are currently available in western countries (AstraZeneca, Janssen, Moderna and Pfizer/BioNTech). Second, local health authorities have established prioritization schemes: it will take many months between the first and the last population groups to have access to a TUA vaccine. Third, currently healthcare providers have access to a single TUA vaccine, so individuals must accept the one offered or wait an indetermined number of time for a second opportunity to be vaccinated. This is also applicable to trial participants if they change their minds and would like to withdraw from the RCT, in the case they had received placebo. Not accepting to be vaccinated with an authorized vaccine when it is offered is an attitude of increasing risk, especially due to the widespread of more transmissible SARS-CoV-2 variants in many countries that increases the chances of being infected [12COVID-19 vaccines vs variants - Determining how much immunity is enough.]. Furthermore, recent data have shown that the B.1.1.7 SARS-CoV-2 variant, that is rapidly spreading across Europe and the USA [], is more transmissible [14Davies NG Abbott S Barnard RC Jarvis CI Kucharski AJ Munday JD et al.Estimated transmissibility and impact of SARS-CoV-2 lineage B.1.1.7 in England.] than other previously circulating variants, with a high probability of an increased risk of mortality [15Challen R Brooks-Pollock E Read JM Dyson L Tsaneva-Atanasova K Danon L. Risk of mortality in patients infected with SARS-CoV-2 variant of concern 202012/1: matched cohort study.]. And fourth, TUA vaccines are the standard of prevention [8The granting of emergency use designation to COVID-19 candidate vaccines: implications for COVID-19 vaccine trials., 16Dal-Ré R Orenstein W Caplan A. Trial participants' rights after authorisation of COVID-19 vaccines.]. In the USA more than 64, 50 and 9 million Americans have been fully vaccinated with the Pfizer/BioNTech, Moderna and Janssen vaccines, respectively []. Similarly, 34 million Europeans have received at least one AstraZeneca vaccine dose [].Bearing these eight elements in mind, there seems to be no reason supporting that participants should remain blinded in the trial until its completion. Participants in any placebo-controlled RCT assessing any COVID-19 vaccine candidate must have the chance to decide whether to be vaccinated with a TUA vaccine as soon as they are eligible for vaccination outside the trial. This is applicable to placebo-controlled RCTs conducted for the assessment of COVID-19 vaccine candidates in any developed country.
Declaration of Competing InterestNone
ReferencesDal-Ré R Caplan AL Gluud C Porcher REthical and Scientific Considerations Regarding the Early Approval and Deployment of a COVID-19 Vaccine.
Ann Intern Med. 174: 258-260Rid A Lipsitch M Miller FG.The Ethics of Continuing Placebo in SARS-CoV-2 Vaccine Trials.
JAMA. 325: 219-220Clinical equipoise in COVID-19 vaccine candidates’ trials.
J Clin Pharmacol. ()https://doi.org/10.1002/jcph.1868Emergency Use Authorization of Covid Vaccines - Safety and Efficacy Follow-up Considerations.
N Engl J Med. 383: e107WHO Ad Hoc Expert Group on the Next Steps for Covid-19 Vaccine Evaluation. Placebo-Controlled Trials of Covid-19 Vaccines - Why We Still Need Them.
N Engl J Med. 384: e2New placebo-controlled Covid-19 vaccine trials are ethically questionable; it's now about comparative effectiveness and availability of registered vaccines.
J Clin Epidemiol. 133: 175-176Wendler D Ochoa J Millum J Grady C Taylor HA.COVID-19 vaccine ethics once we have efficacious vaccines.
Science. 370 (): 1277The granting of emergency use designation to COVID-19 candidate vaccines: implications for COVID-19 vaccine trials.
Lancet Infect Dis. 21 (): e103World Medical Association. Declaration of Helsinki. Medical research involving human subjects. October 2013 https://www.wma.net/what-we-do/medical-ethics/declaration-of-helsinki/ Accessed 18 May 2021
ICH harmonised guideline integrated addendum to ICH E6(R1): Guideline for Good Clinical Practice ICH E6(R2) ICH Consensus Guideline. https://ichgcp.net/es Accessed 18 May 2021
World Health Organization. Draft landscape and tracker of COVID-19 candidate vaccines.14 May 2021. https://www.who.int/publications/m/item/draft-landscape-of-covid-19-candidate-vaccines Accessed 18 May 2021
COVID-19 vaccines vs variants - Determining how much immunity is enough.
JAMA. ()https://doi.org/10.1001/jama.2021.3370Centers for Disease Control and Prevention. US COVID-19 cases caused by variants. https://www.cdc.gov/coronavirus/2019-ncov/transmission/variant-cases.html Accessed 18 May 2021
Davies NG Abbott S Barnard RC Jarvis CI Kucharski AJ Munday JD et al.Estimated transmissibility and impact of SARS-CoV-2 lineage B.1.1.7 in England.
Science. 372 ()Challen R Brooks-Pollock E Read JM Dyson L Tsaneva-Atanasova K Danon L.Risk of mortality in patients infected with SARS-CoV-2 variant of concern 202012/1: matched cohort study.
BMJ. 372: n579Dal-Ré R Orenstein W Caplan A.Trial participants' rights after authorisation of COVID-19 vaccines.
Lancet Respir Med. 9 (): e30Centers for Disease Control and Prevention (CDC). COVID data tracker. https://covid.cdc.gov/covid-data-tracker/#vaccinations Accessed 18 May 2021
European Medicines Agency. AstraZeneca's COVID-19 vaccine: EMA finds possible link to very rare cases of unusual blood clots with low blood platelets https://www.ema.europa.eu/en/news/astrazenecas-covid-19-vaccine-ema-finds-possible-link-very-rare-cases-unusual-blood-clots-low-blood Accessed 18 May 2021
Article InfoPublication HistoryPublication stageIn Press Journal Pre-ProofIdentificationDOI: https://doi.org/10.1016/j.jclinepi.2021.07.004
Copyright© 2021 Elsevier Inc. All rights reserved.
ScienceDirectAccess this article on ScienceDirect Related Articles
留言 (0)