Policy ForumEthics: COVID-19

COVID-19 vaccine trial ethics once we have efficacious vaccines

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Science  11 Dec 2020:
Vol. 370, Issue 6522, pp. 1277-1279
DOI: 10.1126/science.abf5084

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  • RE: Promotion of equity cannot be separated from scientific discovery if “social value” is the justification for continuing placebo-controlled vaccine trials
    • Kimberly Khoo, BSA, Research Fellow & MPH Candidate, Johns Hopkins University School of Medicine, Baltimore, MD; Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA
    • Other Contributors:
      • Oluseyi Aliu, MD, Plastic & Reconstructive Surgeon, Assistant Professor, Johns Hopkins University School of Medicine, Baltimore, MD, USA
      • Carisa M Cooney, MPH, Associate Professor of Plastic & Reconstructive Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    We read the article, “COVID-19 vaccine trial ethics once we have efficacious vaccines,” by Wendler et al (1), published December 2020, with great interest. The authors posit that it can be considered ethical to continue placebo-controlled trials for COVID-19 vaccines after an efficacious vaccine is discovered. This argument is based on the acceptability of research participants’ assumption of risk provided the benefits of collecting socially valuable data (aka, the “social value”) outweigh said risk(s) (1).

    Social value is widely endorsed as a requirement for conducting clinical research (2,3). However, the interpretation of what constitutes, and who benefits from, social value is ambiguous. While we agree it should be a pillar of clinical research justification, we also believe the argument of social value only holds true when this benefit is distributed equitably among all members of society.

    It is undisputable that there are inherent inequalities in the social contract of the United States (4-7). These long-standing inequalities which have disproportionately affected Black, Indigenous, and people of color (BIPOC) have created health disparities worsened by the current pandemic (8). BIPOC communities are less likely to experience the timely benefits of social value garnered from COVID-19 vaccine clinical trials and concerning trends in COVID-19 vaccination distribution have been noted in state-level data (9). When the social contract continuously fails ce...

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    Competing Interests: None declared.
  • RE:Are obligations researchers have to their clinical trial participants distinct from obligations clinicians have to their patients?
    • Hasan Yazici, Professor and Former Chair Ethics Committee, Istanbul University Istanbul, Turkey
    • Other Contributors:
      • Yusuf Yazici, Clinical Associate Professor of Medicine, New York University School of Medicine New York, NY, USA

    Wendler and colleagues (1) propose that COVID-19 vaccine trials may continue in a double-blind fashion after an interim analysis shows safety and efficacy and an emergency use approval (EUA) is secured. They additionally imply that it will not be unethical to conduct placebo-controlled trials with a brand-new vaccine. They address those, like us, opposing their contention by saying “This view fails to recognize that the obligations researchers have to their participants are distinct from the obligations that clinicians have to their patients." We surprisingly found out that 3 of the 5 authors of the given reference for this actually disagree with this strong statement (2). We clearly still need more scientific data related to our EUA of vaccines. After all, we still do not have any hard data on the possible effects of the EUA vaccines at hand on mortality (3) and infectivity, let alone the possible long term and rare adverse events. However, in aiming for these data we maintain that we refrain from schemes that tinker with the concept of clinical equipoise (4). Considering the inescapable long time span required to administer these vaccines to large volunteer populations we propose step-wedge clinical trials (5) with individually randomized (instead of the more common cluster randomized) vaccine and placebo control groups assuring all volunteerswill eventually get vaccinated. After the randomized initial phases, the long-term follow-up of the participants would sur...

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    Competing Interests: None declared.
  • RE: Allergic Anaphylactoid reactionsas a serious adverse effect og Pifizer BioNTech covid 19 vaccine cause must be investigated and guideline and fixing responsibility and compensation must be there from company for any adverse effects with the vaccine
    • Professor Dr. Pranab Kumar Bhattacharya, Professor of Pathology Department, Calcutta School of Tropical Medicine,108 Chittaranjan Avenue, Kolkata 70073, West Bengal India,
    • Other Contributors:
      • Dr Amartya Misra, Assistant Professor department of Tropical medicine, Calcutta School of Tropical medicine

    People who have a history of a significant allergic reaction to any vaccine, or in any medicine, or in food or who have been advised to carry an adrenaline autoinject.must not receive the Pifizer/BioNtech covid-19 BNT162b2 vaccine.
    The Medicines and Healthcare Products Regulatory Agency (MHRA) is investigating eight (08)cases of anaphylactoid reactions happened in those who received the vaccine on 8 -24 December. All these 8 people—who have recovered—had a history of severe allergic reactions to substances and two of them carried adrenaline auto injectors
    The MHRA,uk,told people running sites that those administer the vaccine to report any suspected adverse reactions through a yellow card scheme website( 2 )and to ensure that they must have all appropriate resuscitation facilities available at site where vaccine will be given if anaphylaxis happen to any one
    The mRNA 1273 (BNT162b2 )
    vaccine has so far been approved in Canada and in UK, where people over 80 who are attending hospital or being discharged, as well as all healthcare workers, are being prioritised to immunize first . A phase 2/3 trial found the pifizer vaccine for covid 19 to be as much as 52%-95% effective, 28 days after the first dose given in development of neutralizing antibodies against s protein . The data from the trial have not yet been however published or peer reviewed.by any journal so far
    MHRA already issued temporary guidance to the NHS while it conducts an in...

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    Competing Interests: None declared.
  • RE: In pursuit of the Common Good for COVID-19 Global Vaccination
    • Yotam Levin, Medical Advisor, Israel Institute for Biological Research
    • Other Contributors:
      • Noa Madar Balakirski, Biologist, Israel Institute for Biological Research
      • Hadar Marcus, Immunologist. Clinical Development Lead., Israel Institute for Biological Research

    Last week, VRBPAC (CDC’s Vaccines and Related Biological Products Advisory Committee) and FDA have approved Pfizer’s BNT162b2 EUA (2, 3), COVID-19 vaccine, the first in class novel mRNA vaccine for COVID ever registered for this platform. Yesterday, Moderna’s mRNA vaccine has undergone the same process, affording the US its first vaccines to curb the most devastating pandemic in the last 100 years.
    At the same time, there are about sixteen Phase III clinical programs ongoing in multiple locations globally (4), and 38 vaccine candidates in clinical testing, recruiting an unprecedented number of subjects, up to several hundreds of thousands. Most of these Phase III studies have a 1:1 active to placebo ratio, thereby potentially exposing 50% of recruits (which are unprotected), to potential harm from the virus.
    Wendler et al, (1) have eloquently addressed the issue of ethics in maintaining vaccine placebo, recognizing that randomized, blinded, placebo-controlled studies, remain our best tool, to date, to control both safety and efficacy readouts (and to a lesser degree, immunogenicity). On the other hand, investigators and subjects alike put the welfare of an individual subject on the line, arguing that an approved vaccine should be awarded to all placebo subjects who are eligible and present interest.
    It is further understood by most stakeholders that non-inferiority of new entrant vaccines to incumbent vaccines as a measure to replace the placebo arm and p...

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    Competing Interests: None declared.
  • RE: What Came First, Effective COVID-19 Vaccines or Trial Ethics?

    Safe, effective, durable, affordable, ethically approved, and widely distributed vaccines are essential to mitigate, and possibly control, the COVID-19 pandemic.  

    If two injections are required for some vaccines, possibly over a period of 3 weeks, might a patient become infected between the first and second injections?

    It is presumed that all essential ethical considerations have been satisfied before any clinical trials are conducted.

    How is this possible when vaccines are being approved at warp speed, without any discussion of durability, affordability, and wide distribution.

    Who is going to pay for the vaccines, federal, state or local governments, or patients?

    Competing Interests: None declared.

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