a letter to the senior investigator and the chair of the Research Ethics Committee
9th August 2022
Professor Matthew Snape, Chief Investigator
Centre for Clinical Vaccinology and Tropical Medicine University of Oxford,
Churchill Hospital, Old Road, Headington, Oxford, OX3 7LE
Mr David Carpenter, Chairman, South Central – Berkshire Research Ethic Committee
Bristol REC Centre, Temple Quay House, 2 The Square, Temple Quay, Bristol BS1 6PN
Dear Professor Snape and Mr Carpenter,
re: Com-COV3 trial protocol
We are writing to you both on behalf of the Children’s Covid Vaccines Advisory Council (CCVAC) to express our concerns at a number of ethical and other issues in the above trial of Covid vaccination booster combinations in 12-15-year-olds which is currently advertising for participants.
The Declaration of Helsinki:
First and most important, the study protocol[i] states in para 18.1 “The Investigator will ensure that this trial is conducted in accordance with the principles of the Declaration of Helsinki.”
As you will know, Paragraph 3 of the declaration[ii] states: “The health of my patient will be my first consideration”. Paragraph 20 states, “Medical research with a vulnerable group is only justified if the research is responsive to the health needs or priorities of this group and the research cannot be carried out in a non-vulnerable group. In addition, this group should stand to benefit from the knowledge, practices or interventions that result from the research.”
Lack of potential benefit:
The generally mild nature of SARS-CoV-2 infection in children [iii],[iv] is not fully discussed in the protocol, nor the fact that the latest omicron variant is much milder still [v]. The reduced efficacy of the vaccines against omicron and the rapid waning of effect after successive doses is also not discussed [vi]. This information, some of which will have only become available after the original Ethics approval for the study, must bring into doubt the possibility of any real benefit to children from continuing with the vaccination programme, especially given that 99% of school children are now estimated to have had SARS-CoV-2 infection[vii].
Thus, it is hard to see how this complies with the Helsinki requirement that medical research with a vulnerable group is only justified “if the research is responsive to the health needs or priorities of this group and the research cannot be carried out in a non-vulnerable group. In addition, this group should stand to benefit from the knowledge, practices or interventions that result from the research.”
The lack of potential benefit is worrying enough, but more concerning still is the limited consideration of potential harm, at a time when the MHRA Yellow Cards have reported for the first time, six deaths of children in association with Covid-19 vaccines [x]. We note also that at present the trial protocol states that no SAEs are anticipated after Novavax. Can you confirm that the protocol has been updated in light of the EMA’s recommendation [xi] for “myocarditis and pericarditis to be listed on the patient information leaflet.”?
We would be grateful for a copy of the latest information sheet for parents and teenagers and urge that a copy of this letter be provided to them.
In addition to serious side effects of death, myocarditis and pericarditis, even expected reactogenicity and minor side effects are likely to lead to time off school for a significant proportion of participants [xiv].
On what basis was it decided that the trial should only be single-blind?
Why is the designation of whether an adverse event is or is not vaccine-related, being carried out by a member of the trial team rather than an independent assessor?
Why does the trial anticipate unblinding after 56 days and the early offer of vaccination to the control group? This is contrary to the advice of the ICMRA[xv] recommending vaccine trials are “planned with a follow-up of at least one year or more from completion of assigned doses. In making this recommendation, we recognise that the feasibility of maintaining the group assignment for at least one year will depend on factors such as the population enrolled into a trial (e.g. in terms of whether they are young and healthy or have reasons to be predisposed to develop severe COVID-19)”.
Given this study is recruiting children at known very low risk from Covid-19, it is hard to see the justification for early loss of the control group, which has presented such a problem for interpretation of safety and efficacy in the original adult trials. We call for transparency in any data collection.
In light of the progress of the pandemic and the worsening loss of efficacy of vaccines, there is no likelihood of benefit to healthy children from any knowledge accrued by this study. The risks of spike-protein-based vaccines in this age group appear to greatly exceed any potential benefit .
We therefore urge that recruitment for this trial is immediately halted, pending an urgent review of the Research Ethics Committee approval for this study.
We look forward to a response to these concerns.
Dr Rosamond Jones, MBBS, MD, FRCPCH, retired consultant paediatrician, convener CCVAC
Dr David Critchley, BSc (Hons), PhD, Clinical Pharmacologist
Katherine MacGilchrist, BSc (Hons), MSc, CEO/Systematic Review Director, Epidemica Ltd.
Dr Geoffrey Maidment, MBBS, MD, FRCP, Consultant physician, retired
Dr Ayiesha Malik, MBChB, General Practitioner
Dr Livia Tossici-Bolt, PhD, Clinical Scientist
[vi] Fleming-Dutra KE, Britton A, Shang N, et al. Association of Prior BNT162b2 COVID-19 Vaccination With Symptomatic SARS-CoV-2 Infection in Children and Adolescents During Omicron Predominance. JAMA. 2022;327(22):2210–2219. https://jamanetwork.com/journals/jama/fullarticle/2792524?guestAccessKey=0b85bec0-b0e4-40d7-9553-03ae3e77bf45&utm_source=silverchair&utm_medium=email&utm_campaign=article_alert-jama&utm_term=mostread&utm_content=olf-widget_05262022
[xiii] Raw RK, Kelly CA, Rees J, Wroe C, Chadwick DR. Previous COVID-19 infection, but not Long-COVID, is associated with increased adverse events following BNT162b2/Pfizer vaccination. J Infect. 2021 Sep;83(3):381-412. https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC8164507/
[xiv] Hause AM, Baggs J, Marquez P et al. COVID-19 Vaccine Safety in Children Aged 5–11 Years — United States, November 3–December 19, 2021. https://www.cdc.gov/mmwr/volumes/70/wr/mm705152a1.htm