Medical Ethics have gone AWOL…again!!

The NextCOVE Saga Part 2

By Dr Rosamond Jones, HART member and retired consultant paediatrician

Regular HART readers may remember last summer, we highlighted problems with a trial of a new Moderna mRNA booster which was recruiting in the US and the UK including healthy children from 12 years upwards. A letter was sent by the Children’s Covid Vaccines Advisory Council, signed by 125 health professionals and academics, to the CEOs and Chairmen of the 35 UK centres involved, pointing out the emotionally charged recruitment leaflet, the lack of compliance with Helsinki Agreement, and even the offer of money to children on trial completion, in contravention of research governance guidance. 

We received replies promptly from several centres assuring us that either they were not taking part in the trial at all, or certainly were not recruiting any under 18s. Indeed, one medical director replied, “I share your concern about the quality of the information leaflet.  HMR has done almost 1,000 early clinical trials since we started in 1993, all of which have been approved by the MHRA and a Research Ethics Committee (REC).  We’ve never done a trial in children, nor do we intend to do so.  Best wishes” 

Another to whom I spoke on the phone sounded equally shocked.

Those who failed to reply were then sent a Freedom of Information request and replies dribbled in and reminders were sent to the rest. Five centres confirmed they were recruiting 12-17-year-olds. Of those, three said they were only offering a maximum of £50 for expenses and a fourth were offering small payments of £20 for each clinic attendance to a total of £185. 

This left me with the quandary of Barts and the Royal London Hospital, where incidentally I did my medical training, who seemed quite unable to explain how a researcher of theirs had posted on WhatsApp an offer of £1500 for any child completing the trial. 

The FOI response initially stated they had not recruited any 12-17s and replied N/A to all my other questions. We were already aware they had not recruited as a parent phoning to try and enroll her children was told the study was closed. Similarly, a call to Rotherham research centre, confirmed that Moderna had already closed the study – there was an air of disappointment and frustration from the staff member there, who had set up clinics for teenagers only to have the plug pulled because of speedier recruitment presumably in the north american centres (I’m not sure being in a race to recruit trial participants for an international trial would be conducive to careful informed consent).

Further correspondence with the Governance Lead at Barts Healthcare NHS Trust resulted in the following reply: “I can advise, that any offers of payment to participate in the trial would be as agreed with the sponsor, and which aligns with the Research Ethics approval for the study. So, in response to question 3, staff would have been authorised to offer payments to participate in the trial. 

In response to question 4, please find attached the Research Ethics approval, Participant Information Sheet and Informed Consent Form, and the recruitment brochure as requested.”

Meanwhile a colleague had done an FOI to the Research Ethics Committee (REC) requesting the minutes of the meeting at which the trial was approved, and which made for some very interesting reading. 

It transpired that the application for ethical approval  had originally been refused with several major reservations. One of these was because of the size of Moderna’s proposed payments to children and another raised the question of why children were needed at all. The minutes noted that the Approvals Manager was concerned that the size of proposed payments would contravene the Medicines for Human Use (Clinical Trials) Regulations (2004) and that the proposed payments would also place the children at risk of coercion.

The Approvals manager had also requested expert paediatric “Advice on the clinical, ethical and psychosocial problems that may arise in relation to the inclusion of children within trial.” The expert invited was a paediatric oncologist who replied, “as we are vaccinating young people, the inclusion of those 12+ is VERY reasonable.”  But this was factually incorrect as spring boosters were not being given to healthy under 75s, let alone to healthy children. Indeed by the time this trial started recruiting, even a primary course of covid vaccination had been withdrawn for children in the UK. As a paediatric oncologist, the expert’s own patients would indeed have been offered covid vaccines, but this group of immunosuppressed children were excluded from the trial. He/she never answered the REC’s question on ethics. 

The MHRA’s letter stating Grounds for Non-Acceptance (GNA), also highlighted the inappropriate use of ‘Safe’ in the participant information sheets to describe the licenced Moderna covid vaccine being used as a comparator. 

The sponsor put in a fresh application on the same day that they received the GNA letter. They submitted updated patient information leaflets with a total payment for £185 down from the original £1500. Many of the other requests or recommendations for action by the REC appear to have either received superficial attention at best, or been rejected entirely, by the sponsors. Despite this, the trial was subsequently approved in May 2023.

Armed with the REC minutes, I returned to the Head of Information Governance at Barts and two months along the line, received two contradictory replies on the same day, one saying everything was hunkydory (or words to that effect) and a second rather more honest reply three hours later.  The upshot was that they confirmed the £1500 payment had never been approved and was based on an out of date first version, in fact one that had actually been rejected by the REC. These sloppy practices in terms of version control are shocking. It appears Moderna inappropriately shared with their potential research centres a version 1 pre-approval information leaflet which had no ‘DRAFT’ watermark or anything else to alert the researcher to this status.  Perhaps Moderna are used to getting their way first time around. The new version with the agreed payments is labelled version 2, but again no effort appears to have been made to ensure centres discarded or archived the original version. 

Formal letters of complaint have been sent to Philip Cruz, Medical Director, Moderna UK, and to Matthew Westfield, CEO of the Health Research Authority. The HRA have refused to share the trial protocol on the grounds of ‘commercial confidentiality’ even though they have been invited to redact any content they consider to be personally or commercially sensitive. 

It is noteworthy that the HRA recently held a ‘Make it Public Week’ aiming to get 100% of trials registered on a publicly accessible site.  The current state is that 92% of all trials approved in the UK are listed on a central register, which is good news.  However, the details provided on these registries are often sketchy and as in this case, often omit the trial protocol. 

So what now? A formal complaint on Moderna’s behaviour regarding the payments has now also been sent to the Prescription Medicines Code of Practice Authority (PMCPA). To my amazement, after one further letter of clarification, they have agreed to take this up with Moderna. However, I am not holding my breath for a judgement any time soon, and when it comes, the most one could expect would be a tiny fine, effectively a slap on the wrist. Will keep readers posted!

Meanwhile, Moderna booster shots have been approved for adolescents. JCVI are not recommending boosters to any healthy under 75s, but presumably they will soon be available privately to those children whose parents have succumbed to the propaganda.

The results of the NextCOVE trial have, as so often, been announced by press release from Moderna who are “excited to announce our fourth infectious disease vaccine programme, with positive Phase 3 data further validating our robust mRNA platform…and this milestone gives us confidence in our ability to bring this much-needed vaccine to market.”

The second page of their statement contains the apparently standard caveat: “the forward-looking statements in this press release are neither promises nor guarantees and you should not place undue reliance on these forward-looking statements because they involve known and unknown risks, uncertainties and other factors…”

So that’s really reassuring!