Some thoughts triggered by the NextCOVE study
By Dr Ros Jones, Retired Consultant Paediatrician, HART spokesperson
Last week, HART drew attention to a new Moderna booster trial recruiting children, NextCOVE.
Digging into the trial centres and the sponsorship has highlighted the current state of medical research in the UK and the influence of the drug company sponsor. Several of the centres involved are commercial companies with clearly a need to undertake drug company sponsored research in order to make a profit for their organisation. Websites are shown here, here and here.
Whilst working as a private company does not mean that their research credentials are necessarily flawed, it certainly makes it harder for them to question the sponsors on a ‘don’t bite the hand that feeds you’ basis. Even those centres based in NHS facilities are often run by embedded research departments. For example the study in Bradford Teaching Hospitals Trust which appears to be the first to recruit children, is supported by a team called Grounded Research in a neighbouring mental health trust.
The letter we have sent to 35 participating centres and to the MHRA, has so far received 10 replies, two saying that are not taking part in this trial at all, and seven quickly pointing out that they have not and are not planning to recruit any under 18s, indeed the Director of one research unit went so far as to say, ‘I share your concern about the quality of the information leaflet’.
Only Bradford so far has confirmed that children have been recruited. It was a phone call to their linked Grounded Research team which revealed that recruitment had currently been stopped by the sponsor, as they had already reached the target number. I was told by a friendly young researcher that this was quite common with ‘competitive recruitment’ but was a bit of a ‘nuisance’ as they had got ‘clinics all set up for the next few weeks which we’ve had to cancel’. Racing to get recruits before other centres doesn’t sound like the best route for getting fully informed consent. Maybe that was the motivation for the Royal London Hospital offering a £1500 inducement to recruits, as shown in this WhatsApp forwarded to the HART team.
I’m Joseph, a paediatrician at the Royal London Hospital Children’s Clinical Research Facility at Barts Health NHS Trust.
We’re currently recruiting to the Moderna COVID booster vaccine study and inviting potential participants.
Who is eligible?
Children aged 12-18 years who have had any UK approved vaccine (Moderna, AZ, Pfizer-BionTech) more than 3 months ago, and who don’t have COVID now.
– A brief screening visit to the Royal LondonA visit to receive the booster dose of vaccine
– 3 monthly brief visits to the hospital as follow up
– Completing a daily e-diary saying how they feel for a year (v simple to do)
What’s in it for them?
£1500 on completion of the study.
Let me know here, or email [email protected], or call us on 020 3594 1551
We’d love to have you on board!
As well as concerns about the total inadequacy of the information leaflet and the likelihood that the study is in breach on the Medicines for Human Use (Clinical Trials) Regulations 2004, there is also a serious problem with transparency. Bradford’s CEO declined to share the trial protocol or the Research Ethics approval letter, telling us instead to contact the sponsor, Moderna.
Another respondent confirmed that, ‘NHS Trusts in England and Wales do not approve research to take place within their organisations… The sponsor, not the recruiting sites, is responsible for writing the participant information sheets that are provided to potential participants or their carers when they are considering taking part in the research’. He helpfully provided all the references to the various approvals. This led me to the Health Research Authority (HRA) website but I could find no mention of the NextCOVE study. Eventually, and only after I had supplied the so-called IRAS ID number, were they able to confirm it had been approved by Berkshire B REC but they refused to send me a copy as I had no direct involvement with the study. So presumably a parent considering entering their child is also unable to double check the full protocol. This is in stark contrast to the various statements on their website about transparency and public involvement. Under a heading ‘Research Transparency’ is the statement:
Our vision is that trusted information from health and social care research studies is publicly available for the benefit of all.
Research transparency is central to ethical research practice. When research is carried out openly and transparently, everyone will be able to see what research is happening and the outcomes from finished studies.
Promoting transparency across the research landscape is central to our role to facilitate safe and ethical research.
Indeed, they have launched a ‘Make it Public’ campaign
Berkshire REC were the same team who in 2022 approved the Com-COV 3 study, ‘University of Oxford-led Com-COV programme have launched a further study of COVID-19 vaccination schedules in young people aged 12 to 15 – with a focus on assessing different options for a third dose booster vaccination.
The Com-COV 3 study has been commissioned through the NIHR and backed by £2.8 million government funding, with support from both the Vaccine Taskforce and National Institute for Health and Care Research (NIHR). This new stage of the study – which will look to enrol 380 volunteers – is funded entirely by the Coalition for Epidemic Preparedness Innovations (CEPI) and will run across nine NIHR-supported sites plus one Health and Care Research Wales site by the National Immunisation Schedule Evaluation Consortium (NISEC).
An open letter to their chairman received no reply.
In 2021, Berkshire REC also approved the ill-fated children’s AstraZeneca trial, which had to be suspended when young adults started dying of Vaccine-induced Thrombotic Thrombocytopaenia (VITT).
Capture and lack of transparency
Concerns about capture and loss of transparency are of course nothing new. It has become apparent over the last 20 years or more, that academia has become gradually more dependant on pharmaceutical industry funding. Concerns have been raised in the BMJ that this has led to an illusion of evidence-based medicine. This essay by Professor John Ioannidis are well worth reading – ‘Why Most Published Research Findings Are False’. And there is plenty more food for thought on the ‘Epidemic of Sickness and Death from Prescription Drugs’ here.
Examples from recent history
Opren was a nonsteroidal anti-inflammatory drug launched by Eli Lilli in 1980. Lavish marketing included taken a large group of rheumatologists on the Orient Express. Its use spread widely and by the time the first deaths were acknowledged, almost 4000 people had been seriously harmed with 83 fatalities. Compensation was erratic with UK victims receiving around 1% of their American counterparts. Jack Ashley, MP, amongst others pushed for a proper government response. Following this scandal, the level of Big Pharma ‘freebies’ which doctors were allowed to receive was seriously curtailed. ‘Drug lunches’ were replaced with sandwiches, and trips in hot air balloons by a biro and a jotter pad.
Gabapentin is an anti-epileptic drug first licenced in 1993 for use in partial complex seizures. Over the next three years it was heavily marketed for ‘off-label’ use for conditions such as pain, migraine and psychiatric disorders. A lawsuit was filed in 1996 and eventually in 2004 the drug company Warner-Lambert (now owned by Pfizer) pleaded guilty and paid $430,000,000 criminal and civil liability. Details of the marketing methods used have been published, including recruitment of ‘local champions’ and engagement of ‘thought leaders’.
Pandemrix, the 2009 rushed-to-market swine flu vaccine, was eventually withdrawn after Finland observed an increase in teenagers developing narcolepsy, a previously rare neurological condition. Peter Doshi, associate editor of the BMJ, has reported on adverse events reports released by the drug company, Glaxo Smith Klein (GSK), seven years later, only in response to litigation, which had not been acted on at the time.
Paroxetine, an SSRI antidepressant, when a reported study was reviewed in detail led to this comment:
‘Selective reporting is prevalent in the medical literature, particularly in industry-sponsored research. In this paper, we expose selective reporting that is not evident without access to internal company documents. The published report of study 329 of paroxetine in adolescents sponsored by GlaxoSmithKline claims that “paroxetine is generally well tolerated and effective for major depression in adolescents”. By contrast, documents obtained during litigation reveal that study 329 was negative for efficacy on all 8 protocol specified outcomes and positive for harm.’
Pharmaceutical industry sponsorship and research outcome has been systematically reviewed and not surprisingly found that:
‘Research funded by drug companies was less likely to be published than research funded by other sources. Studies sponsored by pharmaceutical companies were more likely to have outcomes favouring the sponsor than were studies with other sponsors’.
So what is the answer?
A good starting point would be an overall root and branch reform of the MHRA, returning it from ‘Enabler’ to ‘Watchdog’ as recommended in the Perseus report.