WHEN Pfizer conducted a large clinical trial of a new respiratory syncytial virus (RSV) vaccine for pregnant women, aimed at protecting their babies, the pharmaceutical giant failed to inform participants that GlaxoSmithKline Biologicals (GSK) had halted its trial for a similar vaccine due to a concerning safety signal showing a potential risk of preterm (premature) birth.
Even though Pfizer knew about the GSK trial and safety signal, it continued enrolling thousands of unsuspecting pregnant women without disclosing the preterm birth risk in its consent forms, according to an investigation by the BMJ.
To many healthcare advocates and experts, Pfizer’s omission represents an egregious violation of informed consent and a disregard for the autonomy of pregnant women participating in clinical research.
‘Any failure to provide new and potentially important safety information data to trial participants is ethically problematic,’ Dr Charles Weijer, bioethics professor at Western University in London, Ontario, Canada, told the BMJ.
Children’s Health Defense CEO Mary Holland told The Defender:
‘I am horrified that it’s even a question whether Pfizer should have told pregnant women that a previous clinical trial was halted because the RSV vaccine caused preterm birth. Of course it should have told them . . . This cavalier attitude towards the truth and human life is alarming.’
After the safety signals emerged in GSK’s study, the U.S. Food and Drug Administration (FDA) took no action to halt enrolment or to pause or restrict Pfizer’s ongoing maternal RSV vaccine trial.
Months after GSK’s revelation of the concerning safety signal, Pfizer also began detecting a numerical imbalance in preterm births in its own trial data but said the data were not statistically significant.
According to the BMJ, Pfizer was tracking preterm births as an ‘adverse event of special interest’ in its trial. But the company did not disclose this on consent forms given to thousands of pregnant trial participants across 18 countries.
‘Once the results of the GSK trial on premature births became public, RSV vaccine studies in pregnant women should have been updated to include this possible preterm risk,’ said Klaus Überla, Ph.D., chair of Clinical and Molecular Virology at the University Hospital Erlangen, in the BMJ report.
However, regulators took little action to encourage disclosure. The FDA ultimately limited approval of Pfizer’s vaccine to late pregnancy — specifically, for administration between 32-36 weeks only — due to preterm concerns. But the agency did nothing to restrict trial enrolment or require risk disclosure after the GSK findings emerged.
Some defend Pfizer’s lack of disclosure to trial participants by arguing the preterm risk was inconclusive. Dr Joop van Gerven, an ethics chair in the Netherlands, told the BMJ that informing women ‘would have caused too much uncertainty.’
However, others challenged this notion. ‘The renewal of informed consent is a must,’ Rose Bernabe, PhD, told the BMJ. Bernabe, a professor of medical research ethics at the University of South-Eastern Norway, referenced guidelines from the Council for International Organizations of Medical Sciences which state: ‘Researchers must renew the informed consent . . . if new information becomes available that could affect the willingness of participants to continue.’
Justine Tanguay, CHD lawyer and director of campaign research for Reform Pharma, told the Defender: ‘It’s no surprise that regulatory agencies such as the FDA are prioritising Big Pharma’s profit over the health interests of its pregnant trial participants when you pull back the curtain and expose the revolving door between government’s top federal employees and key executives for Big Pharma — the industry that FDA is supposed to be regulating.
‘In fact, the revolving door has become so commonplace that it is hard to decipher the tangled mess between the private sector and governmental agencies.
‘For instance, a former deputy director at the FDA who ran the Office of Vaccines Research and Review and pushed for the licensure of COVID-19 vaccines now works for Moderna as the head of the Infectious Diseases Early Clinical Development and Translational Medicine Program. For the sake of public health, such egregious conflict of interests must end.’
According to the BMJ investigation, in February 2022 GSK reported that a safety signal had emerged in its maternal RSV vaccine trial, indicating a concerning imbalance in preterm births between the vaccine and placebo groups.
Specifically, GSK observed that 6.81 per cent of births in the vaccine arm were preterm, compared with 4.95 per cent of births in the placebo arm. Additionally, neonatal deaths were 0.37 per cent in the vaccine group versus 0.17 per cent in the placebo group.
This unexpected safety signal prompted GSK immediately to halt its Phase 3 trial and discontinue the development of its vaccine.
In Pfizer’s Phase 3 data, 5.7 per cent of births in the vaccine arm were preterm compared with 4.7 per cent in placebo. Ten stillbirths occurred in the vaccine group versus eight in the placebo group. Neonatal deaths in the placebo group (0.3 per cent) exceeded those in the vaccine group (0.1 per cent). One vaccine recipient died from postpartum haemorrhage and hypovolemic shock.
Pfizer reported the increase in preterm births was most pronounced in trial participants from upper-middle-income countries, according to the May 18 meeting of the FDA Vaccines and Related Biological Products Advisory Committee (VRBPAC).
While Pfizer claimed these numbers were not statistically significant, experts noted this numerical increase in preterm births mirrored the safety signal in the halted GSK trial, raising further questions about the risks of maternal RSV vaccination.
Four of the 14 VRBPAC members were sufficiently concerned that they voted against finding the drug safe for pregnant women. Notably, one of the dissenting votes came from Dr Paul Offit, a paediatrician at Children’s Hospital of Philadelphia, who said, ‘If GSK truly abandons a program on a similar, almost identical vaccine, that is going to hang over [Pfizer’s] program. I think it needs to be addressed.’
After the Centers for Disease Control and Prevention (CDC) recommended the vaccine for pregnant women in September, Dr Peter McCullough told the Defender, ‘Vaccination of the mother for passive immunization of the infant is an unnecessary and risky strategy that will undoubtedly lead to fetal loss or premature deliveries when deployed on a large scale.’
A longer version of this article appeared in the Defender on November 17, 2023, and is republished by kind permission.