Trials

Can Anything About the Pfizer Vaccine Trial be Trusted?

In a recent article in the BMJ, a whistle-blower exposed serious problems she had observed first-hand in the Pfizer vaccine trial in Texas.

A regional director who was employed at the research organisation Ventavia Research Group has told the BMJ that the company falsified data, unblinded patients, employed inadequately trained vaccinators, and was slow to follow up on adverse events reported in Pfizer’s pivotal phase III trial. Staff who conducted quality control checks were overwhelmed by the volume of problems they were finding. After repeatedly notifying Ventavia of these problems, the regional director, Brook Jackson, emailed a complaint to the US Food and Drug Administration (FDA). Ventavia fired her later the same day. Jackson has provided the BMJ with dozens of internal company documents, photos, audio recordings, and emails.

Another Ventavia employee said of the data the company generated for the Pfizer trial: “I don’t think it was good clean data. It’s a crazy mess.”

The six-month trial results for the Pfizer vaccine have now been published in the New England Journal of Medicine. These findings, the researchers note, “contributed to the full approval of BNT162b2 [the Pfizer vaccine] in the United States”. A close inspection of the study, however, reveals a number of problems that raise serious questions about the reliability of its findings, as well as about the safety of the vaccine.

Here is the graph of cumulative incidence for the two trial arms, vaccine and placebo, over the six months of the study period, showing how the symptomatic Covid PCR-positives added up following receipt of the first dose.

Preg-CoV: New Trial to Study Potential Side-Effects of Covid Vaccination on Pregnant Women on Babies

A new clinical trial based in the U.K. will seek to determine the most suitable gap between the first and second Covid vaccine jabs for pregnant women, as well as the potential side effects on their unborn children. Those running the trial hope it will make pregnant women feel more comfortable about getting vaccinated. The Guardian has the story.

Last week, Professor Jacqueline Dunkley-Bent, Chief Midwifery Officer for England, urged expectant mothers to get vaccinated as soon as possible, with evidence suggesting the Delta variant poses a significantly greater risk to pregnant women than previous forms of the virus.

A clinical trial called Preg-CoV has been launched to help determine the best gap between doses for pregnant women as well as exploring in greater detail potential side-effects and the impact on babies – something the researchers hope will offer reassurance. …

Asma Khalil, Lead Obstetrician for the trial and Professor of Obstetrics and Maternal Fetal Medicine at St George’s, said that while the U.K. Covid vaccination programme had been a success, uptake has been low among pregnant women.

According to research in her own hospital, “among pregnant women who’ve given birth between March this year until beginning of July, less than one third – 28% – of women who were eligible according to the guidance actually received [at least one dose of] the Covid vaccine” during pregnancy, said Khalil. …

“Pregnant women are still concerned because pregnant women were not included in initial Covid vaccine trials,” said Khalil.

In the first phase of the Preg-CoV trial, the team hope to recruit 600 pregnant women, aged between 18 and 44, from 13 sites across England.

Two groups of 200 unvaccinated pregnant women at different gestation times will be randomised both with respect to whether they receive a Moderna or Pfizer/Biontech jab and to whether they are given their second dose four to six weeks or at eight-12 weeks after the first dose. 

Participants will not know which Covid jab they are given… while a routine vaccination to protect against whooping cough will also be included in the schedule so that participants are not aware which dosing regime they are following.

A third group of about 100 pregnant women will be given one dose of a Covid jab at 28-34 weeks gestation, with the second dose of the same vaccine given after delivery, while the fourth group of 100 women will already have had their first dose of any Covid jab before or very early in pregnancy and will get the second dose of the same vaccine.

All the women will have follow-up visits and blood tests, and fill in an electronic diary to help the researchers monitor any potential vaccine side-effects. The team will also track outcomes for the babies up to 12 months of age to explore safety and impact on their development. …

“I think there will be some lessons learned from this pandemic,” said Khalil. “And one of them is that we should consider including pregnant woman at a relatively early stage for vaccine trials.”

Worth reading in full.

Lancet Study Shows Real World Patients Are up to 400% More Likely to Suffer Adverse Events Than Drug Trials Show

Dr Sebastian Rushworth has written today about the serious problem of the underestimation of side-effects in drug trials, which he says should “shake the very foundations of evidence based medicine”.

His article reports on the results of a study recently published in the Lancet Healthy Longevity, funded by the UK Medical Research Council and the Wellcome Trust, which seeks to establish the extent to which drug trials underestimate side-effects by comparing trial data to real world data. The study focuses in particular on blood pressure drugs known as RAAS blockers, which Dr Rushworth explains were chosen because of the number of trials that have been done by different companies. There is no reason the results should not apply equally to other drugs, he says, including Covid vaccines (for which there have been an unprecedented number of adverse event reports despite the trials showing them to be safe).

The results are shocking. The difference was not marginal but out by a factor of three or four.

The real world patients were between 300% and 400% more likely to experience a serious event than the participants in the trials! That is in spite of the fact that the trials, as mentioned above, were using a broader definition of what constituted a serious event. If the trials were representative of reality, then they should have a higher rate of events than is seen in the real world data. Instead they have a rate that is several times lower!

The difference was just as large in trials specifically involving older people, so age differences can’t be the full explanation, he says (though he allows part of it may be that participants in the trials of older people may be healthier and younger than real world patients).

His main explanation, however, is darker. Are the drug companies simply under-reporting adverse events, both in the drug and placebo treatment groups?