Nowhere are these journals more important that in the understanding and experience of the production of antiviral drugs (medication used for treating viral infections by inhibit their development) and vaccines. This is more so because production is overwhelmingly dominated by large pharmaceutical companies (often referred to as ‘Big Pharma’).
These companies driven by profit-maximisation. not just profitability, are a risky fit for the provision of a public good such as vaccines. Until the current coronavirus pandemic this meant that their vaccine research and development was a lower priority. However, the pandemic generated a new lucrative market opportunity.
‘Big Pharma’ does not intentionally produce ineffective or dangerous vaccines. At the very least the reputational damage would be bad for business. Similarly, it is counter-intuitive for ‘Big Pharma’ to employ second-rate scientists.
But profit-maximisation creates opportunities for standards and carefulness to slide. On 2 November the BMJ (2021;375:n2635) published a timely reminder of this with lessons for New Zealand:
https://www.bmj.com/content/375/bmj.n2635?fbclid=IwAR1-Kai-DKSWCJXIcodzN4bJ9On6EYd8-O9Gk8bd0LdZEAKSqf6y5bYZk84.
Blowing the whistle on Pfizer in Texas
The article written by Paul Thacker is headed ‘Covid-19: Researcher blows the whistle on data integrity issues in Pfizer’s vaccine trial’. Thacker is an American journalist specialising in science, medicine, and environmental reporting. He is well published including with Science and the Journal of the American Medical Association.
Thacker reveals poor practices at Ventavia, a research company contracted to help to carry out Pfizer’s pivotal Covid-19 vaccine trial in Texas. Speed appears to have come at the cost of data integrity and patient safety.
Brook Jackson, a regional director employed by Ventavia believed it had “…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 conducting quality control checks were overwhelmed by the volume of problems they were finding.”
Former Ventavia employees have endorsed Jackson’s concerns. One described the work environment as “helter skelter”.
Jackson is a trained and experienced clinical trial auditor. During her short period of employment with Ventavia in September 2020, she repeatedly informed her superiors of poor laboratory management, patient safety concerns, and data integrity issues. Exasperated by non-responsiveness she documented several matters including taking photos.
After repeatedly notifying the company of these problems, Jackson emailed a complaint to the United States’ regulatory authority, the Food and Drug Administration (FDA). That same day she was dismissed by Ventavia.
The article written by Paul Thacker is headed ‘Covid-19: Researcher blows the whistle on data integrity issues in Pfizer’s vaccine trial’. Thacker is an American journalist specialising in science, medicine, and environmental reporting. He is well published including with Science and the Journal of the American Medical Association.
Thacker reveals poor practices at Ventavia, a research company contracted to help to carry out Pfizer’s pivotal Covid-19 vaccine trial in Texas. Speed appears to have come at the cost of data integrity and patient safety.
Brook Jackson, a regional director employed by Ventavia believed it had “…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 conducting quality control checks were overwhelmed by the volume of problems they were finding.”
Former Ventavia employees have endorsed Jackson’s concerns. One described the work environment as “helter skelter”.
Jackson is a trained and experienced clinical trial auditor. During her short period of employment with Ventavia in September 2020, she repeatedly informed her superiors of poor laboratory management, patient safety concerns, and data integrity issues. Exasperated by non-responsiveness she documented several matters including taking photos.
After repeatedly notifying the company of these problems, Jackson emailed a complaint to the United States’ regulatory authority, the Food and Drug Administration (FDA). That same day she was dismissed by Ventavia.
Regulatory oversight failure
Especially in the context of ‘Big Pharma’ driven by profit-maximisation, independent regulatory oversight is critical. Unfortunately the FDA’s oversight capacity is severely under-resourced. When the FDA receives a complaint about a clinical trial, it “…rarely has the staff available to show up and inspect.” Oversight can and does occur too late.
The article records Dr Jill Fisher, a professor of social medicine in North Carolina, as advising that “There’s just a complete lack of oversight of contract research organisations and independent clinical research facilities.”
Thacker notes that in 2007 the Department of Health and Human Services’ Office of the Inspector General released a report on FDA’s oversight of clinical trials conducted between 2000 and 2005. The report found that the FDA inspected only 1% of clinical trial sites.
Since then it has not got better. Inspections carried out by the FDA’s vaccines and biologics branch have been decreasing in recent years, with just 50 conducted in 2020.
Especially in the context of ‘Big Pharma’ driven by profit-maximisation, independent regulatory oversight is critical. Unfortunately the FDA’s oversight capacity is severely under-resourced. When the FDA receives a complaint about a clinical trial, it “…rarely has the staff available to show up and inspect.” Oversight can and does occur too late.
The article records Dr Jill Fisher, a professor of social medicine in North Carolina, as advising that “There’s just a complete lack of oversight of contract research organisations and independent clinical research facilities.”
Thacker notes that in 2007 the Department of Health and Human Services’ Office of the Inspector General released a report on FDA’s oversight of clinical trials conducted between 2000 and 2005. The report found that the FDA inspected only 1% of clinical trial sites.
Since then it has not got better. Inspections carried out by the FDA’s vaccines and biologics branch have been decreasing in recent years, with just 50 conducted in 2020.
The complaint
Jackson was very specific in In her formal complaint to the FDA. She identified several serious concerns including:
On 10 December Pfizer submitted a briefing document to an FDA advisory committee meeting to discuss its application for emergency use authorisation of its Covid-19 vaccine. No mention was made of problems at the Ventavia site. The next day FDA issued the authorisation of the vaccine.
In total Pfizer held clinical trials in 153 sites, three of which were run by Ventavia in Texas. In August 2021 the FDA published a summary of its inspections of the trials. Only nine of the 153 sites were inspected. Ventavia’s were not listed among them.
FDA’s inspection officer noted: “The data integrity and verification portion of the BIMO [bioresearch monitoring] inspections were limited because the study was ongoing, and the data required for verification and comparison were not yet available to the IND [investigational new drug].”
Jackson was very specific in In her formal complaint to the FDA. She identified several serious concerns including:
- participants placed in a hallway after injection and not being monitored by clinical staff;
- lack of timely follow-up of patients who experienced adverse events;
- protocol deviations not being reported;
- vaccines not being stored at proper temperatures;
- mislabelled laboratory specimens; and
- targeting of Ventavia staff for reporting these types of problems.
On 10 December Pfizer submitted a briefing document to an FDA advisory committee meeting to discuss its application for emergency use authorisation of its Covid-19 vaccine. No mention was made of problems at the Ventavia site. The next day FDA issued the authorisation of the vaccine.
In total Pfizer held clinical trials in 153 sites, three of which were run by Ventavia in Texas. In August 2021 the FDA published a summary of its inspections of the trials. Only nine of the 153 sites were inspected. Ventavia’s were not listed among them.
FDA’s inspection officer noted: “The data integrity and verification portion of the BIMO [bioresearch monitoring] inspections were limited because the study was ongoing, and the data required for verification and comparison were not yet available to the IND [investigational new drug].”
Lessons for New Zealand
Despite Pfizer proving to date to be a successful vaccine against Covid-19, the Texas experience is very concerning and offers New Zealand important lessons. One is that we can’t assume that ‘Big Pharma’ will provide the thorough, methodical and transparent rigour necessary to ensure the safety and integrity of vaccines.
Another lesson is the importance of well-resourced and vigilant independent regulatory authorities. This is particularly the case in countries like the United States where these authorities have to cope with a high level of corruption.
On 29 November Stuff published a scary article by Eric Crampton from the New Zealand Initiative: https://www.stuff.co.nz/business/opinion-analysis/127121998/burden-of-proof-is-on-medsafe-to-justify-its-existence. He argued that the pharmaceutical companies had sufficient motivation to give confidence over safety and that New Zealand’s regulatory authority MedSafe was unnecessary because we could leave it to similar authorities in other countries such as the United States.
Crampton could not be more wrong. MedSafe should take as long as is needed before approving a vaccine application. Relying on what the results of clinical trials reveal or what other regulatory authorities in a small number of ‘approved’ countries decide is insufficient.
MedSafe should also assess the performance of vaccines in those countries where they have been approved and rolled out, particularly those with big populations. This includes the extension of Pfizer to children between 5 and 12 Years.
A further lesson is that New Zealand should start planning to produce its own vaccines through a new ‘not-for-profit’ statutory entity. We already produce some animal vaccines. Why not extend the species scope? If a small country facing over 60 years of economic warfare like Cuba can do it, why not Aotearoa in a much more peaceful environment?
Ian Powell is the editor of the health systems blog Otaihanga Second Opinion HERE, a health commentator, and a former Executive Director of the Association of Salaried Medical Specialists.
Despite Pfizer proving to date to be a successful vaccine against Covid-19, the Texas experience is very concerning and offers New Zealand important lessons. One is that we can’t assume that ‘Big Pharma’ will provide the thorough, methodical and transparent rigour necessary to ensure the safety and integrity of vaccines.
Another lesson is the importance of well-resourced and vigilant independent regulatory authorities. This is particularly the case in countries like the United States where these authorities have to cope with a high level of corruption.
On 29 November Stuff published a scary article by Eric Crampton from the New Zealand Initiative: https://www.stuff.co.nz/business/opinion-analysis/127121998/burden-of-proof-is-on-medsafe-to-justify-its-existence. He argued that the pharmaceutical companies had sufficient motivation to give confidence over safety and that New Zealand’s regulatory authority MedSafe was unnecessary because we could leave it to similar authorities in other countries such as the United States.
Crampton could not be more wrong. MedSafe should take as long as is needed before approving a vaccine application. Relying on what the results of clinical trials reveal or what other regulatory authorities in a small number of ‘approved’ countries decide is insufficient.
MedSafe should also assess the performance of vaccines in those countries where they have been approved and rolled out, particularly those with big populations. This includes the extension of Pfizer to children between 5 and 12 Years.
A further lesson is that New Zealand should start planning to produce its own vaccines through a new ‘not-for-profit’ statutory entity. We already produce some animal vaccines. Why not extend the species scope? If a small country facing over 60 years of economic warfare like Cuba can do it, why not Aotearoa in a much more peaceful environment?
Ian Powell is the editor of the health systems blog Otaihanga Second Opinion HERE, a health commentator, and a former Executive Director of the Association of Salaried Medical Specialists.
1 comment:
I would recommend Rebecca Weisser Are the kids OK article in Australian Spectator and to watch dr. John Campbell dr. Mobeen Syed and dr. Seheult on YouTube who reported about the above mentioned article immediately.
Alexandra Corbett Dekanova.
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