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Before we look into the findings from the court mandated documents released by FDA, I would like to share some points from an article published in BMJ – British Medical Journal. It was written by the investigative journalist Paul D. Thacker and published in November 2021.
The article is about revelations of poor practices at a contract research company which was carrying out Pfizer’s pivotal Covid-19 vaccine trial. CROs – Clinical Research Organizations are independent entities which carry out clinical trials for pharmaceutical companies. They are regulated separately to ensure that the trials are conducted and reported as per prescribed protocols. CROs is a lucrative business and therefore these have come up in all developed countries. In addition, many CROs are based in China and India because large population of these countries is fertile ground for testing drugs.
Data integrity breaches have been highlighted in the recent past and some very large companies were implicated in questionable data integrity.
Pfizer-BioNTech studies were conducted across several countries and sites, and by multiple CROs to expedite data collection. Ventavia Research Group, based at various locations in Texas, USA, was a major CRO doing clinical trials of Pfizer-BioNTech vaccine in 2020. Ventavia calls itself the largest privately owned clinical research company in Texas.
The report is largely based on the feedback and material provided by Ms. Brook Jackson, who was employed there in September 2020. Jackson is a trained clinical auditor and carried more than 15 years’ experience in clinical research coordination and management. During her short stay there, she found and informed her superiors about poor laboratory management, patient safety concerns, and data integrity issues. When they did not take any action, Jackson documented several matters late one night, and took photos on her mobile. For example, the waste was not being handled as per protocol, which could be hazardous. She also documented potential unblinding of patients.
For information, clinical studies for new drugs are double-blind, and placebo controlled. Double-blind means that both the physicians and the patients do not know what they are getting. The drugs are not given in original packing, these are supplied in simple, unmarked packing so that there is no clue about the identity. Placebo means a drug which looks like the drug but is not the drug. Just visualize that apparently two drugs are being given but the real identity of these is not known to physicians and patients. The results are gathered, compiled, and analyzed, and then the identity of medications is opened. This method is adopted to eliminate probable biases among physicians and patients. Jackson revealed that the handling of trial was being done in a careless way which could unblind the trial. If it would happen, it would be a critical error rendering the trial unacceptable to overseeing committee.
“Ventavia was not keeping up with data entry queries, shows an email sent by ICON, the contract research organization with which Pfizer partnered on the trial. ICON reminded Ventavia in a September 2020 email: “The expectation for this study is that all queries are addressed within 24hrs.” ICON then highlighted over 100 outstanding queries older than three days in yellow. Examples included two individuals for which “Subject has reported with Severe symptoms/reactions … Per protocol, subjects experiencing Grade 3 local reactions should be contacted. Please confirm if an UNPLANNED CONTACT was made and update the corresponding form as appropriate.” According to the trial protocol a telephone contact should have occurred “to ascertain further details and determine whether a site visit is clinically indicated.”
Elizabeth Woeckner, president of Citizens for Responsible Care and Research Incorporated (CIRCARE) says that the oversight capacity of USFDA is severely under-resourced. If they receive a complaint, they rarely have staff available to visit and inspect, and sometimes it occurs too late.
On September 25, Jackson called the FDA and warned about unsound practices in Pfizer’s clinical trial at Ventavia. She then detailed her concerns in an email to FDA. Some of the concerns expressed were these.
- 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
- Mislabeled laboratory specimens
The same afternoon, Ventavia fired Jackson.
In Pfizer’s briefing document submitted to an FDA advisory committee meeting held on 10 December 2020 to discuss Pfizer’s application for emergency use authorization of its Covid-19 vaccine, the company made no mention of problems at the Ventavia site. Next day, FDA issued the authorization of vaccine.
Since Jackson reported problems with Ventavia to the FDA in September 2020, Pfizer has engaged Ventavia as a research sub-contractor on four other vaccine trials – Covid 19 vaccine in children and young adults, pregnant women, booster dose, and an RSV – Respiratory Syncytial Virus.
The summary is that there might have lapses in reporting of adverse events. These may have been due to poor management, rather than bad intentions. However, it might have had important implications.
To be Concluded……
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