Evidence based medicine has been corrupted by corporate interests, failed regulation, and commercialisation of academia, argue these authors
The advent of evidence based medicine was a paradigm shift intended to provide a solid scientific foundation for medicine. The validity of this new paradigm, however, depends on reliable data from clinical trials, most of which are conducted by the pharmaceutical industry and reported in the names of senior academics. The release into the public domain of previously confidential pharmaceutical industry documents has given the medical community valuable insight into the degree to which industry sponsored clinical trials are misrepresented. Until this problem is corrected, evidence based medicine will remain an illusion.
Anti-lockdown scientists were viewed as having ‘fringe’ ideas because those calling for draconian restrictions had more followers on social media, a study has shown.
Professor John Ioannidis, of Stanford University, an expert in data science and the reliability of research, studied the expertise of authors who signed the Great Barrington Declaration (GBD) compared with signatories of the John Snow Memorandum.
…In an article published in BMJ Open Research, he found that both letters were authored by very influential experts, but that the John Snow Memorandum authors had a far greater reach on social media, which made it appear that their view had more support.
…Prof Ioannidis concluded: “Both the Great Barrington Declaration and John Snow Memorandum include many stellar scientists, but JSM has far more powerful social media presence and this may have shaped the impression that it is the dominant narrative.
In the pages of The BMJ a decade ago, in the middle of a different pandemic, it came to light that governments around the world had spent billions stockpiling antivirals for influenza that had not been shown to reduce the risk of complications, hospital admissions, or death. The majority of trials that underpinned regulatory approval and government stockpiling of oseltamivir (Tamiflu) were sponsored by the manufacturer; most were unpublished, those that were published were ghostwritten by writers paid by the manufacturer, the people listed as principal authors lacked access to the raw data, and academics who requested access to the data for independent analysis were denied.
Results Among the 47 key GBD signatories, 20, 19 and 21, respectively, were top-cited authors for career impact, recent single-year (2019) impact or either. For comparison, among the 34 key JSM signatories, 11, 14 and 15, respectively, were top cited. Key signatories represented 30 different scientific fields (9 represented in both documents, 17 only in GBD and 4 only in JSM). In a random sample of n=30 scientists among the longer lists of signatories, five in GBD and three in JSM were top cited. By April 2021, only 19/47 key GBD signatories had personal Twitter accounts versus 34/34 of key JSM signatories; 3 key GBD signatories versus 10 key JSM signatories had >50 000 Twitter followers and extraordinary Kardashian K-indices (363–2569). By November 2021, four key GBD signatories versus 13 key JSM signatories had >50 000 Twitter followers.
Conclusions Both GBD and JSM include many stellar scientists, but JSM has far more powerful social media presence and this may have shaped the impression that it is the dominant narrative.
The analysis identified 72 studies that might potentially have provided evidence on the effectiveness of masks, social distancing and hand washing. Of those, just six (not eight, 30 or 72) were sufficiently relevant — and of sufficient quality — that they could provide any useful information on mask efficacy. And how reliable were the six? Four were assessed to have a moderate risk of bias, and two to have a serious or critical risk.
Health at a Glance provides a comprehensive set of indicators on population health and health system performance across OECD members and key emerging economies. These cover health status, risk factors for health, access to and quality of health care, and health resources. Analysis draws from the latest comparable official national statistics and other sources.
Alongside indicator-by-indicator analysis, an overview chapter summarises the comparative performance of countries and major trends. This edition also has a special focus on the health impact of COVID-19 in OECD countries, including deaths and illness caused by the virus, adverse effects on access and quality of care, and the growing burden of mental ill-health.
Commentary by The Daily Sceptic:
UK Life Expectancy in 2020 Was Still at 2010 Levels and Over 80, OECD Report Shows – The Daily Sceptic
Despite all the daily reports of deaths, the running total of over 165,000 Covid deaths, and the repeated lockdowns imposed to protect a health service ever on the brink of collapse, the country has experienced a mortality rate no worse than 2009. I don’t know about you, but I can remember 2009. I don’t recall any lockdowns and panicking, or coerced experimental medicine, or bodies piling up in the morgues. Yet it was a worse year for deaths than the great pandemic year of 2020. Let that sink in.
…The OECD analysis is in line with the analysis done in April by economist John Appleby writing in the BMJ. The chart below shows that age-standardised mortality in 2020 was lower than in 2008 and every year prior to it.
Revelations of poor practices at a contract research company helping to carry out Pfizer’s pivotal covid-19 vaccine trial raise questions about data integrity and regulatory oversight. Paul D Thacker reports
In autumn 2020 Pfizer’s chairman and chief executive, Albert Bourla, released an open letter to the billions of people around the world who were investing their hopes in a safe and effective covid-19 vaccine to end the pandemic. “As I’ve said before, we are operating at the speed of science,” Bourla wrote, explaining to the public when they could expect a Pfizer vaccine to be authorised in the United States.1
But, for researchers who were testing Pfizer’s vaccine at several sites in Texas during that autumn, speed may have come at the cost of data integrity and patient safety. 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.
Poor laboratory management
On its website Ventavia calls itself the largest privately owned clinical research company in Texas and lists many awards it has won for its contract work.2 But Jackson has told The BMJ that, during the two weeks she was employed at Ventavia in September 2020, she repeatedly informed her superiors of poor laboratory management, patient safety concerns, and data integrity issues. Jackson was a trained clinical trial auditor who previously held a director of operations position and came to Ventavia with more than 15 years’ experience in clinical research coordination and management. Exasperated that Ventavia was not dealing with the problems, Jackson documented several matters late one night, taking photos on her mobile phone. One photo, provided to The BMJ, showed needles discarded in a plastic biohazard bag instead of a sharps container box. Another showed vaccine packaging materials with trial participants’ identification numbers written on them left out in the open, potentially unblinding participants. Ventavia executives later questioned Jackson for taking the photos.
Early and inadvertent unblinding may have occurred on a far wider scale. According to the trial’s design, unblinded staff were responsible for preparing and administering the study drug (Pfizer’s vaccine or a placebo). This was to be done to preserve the blinding of trial participants and all other site staff, including the principal investigator. However, at Ventavia, Jackson told The BMJ that drug assignment confirmation printouts were being left in participants’ charts, accessible to blinded personnel. As a corrective action taken in September, two months into trial recruitment and with around 1000 participants already enrolled, quality assurance checklists were updated with instructions for staff to remove drug assignments from charts.
In a recording of a meeting in late September2020 between Jackson and two directors a Ventavia executive can be heard explaining that the company wasn’t able to quantify the types and number of errors they were finding when examining the trial paperwork for quality control. “In my mind, it’s something new every day,” a Ventavia executive says. “We know that it’s significant.”
Ventavia was not keeping up with data entry queries, shows an email sent by ICON, the contract research organisation with which Pfizer partnered on the trial. ICON reminded Ventavia in a September 2021 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.”
Worries over FDA inspection
Documents show that problems had been going on for weeks. In a list of “action items” circulated among Ventavia leaders in early August 2020, shortly after the trial began and before Jackson’s hiring, a Ventavia executive identified three site staff members with whom to “Go over e-diary issue/falsifying data, etc.” One of them was “verbally counseled for changing data and not noting late entry,” a note indicates. At several points during the late September meeting Jackson and the Ventavia executives discussed the possibility of the FDA showing up for an inspection (box 1). “We’re going to get some kind of letter of information at least, when the FDA gets here . . . know it,” an executive stated.
A history of lax oversight
When it comes to the FDA and clinical trials, Elizabeth Woeckner, president of Citizens for Responsible Care and Research Incorporated (CIRCARE),3 says the agency’s oversight capacity is severely under-resourced. If the FDA receives a complaint about a clinical trial, she says the agency rarely has the staff available to show up and inspect. And sometimes oversight occurs too late.
In one example CIRCARE and the US consumer advocacy organisation Public Citizen, along with dozens of public health experts, filed a detailed complaint in July 2018 with the FDA about a clinical trial that failed to comply with regulations for the protection of human participants.4 Nine months later, in April 2019, an FDA investigator inspected the clinical site. In May this year the FDA sent the triallist a warning letter that substantiated many of the claims in the complaints. It said, “[I]t appears that you did not adhere to the applicable statutory requirements and FDA regulations governing the conduct of clinical investigations and the protection of human subjects.”5
“There’s just a complete lack of oversight of contract research organisations and independent clinical research facilities,” says Jill Fisher, professor of social medicine at the University of North Carolina School of Medicine and author of Medical Research for Hire: The Political Economy of Pharmaceutical Clinical Trials.
Ventavia and the FDA
A former Ventavia employee told The BMJ that the company was nervous and expecting a federal audit of its Pfizer vaccine trial.
“People working in clinical research are terrified of FDA audits,” Jill Fisher told The BMJ, but added that the agency rarely does anything other than inspect paperwork, usually months after a trial has ended. “I don’t know why they’re so afraid of them,” she said. But she said she was surprised that the agency failed to inspect Ventavia after an employee had filed a complaint. “You would think if there’s a specific and credible complaint that they would have to investigate that,” Fisher said.
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.6 Inspections carried out by the FDA’s vaccines and biologics branch have been decreasing in recent years, with just 50 conducted in the 2020 fiscal year.7
The next morning, 25 September 2020, Jackson called the FDA to warn about unsound practices in Pfizer’s clinical trial at Ventavia. She then reported her concerns in an email to the agency. In the afternoon Ventavia fired Jackson—deemed “not a good fit,” according to her separation letter.
Jackson told The BMJ it was the first time she had been fired in her 20 year career in research.
In her 25 September email to the FDA Jackson wrote that Ventavia had enrolled more than 1000 participants at three sites. The full trial (registered under NCT04368728) enrolled around 44 000 participants across 153 sites that included numerous commercial companies and academic centres. She then listed a dozen concerns she had witnessed, 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.
Within hours Jackson received an email from the FDA thanking her for her concerns and notifying her that the FDA could not comment on any investigation that might result. A few days later Jackson received a call from an FDA inspector to discuss her report but was told that no further information could be provided. She heard nothing further in relation to her report.
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 authorisation of its covid-19 vaccine, the company made no mention of problems at the Ventavia site. The next day the FDA issued the authorisation of the vaccine.8
In August this year, after the full approval of Pfizer’s vaccine, the FDA published a summary of its inspections of the company’s pivotal trial. Nine of the trial’s 153 sites were inspected. Ventavia’s sites were not listed among the nine, and no inspections of sites where adults were recruited took place in the eight months after the December 2020 emergency authorisation. The 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].”
Other employees’ accounts
In recent months Jackson has reconnected with several former Ventavia employees who all left or were fired from the company. One of them was one of the officials who had taken part in the late September meeting. In a text message sent in June the former official apologised, saying that “everything that you complained about was spot on.”
Two former Ventavia employees spoke to The BMJ anonymously for fear of reprisal and loss of job prospects in the tightly knit research community. Both confirmed broad aspects of Jackson’s complaint. One said that she had worked on over four dozen clinical trials in her career, including many large trials, but had never experienced such a “helter skelter” work environment as with Ventavia on Pfizer’s trial.
“I’ve never had to do what they were asking me to do, ever,” she told The BMJ. “It just seemed like something a little different from normal—the things that were allowed and expected.”
She added that during her time at Ventavia the company expected a federal audit but that this never came.
After Jackson left the company problems persisted at Ventavia, this employee said. In several cases Ventavia lacked enough employees to swab all trial participants who reported covid-like symptoms, to test for infection. Laboratory confirmed symptomatic covid-19 was the trial’s primary endpoint, the employee noted. (An FDA review memorandum released in August this year states that across the full trial swabs were not taken from 477 people with suspected cases of symptomatic covid-19.)
“I don’t think it was good clean data,” the employee said of the data Ventavia generated for the Pfizer trial. “It’s a crazy mess.”
A second employee also described an environment at Ventavia unlike any she had experienced in her 20 years doing research. She told The BMJ that, shortly after Ventavia fired Jackson, Pfizer was notified of problems at Ventavia with the vaccine trial and that an audit took place.
Since Jackson reported problems with Ventavia to the FDA in September 2020, Pfizer has hired Ventavia as a research subcontractor on four other vaccine clinical trials (covid-19 vaccine in children and young adults, pregnant women, and a booster dose, as well an RSV vaccine trial; NCT04816643, NCT04754594, NCT04955626, NCT05035212). The advisory committee for the Centers for Disease Control and Prevention is set to discuss the covid-19 paediatric vaccine trial on 2 November.
Provenance and peer review: commissioned; externally peer reviewed.
Competing interests: PDT has been doubly vaccinated with Pfizer’s vaccine.
This article is made freely available for use in accordance with BMJ’s website terms and conditions for the duration of the covid-19 pandemic or until otherwise determined by BMJ. You may use, download and print the article for any lawful, non-commercial purpose (including text and data mining) provided that all copyright notices and trade marks are retained.
* Bourla A. An open letter from Pfizer chairman and CEO Albert Bourla. Pfizer. https://www.pfizer.com/news/hot-topics/an_open_letter_from_pfizer_chairman_and_ceo_albert_bourla.
* Ventavia. A leading force in clinical research trials. https://www.ventaviaresearch.com/company.
* Citizens for Responsible Care and Research Incorporated (CIRCARE). http://www.circare.org/corp.htm.
* Public Citizen. Letter to Scott Gottlieb and Jerry Menikoff. Jul 2018. https://www.citizen.org/wp-content/uploads/2442.pdf.
↵Food and Drug Administration. Letter to John B Cole MD. MARCS-CMS 611902. May 2021. https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/warning-letters/jon-b-cole-md-611902-05052021.
* Department of Health and Human Services Office of Inspector General. The Food and Drug Administration’s oversight of clinical trials. Sep 2007. https://www.oig.hhs.gov/oei/reports/oei-01-06-00160.pdf.
* Food and Drug Administration. Bioresearch monitoring. https://www.fda.gov/media/145858/download.
* FDA takes key action in fight against covid-19 by issuing emergency use authorization for first covid-19 vaccine. Dec 2020. https://www.fda.gov/news-events/press-announcements/fda-takes-key-action-fight-against-covid-19-issuing-emergency-use-authorization-first-covid-19.
Original article: https://www.bmj.com/content/375/bmj.n2635
Part of the rush to dismiss women on the basis of little to no evidence comes – no doubt – from a well-meaning, but ultimately misguided effort to reduce vaccine hesitancy in young women, although if anything will drive hesitancy it is surely exactly this kind of medical gaslighting. More broadly, being disbelieved and dismissed by the medical establishment is nothing new for women, who are used to being, for example, prescribed antidepressants when they present to doctors in pain (men who present with similar symptoms are more likely to be prescribed painkillers). Women are simply not considered to be reliable narrators of their own bodies.
Government agencies such as health departments might be more inclined to intervene if findings from a study they commissioned are not as expected or if they are heavily invested in the health intervention — such as an education or health programme — being trialled, she adds.
A 2016 inquiry into the delayed publication of research commissioned by UK government agencies identified cases in which publication was “manipulated to fit with political concerns”. More recently, the British Medical Journal reported four instances of politicization and suppression of science in the United Kingdom during the COVID-19 pandemic.
Stephen Lock, my predecessor as editor of The BMJ, became worried about research fraud in the 1980s, but people thought his concerns eccentric. Research authorities insisted that fraud was rare, didn’t matter because science was self-correcting, and that no patients had suffered because of scientific fraud. All those reasons for not taking research fraud seriously have proved to be false, and, 40 years on from Lock’s concerns, we are realising that the problem is huge, the system encourages fraud, and we have no adequate way to respond.
THE CENTERS for Disease Control and Prevention’s safety committee has provided an update on the association between Pfizer-BioNTech and Moderna COVID-19 vaccines and heart inflammation.
On 23 June the US Centers for Disease Control and Prevention’s safety committee said there was a “likely association” between the Pfizer-BioNTech and Moderna COVID-19 vaccines and myocarditis (the medical term for heart inflammation) and pericarditis (inflammation of the tissue that surrounds the heart) in some young adults. The CDC’s Advisory Committee on Immunization Practices said there was a higher than expected number of reports of heart inflammation in people aged 16-24 who had received the mRNA vaccines but that the benefits of vaccination still clearly outweighed the risks.
To this day, many commentators think that coercion is justified in defence of public health. Arguments over ‘vaccine passports’ and obligations to get vaccinated in contracts of employment are already raging. The voluntary principle, however, is a good one. It is what allowed Britain’s vaccination programme to move beyond the controversies of the 1880s, squaring the circle of vaccination and opposition by letting people opt out. Pointedly, the conscientious objection clause over time killed off Britain’s anti-vaccine campaigns by removing the causes célèbres of vaccine martyrdom.
Resources use inappropriate emotional pressure
The Human Medicines Regulations 2012 (the ‘Regulations’) apply to anything ‘designed to promote the … supply … or use of that [medicinal] product’, which according to the regulations amounts to an advertisement. As the materials do not properly encourage critical thinking and present information as fact without substantiation, it is entirely possible that the teaching materials and lessons delivering those materials amount to an advertisement and may constitute an offence.
However well meaning these materials might be, it appears that they have at least the potential to put emotional pressure on children and — potentially — coercively control children’s decisions in relation to the vaccine. The materials are therefore incompatible with the NC and the government’s advice on Teachers’ Prevent Duty, which are there to help protect children.
Hard to justify right now for most children in most countries
Following widespread vaccination against SARS-CoV-2 of older adults and other highly vulnerable groups, some high income countries are now considering vaccinating children; just days ago, the US Food and Drug Administration authorized the use of the Pfizer/BioNTech vaccine in children 12-15 years of age. Young people have been largely spared from severe covid-19 so far, and the value of childhood vaccination against respiratory viruses in general remains an open question for three reasons: the limited benefits of protection in age groups that experience only mild disease; the limited effects on transmission because of the range of antigenic types and waning vaccine induced immunity; and the possibility of unintended consequences related to differences in vaccine induced and infection induced immunity. We discuss each in turn.
Nevertheless, what I am currently struggling with is the failure to report the reality of the morbidity caused by our current vaccination program within the health service and staff population. The levels of sickness after vaccination is unprecedented and staff are getting very sick and some with neurological symptoms which is having a huge impact on the health service function. Even the young and healthy are off for days, some for weeks, and some requiring medical treatment. Whole teams are being taken out as they went to get vaccinated together.
Adults who lived with children during the pandemic’s second wave were only slightly more at risk of Covid-19 than those who lived without them, suggesting school attendance has minimal impact on infection rates, a new study has found.
While there was a small increased risk of infection and hospitalisation for those aged 65 and under who lived with school-aged children between September and December last year, they were no more likely to be admitted to intensive care or die than those who lived without children.
The peer-reviewed study, published in the British Medical Journal, found no evidence of a noticeably increased risk of infection during the first wave in the UK between February and August, compared to those adults who do not live with children.
Leaked documents show that some early commercial batches of Pfizer-BioNTech’s covid-19 vaccine had lower than expected levels of intact mRNA, prompting wider questions about how to assess this novel vaccine platform, writes Serena Tinari
Some 8.8 million schoolchildren in the UK have experienced severe disruption to their education, with prolonged school closures and national exams cancelled for two consecutive years. School closures have been implemented internationally1 with insufficient evidence for their role in minimising covid-19 transmission and insufficient consideration of the harms to children.
This is a BMJ Rapid Response letter by Dr Janet Menage, Wales, UK, in response to Covid-19: Social murder, they wrote-elected, unaccountable, and unrepentant, by Kamran Abbasi. You can find the full response in the link below.
From a medical perspective, it was clear early on in the crisis that disregarding clinical acumen in favour of blind obedience to abnormal ventilation measures, reliance on an unsuitable laboratory test for diagnosis and management, and abandoning the duty of care to elderly hospitalised patients and those awaiting diagnosis and treatment of serious diseases, would create severe problems down the line.
Doctors who had empirically found effective pharmaceutical remedies and preventative treatments were ignored, or worse, denigrated or silenced. Information regarding helpful dietary supplements was suppressed.
Little is known about the interests of the doctors, scientists, and academics on whose advice the UK government relies to manage the pandemic. Attempts to discover more are frequently thwarted, finds Paul D Thacker.