No child under 5 should get these injections. No healthy child of any age. This is criminal, reckless, dangerous, and many healthy children will be harmed by these vaccines.
I was on the INSIDE & wrote Hahn, CDC, NIH with vax problems, they did not listen to me, nor to Trump, nor to Atlas…they did not care what we had to say, this is the deepstate bureaucracy we mean…but I argue they went too far and must be held to account in proper legal public inquiries. We financially penalize them and jail those we have to if it is shown they did wrong and were reckless and dangerous. We have to!
See my letter again, I wrote it as a research commentary but it was my warning to Redfield, Fauci, Hahn, the CDC, NIH…all of them on the inside. I wrote them. I spoke, I shared, I tried. Scientists and doctors from CDC and NIH and FDA and Moderna etc. met me quietly and secretly, at HHS, on the Washington Mall, to share, to tell me that Atlas is right, that I am right but they fear for their life and job, salary. I laid out the flaws in the vaccine OWS and what they had to address. I used the work ‘WARN’….
I used this phase yet they did not listen and look at the insanity of the vaccine today:
“This commentary serves as guidance but more as a warning to all COVID-19 vaccine developers”
Letter to Dr. Hahn, Commissioner of the FDA, 2020:
Clinical trials stopped early for efficacy or benefit at risk of overestimating treatment effects and distorting risk-benefit assessments: some guiding principles for the SARS-CoV-2 COVID-19 vaccine search
Paul Alexander1 MSc, PhD
1McMaster University, Evidence-Based-Medicine, Health Research Methods, Evidence and Impact (HEI), Faculty of Health Sciences, McMaster University, Hamilton, Ontario, Canada
Keywords: COVID-19, vaccine, clinical trial, early stopping, interim analysis
Corresponding author: Paul E. Alexander, Health Research Methods, Evidence and Impact (HEI), Faculty of Health Sciences, McMaster University, 1280 Main Street West, 2C Area, L8S4K1, Tel: 905-554-7283 or 905-525-9140 EXT 26771
e-mail correspondence to: [email protected]
What is new?
There is unprecedented need to deliver effective therapeutic and preventative agents in the context of the global COVID-19 pandemic. This commentary emphasizes the methodological consequences of stopping clinical trials early, specifically COVID-19 vaccine trials, and particularly from seemingly beneficial results during multiple, early interim analysis of study data. This commentary reviews the evidence to declare a needed event number of at least 500 if the vaccine trial is to be stopped early for benefit. In addition, it is critical that a prespecified stopping rule explicitly outlines all facets of the stopping rule that includes not too many interim looks at the data by the DSMB. As much sample size accrual is critical and most critically, is the at least 500 events (infections) combined in both trial arms. There must be a stricter stopping rule/boundary of p<0.001 if stopping early for benefit is considered.
Commentary
In the context of the quest to produce a vaccine for SARS-CoV-2 coronavirus disease under the present pandemic emergency, it is essential to understand the methodological ramifications in randomized clinical trials (RCTs) that are stopped early for efficacy or benefit (immunogenicity), such trials also known as truncated trials (T-RCTs). Our concern surrounds whether the estimates of effect reflect the true effect of the vaccine. Importantly, we reflect on the safety which can be considered a far more critical consideration than efficacy/effectiveness. We must ensure the latter in this COVID-19 vaccine search with no room for error in this regard.
As a case in point in this rapid race to a COVID-19 vaccine, the United States Operation Warp Speed (OWS) is coordinating ongoing clinical trials development research in tandem with regulatory, manufacturing, and distribution processes to avoid delays in disseminating vaccines to the public to prevent the spread of SARS-CoV-2 coronavirus and potential COVID-19 disease (1). The public-private partnership is innovative and thus far quite favourable in driving towards an efficacious/effective vaccine (s), and involves the synchronous trialing of various vaccine platforms with a multiplicity of vaccines to deliver vaccines. While a near majority of vaccine development is based in the United States, the race for a COVID-19 vaccine is global effort, with China, Asia, Australia, and Europe also centers for rapid vaccine development(2). This commentary guidance applies to all global parties involved in vaccine development and as such, in the process of spearheading vaccine clinical trials.
Applicable to global COVID-19 pandemic vaccine rapid trial approach, are potential risks and justifiable questions on vaccine safety and efficacy, with the demand to ensure that only a safe vaccine will come to market. The public, clinical, and scientific community must be assured that no aspects of a safe and effective vaccine development have been breached before approval of a fast-tracked vaccine. The public must always ‘only’ receive therapeutic interventions (vaccine) that were based on the highest quality, most robust and trustworthy evidence that is underpinned by high certainty, precise estimates of effect. This commentary serves as guidance but more as a warning to all COVID-19 vaccine developers, of what must be in place to derive confidence by researchers and the public.
One such area that deserves acute attention surrounds the issue of stopping a trial early for benefit that has been discussed in the media, versus continuation of recruiting trial participants. No doubt it is best not to stop early when there are initial benefits shown because there is a very high risk of making the decision to stop early based on incomplete and inaccurate trial information. Enough data is likely to have not yet emerged for the estimate of effect to be definitive or as we argue, even accurate. Should we stop the trial if the early benefits are very substantial? Can the observed results possibly be too good to be true? What happens if a trial is not stopped before early indications of efficacy, and then goes on to reveal no effect or even serious harm? Then had the trial stopped early for benefit, this could have been catastrophic for future patients. Limited adverse event safety data is a real cause for concern if a trail is stopped early, and researchers must carefully consider and balance this need, and plan to ensure this safety data is clear enough and collected longer-term even when a decision is made to truncate.
Researchers must also consider the substantial ethical elephant in the room of enrolling participants who have a random chance of being assigned to the placebo group when you have earlier indications of a potentially large treatment effect (3). What should be done? Does appropriate adherence to study methodology then exclude control groups from the possibly beneficial treatment? Should we deny the control group a potentially beneficial vaccine? Is it more important to focus on the safety of prospective patients and the larger society so that they do not make treatment decisions based on inaccurate or incomplete or even dangerous information, while there is clinical equipoise? These are the issues that the data safety monitoring board (DSMBs), also known as the data monitoring committee (DMC), who will be assessing vaccine trial data, must confront.
Some RCTs are stopped early when investigators conclude that the magnitude of effects of treatment are so large and not due to random error or chance that they must stop the trial early for benefit and administer the treatment, or vaccine. Our primary concern is that if this is based on an interim analysis of the data, that this could indeed be very misleading and drive inaccurate results. This is also very different to when researchers stop a RCT for futility (4) or harm (5). It is crucial to raise the cardinal issues that must be considered if a SARS-CoV-2 coronavirus vaccine is stopped early for benefit to ensure confidence by the public and the scientific community in the effectiveness and safety of the vaccine candidate.
