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Return of the revenge of “no saline placebo RCTs” for childhood vaccines

Thanks to RFK Jr. the deceptive claim that the childhood vaccine schedule has never been tested in a randomized controlled trial with a saline placebo control is making the rounds again.This is an old and deceptive antivax half-truth that ignores both what constitutes a scientifically valid placebo and the ethical requirement that RCTs have clinical equipoise.

Here we go again with the old antivax “no saline placebo” trope.

There are days when I feel like a character common in fiction, the old gunslinger being forced by circumstance to reluctantly get back in the saddle one more time for one last fight. It’s such a common trope that I’m seeing it in the new Marvel series Secret Invasion, in which Nick Fury, having in essence gone into semiretirement by leaving earth for a space station, where he was working on defenses against alien invasion, is forced back to earth one more time to confront a threat from aliens. (Samuel L. Jackson is perfect as the grizzled, bearded veteran leader of SHIELD Nick Fury.) Of course, it’s worse than that, because every time I get back in the saddle again for one more fight, it seems that it’s not long before the very same threat emerges again, forcing me to get the six shooters out of storage and saddle up again.

Placebos...it had to be...placebos.
No RCTs with saline placebos for childhood vaccines? Orac is starting to feel like Nick Fury again. Well, I guess it’s time to go back into the fray to look for Skrulls.

This week, I got that very distinct feeling after observing how a very common (and old) antivax trope has not only been resurrected but gone viral, thanks to frequent repetition in interviews and on campaign stops by longtime antivaxxer turned Presidential candidate Robert F. Kennedy, Jr. Longtime debunkers of antivax disinformation will recognize it immediate: The claim that almost none of the vaccines in the childhood vaccine schedule has never been tested in a “true” randomized controlled clinical trial using a saline placebo as control. It’s a half-truth that antivaxxers have long employed to frighten the public with insinuations that vaccines are unsafe and/or ineffective and that they were somehow approved based on poor quality clinical trial evidence, thanks the nefarious machinations of big pharma, the CDC, and the FDA.

Clinical trialists, even ones who know very little about vaccines and the clinical trials used to approve them, will likely immediately recognize the simplistic assumption at the heart of what I like to call the “no true saline placebo” trope: That the only appropriate placebo in a randomized controlled trial (RCT) of an injectable medication or vaccine is saline and that anything else is suspect. Learning a bit about the specific subject, they would soon also realize that a very important bit of context is missing from this narrative, specifically the issue of clinical equipoise. Since it’s been quite a while since I’ve written about the “no true saline placebo” trope and since it’s been all over social media lately, I reluctantly got my debunking six shooters out of storage, cleaned and oiled them up, and saddled back up to ride. I’m not happy about it, but it needs to be done, if only because this “no true saline placebo,” like so many other old antivax narratives and conspiracy theories, rests on a grain of truth that is presented without context in a deceptive manner to make it sound nefarious. It’s a narrative that dates back years and years and that I last wrote about (albeit not in as much detail as I intend to do now) in 2017.

What are randomized controlled clinical trials (RCTs)?

Randomized controlled clinical trials are just that: Clinical trials in which subjects are randomized to receive either the intervention or a control (such as a saline placebo) and then followed to determine which group has the best outcomes, the specific outcomes having been prespecified in the clinical trial protocol. The reason for randomization is to ensure that the two groups being compared resemble each other as closely as possible in characteristics relevant to the outcomes being tested. For example, if you’re testing a drug to treat hypertension, you would want the groups to be matched as closely as possible for, among other characteristics, age, race, sex, severity of hypertension, and relevant risk factors for poor outcomes. Ideally, these RCTs are then double-blinded, so that neither the subjects nor the doctors or medical personnel administering the drugs and assessing outcomes know which group any given subject is in. Double blinding is especially important in clinical trials with more subjective outcomes such as pain, for which placebo effects can be strong, but it’s also important even in trials with “hard” outcomes like tumor progression because it could affect how clinicians interpret tests and radiology studies if they know which group a given patient is in.

In general, during drug development promising compounds are first tested in what are called phase 1 trials, which involve giving the drug to small numbers of patients at different doses to find (1) obvious severe toxicities and (2) an optimal dose to test for RCTs, which is why such trials are often also serve as dose-finding studies to determine the drug dose to use in the early RCTs done in phase 2 and the large RCTs done in phase 3. Note that phase 1 trials do not look for efficacy; that is not their purpose. If they find evidence of efficacy, that’s all great and promising, but it’s not expected. The number of subjects is too low, and they are generally not randomized. Phase 2 clinical trials are generally smaller RCTs that serve as the first real test of whether the drug works. If the drug shows promise in phase 2, then large phase 3 RCTs are carried out. In the case of vaccines, these RCTs often involve tens of thousands of subjects.

I like to refer to this graphic from this article to sum it up:

Clinical trial phases, whether saline placebo controlled or not.
This is the traditional four phase clinical trial paradigm. (Phase 4 studies are postmarketing studies that look for safety signals missed in the studies used for FDA approval.)

The above is, of course, the simple, “classic” paradigm. There have developed a number of variations, such as combining phase 1 and 2 trials, adaptive trial designs, and the like.

Let’s take a look at a practical hypothetical example. Let’s say I’ve developed a new drug that preclinical evidence suggests to me will be an effective treatment for a given condition, say X Disease). To get that drug approved by the FDA to treat X Disease, I would propose an RCT in which I recruit patients with the given condition, randomize them into a group receiving the new drug or a control group receiving a placebo. Then I would follow the two groups and see which one does better with respect to X Disease. What percentage, for instance, of the treated group gets better compared to what percentage of the control group? What percentage of the treated. group dies of X Disease compared to the percentage in the control group that dies? What percentage of subjects in the treatment group suffers known complications of X Disease compared to control? As you might imagine, it gets a lot more complicated than that fairly fast, and I will discuss those complications in a moment because widespread ignorance of them are what the “no true saline placebo” trope depends upon. Basically, what I have presented is an idealized version of what an RCT is and how it works, because that is what most lay people understand about RCTs; that is, if they even know what an RCT is at all, just as their understanding of what constitutes an acceptable placebo to use for a placebo control is the simplest “ideal” placebo; i.e., completely “inert,” like saline.

Also contributing to the effectiveness of the “no saline placebo” trope is that many educated lay people are also at least vaguely aware that in the evidence-based medicine (EBM) paradigm, RCTs are considered the top of the hierarchy of clinical scientific evidence supporting a health intervention. (Meta-analyses of RCTs are higher, but as individual studies rather than existing studies lumped together RCTs are at the top.) So when they hear antivaxxers claim and show that there are vaccines on the childhood vaccine schedule that have never been tested against a “saline placebo” in an RCT, it sounds fishy to them. Why weren’t these vaccines tested against a saline placebo? What were those evil pharmaceutical companies doing? Why did the FDA and CDC let them get away with it? It’s all understandable that one might become suspicious; that is, if one doesn’t know much or anything about all the other considerations that must go into any RCT for anything.

Let’s look at one article—on Substack, of course—that is popping up all over the place, in particular the chart included with the article. Then we will consider why this chart might show what it shows and, more importantly, why its finding that many approved vaccines lack studies with what antivaxxers call a “true saline placebo” control is not evidence that corners were cut to approve these vaccines or that the vaccines are in any way unsafe.

Robert F. Kennedy Jr. and the “no saline placebo” gambit

What brought this o my attention was the response to pediatrician, vaccine scientist, and advocate Dr. Paul Offit’s Substack post outlining the many lies of Robert F. Kennedy, Jr., who has of late taken up the “no true saline placebo” gambit as supposed evidence that the vaccines in the childhood schedule were somehow not thoroughly tested and therefore have unproven safety and efficacy:

This is not quite the “gotcha” that Mr. Siri thinks that it is, although Dr. Offit was a bit sloppy.

To me this example is a good cautionary tale about how even someone as knowledgeable about vaccine development and approval as Dr. Offit can be tripped up by being insufficiently careful in his language. But who is Aaron Siri? First of all, he is the author of a deceptive Substack post making the rounds entitled Clinical Trial to License RotaTeq, Like Almost All Childhood Vaccines, Did Not Use a Placebo Control, in which he concludes that “those attacking RFK Jr. are wrong.” More importantly, he is an antivax lawyer who describes himself as “Managing Partner of Siri & Glimstad, has extensive complex civil litigation experience, including civil rights involving mandated medicine, class actions, and high stakes disputes.” The fact that he appears on the antivax Epoch Times to rail about how vaccine manufacturers are supposedly the “most protected companies in America” should tell you all you need to know about his proclivities, which are on display in the deceptive arguments he uses.

The main part of his Substack article that’s gone viral is this chart:

No saline placebo vaccine chart
This is what I like to call lying with mostly accurate information presented without proper scientific context.

Siri, being a lawyer (like RFK Jr.), makes a deceptive lawyerly opening statement:

Robert F. Kennedy, Jr. is on record stating that almost all childhood vaccines were licensed based on clinical trials that did not include a placebo control. He is correct.

Nonetheless, numerous news outlets, such as Stat News in its article titled “Correcting Robert F. Kennedy Jr.’s vaccine ‘facts’”, are stating Mr. Kennedy is wrong because they claim the clinical trial relied upon to license the rotavirus vaccine, RotaTeq, did include a placebo control. They are wrong.

A placebo is defined by the CDC as a “substance or treatment that has no effect on living beings.” This means a saline injection or water drops in mouth.

Again, the CDC falls into the trap of using too simplistic a definition of placebo. “No effect on living beings” is a cringeworthy definition. There are, in fact, a number of considerations that go into choosing a placebo, and, in fact, placebos are not always chosen because they are “completely inert.” Not even saline is “completely inert”! If, for instance, you give enough saline you can cause fluid overload, hypernatremia (too much sodium) and a number of other issues. Not even the classic example of a sugar pill used as a placebo in RCTs of orally administered drugs is “completely inert.” I will argue that a much better way of looking at a placebo control is that it should be “inert” with respect to the outcomes being studied in the RCT.

First, why do we use placebos in the first place? I like this description, provided in these clinical trial guidelines Tweeted by Ed Nirenberg:

In a placebo-controlled trial, subjects are randomly assigned to a test treatment or to an identical-appearing treatment that does not contain the test drug. The treatments may be titrated to effect or tolerance, or may be given at one or more fixed doses. Such trials are almost always double-blind. The name of the control suggests that its purpose is to control for “placebo” effect (improvement in a subject resulting from thinking that he or she is taking a drug), but that is not its only or major benefit. Rather, the placebo control design, by allowing blinding and randomization and including a group that receives an inert treatment, controls for all potential influences on the actual or apparent course of the disease other than those arising from the pharmacologic action of the test drug. These influences include spontaneous change (natural history of the disease and regression to the mean), subject or investigator expectations, the effect of being in a trial, use of other therapy, and subjective elements of diagnosis or assessment. Placebo-controlled trials seek to show a difference between treatments when they are studying effectiveness, but may also seek to show lack of difference (of specified size) in evaluating a safety measurement. In that case, the question of whether the trial could have shown such a difference if there had been one is critical (see section 1.5).

Again, “inert” does not have to mean “completely inert” or “no effect on living beings.” Quite frankly, the CDC definition is wildly simplistic and actually biologically close to impossible, which is likely why RFK Jr. and Aaron Siri chose it instead of other definitions of placebo.

Let me describe one example. It is not uncommon for vaccine trials to choose a placebo that has everything in the vaccine except the active ingredient, that “active” ingredient being the antigen chosen to incite an immune response. That means that the placebo will contain buffer, saline, and whatever adjuvant is used (if an adjuvant is used), such as aluminum. One advantage of this choice is that, unlike the case with a placebo injection that is unlikely to cause a reaction, many subjects receiving the placebo will have a reaction at the injection site similar to that caused by the complete vaccine and will thus be less likely to guess correctly about whether they are in the placebo group or not. The second advantage of such a design is that it demonstrates specificity. If the trial is positive, then one can say confidently that it was due to the antigen in the whole vaccine, not any nonspecific effects due to the rest of the ingredients in the vaccine. Antivaxxers hate this design because they believe incorrectly that it is meant to deceive because to them, despite their decades-long record of safety, aluminum adjuvants (for example) are dangerous and part of what they view as the toxic brew that causes autism, sudden infant death syndrome (SIDS), etc. And if it’s not aluminum, then it must be one of the other vaccine ingredients.

Indeed, Siri makes this very error in his attack on Dr. Offit and the vaccine that he co-invented:

RotaTeq is administered via oral drops. A “placebo” would have been water drops in the mouth. The control used in the trial, however, included bioactive ingredients including almost all the ingredients in the RotaTeq vaccine itself.

Orac retorts: Tell me you don’t understand what constitutes an appropriate placebo without telling me you don’t understand what constitutes an appropriate placebo.

Siri goes on about there being sucrose, sodium phosphate, sodium citrate, and polysorbate-80 in the placebo:

These same four ingredients are also contained in RotaTeq. The only difference between the vaccine and the control is that RotaTeq also included tissue culture medium and rotavirus reassortments. So, bottom line: the control used in the RotaTeq clinical trial was not a placebo since it included bioactive ingredients.

He then goes into incredible contortions to portray sodium phosphate as dangerous:

For example, here is what the NIH explains about sodium phosphate, one of the ingredients in the control:
Sodium Phosphate can cause serious kidney damage and possibly death. In some cases, this damage was permanent, and some people whose kidneys were damaged had to be treated with dialysis (treatment to remove waste from the blood when the kidneys are not working well). Some people developed kidney damage within a few days after their treatment, and others developed kidney damage up to several months after their treatment.

I apologize to any nephrologist out there who just spit up their drink onto their laptop after having read this steaming, stinking pile of pure stupidity. Let’s just say that Mr. Siri left out a very important bit of context: The dose of sodium phosphate required to cause these harms. Let’s just say that the minute amount of sodium phosphate used to buffer vaccines is minuscule compared to the huge amount of phosphate administered with lots of water in preparation for colonoscopy (which is the context of the document cited). It’s also a nice bit of deceptive appeal to authority to represent this as being the NIH saying this. It’s actually Medline Plus, which is published by the National Library of Medicine, which is part of the NIH. So, technically, it is the NIH, but to represent this as some sort of definitive proclamation of the NIH is another example of deceit by leaving out context.

Siri then doubles down:

And as these studies and data sheet make clear, polysorbate-80 is far from an inert substance, is bioactive, and can have safety concerns, especially when given to infants.

Bottom line, Robert F. Kennedy, Jr.’s claim that virtually all childhood vaccines were licensed based on clinical trials that did not include a control group that received a placebo is correct. The undisputable evidence for this claim, all from FDA or pharma sources, is detailed on pages 3 to 7 of a response we sent to HHS on December 31, 2018. (In sharp contrast to virtually all other childhood vaccines, the clinical trial relied on to license Pfizer’s Covid-19 vaccine for teenagers 12 to 17 years of age appears to have had a placebo control group, though we are still reviewing that claim.)

Orac adds: Tell me you either don’t understand or are lying about placebo design for clinical trials without telling me you don’t understand or are lying about placebo design for clinical trials.

The bottom line is actually that either Mr. Siri doesn’t understand placebo design for clinical trials or does understand but is lying about placebo design for clinical trials. Take your pick or suggest a third alternative.

This brings us to the table above touted by Mr. Siri and spread all over social media. My response to the assertion that many vaccines were not tested against a saline placebo is simple: So what? I’ll explain why.

Clinical equipoise: How does that work? (And how does Aaron Sir totally ignore it?)

RFK Jr. and his sycophants, toadies, lackeys, and lickspittles like Mr. Siri would have you believe that the only thing that goes into clinical trial design is rigorous science and that rigorous science always demands that one have a “completely inert” placebo that, in the case of injectable drugs like vaccines, must be saline. This is a risibly simplistic view of drug and vaccine development and clinical trials, chosen intentionally to be used as misinformation about vaccines and ignores a very important standard that all clinical trials, in particular RCTs, must meet: Clinical equipoise.

I’ve discussed clinical equipoise before, but before I define it, let me use an example to illustrate it. Let’s say we have a new chemotherapy drug for breast cancer that we want to test in a clinical trial. If you were to accept Mr. Siri’s intentionally simplistic view of RCTs, you would think that any RCT testing this new drug must be designed with a placebo control group that receives only saline placebo. You would be so very, very incredibly wrong. The reason is that such a trial would totally unethical, for the simple reason that you would be leaving cancer patients in the control group untreated and it is completely unethical to randomize subjects to a group that will deny them existing effective treatment and thus cause them harm and even death.

This is why many cancer therapies are tested in so-called add-on RCTs, as described by the guidelines I cited above:

The use of a placebo control group does not imply that the control group is untreated. In many placebo-controlled trials, the new treatment and placebo are each added to a common standard therapy (so called add-on studies, see section 2.1.5.2.1).

This design means that the placebo group still receives at least the existing standard-of-care treatment for their cancer and is not intentionally left untreated—or even just undertreated. However, we might have reason to believe that the new treatment is as good or better than existing standard-of-care treatment but that adding it to these drugs would increase toxicity beyond what is tolerable. In this case, the proper control group is not a saline placebo control that would leave the group untreated but to compare the new drug against standard-of-care:

In an active control (or positive control) trial, subjects are randomly assigned to the test treatment or to an active control treatment. Such trials are usually double-blind, but this is not always possible; many oncology trials, for example, are considered difficult or impossible to blind because of different regimens, different routes of administration (see section 1.3.2), and different toxicities. Active control trials can have two distinct objectives with respect to showing efficacy: (1) to show efficacy of the test treatment by showing it is as good as a known effective treatment or (2) to show efficacy by showing superiority of the test treatment to the active control. They may also be used with the primary objective of comparing the efficacy and/or safety of the two treatments (see section 1.4). Whether the purpose of the trial is to show efficacy of the new treatment or to compare two treatments, the question of whether the trial would be capable of distinguishing effective from less effective or ineffective treatments is critical (see section 1.5).

To expand upon this explanation, the design of these sorts of studies is either what we refer to as “non-inferiority,” in which the goal is to show that the new treatment is at least not inferior to—or, colloquially, is at least as good as—the existing standard of care. Given such a result, there might be reasons to favor the new treatment even if it is only “as good” as the older treatment if, for example, it’s cheaper, easier to dose, or has a more tolerable side effect profile. Of course, ideally, we would prefer to be able to show that the new drug is better than the existing standard-of-care, but this is often very difficult to do, which is why noninferiority trials are more common.

In any event, regardless of the scientific rigor of the trial, there must be clinical equipoise, which is the existence of genuine uncertainty based on existing science and evidence over which group, the control group or experiment group, will do better. Clinical equipoise does not mean that there is no evidence that a treatment works or is better than existing treatments. After all, the reason we do clinical trials is to find drugs that work where there currently are none and to find drugs that work better than current therapy. But there has to be genuine scientific uncertainty, even if, as is usually the case, investigators think that it is more likely than not that the experimental group will do better than the control group. Absent that legitimate uncertainty, an RCT to test an intervention is unethical.

That brings us to vaccines. The only time that a placebo-controlled RCT of a vaccine can be ethically justified is when there currently does not exist a safe and effective vaccine against the disease for which the experimental vaccine has been designed. Again, just as it is unethical to randomize a cancer patient to a placebo control group when there exists effective chemotherapy that is standard-of-care, so too is it unethical to randomize a subject to a saline placebo group in a vaccine RCT when there exists an already licensed vaccine for the same disease that is considered standard-of-care. You can’t ethically deny subjects in the control group a vaccine against measles, for example, to test a new vaccine against measles. It is unethical to leave a child unprotected against measles in order to test a new measles vaccine. My guess is that Mr. Siri probably knows this but leaves it out.

I’m going to steal from Ed Nirenberg again:

Clinical equipoise: Clinicians and clinical trialists understand it. Antivaxxers either do not or deny it.

Now look at Mr. Siri’s list above that’s been going around social media. Do you notice anything? Almost none of the vaccines on the list that weren’t licensed based on RCTs using saline controls are not first generation vaccines, which means that it would have been unethical to test them against a saline control. So they were tested against some other comparator, usually an earlier licensed version of a vaccine against the same disease, for example DTaP vaccines being tested against the older DTP vaccines, flu vaccines like Fluvaria being tested against older flu vaccines like Fluarix or Fluzone, or Hiberix being tested against older vaccines against Hib like ActHIB. The bottom line is that, if you trace back the history of the vaccines developed for a disease like, say, measles, you will eventually find the RCT testing the first effective vaccine against it and that vaccine will have had a placebo control. It might not have been saline (although in most cases decades ago it was), but it will have been a placebo that is “inert” with respect to preventing that disease. Also, clinical trial standards have evolved over the last 70 years. If a vaccine was approved 60+ years ago using methodology that today we would consider inadequate, that does not change the calculous when it comes to testing new vaccines against the same disease. Such vaccines can’t ethically be tested against saline placebo.

Next, I’ll quote Ed again:

Clinical trial ethics: How does that work? And why do antivaxxers completely ignore it?

When I first decided to write this post, I initially thought that I’d have to look up each and every clinical trial on the table, but then I realized that that’s not necessary. All I really need to do is to show how intellectually dishonest this narrative by RFK Jr. and Aaron Siri is by pointing out that a lot of current vaccines were never tested against a saline placebo control and that’s OK. The reason it’s OK is because clinical trial ethics, specifically, clinical equipoise demanded it. It is unethical to use a saline placebo control for an RCT of any vaccine that is not a brand new vaccine against a disease for which there are currently no safe and effective vaccines. Then, to add to that, contrary to the narrative promoted by RFK Jr. and Aaron Siri, an appropriate placebo control for an RCT of a new vaccine against a disease for which there is currently no licensed vaccine is not necessarily saline. There are often good scientific reasons to pick a comparator other than saline, and I’ll quote Ed one last time before I move on, because he explains why some clinical trials might use a vaccine against a different, unrelated disease as a comparator in order to make blinding more effective:

Clinical trial ethics, how does that work? RFK Jr., Aaron Siri, and antivaxxers sure have no clue—or they lie about it. They should read the suggested book, not that they will do anything other than misinterpret quote-mined passages from it to justify their fear of vaccines.

Exactly. Basically, to delude yourself into thinking that there is clinical equipoise for a vaccine RCT using a saline placebo as control for anything other than a vaccine against a disease that doesn’t already have a licensed safe and effective vaccine against it, the most recent example being COVID-19 vaccines, you have to believe, as antivaxxers falsely do, that vaccines are more harmful than the diseases against which they protect.

RFK Jr. and Aaron Siri exploit poor messaging

Unfortunately, I feel obligated to finish by taking those who should know better about messaging regarding vaccines to task. As much as I admire him and his work, both developing a vaccine and defending vaccines against antivax disinformation, I have to admit that Dr. Offit slipped up here. He of all people knows full well that most of the current vaccines on the childhood schedule were approved in RCTs that didn’t use saline placeboes in the control groups. After all, he’s served on the CDC Advisory Committee for Vaccination Practices (ACIP) and has been involved in vaccine development, science, and licensure for decades. I suspect that when he wrote that all vaccines are tested against placebo control, it was likely mental shorthand for saying that all the original first vaccines against the diseases vaccinated against in the childhood schedule were initially tested against appropriate “inert” controls. I trust that he will not make the same mistake again. Unfortunately, though, because he is Dr. Paul Offit and thus a combination of Sauron, Voldemort, and Darth Vader when it comes to vaccines, his mistake is likely to be harped on by antivax propagandists like Aaron Siri for years to come.

Similarly, it is frustrating that the CDC has such a simplistic definition of what a placebo is. Such a simplistic definition leaves a huge opening for antivaxxers like RFK Jr. and Aaron Siri to selectively cite it instead of more complete and accurate definitions of a placebo. The important thing to know about appropriate placebo comparators for an RCT is that they do not need to be “completely inert.” (Nothing is “completely inert.”) They just need to be “inert” with respect to the outcomes being measured in the RCT. Dr. Offit has referred to placebos for vaccine RCTs as “immunologically inert,” which is as good a definition of a placebo for a vaccine trial as I can think of.

Finally, I will conclude by emphasizing once again that, contrary to the fevered rantings of antivaxxers,, there is nothing nefarious in there existing a number of vaccines that were tested against older versions of a vaccine against the same disease or that were not tested against a “saline placebo.” That’s literally how ethical clinical trials work. They balance scientific rigor against ethics, which often leads to compromises because ethics always trumps rigorous clinical trial design. If that weren’t the case, then we’d be leaving cancer patients untreated so that we can test new chemotherapy drugs against an “appropriate” placebo control. Moreover, an “appropriate” placebo for an injectable drug or vaccine does not have to be saline. There are many more placebos that are entirely appropriate to use as a control in a vaccine RCT other than just saline.

I’m sure that there are also many more lies that antivaxxers will tell about vaccine RCTs, placebo controls, and control group comparators as well.

By Orac

Orac is the nom de blog of a humble surgeon/scientist who has an ego just big enough to delude himself that someone, somewhere might actually give a rodent's posterior about his copious verbal meanderings, but just barely small enough to admit to himself that few probably will. That surgeon is otherwise known as David Gorski.

That this particular surgeon has chosen his nom de blog based on a rather cranky and arrogant computer shaped like a clear box of blinking lights that he originally encountered when he became a fan of a 35 year old British SF television show whose special effects were renowned for their BBC/Doctor Who-style low budget look, but whose stories nonetheless resulted in some of the best, most innovative science fiction ever televised, should tell you nearly all that you need to know about Orac. (That, and the length of the preceding sentence.)

DISCLAIMER:: The various written meanderings here are the opinions of Orac and Orac alone, written on his own time. They should never be construed as representing the opinions of any other person or entity, especially Orac's cancer center, department of surgery, medical school, or university. Also note that Orac is nonpartisan; he is more than willing to criticize the statements of anyone, regardless of of political leanings, if that anyone advocates pseudoscience or quackery. Finally, medical commentary is not to be construed in any way as medical advice.

To contact Orac: [email protected]

184 replies on “Return of the revenge of “no saline placebo RCTs” for childhood vaccines”

Going back to the sad reality that very few things are new in anti-vaccine world, and old anti-vaccine claim don’t die, even long after they were disproven.

Thank you for going through this.

If it helps, I addressed the same claim for a rotavirus vaccine for the second set of trials in this review of an anti-vaccine book – look for “sucrose”. https://www.skepticalraptor.com/skepticalraptorblog.php/turtles-all-the-way-down-repeats-anti-vaccine-misinformation/

Although I am aware of it I didn’t have the energy to get into a related issue in this post. ICAN likes to invoke the “no saline placebo control RCT” and then say that it’s all a pyramid scheme in which new vaccines are approved by being compared with old vaccines, going all the way back to original vaccines that, according to them, didn’t use the right placebo comparator; e.g., a saline placebo control. Dealing with that one will require considerably more effort because it would require looking up all the licensure studies. Brandolini’s law strikes again.

Yes. My post does some of it, but not a complete job, since it’s in the context of the book.

It’s also why I used the measles vaccine for my main example. That is one vaccine that I am sure of.

I see that Siri conveniently left IPV out of his chart. It’s not as though the Salk field trials included nearly 2 million participants and used a saline placebo or something.

Siri and his firm are Del Bigtree’s reps for ICAN. He is a frequent guest on The Highwire where he explains his intricate wrangling as he seeks FOIAs on various PH supporters. Interesting that he’s speaking up for RFKjr too.

I listened to his interviews with Del and notice his abilities to divert/ distort without technically lying about an issue. I concur with Prof Dorit who once said that he is very smart. He presents himself well, using language effectively and doesn’t at all present as a skeevy bottom feeder intent only on his pay not the public good.

If the investigational vaccine causes injection site soreness or low-grade fever, then a saline injection used as control would allow subjects, caregivers, & physicians to correctly infer what treatment was given. Then the anti-vaxxers would complain that even though a saline placebo was used, the trial wasn’t fully blinded. Those goalposts move faster than a speeding bullet.

The concern that many people/parents have regarding the placeboes used to test vaccines is that using “a placebo that is ‘inert’ with respect to preventing that disease” is that if it is not considered inert with respect to potential adverse effects, then it doesn’t allow a computation of the risks of various side effects due to receiving the vaccine. This may not be due to nefarious intent, but it does leave the consumer without a good estimate of the risk of getting that vaccine versus not getting that vaccine. The placebo group can be expected to have some level of similar side-effects from the placebo ingredients and all we can say is whether or not they are at a level similar to the vaccine, not whether or not they are at a level similar to not getting the vaccine. For new vaccinations this issue remains unaddressed by the body of research available.

That this continues to be standard operating procedure over many years, with vaccines being approved after being compared only to active placeboes that can produce adverse effects, it shows how people who have questioned vaccines are ignored and their concerns regarding the safety of vaccines remain unanswered with regard the risk of adverse events due to the vaccine. While it’s arguable that their are good scientific reasons for using an active placebo that mimics the expected side effects, that doesn’t preclude using an inert placebo for injected vaccines as well. This was done in the Gardasil trial although the size of the saline placebo arm was too small for accurate assessments of relatively rare side effects.

Complaining about how this is a repeated “anti-vaccine” point doesn’t refute their point – i.e. that consumers are left without a good estimate of the risk of harm from being vaccinated versus not being vaccinated. If you want to refute their point, then point to the studies that show what they are interested in knowing before agreeing to a vaccination for themselves or their children – i.e. studies that use an inert placebo like saline rather than an active imitator of the vaccine side-effects. But the fact is that it is a legitimate concern that many people have that is rarely addressed by vaccine safety research.

It is the fact that to those without background this could sound convincing that makes this such an effective tactic of disinformation.

If you use a vaccine with known side effects, or something else with known side effects, that works well as a control. If you know that the side effects of the inactivated polio vaccine are sore arms, swelling and redness in site of injection, mild fevers, and a theoretical but not seen risk of allergic reaction, it’s a fine control for an unknown vaccine – you know what to expect, so you know what the risks are. And these are not risks that would change the balance: sore arms are not the concern these trials are meant to catch. If a new vaccine caused substantially more sore arms than an old one, the trial would show that; but it would likely not be a deal breaker. If the level of sore arms was the same but more than without a vaccine, that’s not a deal breaker either.

When anti-vaccine activists make the argument you made – you can’t discern side effects – about this kind of comparator, they are, at best, misleading through ignorance, at worst, intentionally misleading.

When you know the other inactive ingredients and know what their potential issues are, the same point stands: you know what the solution does. When anti-vaccine leaders say you don’t know the side effect, they are, again, misleading – whether intentionally or from lack of knowledge.

And when you compare a new vaccine to an existing vaccine with decades of data, the same point stands: you know the risks of the existing vaccine.

So no. Using a known comparator does not hide safety risks. Anti-vaccine leaders who say that hit on a way to mislead people into not protecting children from disease.

There is nothing good about the tactic. It’s a disinformation strategy.

When anti-vaccine activists make the argument you made – you can’t discern side effects – about this kind of comparator, they are, at best, misleading through ignorance, at worst, intentionally misleading.

When someone like Beth makes it, it’s almost certainly ignorance. When someone like Aaron Siri makes it, it’s almost certainly intentionally misleading for the purpose of disinformation. Yeah, I think he’s smart enough to know better and is likely therefore lying.

The anti-Gardasil contingent usually claims there were no trials involving saline placebo. Beth at least admits there was one such trial (in the group of 7 trials conducted prior to FDA approval) but alleges it was “too small” to assess rare side effects (I’ll leave the audience to decide whether a trial involving nearly 600 participants can be disregarded as “too small”).

What Beth does not inform us is that there have been at least 195 clinical trials involving Gardasil, and that in multiple cases saline placebo was used. All you need to do to confirm this is to do a Pub Med search on the topic. Clinicaltrials.gov also has relevant information. Furthermore, in the 17 years since the FDA first approved Gardasil, none of the serious side effects alleged by antivaxers have been confirmed (we are now talking about millions of women and men who’ve received Gardasil and other HPV vaccines. Perhaps those numbers are “too small” to identify the claimed side effects?

Beth further ignores the many examples of clinical trials of other vaccines using saline placebos where appropriate. She opines that use of different placebos “may not be due to nefarious intent”. Why thank you, Beth for acknowledging that those who develop and test vaccines may not be acting out of sheer evil criminality. How reassuring.

A “legitimate concern” about vaccine testing and safety is best resolved by facts of the kind presented in today’s post, and not the sort of deceptive arguments we’ve come to expect from Beth.

Beth at least admits there was one such trial (in the group of 7 trials conducted prior to FDA approval) but alleges it was “too small” to assess rare side effects (I’ll leave the audience to decide whether a trial involving nearly 600 participants can be disregarded as “too small”).

Very rare side effects can be missed in a clinical trial involving thousands of subjects. That’s why we have phase 4 postlicensure studies and pharmacovigilance surveillance programs, to detect those rare adverse events.

Before any antivaxxer complains about the trials being too small to detect such rare adverse events, remember that all clinical trials are a balance between what is practical and feasible (and what the researchers and funders can afford) and the best scientific design we can use.

This is true, we have limited resources and have to allocate them according to the value we place on the return it brings. It comes down to how much of the $ required to run the trial will be spent on that branch of the experiment that provides valuable information to vaccine consumers. In the Gardasil trial, I think it was ~10% of the total subjects rather than the 1/3 that would indicate they were all equally important.

This illustrates the value that the system places on the needs of the consumers of vaccines compared with the manufacturers of vaccines.

You, of course, are not interested about the fact that saline group and vaccine group reported comparable numbers AEs. This is no interest to vaccine consumers ?

The concern that many people/parents have regarding the placeboes used to test vaccines is that using “a placebo that is ‘inert’ with respect to preventing that disease” is that if it is not considered inert with respect to potential adverse effects, then it doesn’t allow a computation of the risks of various side effects due to receiving the vaccine.

Yes, I’ve heard this particular claim too. Siri makes it, and ICAN makes it endlessly, such that maybe I should do a followup post addressing it. Briefly, It’s absolute rubbish. All the placebos chosen have very well known profiles with respect to what they do and do not do. That’s a huge reason why they are chosen as placebos in the first place. Are you, for instance, going to argue that minuscule doses of, say, sucrose or of sodium phosphate are going to cause adverse events so significant that they can confound a clinical trial? Siri and ICAN do, and, I will call bullshit on their claims, because such a claim is bullshit. I would also be willing to bet that Siri knows the claim is bullshit, but he knows that it is persuasive to people who do not understand medicine or clinical trial design.

Ditto similar claims for formaldehyde, aluminum, traces of cell culture medium or fetal bovine serum, etc., etc. etc.

I look forward to that. I would like to see profiles of the placeboes that could be compared to the results in the vaccine trials that used them in order to establish that they fit the expected profile reasonably well with regard to the adverse events recorded during the trial. If you can’t provide that, they I think Siri and ICAN have a valid point.

Beth, what is your real motivation here? you obviously pretend to knowledge you do not have, so what? do you get paid to lie? was your own child harmed in a vaccine event?
what is it exactly, that causes you to lie?

“do you get paid to lie?”

I think we should avoid this sort of thing, leaving it to the antivaxers and alt med enthusiasts who use the shill gambit with such enthusiasm.

A single-minded devotion to the Cause is sufficient to explain the deception, willful ignorance and JAQing off that characterizes antivaxers like Beth, who has put them on full display here for years.

Oh, and here’s another Gardasil clinical trial using saline placebo for antivaxers to ignore. More injection site reactions in the adjuvanted vaccine group as you’d expect, but similar systemic profiles among the vaccine and saline placebo groups. One reaction described as serious in each of the vaccine and saline placebo groups.

http://pubmed.ncbi.nlm.nih.gov/26411885/

Beth, originally my assumption was you were unfamiliar with the issues , that your comments were simply a matter of not knowing certain things.
However the more you write the more I suspect dishonesty and trolling.

All your alleged issues were answered.

“I would like to see profiles of the placeboes that could be compared to the results in the vaccine trials that used them in order to establish that they fit the expected profile reasonably well with regard to the adverse events recorded during the trial.”

complete and utter jargon filled gibberish. laughable. Do people who spout stuff like this really expect to be taken seriously by educated people? I hope not.

Eh, just an endlessly moving goalpost for antivaxxers to trot out. If we did all the tests you demanded, it would suddenly be “But we didn’t test what happens if the kid is currently experiencing hay fever” and on and on.

@ Terrie:

Didn’t one of Orac’s most virulent scoffers once propose that all children’s levels of something-or-other be tested prior to all vaccines?

For the typical antivaxer who chants “no true placebo!”, it would be fun to spring the following on them in a formal face-to-face debate setting (the kind they say is the only way to impart knowledge):

“Please define “placebo” for the audience.”

Much stammering and confusion would ensue.

My guess is that most would say something similar to Aaron Siri’s channeling of the CDC’s cringeworthy definition: A completely inert substance. They would, of course, be wrong, having regurgitated the sort of definition of placebo we teach in junior high science class.

I think the most salient point is that they use the “no placebo trial” line of attack to argue that vaccines aren’t safe. The point of the RCTs isn’t to establish safety as that was addressed in the earlier phase studies.

So basically, the argument is a bait and switch mixed with a red herring (it is it a motte and baily?)

It’s useful in arguing we can’t know that they’re safe. And useful in arguing authorities have no interest in confirming their safety. And that’s sufficient.

@johnlabarge

It’s useful in arguing we can’t know that they’re safe.

But we know that vaccines are safe. There are literally thousands of studies by well-educated, respected scientists as well as institutional organizations from governments around the world that ALL confirm this. They can’t find any of the adverse health effects that antivaxxers claim to see all the time.

And useful in arguing authorities have no interest in confirming their safety.

Authorities already HAVE confirmed vaccine safety in lots of different ways. The problem is that antivaccine people reject all evidence to that extent, and dream up all sorts of lies and fallacies why they are right and the why all the medical academic world is wrong/incompetent/fraudulent etcetera.

VAERS? Are you serious? VAERS is a passive reporting system! Anyone can report a supposed adverse reaction at any time. That you reference VAERS as evidence for your claims tells me all I need to know.

I believe the people reporting the reactions more than I believe the people paid to say the jabs are safe.

@johnlabarge

See VAERS.

Yes, I know about VAERS – and it many counterparts in other countries. And I also know that antivaxx dimwits routinely make the colossal mistake of interpreting VAERS reports as actual proven side effects – one of the many, many very bad mistakes that antivaxx dimwits make all the time.

And the sad fact is that dimwits like you keep pointing to VAERS, even though VAERS itself has a not-to miss-disclaimer ON EVERY F’ING DATA PAGE that you have to read and agree with BEFORE going further – here’s the gist of it:
VAERS reports alone cannot be used to determine if a vaccine caused or contributed to an adverse event or illness.

You clearly have not read or understood this disclaimer – or perhaps worse, you decided that you could simply ignore it, and go ahead and push your dumb antivaxx propaganda falsely based on VAERS data anyway.
In my book, this disqualifies you from any further sensible discussion about this topic. Goodbye, and don’t bother to return.

VAERS? Are you serious?

Labarge is either as dense as osmium and has utterly failed to comprehend what has been discussed about VAERS hereabouts or he is just flagrantly intellectually dishonest. While that is an inclusive-OR, I think the latter factor is by far the greater player.

Since you’re all about good data, how is all the background noise removed from VAERS so that we’re only getting reactions directly caused by vaccines and not random, unrelated incidents? Or people deliberately reporting deliberately bad/made up data?

And before you say you trust the people reporting the data to know if the vaccine caused what happened to them/their loved ones, you have no way of knowing whether or not I reported to the database that, after a recent vaccine, I turned into 9ft 6in vampire lady.

Did I do that? You have no way of knowing. But if I did and you believe that everything reported to VAERS is 100% accurate and directly related to vaccines, then could you hook me up with the guy who got turned into the Incredible Hulk by the influenza vaccine since you must believe that to be true as well? because it’s so hard to find a guy who’s not intimidated by a woman of my stature.

I didn’t say everything reported to VAERs is 100% accurate. That’s impossible. But most of it is probably real.

“I believe the people reporting the reactions more than I believe the people paid to say the jabs are safe.”

Don’t be silly. How on earth can they possibly know, for a fact, that the vaccine caused whatever they are reporting? It’s not possible. They can honestly believe it. They can report it (which they should). But they cannot know that it is true.

You have this weird idea that if someone reports something in good faith, it must be true. How have you survived into adulthood being that naive?

No I think that’s fair, however if say the number of similar reactions goes beyond some threshold I would shift the burden to the vaccine advocate to show no cause.

I’ve lost track of how many times labarge has been informed of the limitations of VAERS, and how it should only be used to identify potential problems that are investigated through other systems set up to look at vaccine safety (such as CISA, VSD and BEST) and through studies with access to medical records that confirm diagnoses. And contrary to what John apparently believes, health agencies do flag VAERS reports for further action.

http://publichealth.jhu.edu/2022/what-vaers-is-and-isnt

If John had a minimum of intellectual curiosity and honesty, he’d study the matter further and find that reporting rates to VAERS for death in conjunction with recent Covid-19 vaccination are actually considerably lower than expected all-cause mortality rates, i.e. background deaths. Not every adverse event is reported to VAERS; the reporting rate however is much higher for serious events or death compared to expected things like vaccine site reactions.
\
http://onlinelibrary.wiley.com/doi/10.1002/pds.5605

Sad to say, John can be counted on to keep recycling his unfounded claims. We should be understanding; maybe he has a disability that causes actual pain at the prospect of contemplating evidence that contradicts his views.

,

… more than I believe the people paid to say the jabs are safe

Of course the portion in bold is pure bullshit. Nobody is simply “paid to say” things are safe. People who understand far more about science and statistics are paid to design experiments, collect the data, and analyze it, and pass the results on to people who issue guidance and recommendations based on that work.

The fact that you are willing to continue pushing your “the entire field and everyone it it is and are corrupt” conspiracy doesn’t matter: ignoring the science and statistical results as you do simply shows you to be another attention-seeking buffoon.

@john labarge There indeed is a treshold. Signal is vaccine SAEs minus threshold SAEs

There are literally thousands of studies by well-educated, respected scientists as well as institutional organizations from governments around the world that ALL confirm this. They can’t find any of the adverse health effects that antivaxxers claim to see all the time.

john has countered that by repeatedly asserting that everyone of the people involved with these studies is on the take and corrupt. There’s no such thing as a little dishonesty from him.

john has countered that by repeatedly asserting that everyone of the people involved with these studies is on the take and corrupt.

Yes, interesting, isn’t it? I wonder how susceptible to corruption people like John are themselves, given that they apparently believe that virtually every doctor and scientist would be willing to lie, betray their ethical standards and harm children for a mere handful of pennies.

There goes John with his daily dose of lies again.

yes John, you are lying. What do YOU personally get, out of trying to so obviously lie to everybody watching?

you are not getting paid to do so, you have no personal vested interests involved. Are you mentally ill? do you require medical assistance? what? be specific. You have repeatedly been caught in obvious lies here. why do you persist? do you even HAVE an answer?

A Midwestern Doctor? LOLOL.

He’s been on my radar for a while and has been due for some Insolence for quite some time now, but whenever I thought it was time to write about one of his bits of misinformation other things always caught my attention. That might change soon.

“so-called ‘misinformation’”

you mean, like you dribble out here constantly?

why John? why? you aren’t getting paid, you are protecting nobody, including yourself. you are not contributing to anybody’s knowledge…

so why? I want an answer. CAN you even answer honestly?

Immediately it asked for money lol. “I’m bringing back forgotten medicine” like what? Leeches? Lobotomy? Thalidomide?

We have a name for doctors who say things like the stuff plastered all over that substack: “Dinosaur.” Never does CME, probably can’t get credentialed anywhere, may not even have an active license anymore, thinks the best medicine was practiced “In the 70s.”

I’m a real doctor from near the Midwest who doesn’t want a cent and doesn’t pretend to have secret knowledge. You don’t listen to a thing I say.

Sad sack.

Midwestern Doctor, in addition to being stoutly antivax, has a weird obsession with water, leading to Substack article titles like
“How to Improve Zeta Potential and Liquid Crystalline Water Inside the Body”
“Exploring the Wild West of Water Cures and the legitimate options I have come across.”

The water vibes are similar to those given off by fellow antivaxer Thomas Cowan, a germ theory denialist who thinks cancer is caused by disordered intracellular water structure, and who surrendered his medical license under scrutiny from the California medical board. Cowan, who now lives in upstate N.Y. has launched a subscription-based New Biology Clinic run through intermediaries, to complement his vegetable powder business. For the low low price of $69/month (minimum 6-month subscription plus $150 “activation” fee) you get fabulous advice and other benefits, with Cowan serving as “cheerleader” and advisor. Family subscriptions cost more, but think what’ll you’ll learn about outmoded germ theory, failed genetic science and cell structure paradigms.

Cowan also keeps sheep on his farm.

Yes, but he wants you to link the article because he’s so upset that he didn’t see it and now he’s worried that his Zeta isn’t reaching its full potential and that the vaccine microchips are interfering with his internal LCD screen so that the government can use radio waves to see his thoughts via his fillings.

He desperately needs to find that article to protect himself before it’s too late. How can you be so heartless as to not provide it for him?

Come on now, be fair: john provided the link. You can’t really expect that he read the content as well.

” Read hm, not substack” “.. read Wikipedia..”

–I find the most outlandish crap on Substack written by alties/ anti-vaxxers/ trolls- they can say anything and followers quote them.

I’ve toyed with the idea of creating an account where 90% of what I present is made up ( and the other 10% is grammatically correct).
I would be Yukiko who received a doctorate in molecular biology from U Kyoto, worked for pharma, knows all the secrets of their evil vaccine empire and now
wants to reveal EVERYTHING! Because she is pure of heart and afraid of their machinations, she remains nearly anonymous. I’ll include a photo of her and her white cat, Hana.

— alties like those I survey despise Wikipedia and discourage its use, writing dozens of diatribes about its lies, compromised status and how it attacks real science. prn.live articles.

Can I be a fellow whistleblower or something if you actually do this? My lack of any medical background could be a huge advantage for writing Substack articles. Like it’d be a great parody idea.

Just give me prompts and a word count (within reason) and you’d be surprised by what I can turn out.

@ Silex:

Go ahead! She doesn’t have to be Japanese – I used that because I know a little language, names, culture. She could be Ukrainian .
Basically, she is an honest, idealistic, brilliant graduate/ young employee of a major pharmaceutical who has been working on vaccines and discovered that the entire system is corrupt: fake data, deaths/ injuries hidden, bribes, threats, governmental collusion, media cover ups.

She is all alone and afraid to go to authorities because they are also compromised. She hopes that her revelations will be shared by readers- she has incriminating documents that reach beyond borders. Because of her background in biology, she understands precisely how spike proteins behave after vaccination: they behave BADLY, destroying the very foundations of life.
She needs a champion: readers together fighting the power!

I truly admire your tireless debunking and denouncing of all those decade-old antivaxx lies, nonsense and demands for (in their eyes) ‘proper testing’.

However, I am 100% certain that even if such a highly unethical and hugely impractical double-blind long-term RCT with saline placebo were carried out exactly as demanded by RFK and his ilk, then THEY WOULD STILL REJECT THE OUTCOME if that outcome would confirm that vaccines are, yes indeed, effective and very safe. They would simply accuse the researchers of fraud and/or incompetence, or dream up any number of other reasons why this was no True Scotsman valid trial after all.

I think that one underlying mechanism is an extreme consequence of the sunk cost fallacy: they have invested so much time, effort, emotions and even money in the premise-turned-into-belief that All Vaccines are Bad, that it has become literally impossible to entertain the idea that they may be wrong about it after all. So when confronted with evidence to that extent, they will move heaven and earth to find reasons and ‘evidence’ proving them right. Nothing else is acceptable to them.

I myself have had some discussions with fervent antivaccine people in the street, and simply asked them what they would do or say if it would turn out that they were wrong about Covid vaccines. Almost all answers were variations on the theme “We are not wrong, just look at [fill in crank YT video substack nonsense etc.]”. Even when pressed by asking them “but what if you’re wrong after all?”, the answer would usually be “We know that we aren’t, period.”
IIRC, only one person admitted that she might have to rethink her position in such a case.

I myself have had some discussions with fervent antivaccine people in the street, and simply asked them what they would do or say if it would turn out that they were wrong about Covid vaccines. Almost all answers were variations on the theme “We are not wrong, just look at [fill in crank YT video substack nonsense etc.]”. Even when pressed by asking them “but what if you’re wrong after all?”, the answer would usually be “We know that we aren’t, period.”

The interesting contrast here is that nearly all vaccine advocates would answer the question along the lines of: I’d have to rethink my position and maybe admit that some vaccines do cause the things attributed to them by antivaxxers, meaning that I have to rethink my support for them being on the recommended vaccine schedule. You’ll almost never see an antivaxxer answer the question that way.

If I’m wrong then I have a 99.99% chance of surviving the disease (based on vastly inflated death counts). And a less than 1% chance of hospitalization. And since the vax doesn’t prevent transmission; that downside on me alone. What’s more I avoid the ultimate negative efficacy such that I have less chance of contracting covid than the vaccinated and ultra-boosted. The covid vax calculation is just not close. And most people at this point are waking up to that.

“If I’m wrong”

Your posting something means there’s no “if” about it.

Vaccine do prevent transmission and deah certificates are not falsified, so you are obviously wrong
Where you got tha ransmission thing, btw ?

“If I’m wrong”

you are.

why will you never admit this? you are clearly, wrong. nobody here supports the drivel you keep spouting. not a single person. you are very, VERY clearly, wrong. Fractally wrong. Laughably wrong.

yet you persist. why?

“If I’m wrong then I have a 99.99% chance of surviving the disease”

Well, in less than 10 years, your survivability will drop to 99.9%. Then to 99% 10 more years after. Then…
I guess you are planning to die young, so you won’t die of some bug caught during your twilight years.

I also guess you are an orphan and don’t have to worry about giving a deadly illness to your parents or grandparents.
Or to your young baby. Infants under 1 year old don’t do well with respiratory infections.

Death is not the only bad outcome. There is also something like long covid, which might make you unable to do work.

If I’m wrong then I have a 99.99% chance of surviving the disease

This is the ecological fallacy, no? I do have trouble keeping that one straight.

That’s right. I took a long, hard look after the myocarditis and thrombosis issues. It was immediately clear there was no need to change clinical practice; however, I asked myself that question and did the work to answer it.

Labarge and his I’ll think we just say “baaaah” and trundle along to whatever matching orders we get from…who is it this week? The NWO? The CDC? Space aliens?

From what I see, vaccine advocates will readily accept any adverse effects of vaccines, even if those effects are unexpected and serious. For instance I have not seen even one vaccine advocate denying that the AstraZeneca vaccine could cause blood clots – even if it is only in about 1 in every 150,000 vaccinations. And yes, all vaccine advocates readily admit that the Pfizer vaccine can cause myocarditis in younger age groups. OK, they will only accept and admit these things AFTER at least warning signals were picked up, followed by proper study – NOT when anti-vaccine people make such claims. But that is because anti-vaccine claims have NEVER been proven correct, not even once. So what they claim, can be safely dismissed (and hopefully also debunked).

Right.
With anti-vax shrieking about vaccine injuries, I do not see them ever including actual figures of exactly how many cases of blood clotting disorders ( for AZ or J&J) or myocarditis ( for Moderna or Pfizer) occur. I wonder why that is?
Can it be because they are very rare and saying so would work against their scare tactics?

” For instance I have not seen even one vaccine advocate denying that the AstraZeneca vaccine could cause blood clots”

and I never see an antivaxxer talk about all the deaths that happen from over hydration. BAN WATER!

This is the gist of your entire argument. you should be ashamed, but sadly, you are just dumb.

THEY WOULD STILL REJECT

Whoever designed this typeface clearly didn’t think it all the way through.

@ johnlabarge

You write: “It’s useful in arguing we can’t know that they’re safe. And useful in arguing authorities have no interest in confirming their safety. And that’s sufficient.”
I’ve already written this several times and you ignore; but PubMed, the National Library of Medicine’s online database, with simple search words “vaccine safety” give 34,740 results; that is, mainly actual studies, review papers, etc.

The CDC has a website devoted to Vaccine Safety where it gives a number of different “programs” like VAERS, Vaccine Safety Datalink. The Clinical Immunization Safety Assessment (CISA) Project.

The FDA has a website “Vaccine Safety & Availability” which includes a number of subcategories

The WHO has a number of websites, including an introductory course “Vaccine Safety Basics”

And there is an EXCELLENT book that goes through each vaccine, history, early problems, review of research, etc: Stanley A. Plotkin et al (2018). Plotkin’s Vaccines. I own it; but quite expensive; but some local university library has one.

You just keep claiming we don’t know about vaccine safety, we haven’t done sufficient research, etc. When we have a plethora of programs that have done vaccine safety studies as well as those done by researchers around the world. And by the way, the authorities you claim aren’t interested, vaccinate themselves and their children, etc. I have colleague and my primary care physician have ALL been vaccinated, including COVID. I have received ALL the Moderna COVID vaccines and will get the next booster in September and also the new Respiratory Syncytial Virus vaccine and flu vaccine. I have NEVER worked for a pharmaceutical company nor own stock in them; but I have studied/learned immunology, microbiology, infectious diseases, public health, epidemiology, including reading history of many infectious diseases over more than 40 years.

And openstack has NO peer-review. Anyone, regardless of their bias, lack of scientific validity, etc. can post on it. One can find all kinds of stupid posts on the internet.

You just keep proving what a dishonest lying antivax biased ASSHOLE you are.

And I’m sure you will ignore the above and just keep MAKING A FOOL OF YOURSELF.

As someone who was hospitalized with COVID-19 pneumonia 1 month before the vaccine came out and on behalf of the 1,200,000 people in the US who died from this—you are a uncaring, uneducated jerk.

@ Beth Clarkson

You write: “I look forward to that. I would like to see profiles of the placeboes that could be compared to the results in the vaccine trials that used them in order to establish that they fit the expected profile reasonably well with regard to the adverse events recorded during the trial. ”

Start with Wikipedia articles. Nocebo and Placebo.

In a double-blind placebo randomized clinical trial, of course, the controls must believe they have been treated the same, so injecting them with a harmless substance; e.g., saline solution allows them to experience same injection and feeling of substance entering body as the group receiving the vaccine.

And a quick search on National Library of Medicine’s online database PubMed using search word “placebo” resulted in 265,579 papers, many research or review of research. So, I think we know quite a bit about placebos.

You statement is just plain STUPID as usual from you. No indication ever that you have taken the time to actually study placebos.

Joel:

I see you are as delightful a conversational partner as ever. I rarely read your posts these days. You are basically saying I’m too stupid to understand that such a comparison is inappropriate. I’ll respectfully disagree with both assumptions.

I will give you this much, like many of my beloved mathematical mentors, you are not sexist in your abuse of others. You treat people badly for the sin of disagreeing with you without regard to the claimed gender or ethnic background.

And you did not answer him. My advice is to do Google Scholar search for alum adjuvant side effects, 28000 hits. Quite well known safety profile,that

28,000 is a huge number of studies, but that doesn’t mean any of them answer the question posed regarding their safety. Can you provide a single link that provides an assessment of the serious adverse events resulting from the use of aluminum adjuvants in vaccine study placeboes compared with those from a saline placebo or other inert placeboes? I have never found a study or other assessment of the safety of active placeboes. Such an assessment is necessary to judge the risk of the vaccine versus not getting the vaccine.

Ah this one paper thing. Many paperss are better than one, surely..
Point is of course that you can always find problems in one study, problems another study may have answered.
If you want one study consider Gardasil trial. They had alum control and saline placebo arms. There is data you want.

@ Beth Clarkson

You disagree with me. Based on what? I have over 40 years education, training, work experience with immunology, microbiology, infectious diseases, epidemiology, and public health. Right now I am editing next edition of colleagues undergraduate Intro Microbiology text. So, you disagree, not based on actually any level of scientific understanding; but simply your antivax ignorant bias.

If you are even slightly open-minded I recommend to start with a short, 160 pages, intro to immunology. Lauren Sompayrac’s “How the Immune System Works (6th Edition)” Available on Amazon.com. Inexpensive, well-written.

And NOPE I do not address women, minorities, etc. any differently than men. I address individuals. Some of the most brilliant creative people I have known and worked with have been women, even Black women. Melanin, a skin pigment, doesn’t influence ones brain.

“I see you are as delightful a conversational partner as ever”

and you are just as vapid as ever.

I for one prefer substance over tone, every time.

not to put too fine a point on it but

Now now, give some credit when she gets something right.

Prasad’s substack today is the idiocy of Siri x 100. Basically he wants every vaccine RCT’d across millions for many, many years. I don’t understand how this fool can be an oncologist and and say these things.

I saw that. It might well be my topic on my not-so-super-secret other blog on Monday; that is, if I can wait that long to lay down some Insolence on the fool.😂

I’m not so undone about the CDC definition of placebo; I’m more interested in Mr Siri’s misunderstanding of authority. I thought that lawyers had to understand appropriate authority so that they could figure out where cases go for decisions and, ya know, applicable laws. Dorit, feel free to correct me.
Does the CDC have the authority to approve/license a new vaccine? Nope, that’s the FDA’s authority.
Does the CDC have the authority to define placebos used in clinical trials in the US? Nope, that’s the FDA’s authority, and they also oversee clinical trials, so they also have the authority to halt a trial that has processes or definitions that they disagree with.
So what is the FDA definition, since it seems to “actionable” to use a legal term I don’t always understand. “Placebos, defined as inert substances with no pharmacologic activity, are commonly used in double-blind, randomized controlled clinical trials”. It’s a broad definition, and similar to other NRAs (national regulatory authorities) definitions (at least in high income countries), so not just a US pediatric vaccine issue. Does Mr Siri have proof of a global regulatory conspiracy? I can’t wait to see the Daily Mail coverage.

Why didn’t Mr Siri point to the important authority as regards placebo definition and determination?

Certainly there is no regulatory requirement to only use saline placebo in the US during drug/saline development. If Mr Siri and RFK jr are so convinced that it should be a requirement they could use their table as evidence and take action. If they have a scientific point, wouldn’t they, as part of a group that claims to be Defending Children’s Health, make this claim actionable? Given RFK jr’s estate they can’t claim shortage of funds, so why don’t they take action? Could it be that they doubt the veracity of their own “interpretation”?

Global regulatory conspiracy like the private sector pays more so people readily jump from regulator to Pharma exec? I mean, golly gee does that ever happen? 🙈🙉🙊

Global regulatory conspiracy like the private sector pays more so people readily jump from regulator to Pharma exec?

Exactly like that bit of bullshit.

And stop being regulators, did notice that ?
FDAs definiion of placebo is here
https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/cfrsearch.cfm?fr=314.126
“Placebo concurrent control. The test drug is compared with an inactive preparation designed to resemble the test drug as far as possible. A placebo-controlled study may include additional treatment groups, such as an active treatment control or a dose-comparison control, and usually includes randomization and blinding of patients or investigators, or both.”
However, active treatment concurrent control.is another possibility:
“The test drug is compared with known effective therapy; for example, where the condition treated is such that administration of placebo or no treatment would be contrary to the interest of the patient. “

I haven’t thought of this, but you have a very good point. I don’t think it’s an understanding of authority issue so much as cherry picking. Mr. Siri likely looked for a definition it can use, and the CDC provided one that… needs work (and I do agree that the CDC should do better; it has experience in messaging on vaccine safety).

You are right, of course, that the relevant definition is the FDA’s – and it’s not as if Siri did not interact with the FDA before: he filed several petitions with them about vaccines.

Ignoring their discussion of this – and the documents from other expert sources about when placebo trials are appropriate – is likely intentional.

But CDC should change their definition so it would not be so easily misused. Anti-vaccine activists do this: it’s what they use. Agencies may make occasional mistakes, but should learn from them.

@ johnlabarge

You write: “So how many boosters is that so far for the Covid cold?”

“cold?” Just how stupid are you? How many people die over two years from a cold? So far over 1.1 million have died from COVID. And many more have been hospitalized and many more have developed long COVID.

As for how many boosters, for anyone who is honest and understands immunology, including that viruses mutate, boosters are a lot better than getting the disease. Of course, given just how stupid, ignorant of science, immunology, virology, infectious diseases, epidemiology, etc. you are not surprising you continue to MAKE A FOOL OF YOURSELF. A FOOL AND ASSHOLE.

If only vaccines had such wonderful side effects as penile enlargement for men, breast enhancement for whom ever, acne resolution, and weight loss? The antivax movement would vanish overnight

No matter how much you design and test a vaccine, it will never be enough for anti-vaxxers. Even Salk’s polio vaccine would still be in testing (and they’d be claiming us physicians are killing children paralyzed with polio by putting them on ventilators just like they did with COVID-19 patients). And then they will lie and claim none of the diseases vaccines prevent are dangerous or fatal. Heck, Paul Thomas lost a playmate to measles growing up and he laments it was because the 5 year-old didn’t have enough vitamin A in his diet and not because he wasn’t vaccinated. Thomas saw a child die (unvaccinated as the vaccine wasn’t out yet) from varicella during his residency and yet he will tell you the varicella vaccine was not approved to save lives but to save money because parents had to stay home from work if their kids got varicella. He will also falsely claim more people are dying from shingles since the varicella vaccine came out. We could double-blind RCT saline placebo every vaccine on 1 million kids and they would tell us that there is still some “subset” we missed for vaccine injury. They accuse us of lying on death certificates and killing patients in ICUs from profit. We’re all part of some conspiracy of all physicians or we’re all brainwashed idiots too stupid to think for ourselves. They now have their fake science branch with their fake science journals set up and churning out BS monthly. And given how poorly we teach science in the US, a whole lot of parents are gonna fall for their lies which they megaphone all over social media while screaming simultaneously we are somehow censoring them.

Anti-vaccinationists have killed and are going to continue to kill a lot of people with their grift and lies. Even worse, they are now targeting children.

I disagree. Pharma companies just need to be responsible in tort for their products. Until then, they are. It trustworthy.

@ johnlabarge

You write: “I disagree. Pharma companies just need to be responsible in tort for their products. Until then, they are. It trustworthy.”

I’ve explained and you just ignore in your immense dishonesty. If the pharmaceutical company goes through ALL phases of clinical trials and a drug is approved by the FDA, then they are NOT responsible. Otherwise, one lawsuit could put them out of business and we would not have the drug or vaccine. So, for vaccines, since regardless of how effective they are, impossible to avoid rare serious complications, the National Vaccine Court reimburses families. And juries do award sometimes outrageous amounts.

However, if it is shown that the pharmaceutical company deviated in any way from the FDA approved manufacturing, then they can be directly sued.

And, if someone goes through Vaccine Court and still not satisfied, they can sue pharmaceutical company; but could take years and chances of winning minuscule.

So, I’ve explained this before and you, being the DISHONEST ASSHOLE YOU ARE, just continue to post such comments.

Vaccine companies are sued all the time: https://www.millerandzois.com/products-liability/gardasil/
And there is this:
The court has granted in part and denied in part last week a plaintiffs’ motion to withhold expert reports filed in the Vaccine Program by their consulting experts.
So as everybody has told you all the time, you can sue, just go Vaccine court first.

‘what is the lie”

literally exactly what came after the word: “disagree”. exactly as I said. and that is just ONE of your lies. I would post a complete list, just for this topic alone, but your addled brain would not register it. I have concluded your problem is indeed mental.

You keep making these general statements – What would you make them liable for?
And why do you think that enabling them to be sued makes them trustworthy?

Today there is in Germany a case against one German manufacturer of the covid-vaccine, because someone claims he got blind on one eye, because of the vaccine. If he gets a compensation it is paid by the German government.
There are 2 German lawfirms responsible for all (a couple of 100s) cases where compensation for vaccine damage is claimed.

From an outside perspective the whole argument reads here:

“We know that vaccines are safe, and therefore we can use vaccines as control group of RCTs, as we are only interested in the effectiveness of vaccines, compared to an other (or older vaccine), not about the risk or side effects.”

The question remains then? How do you know that vaccines are safe? If you never test vaccines against a completely inert placebo to avoid any potential bioactive impact?

For example, one of the hypothesis is that adjuvants, such as aluminum salts, might cause risks for children. The only way to know that those adjuvants don’t cause any risks is if there is a clinical trial done on children where the control group got a real placebo (and not another vaccine with aluminum salts).

I have been trying to search for such a trial, but I couldn’t find any. I found this really worrying.

I’m not trying to say, at all, that this aluminum salt hypothesis is true. But I do think it is a valid point being made here. We can not fully understand the risk profile, of aluminum salts in vaccines, if we never test it against a placebo.

We can say that anti-vaxers are stupid and dishonest, and what not, but wouldn’t it be much more helpful to just really test vaccines in a way that is done for any other medicine? And remove any doubt that one could have. Or at least making sure that vaccines are tested in a similar was as other medicines are.

“If you never test vaccines against a completely inert placebo”

If you read Orac’s post and followup comments, you’ll see that 1) many vaccines have been tested against saline placebos, that 2) saline placebos are not always appropriate for vaccine testing, and 3) even saline placebos are not “completely inert” – in fact, it’s impossible for any placebo to meet that requirement; even sugar pills have occasionally caused serious reactions.

Vaccine is tested against existing vaccine only when one is available. Thus placebo testing of Gardasl.

@ Kasper Peulen

As Dangerous Bacon writes, many clinical trials of vaccines used saline as placebo. Just type in PubMed: vaccine trials saline placebo

You will find a ton! !

The only way to know that those adjuvants don’t cause any risks is if there is a clinical trial done on children where the control group got a real placebo (and not another vaccine with aluminum salts).

This would be the Tuskegee experiment all over again. The kids who got the “real placebo” would not be protected, despite a known effective preventive (vaccine) being available.

wouldn’t it be much more helpful to just really test vaccines in a way that is done for any other medicine? And remove any doubt that one could have.

It would be pointless. The antivaxxers would dream up some other reason why it wouldn’t be a “true” placebo-controlled study. Or they would claim that the researchers were corrupt and paid off by Big Pharma or other Villain de Jour.

Actually Gardasil trial had alum control group and saline placebo group (there was additives group, too), so this trial as been done. Of course, context was avaccine RCT.

Can you explain why those who believe in this ‘aluminum salt hypothesis’ don’t take non-aluminum formulations? Because, if that was their rational for not getting vaccinated, I would expect them to take an aluminum free vaccine or formulation. The removal of mercury did not seem to have any affect on vaccination rates (or on the rate of those side effects linked vaccines).
So, while you may not approve of the methodology, I doubt that any additional studies would convince may who are still hesitant.

Can you explain why those who believe in this ‘aluminum salt hypothesis’ don’t take non-aluminum formulations?

Adjuvants, when present, are there for a reason. It’s not like switching to diet soda or decaf, and there is no supply of such “formulations.”

Perhaps there are cases in which a different vaccine for the same VPD could accomplish this, but I’m in the hospital and my phone is not the tool for poking around to see.

“[varicella vaccine] was not approved to save lives but to save money because parents had to stay home from work if their kids got varicella”

Even if it was so, why is it a bad thing?
Spoken like a rich guy who doesn’t have to stay home and raise his kids.

I would like to thank Michael Hiltzik for his article critiquing, fact checking, and criticizing RFK, Jr’s recent town hall meeting on “News Nation”.
It debunked and exposed RFK’s dishonest anti-vaccine agenda and methods to the wide audience that a popular columnist enjoys.
All these links below lead to reprints of his column in various news and magazine publications.
His exposition of RFK, Jr. includes a short blurb and a hat-tip and link to this article by Orac including an explanation of the use of placebos and the moral issues involved.
.
Once again – Thank you Mr. Hiltzik.

Are you joking? I came here after reading Hiltzik’s LA Times article because he doesn’t ever say why demanding true saline placebo trials is “wrong”. I don’t think he understood the post here and just links to it without summarizing or explaining it. “But that’s wrong. Indeed, in many cases it’s unethical, as pseudoscience debunker David Gorski explains in this lengthy post.”

I’m not surprised either, because after reading through this word salad of a post, I finally get to the meat of the issue. “There are often good scientific reasons to pick a comparator other than saline, and I’ll quote Ed one last time before I move on”. OK, so I am still trying to find out why we can’t, or shouldn’t, do saline placebo trials – the gold standard in normal drug trials – for vaccines given to infants, and the author here punts and links to “The Oxford Textbook of Clinical Research Ethics”.

Am I suppsed to be impressed? Ooh, Oxford! the experts must really know what they’re doing. Here let me inject my baby with 10 vaccines that I never had to get as a child.

When I read Aaron Siri, or RFK, Jr, they always get straight to the point, asking the kinds of rational, sensible questions that I am asking myself. The nonsense here seems to be intended to intentionally obfuscate things.

And this is supposed to represent unassailable science that cannot be debated? The more I learn about vaccine safety science (or lack thereof) the more resolute I become that I will never, ever, go near one again.

When I read Aaron Siri, or RFK, Jr, they always get straight to the point, asking the kinds of rational, sensible questions that I am asking myself. The nonsense here seems to be intended to intentionally obfuscate things.

That’s because they misinform and lie, rather than trying to explain things correctly. Oh, did you get impatient because I explained what RCTs were and how they’re conducted before I addressed the “no saline placebo” bullshit coming from RFK Jr.? I did that because I assumed nothing when it comes to what readers already know about clinical trials.

That bit about my citing Ed made me laugh because you (1) didn’t address what Ed said that I cited that you consider incorrect and (2) clearly didn’t read where I sad when it is and isn’t ethical to do a saline placebo-controlled vaccine trial, using the example of a hypothetical cancer drug to illustrate the concept of clinical equipoise and then saying:

In any event, regardless of the scientific rigor of the trial, there must be clinical equipoise, which is the existence of genuine uncertainty based on existing science and evidence over which group, the control group or experiment group, will do better. Clinical equipoise does not mean that there is no evidence that a treatment works or is better than existing treatments. After all, the reason we do clinical trials is to find drugs that work where there currently are none and to find drugs that work better than current therapy. But there has to be genuine scientific uncertainty, even if, as is usually the case, investigators think that it is more likely than not that the experimental group will do better than the control group. Absent that legitimate uncertainty, an RCT to test an intervention is unethical.

That brings us to vaccines. The only time that a placebo-controlled RCT of a vaccine can be ethically justified is when there currently does not exist a safe and effective vaccine against the disease for which the experimental vaccine has been designed. Again, just as it is unethical to randomize a cancer patient to a placebo control group when there exists effective chemotherapy that is standard-of-care, so too is it unethical to randomize a subject to a saline placebo group in a vaccine RCT when there exists an already licensed vaccine for the same disease that is considered standard-of-care. You can’t ethically deny subjects in the control group a vaccine against measles, for example, to test a new vaccine against measles. It is unethical to leave a child unprotected against measles in order to test a new measles vaccine. My guess is that Mr. Siri probably knows this but leaves it out.

That’s why saline placebo controlled clinical trials are unethical for new vaccines against diseases for which effective vaccines already exist. You cannot ethically leave the control group unprotected by randomizing them to a saline placebo group. I realize that clinical trial ethics aren’t antivaxxers’ strong suit, but come on. This is basic Clinical Trial Design 101.

So your argument is then: “yes, it is true that the vaccines on the CDC schedule have not undergone saline placebo controlled trials, but this is OK because they were tested against older vaccines targeting the same disease that themselves were tested in a rigorous saline placebo trial. The reason for doing things this way is that it is considered unethical to give a placebo to a control group to test a vaccine for which there already exists a safety tested vaccine as this would leave the placebo group vulnerable to said disease.”

Respectfully then, a better approach to your post would have been to go through Aaron Siri’s table and for each listed vaccine, post the control vaccine that was used and show the safety testing that it underwent – presumably against a saline placebo or another previous vaccine for the same disease. By working backwards through the inserts you would eventually arrive at a saline placebo trial.

But there is a problem here, because Aaron Siri has provided the control for each one of the vaccines listed and they do not back your statement. For example Engerix-B, Recombivax HB, Ipol, and MMR-II were not tested against a control group. The following vaccines were not tested against a previous vaccine for the same disease: ActHib (control = Hep B vaccine), Havrix (c = Engerix B, a Hep B vaccine), Vaqta (tested against an aluminum adjuvant and thimerosol), Varicella (tested against a stabilizer and Neomycin), Fluarix (IIV4) (tested against Prevnar13, Havrix, Varivax).

So is Aaron Siri’s table wrong? Then you have an excellent case for calling him a liar, and please go ahead and provide your table of what the actual controls for these vaccines were and how by following the insert history you eventually end up at a saline placebo trial.

Respectfully then, a better approach to your post would have been to go through Aaron Siri’s table and for each listed vaccine, post the control vaccine that was used and show the safety testing that it underwent – presumably against a saline placebo or another previous vaccine for the same disease. By working backwards through the inserts you would eventually arrive at a saline placebo trial.

Be careful what you ask for…

@banana silver You notice MMR II. It is obviously a second vaccine, based on name. This is reason not to use saline
Engerix is actually Engerix B, another obvious second vaccine
You yourself, and Siri, should go trough the vaccines.

I sense a functionally illiterate anti-vaxxer a…gain.
How unusual. /sarc
Back to your remedial reading class, troll.

Of course you love what those two lawyers tell you. You wanna believe, and it seems your favorite way to get medical advice is from lawyers. Just remember to call you favorite lawyer whenever you need medical care.

This is a study done for an early measles vaccine: Efficacy of measles vaccine

Look at Table 1. Please explain the significance of the second and third columns.

Now tell us why the location of the study is a problem.

Finally, please provide us your design of an adequate RCT of the present MMR vaccine. Make sure it would conform to the Belmont Report (which was created years after that study for good reason): https://www.hhs.gov/ohrp/regulations-and-policy/belmont-report/index.html

“And this is supposed to represent unassailable science that cannot be debated?”

You have obviously never been to a science nor engineering conference. Trust there are arguments. Nor have you ever defended your work in front of an academic nor professional situation. I have done both.

As students at a local aerospace engineering department we got to go to an AIAA (American Institute of Aeronautics and Astronautics) conference to run the slide projectors. I got to witness a very heated discussion of a presentation that was loud enough that it was in another room (also, later I worked for the guy who was yelling… he had reasons, and he was a great supervisor). I had to defend my structural analyses to a costumer that was hostile… and he was very happy when I found the flaw in their analysis of some data.

You are being naive.

“saline placebo trials – the gold standard in normal drug trials”

If you want to understand the ethics of denying standard of care to the control group then just visualise the new product as climbing rope. We already know that rope on a mountain saves lives, what we want to do is find out if the new rope is lighter, stronger, more wear resistant than the old rope. What you describe means one lot of people get to climb the mountain with something that looks like rope but won’t take a fall.

Now, if there was doubt that using climbing rope would save lives……

And let’s test a new parachute against jumping from a plane without a parachute. (Any volunteers?)

Or we could consider clinical trials of new antibiotics for serious infections, such as those caused by gram-negative bacteria that have developed resistance to older antibiotics.

Here’s an example of a clinical trial for a recently-developed cephalosporin antibiotic, cefiderocol, tested against other antibiotics used in standard treatment of such infections. Would those demanding saline placebos for all drug and vaccine trials be willing to take part in a clinical trial for cefiderocol if there was an equal chance they’d be randomized to the group getting only saline solution for a potentially life-threatening infection? Would that type of clinical trial be ethical?

https://pubmed.ncbi.nlm.nih.gov/33058795/

“We demand only saline placebos be used!”

Think about it.

If you develop sepsis and are faced with death, should you reject effective antibiotics if they haven’t been tested against saline placebo?

“Why don’t they use saline placebos??!?

Nevermind.

“do saline placebo trials – the gold standard in normal drug trials”

Not really the gold standard.
If testing a new version of a drug, or the addition of a drug to treatment, the control group will usually receive the old version of the drug or treatment.

That’s the Tl;dr: version of Orac/Ed articles.

Longer version:
Why a saline placebo is unethical for testing a new version of some treatment?
Let’s give a real-life example. A friend of Orac, on another place, helpfully quoted Dr Offit reminding us about the trial of the polio vaccine,

Big trial, 430,000 children in the tested arm, 200,000 children in the saline palcebo arm. Quoting Dr Offit:
“How did we know that Jonas Salk’s polio vaccine was effective? We knew because 16 children died from polio in that study—all in the placebo group. We knew because 34 of the 36 children paralyzed by polio in that study were in the placebo group.”

This is what antivaxers are asking. We know we have an effective treatment, but if we want to test an new one – eh, a better one, more efficient, more safe – drop the old treatment, and set a trial where patients WILL be harmed by the illness.

If you want to see Siri in action, Del’s Highwire today hosts him live ( starts 30 minutes in) and on tape in state hearings ( continues to end 2:28).

@ johnlabarge

Have you ever actually investigated the research conducted on even one vaccine, including going to FDA and reading their extensive documentation for approving? Have you ever searched PubMed, downloaded and read dozens of articles on one vaccine? You think vaccine approval based on dishonesty; but ignore that almost all involved also vaccinate themselves, family, children, and encourage relatives. And you don’t understand the immune system, so you don’t even understand how vaccines work.

However, if you really believe approval of not only vaccines; but all pharmaceuticals totally dishonest and corrupt, then I highly suggest that if you develop Type 2 diabetes, asthma, any chronic condition or you develop cancer that you do NOT use any prescribed medications. Otherwise, you are just a stupid, dishonest, hypocrite.

STOP MAKING A FOOL OF YOURSELF. ASSHOLE! ! !

In other news…
I enjoy looking at reality based tweets and view BS artistry on twitter as well but today I was informed that I need to sign up/ get an account which sounds like another of Elon’s vast new system of improvements on the site. Is the Big Twit trying to get something from lurkers?
Can’t be money.

Thank you, Reality.
I figured it was something that involved amassing greater numbers and monetising them somehow.

““Twitter now blocks visitors from viewing tweets, and profiles unless they’re logged in”

I noticed that, and wondered how all the news agencies that so commonly quote people on twitter were going to handle that. I wonder if Elon even cares that he shot twitter in the OTHER foot? shrug I will not miss twitter. I frankly think it has done more damage to positive communication than any other single thing that humans have ever invented.

@ Ichthyic:

Twitter has become even worse as a mis-information source.
The new rules restrict number of tweets you can view per day based on whether you are paid up or not ( so far, 10K vs 1K per day) although he’s already upped it from lower numbers.
I doubt he’ll allow lurkers like me to view anything.

Supposedly, it’s to limit how AI scavenges/ scrapes material but I imagine he’d rather like more paid checkmarks.
There are other ways to find news/ material to savage. Lots of ways.

Elon Musk is affraid Twitter is getting less trustworthy, due to scraping. As if it needs something to get less trustworthy since Elon Musk took over.

There’s no need to complicate things about Musk: he’s just a terrible person with a lousy record in business.

On July 2 “datahazard” tweeted

Democracy is probably unworkable long term without limiting suffrage to parents. Helps solve the procreation problem too.

Musk agreed and replied

The childless have little stake in the future.

I’ll demonstrate…
Yahoo News:
RFKjr’s campaign had to delete a photo which showed an attractive young woman carrying a cafe drink walking on a fashionable street wearing an RFKjr 2024 shirt. He’ll save the nation!
The problem is that if you look closely, you’ll discover that he signs on stores and signs use Cyrillic letters so I imagine it’s not the US he’ll save.

Errors tell us much more than the intended message. I’ve found that misfires from alties/ anti-vaxxers reveal a lot. Was this error showing a secret alliance – probably not BUT it shows that he sources fashion shoots to sell his messaging and his team was too sloppy/ cavalier to NOT spot an obvious flaw: they were looking at a hip model wearing their shirt. He also is not very supportive of Ukraine.

Something else about RFKjr’s message I ran across a few days ago:
he claims he is pro-choice about abortion and vaccines BUT….
he supports a 12 week limit and used language that might appeal to anti-abortion activists involving seeing a third trimester abortion and calling an aborted fetus something other than that- he didn’t quite say “baby”. I was unable to find the exact article but I’m sure someone else will. Appealing to both sides can enrage both.

“He is also not very supportive of Ukraine”.

Regarding the Ukraine invasion, RFK Jr. has said that Russia acted “in good faith” and blames the U.S. for the conflict.

https://www.independent.co.uk/news/world/americas/us-politics/rfk-russia-ukrain-invasion-good-faith-b2362593.html

A pro-Russia attitude is something that he has in common with Trump, along with announced plans for swamp-cleaning, ending “forever wars” and an amazing talent for lying. Given the amount of support MAGA Jr. has been gaining from Republicans (while his polling among Democrats has been dropping), he probably has a better chance than DeSantis to wrest the G.O.P. nomination away from Trump.

What do you make of those claims from the ICAN?
I have been looking up some of the sources, and it seems quite right what is claimed.
But I would like it if you can rest your expert eyes on this.

“Prevnar 13 provides a good first example of how HHS’s claim is incorrect (78). HHS recommends that every child receive this vaccine at 2, 4, 6, and 12 months of age. HHS licensed this vaccine in 2010 without a clinical trial assessing its safety in children against a placebo control (79). Instead, it permitted a previously licensed vaccine, Prevnar, to act as the control (80). However, like Prevnar 13, HHS licensed Prevnar without a clinical trial assessing its safety against a placebo control (81). Rather, HHS licensed Prevnar based on a clinical trial in which the control was “an investigational meningococcal group C conjugate vaccine [MnCC]” (82). MnCC, in turn, an unlicensed product, was also never licensed based on any placebo-controlled trial (83).

The clinical trial for Prevnar 13 found that “Serious adverse events reported following vaccination in infants and toddlers occurred in 8.2% among Prevnar 13 recipients and 7.2% among Prevnar recipients” (84). Despite this finding, Prevnar 13 was deemed safe and therefore licensed for use in babies because it had a similar serious adverse reaction rate as the control group receiving Prevnar (85).

The second example is Heplisav-B, the most recent vaccine approved by HHS (87). The trials for this new Hepatitis B vaccine, which contains a novel adjuvant, did not use a placebo control (88). Instead, the control was Engerix-B (89). The serious adverse event rate in the primary clinical trial for Heplisav-B was 6.2%, which the researchers deemed similar to the serious adverse event rate of 5.3% for Engerix-B (90). Heplisav-B was therefore deemed safe only because it was as safe as Engerix-B, but Engerix-B was licensed based on a clinical trial without any control, let alone a placebo control (91).

A third example are influenza vaccines (flu shots). In 1980, HHS licensed Fluzone (IIV3) without assessing its safety against a placebo control (92). Nonetheless, Fluzone (IIV3) was used as the control in the trials relied upon to license Afluria (IIV3) in 2007 and Fluzone (IIV4) in 2013 for children (93). Shortly thereafter, Fluzone (IIV4), Fluarix (IIV3) or Havrix were then used as the controls in the clinical trials supporting the licensure of FluLaval (IIV4) (94).

This entire pyramid scheme rests on the safety of Fluzone (IIV3) which was licensed for pediatric use based on a trial without any control, let alone a placebo control (95).

Similarly, Fluarix (IIV4) was licensed for children in 2012 based on a trial using Prevnar 13, Havrix and/or Varivax as controls; Fluarix (IIV4) was then used as the control to license Afluria (IIV4) in 2016 (96). This means Afluria (IIV4) was licensed because it was deemed as safe as Fluarix (IIV4), and that vaccine was licensed because it was deemed as safe as Prevnar but that vaccine was only licensed because it was as safe as “an investigational meningococcal group
C conjugate vaccine. Hence, at bottom, none of those vaccines had its safety profile established based on any placebo-controlled clinical trial. On this basis alone the ethics of recommending routine injection of these vaccines into children is questionable.

78 https://www.cdc.gov/vaccines/schedules/hcp/imz/child-adolescent.html
79 https://www.fda.gov/downloads/BiologicsBloodVaccines/Vaccines/ApprovedProducts/UCM201669.pdf
80 https://www.fda.gov/downloads/BiologicsBloodVaccines/Vaccines/ApprovedProducts/UCM201669.pdf;
http://labeling.pfizer.com/showlabeling.aspx?id=134
81 http://labeling.pfizer.com/showlabeling.aspx?id=134
82 http://labeling.pfizer.com/showlabeling.aspx?id=134
83 See tables above.
84 https://www.fda.gov/downloads/BiologicsBloodVaccines/Vaccines/ApprovedProducts/UCM201669.pdf
85 https://www.fda.gov/downloads/BiologicsBloodVaccines/Vaccines/ApprovedProducts/UCM201669.pdf
86 https://www.ncbi.nlm.nih.gov/pubmed/15479935
87 https://www.fda.gov/downloads/BiologicsBloodVaccines/Vaccines/ApprovedProducts/UCM584762.pdf
88 https://www.fda.gov/downloads/BiologicsBloodVaccines/Vaccines/ApprovedProducts/UCM584762.pdf
89 https://www.fda.gov/downloads/BiologicsBloodVaccines/Vaccines/ApprovedProducts/UCM584762.pdf
90 https://www.fda.gov/downloads/BiologicsBloodVaccines/Vaccines/ApprovedProducts/UCM584762.pdf
91 https://www.fda.gov/downloads/BiologicsBloodVaccines/Vaccines/ApprovedProducts/UCM224503.pdf
92 https://www.fda.gov/downloads/BiologicsBloodVaccines/Vaccines/ApprovedProducts/UCM619664.pdf (Researchers did conduct one
efficacy trial for Fluzone (IIV3) long after it was licensed which found that “the rate of hospitalization was actually higher in the vaccine
group than in the placebo group” with 60% more vaccinated than unvaccinated children being hospitalized for insertion of ear draining
tubes. https://www.ncbi.nlm.nih.gov/pubmed/14506120)
93 https://www.fda.gov/downloads/BiologicsBloodVaccines/Vaccines/ApprovedProducts/UCM263239.pdf (placebo control only used in
adult trials but never in trials to license this vaccine for children); https://www.fda.gov/downloads/BiologicsBloodVaccines/Vaccines/
ApprovedProducts/UCM356094.pdf
94 https://www.fda.gov/downloads/BiologicsBloodVaccines/Vaccines/ApprovedProducts/UCM619548.pdf
95 https://www.fda.gov/downloads/BiologicsBloodVaccines/Vaccines/ApprovedProducts/UCM619664.pdf
96 https://www.fda.gov/downloads/BiologicsBloodVaccines/Vaccines/ApprovedProducts/UCM220624.pdf (44% and 45% of the Fluarix (IIV4)
and comparator vaccine group, respectively, reported an unsolicited adverse event within 28 days and 3.6% and 3.3%, respectively, reported
a serious adverse reaction)

Kasper, great post!

Thanks for providing the links for article references, but where is the original article from? I tried searching for some of the phrases but came up empty.

Thanks for providing the links for article references, but where is the original article from? I tried searching for some of the phrases but came up empty.

You can’t have tried very hard. It appears to be a quote from a letter dated in 2018 from ICAN to the Office of the Secretary, Department of Health & Human Services:
https://icandecide.org/wp-content/uploads/2019/09/ICAN-Reply-1.pdf

The start of the quote is from page 11, and the letter is signed by Del Bigtree,

Prevnar 13 is a second generation pneumococcal vaccine:
http://wayback.archive-it.org/7993/20170722073137/https://www.fda.gov/downloads/BiologicsBloodVaccines/Vaccines/ApprovedProducts/UCM206341.pdf
You cite a combined vaccine trial. It has placebo plus flu vaccine and Prevnar plus flu vaccine. There indeed was placebo v Prevnar.
Hepatitis B vaccine is very old:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7150172/
Maurice Hilleman was involved. His vaccine was approved 1986
FDA license vaccines, where you get HHS ? 1980 very long since,too. A link is needed
II notice that you call medical ethics a pyramid scheme. Read again Orac’s acicle.

I’m not seeing any indication that Prevnar or HepB vaccine was tested against a saline (or other inert) placebo in those links. Could you be more specific about where in those articles such information might be found?

Unless such information can be provided, the ICAN contention appears accurate.

Do you think that ICAN would be happy if the historical chain stopped at an inert placebo trial of an ancestor vaccine?

Do you dispute the ethical dilemma involved in removing an existing form of protection in order test a new one?

@ Beth Clarkson

Here is one study that used alum as the placebo. And a paper that explains why alum sometimes a better placebo. Of course, you will ignore as in your immense ignorance of immunology, thus how vaccines work, you will keep trying to find something that supports your view, ignoring that even if you found such, it would be one or two papers vs literally 10s of thousands by scientists around the world:

Wolf Szmuness et al. (1981). Hepatitis B Vaccine — Demonstration of Efficacy in a Controlled Clinical Trial in a High-Risk Population in the United States. Hepatology; Vol. 1, No. 5. p. 377.

S Djurisic et al, (2017). Aluminium adjuvants used in vaccines versus placebo or no intervention (Protocol) – Cochrane Library.

These are available for free online; but I doubt you will read them; but if you do, probably too stupid to understand them.

There are also numerous studies showing a significant reduction in Hepatitis B following introduction of vaccines.

YOU ARE JUST ONE OF SEVERAL REALLY STUPID ANTIVAXXERS WHO POST ON THIS WEBSITE.

Orac, I had replied to Kasper Peulen asking him where he was quoting from, but apparently my comment was not approved. In searching through ICAN’s website though I did find the original source:

it is the pdf
https://icandecide.org/wp-content/uploads/2019/09/ICAN-Reply-1.pdf
found on this page:
https://icandecide.org/press-release/the-cdcs-still-discussing-how-to-respond-to-vaccine-safety-debate-it-lost-to-ican-over-a-year-prior/

Kasper Paulen’s quote is from the section “(iii) HHS’s “Safety” Pyramid Scheme” which begins on page 11. Not only does this section contain the 3 examples of “following the chain” of licensed vaccines to find that they do not begin with a placebo controlled trial, but ICAN provides 2 tables on page 14 that depict this chain for all vaccines on the childhood schedule and another for the flu vaccines recommended for the 2018-2019 flu season. So ICAN and Aaron Siri did do their due diligence, not only posting the control for the current vaccines on the CDC schedule, but also followed the history chain. As they summarize (page 11):

“Despite its own policy and guidance, HHS does not require this minimal assurance for vaccines. Instead, all vaccines on HHS’s pediatric schedule were licensed based on a clinical trial with no control whatsoever, or another vaccine/substance used as a control which itself was never licensed based on a placebo-controlled trial.”

To summarize, putting it charitably, your entire “debunking” post – that doesn’t post a single vaccine insert, the basis of ICAN’s information – completely falls apart.

So two questions, are you going to correct or retract this post? And are you going to notify Michael Hiltzik at the LA Times that you were wrong, RFK is right, and childhood vaccines do not go through appropriate pre-licensure safety testing?

There is nothing to “retract.”

Aaron Siri’s entire argument about “no placebo controls” is deceptive bullshit from a scientific and ethical standpoint. Even if he were absolutely correct about every detail of his “analysis,” none of his results imply from a scientific and regulatory standpoint that the childhood vaccine schedule is in any way unsafe, untested, inadequately tested, or ineffective. Seriously, I laugh at how blatantly deceptive his entire premise is, the clear contempt that he obviously has for his antivax supporters (and the courts), and how completely he ignores the most basic ethical precepts governing clinical trial methodology. I also suspect that he knows his argument is bullshit from a scientific and ethical standpoint, but he also knows that it will be persuasive because most people don’t understand the basics of clinical equipoise and good placebo design. (Hint: Again, placebos do not have to be “completely inert,” nor do they have to be saline. To argue such is just nonsense.) He is a lawyer, after all. He was hired to push Del Bigtree’s antivax agenda, and that’s exactly what he’s doing to earn his money.

Be very careful what you ask for, though. I’ve already revised and expanded this post to show why Siri’s entire premise is bullshit (which will be published within a week), and I am indeed thinking about eventually going through every single study cited by Siri. Unfortunately, Brandolini’s law, which states that it takes an order of magnitude more energy to refute bullshit than to produce it, is an impediment. (And Brandolini was an optimist. It often takes two to three orders of magnitude more energy to refute bullshit than to produce it.)

Also, you sound familiar, like a commenter who was here before but banned. I might have to investigate, because:

https://www.respectfulinsolence.com/commenting-policy/

It would be great if you can go through the arguments from the ICAN report that I quoted, in a new post!

I do understand your point that a saline placebo is not required, or might be even unethical. Using a known effective and safe treatment as control seems ethical and scientific correct to me. And if the effectiveness and risk profile or similar or better than the control, than you know “enough”, no need for a placebo.

But, this only seems to hold, if the first generation of vaccines are being tested against a placebo. If you don’t test at some point chain against a placebo, how can you know that you are not comparing “cigarette smokers” against “cigar smokers”? At some point, in the chain, you need to be sure that the control hasn’t an increased risk profile.

Please correct me if I’m wrong!

The problem with this argument is that if you go far enough, there were not placebo trials used – but these are exactly the vaccines for which we have the oldest data. The diphtheria vaccine was created in the 19th century. For that vaccine, there would be no placebo trials because at that point, they were not done. But there is a lot of data because it was used that long.

Even for later vaccines, if they are decades old, there is now a lot of data. Because vaccines are heavily monitored in different countries. So looking at a decades old vaccines and saying “it’s not safe because in the 19th century – or the 1920s – they did not do placebo trials, so we need to do placebo trials now” is asking to ignore the existing data and deprive people from protection against a dangerous disease with no good reason: we do have a lot of evidence about these vaccines, and any issues would have been studied, even if there were not original placebo trials.

When ICAN is asking this, they are being either ignorant or dishonest (can’t tell which). The same will be true for very old medicines (think penicillin): there will likely not be placebo-controlled trials, but there is a lot of data. Pretending placebo-controlled trials are the only valid data is another way they mislead.

Here are two examples to make that point. Remember that clinical trials may not answer all questions. So for example, long after DPT got into use, questions arose about whether it causes asthma. You could not ethically do clinical trials then; but you could do retrospective studies and compare children who got the vaccine with those who did not, or children who got it at different times. Those were done, so we have data on this.
For other issues too, doing new clinical trials would be unethical.

Second, let’s go back to your cigarette example. There were no placebo-controlled trials of cigarettes that showed they cause cancer. Instead, that was done through retrospective studies – and they showed it.

We have a lot of data on vaccines safety. Claiming that the lack of clinical trials from the 19th century means diphtheria vaccines (now combined with others) are unsafe is, at best, thoroughly ignorant, at worse – and more likely – thoroughly dishonest.

None other than Tom Jefferson came to the conclusion that ‘we do not recommend that any further research on this topic is undertaken’.

@ Beth Clarkson

One article that summarizes reduction in Hep B cases following vaccinations:

Jade Pattyn et al. (2021). Hepatitis B Vaccines. The Journal of Infectious Diseases (Supplement Article); 224(S4): S343-51

Available for free online.

Note one doesn’t always need placebo controlled trials. Take smallpox. Prior to vaccine regularly attacked large number of people and more than 25% died, others suffered resulting in sometimes blindness, etc. Just during 20th Century prior to World Health Organization compaign ca 300 million died from smallpox. One can see smallpox cases ending as one follows WHO campaign from nation to nation as vaccine introduced. So, nope, no placebo controlled trial of smallpox vaccine. And no placebo controlled trial of rabies vaccine since we know that almost 100% who get rabies die, but if vaccine given early on, saves lives because rabies is a very slow acting virus, crawling up spinal cord, etc.

In the case of Prevnar (licensed in 2000), clinical trial placebos evidently were other vaccines, not saline solution. The purpose behind such selection is not mentioned in the articles I’ve read about the development of Prevnar, but is discussed in this McGill University Office of Science and Society article published in 2020 by Jonathan Jarry.

“So now we arrive at a particularly tricky example: a trial where, by all indications, a saline placebo should be used but is not. A team in the United Kingdom is conducting a trial of a new COVID-19 vaccine (charmingly called ChAdOx1 nCOV-19) and they are comparing it not to a saline injection but to a vaccine against meningitis. It has been reported as the only frontrunner for a COVID-19 vaccine that is not using a true placebo as a control. The World Health Organization’s expert panel on placebos used in vaccine trials does underscore the validity of using a different vaccine as a control (one whose safety is well characterized), but notes that it “may also be less acceptable to regulators or public health authorities and potentially delay approval or adoption of a new vaccine.” I reached out to the team conducting the UK trial and was told the reason they changed their mind from using a saline injection to using the meningitis vaccine was that saline injections don’t cause a sore arm, which might unwittingly reveal to the volunteers what group they are in. No soreness after the injection? You may have received a placebo, which could alter your behaviour and thus add a nasty variable to explain away the results of the trial.

This official explanation, however, is questionable. Injecting a saline solution into a muscle can be associated with side effects, as many vaccine trials have demonstrated. Also, comparing an experimental COVID-19 vaccine that has so far been shown to cause a fair amount of physical reactions (pain, fever) to a meningitis vaccine that can also cause these temporary side effects will certainly paint a kinder picture of the COVID vaccine. But there is a more generous argument to be made for administering the control group with a vaccine against meningitis: to give them something of value.”

It’s likely that in the case of Prevnar, decisions to use a control vaccine were based on having a comparator with a known good safety profile which would nevertheless induce sufficient mild vaccination site reactions to make it a good placebo to compare with Prevnar, and possibly also to give placebo recipients something of value.

What we’re seeing is that some antivaxers are pivoting from their bogus claim of “no saline placebos were ever used in vaccine trials!” to complaining that “well, this particular vaccine trial didn’t use saline placebo!”. There should be a clinical study examining the effects of goalpost-moving involving antivaxers. The control group could be a comparably-sized group of 2020 election deniers. Who would have the sorest muscles from all that goalpost-shifting?

@ Dangerous Bacon

Thanks. Good article. Always appreciate your contributions.

RFKjr not only mis-represents vaccine science but he mis-represents himself:
according to Rebecca Traister ( NY Magazine; guest at MSNBC yesterday) he tries to convince supporters that he’s an ‘outsider’ when he is the ultimate insider coming from a powerful political family, protected by massive wealth and privilege. She believes that there’s something rather “Trumpian” about this position.

I’d place him alongside other angry, white men, many of them well-to-do, who protest that they are victims of prejudice, racism or sexism. Their ideas are “censored” or silenced as they are
“excluded” HOWEVER, for some reason, I am able to access all of their complaints and ideas- I wonder why that is so if they are barred from public discourse.

Here’s a scary idea: what if all these guys get together and formed a club ?
Oh, wait, they already have.

“he tries to convince supporters that he’s an ‘outsider’ when he is the ultimate insider coming from a powerful political family, protected by massive wealth and privilege. She believes that there’s something rather “Trumpian” about this position.”

Trumpian, indeed.
Trump was pretending to be an outsider whereas he was the stereotype of the New-Yorker ultra-rich mogul. Not to mention his big Florida estate.

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