The Petty/Bone RCT

Doc_Ed · February 6, 2025, 7:39am

This is literally what the global research effort in sepsis immunology is striving for, and has been the stated aim of the field for well over a decade. It’s the conversation I have most often with the authors of the sepsis-3 paper. I don’t know what else you could possibly want? Are you aware of the ongoing research in this area?

This is such a strong and demonstrably untrue statement. With respect, it’s hard to debate this from a rational position as it’s such a ridiculous statement. It has the flavour of “I’m the only one who knows the truth”. Which isn’t a rational position to hold when global research efforts require the input of dozens, if not hundreds, of minds to complete successfully. The mass of back and forth critical scientific reasoning in medicine and intensive care medicine in particular is vast. I appreciate that there is research waste. And the interface between science and academia is complex. Just because some of these positions don’t align with your personal view doesn’t render them invalid. Doctors, clinical scientists and scientists from a broad range of fields are engaged in massive efforts of directed scientific research from lab to clinical studies, experimental and observational etc.

To suggest that these people can’t think scientifically undermines your central thesis to such a high degree. I’m honestly perplexed by the statement.

I’m starting to think we are talking cross purposes here. The sepsis research community is well aware of the heterogeneity issue and are directing large scale research efforts to better understand it.

Doc_Ed · February 6, 2025, 8:17am

I agree with this sentiment. I haven’t actually seen much here that isn’t framed as speculative.

If there are concrete proposals of how you propose to move forward in terms of trial design or patient selection, then I’m all ears. At present, I don’t think there is enough here to write an article because it’s all been said before and there isn’t any evidence provided to support the arguments beyond opinions (whether or not I agree with those opinions is irrelevant).

We seem to be stuck in a loop.
So, with the greatest of respect. I’ll bow out.

f2harrell · February 6, 2025, 2:00pm

From now on, let’s tone it down and stick to outlining and detailing future research programs and study designs that will result in real progress rather than any repetition of past thoughts. I hope you don’t bow out @Doc_Ed .

Rafael_Leite · February 11, 2025, 11:02pm

Hi Doc_Ed

I am used to being called ridiculous etc. I don’t care. You are talking to someone who’s reading bad research in our field for +25 years. We must discuss a generation of scientists (starting with J-L Vincent) who wasted their (ours?) lives in unfruitful models like sepsis and ARDS.

I have studied sepsis immunology and started contributing to the sub-field of purinergic signaling in sepsis, before realizing the sepsis construct is a sinking ship. So, yes, I am aware of ongoing research and I am saying with all the words: it will fail. They won’t reach a disease model using a clinical construct like Sepsis-3 or any other. You can’t define a disease as a “dysregulated response to infection” and expect someone will find a treatment.

I keep it. I am not suggesting they can’t think scientifically. I am affirming it. I am not pretending to be the clever guy in the room. Instead, I had the humility to take a few steps back and try to grasp what was wrong in a field that can’t produce innovation. I see a widespread poor understanding of how science works. Our “scientists” should try reading epistemology to understand their mistakes. I extend the recommendation to the biostatisticians because they also can’t see what is wrong, yet, they think advanced statistics can compensate for bad hypotheses derived from poor clinical reasoning.

I recommend Popper, the Vienna inductivists, Kuhn, etc. It won’t take more than a weekend to get started and it will do more for our field than the silly “precision medicine” subgroups they are testing in several trials like Panther, Precise, Pallete, etc.

I thank God I don’t need to network, so be free to think or say anything you like about me, but do it elsewhere, not here as asked by Professor Farrel.

However, if you want to discover how I got to such an extreme position, I invite you to my substack.

My proposition is that we shouldn’t study ARDS or sepsis patients as belonging to a unique syndrome. It’s a bold proposition, to abandon the “heterogeneous syndrome” and the clinical constructs like Sepsis-3. One interesting (maybe unintentional) approach was the STAMINA trial, where they only included pneumonia/ARDS patients. ARDS could be split into several independent nosologies to be studied individually, and patients shouldn’t be triaged using PaO2/FiO2 thresholds, at the risk of missing the whole picture of patients with similar pathophysiology.

Lawrence_Lynn · February 12, 2025, 3:22pm

What a wonderful raw science debate. Raw science disagreement about fundamental methodology in the open is as rare as Bigfoot in critical care.

Yet this is exactly what the public deserves. According to the CDC, 13000 patients died from influenza this season yet there are no RCT to inform physicians the role or lack of thereof of corticosteroids in reducing mortality of severe influenza pneumonia.

This makes those who understand that the research funds were mistakenly spent, for decades on Petty’s ARDS clinical construct rightfully upset when the beribboned remain recalcitrant and refuse to openly introspect and reform. .

In contrast those “in the dogma box” shrug, and say the classic line “the data are scant” and “the trials are coming”.

These battles between those who want introspection and rapid reform, and those who are comfortable with a non introspection based, slow pace has always existed.

Imagine the polar opposite dispositions of two young engineer groups who had been diligently working on much needed bridge for a decade, only to discover the concrete provided by the trusted leaders was not real concrete.

One group would be nonplussed and say “Oh well, let’s keep trying”, while another group would be outraged at their lost work and failure for the public and would demand introspection so this would not happen again.

So this is a healthy debate and one expected when social forces do not prevent open debate. I hope it is widely read because it lays bare the present polar state of the fundamental methodology camps of critical care science.

Lawrence_Lynn · February 13, 2025, 12:08am

Very well. Here is the template. Follow the guidelines set forth here where treatment is tested for an objectively measurable phenotype of a specific objectively definable disease.

In this case the phenotype is alveolar tuberculosis. This is rare in the US today but if you have been a pulmonologist as long as I have you would have seen it. It was common in the past.

Note he was phenotyping downward from the disease of tuberculosis and even pulmonary tuberculosis. He describes the need for a measurable homogeneous thread.

Erin read this landmark article very closely. Note the emphasis on objective (& non lumped) input measurements and output measurements. Follow the guidelines here for influenza A pneumonia, and each of the other pneumonias.

Don’t lump MRSA pneumonia with pneumococcal pneumonia or Influenza pneumonia. Rather study each of them separately. Study aspiration associated respiratory infiltrates in the same way. Modify as needed based on pragmatic of measurement but do not violate the homogeneous thread. ARDS is a severity indication, an artifact.

Work with statisticians to be sure the Bradford Hill method is applied to the best extent possible as early in the trial as objective diagnostic data allows.

If a treatable phenotype of a disease is found look for that phenotype in other diseases and test them each by the Bradford Hill method.

Start with Hill. Then test lumped groups only on objective evidence of probable broader efficacy based on study of individual disease. Bayesian methods may be applied once an objective disease is the target and priors can be defined.

That’s exactly what I would do in conjunction with experts given the 33 years of triage threshold based lumping shortcut failure and which is not a valid technique and is, in any regard, antithetical to the RCT function. But first I would widely promulgate the PettyBone mistake to release the indoctrinated. With this effort I would empathize that a valid RCT must have a homogeneous thread.

If a new RCT is chosen, such as the PettyBone RCT this must be validated mathematically before it can reenter the field but it must be so identified separately by branding to avoid confusion with a standard Bradford Hill RCT.

Of course, I would defer to those expert statisticians who have escaped the lumping shortcut box. I hope others will bring ideas now that we are past the turbulence associated with bursting the 33 year dogma bubble of the research based on “disease lumping by triage threshold set era”.

Again read the history. Spend time following the progression of the RCT. Study the methods. Abandon the shortcuts. Fix the hole in the hull.

Elias_Eythorsson · February 13, 2025, 10:28am

I have read this entire thread and find it interesting. I’ll hazard to contribute.

The central thesis is that lumping many different pathological processes into synthetic syndromes and then studying these syndromes is so problematic as to be practically useless. For arguments sake let us assume I am utterly convinced. But as with other readers, I am a bit perplexed as to what the alternative proposition is, and, I too, find that the responses to these calls for an alternative weirdly combative and unsubstantial.

We are mainly discussing ARDS and sepsis, and yet the examples those who oppose the “petty/bone” RCT offer as a counter point (e.g. tuberculosis) are disease where you can reasonably wait to confirm the pathological cause before treating. When I as a clinician start treating what I presume to be sepsis or ARDS, I do not in most cases know the cause.

Can we have an honest discussion about what inclusion criteria would look like in a critical care trial for severe acute pathology that avoids the pitfalls of “petty/bone”? Let us start with a specific example to help my understanding, what are your thoughts about the recently published BALANCE trial .

Lawrence_Lynn · February 13, 2025, 5:33pm

Thanks for contributing. As you point out this is a complex problem with considerable nuance so we need many more thoughtful participants in this important discussion. Your identification of the Balance Trial is especially illustrative.

First, the use of Bradford Hill’s tuberculosis treatment presentation of the RCT was simply to present the ideal template. Hill’s brilliance is more evident when considered through a contemporary lens.

So if we start with Hill’s template we can identify a group of specific diseases in Petty’s ARDS which can be diagnosed rapidly. For example, post aspiration, post burn, COVID pneumonia, Influenza A pneumonia, post trauma, pancreatitis. Each of these can be studied individually by multi-center RCT.

Petty did not include bacterial pneumonia and Petty’s heterogeneous syndrome was greatly expanded by using P/F triage. So over the decades we further progressed in the broadening direction, away from the homogeneous thread which Petty and Bone had already abandoned.

In the Balance Trial there is lumping but not in the “PettyBone sense”. Petty and Bone taught to lump by non-disease specific chest radiograph and/or non-disease specific thresholds. This was the pitfall which enabled lumping inflation. There is no limit to the broadening in PettyBone based research.

The Balance Trial lumps specifically diagnosed bacteremia with evidence based exclusions (such as Staph. aureus and source control considerations). This is very close to a Bradford Hill RCT but in my view it should have different branding to give the clinician notice that some disease lumping was present. I’m not sure what that branding should be. I call these collectively, “RCT Mods”.

The “PettyBone RCT” brand which I think is absolutely necessary for the clinician (if this RCT mod is not going to be abandoned) refers to a specific type of very broad lumping by non-disease specific triage threshold set.

The thesis here is that RCT should move as closely to Hill’s method as possible.

We can see right away how far a PettyBone mod has moved from a real RCT, where abdominal infection due to perforation after a colonoscopy is lumped with a candida line infection and GAS bacteremia associated with toxic shock.

So the fact that the Balance Trial was able to “thread that heterogeneity needle” is a wonderful example of movement by the designers, as closely to a real RCT function as possible.

With infection there are dimensions by which this “intelligent lumping” can be accomplished. For example the trial could be limited to a source as @Doc_Ed suggested with specified bacterial subsets .

Yet the search for common pathways might be best started with a single disease (eg E. coli bacteremia with a UTI source) thereby setting the rest of the disease related unknown variables as homogeneous across all the trial as possible. Of course this is not the real world but this is rather a means to find the homogeneous biological threads with lumping to follow as defined by evidence.

Thank you again for bringing the Balance Trial to the discussion as it helps illustrate the two polar extremes of Bradford Hill RCT and PettyBone RCT. It also shows the need to brand RCT to alert clinicians so they are immediately aware if a “RCT Mod” is being reported rather than the classic RCT.

Lawrence_Lynn · February 13, 2025, 7:58pm

I wanted to comment on this. I understand the debate is unusual but the purpose of the original post was to teach the PettyBone RCT Mod not to discuss alternatives.

First the pitfall of non disease specific threshold set lumping with substantially unmitigated dimensionality had to be accepted by the reader before we can discuss alternatives. This is why the discussion kept circling back to the original intent of the post. This is also why fireworks developed relating to the tension that always develops when real fundamental dogma which virtually everyone believed and taught are challenged.

Some commenters seemed to desire to “ice” the discussion of PettyBone and to divert discussion to alternatives without debating or accepting the need for alternatives as if this was relevant to the Langmuir pathological science nature of the PettyBone RCT.

There is always the deflection to, “What is the alternative” without the acceptance of the state of pathological science. This deflection prevents introspection.

This type of fireworks seems weird today in the era of consensus driven critical care science but it was once common in science.

My mentor at Wash U Stl. was a proud member of the now defunct “antidogmatic society”. Scientists of that time were sceptics and they wore that badge on their chest so everyone was warned that their dogma could be challenged all the way back to its origin. His famous quote was, “We oppose dogma at every level”.

This was once a highly productive and very enjoyable way to “do science”. The road is wide open because the mentors are not shepherds, they are teachers. In contrast we were all indoctrinated in the opinions of our mentors and shepherds Petty and Bone and their presently extant acolytes. Any sheep that desire to stray are unlikely to be fed.

Today the NIH grant system contributed to the decline of the learned skills of anti-dogmatism which are often replaced with mentor based teaching about networking and consensus task-force class promotion.

This is one of the reasons a deep, historically probing, anti-dogmatic challenge to the fundamental trial methodology in critical care discussed in the open seems weird in 2025 critical care science.

Lawrence_Lynn · February 14, 2025, 1:52am

Grok discusses RCT mods.

Lawrence Lynn discusses the issue of misbranding in medical science, specifically regarding modifications (mods) of Randomized Controlled Trials (RCTs). He argues that calling all mods just “RCTs” inflates their value and misleads clinicians.
He mentions the “PettyBone RCT mod” as an example, suggesting a need for proper branding of RCT mods to avoid confusion and ensure clarity in medical research.
Lynn questions what other RCT mods exist and proposes a naming convention for the mod of the Balance Trial, highlighting a gap in the standardization of RCT terminology in medical literature.

Milos_Zarkovic · February 17, 2025, 5:39pm

As an endocrinologist, I would like to address the fact that the issue at hand is not limited to the intensive care unit (ICU). E.G. Polycystic Ovary Syndrome (PCOS) is prevalent and is diagnosed according to the Rotterdam criteria, which require the fulfilment of two out of three specific criteria for diagnosis:

Oligo- and/or anovulation,
Clinical and/or biochemical indicators of hyperandrogenism,
Presence of polycystic ovaries as observed via ultrasound.

We also recognise that there are subtypes of the disease. However, this is the clinical practice, and the challenge is that we would need to change the entire paradigm to suit RCT.

Furthermore, what about composite outcomes? Major Adverse Cardiovascular Events (MACE) are frequently used and typically encompass myocardial infarction, stroke, and cardiovascular death, with some definitions also including additional events. I believe that the same issue exists as with the Petty & Bone trials.

Lawrence_Lynn · February 19, 2025, 5:24pm

Hello Dr. Zarkovic.

Excellent point. In many fields, where separation of specific diseases was not forthcoming, clinical practice evolved around presentation and clinical manifestation which we all called syndromes. Over time specific diseases were separated off from the syndrome. In some fields like cardiology the syndromes (like CHF) have become subordinate to the primary diseases so PettyBone is no longer a problem. (Although you make an interesting point about MACE).

We have learned that the measurements (criteria) defining these syndromes are not mathematically suitable for entry into a RCT function . In essence, concepts or rule-of-thumb heuristic may be quite useful clinically but an RCT cannot be snapped onto a heuristic. This is what happened in critical care.

Yet (correct me if I am mistaken) it seems that there is a homogeneous causative thread of hyperandrogenism with PCOS and with MACE there is a homogeneous causative thread of atherosclerosis (given that other causes of stroke etc excluded).

So at least an RCT of PCOS (with proper disease exclusions) is not at the extreme level of the PettyBone RCT where the subjects are defined by a task force generated triage set of non-disease specific thresholds. There is no homogeneous causative thread in a PB RCT.

Have the RCT been reproducible in the study of PCOS?

You make a beautiful point about the potential for PettyBone RCT mod to creep into disciplines.

The PettyBone RCT mod is the easiest RCT mod. because subjects are simply scooped up by triage. The case finding and disease diagnosing work and bottleneck are eliminated making this RCT mod the easiest path to a grant.

The statistician should always ask if the criteria capture a single disease or a set of different diseases.

Lawrence_Lynn · February 22, 2025, 3:31pm

For those who have been following this thread might not have ever seen a PettyBone RCT mod.

So here is a classic PettyBone RCT mod. Not even Bone would have performed this RCT because it extends the use of a guessed threshold set to the output not just the input (as in the classic PettyBone RCT mod). It’s a guessed “threshold sandwich” of sorts, whereas the original PettyBone RCT mod only used a guessed set of thresholds as a triage for the subjects.

This present trial uses the 1996 guessed SOFA threshold summation score as the primary outcome. (That by itself has never worked.) see the discussion of the use of guessed threshold sets as measurements broadly in critical science.

Recall that in modern PettyBone science the guessed SOFA score is used as an input (as sepsis 3), an independent variable, and a primary or secondary output. These studies all fail.

https://discourse.datamethods.org/t/what-is-a-fake-measurement-tool-and-how-are-they-used-in-rct/3955?u=lawrence_lynn

The instant Iloprost study (This multicenter PettyBone RCT mod) tests a treatment (Iloprost) for massive SET of different diseases captured by a 1st GUESSED SET of triage thresholds. The primary outcome is the max daily SOFA score comprised of a 2nd GUESSED SET of thresholds.

Results are (secondary outcome of mortality)
“Mortality at 90 days in the iloprost group was 57% (81 of 142) vs 51% (70 of 136) in the placebo group”

Here is the graph of primary outcome (daily mean max SOFA in the time domain).

Note: As patients worsen this SOFA score rises but as patients die they apparently drop out of the calculation so the “mean max SOFA” falls as more patients die. It appears, athough I could not find it stated, that this is the mean max SOFA of the daily residual alive.

————-
This is a beautiful illustration of PettyBone science.

Guessed triage set thresholds as the input measurement .
Guessed set of thresholds as the primary output.
The treated set derived from triage is disease and source agnostic.

Of course it failed, as all PettyBone RCT mod fail.

The worst part is that Iloprost might work for one or more diseases hidden in the mix. Who knows?

This PettyBone RCT mod was published in 2024, on the 35 year anniversary of Bone’s original failed methylprednisilone trial for “sepsis” as defined by his guessed triage threshold set of SIRS.

Note, in the discussion of the trial, there is no discussion of the use of a PettyBone RCT mod as a potential limitation of the trial.

So most respectfully, both @ESMD and @Doc_Ed apparent opinions that this pathological science is known is not correct. It’s entrenched.

Hence the outrage of @Rafael_Leite who was unknowingly indoctrinated and tricked to waste years of research (as most were) is the expected response.

Complacency and complicit resignation to the dogma out of social fear after 35 years of failure relevant the study of one of the greatest killers of adults and children, should be condemned.

———
Now think about a real Bradford Hill RCT testing Iloprost in the treatment Ecoli bacteremia due to UTI with mortality as an endpoint.

Treatment could start immediately pending future results and be withdrawn if E coli is not identified.

Notice how a non-disease agnostic RCT (a Bradford Hill RCT) provides a more homogeneous thread of unknown disease related variables and how a disease agnostic RCT is contaminated with massive unknown disease related heterogeneity which varies from one PB RCT to the next depending on the mix of diseases captured by the triage threshold set.

In any case, it’s time for all with sufficient courage to consider and debate, in the open, why the PettyBone RCT mod always fails and how to go forward without the PettyBone RCT mod.

Lawrence_Lynn · February 22, 2025, 9:30pm

Here is a classic PettyBone RCT, published this month, testing Aspirin to a set of different diseases captured by the triage threshold set of SOFA (sepsis3). The outcome was also the SOFA score so this is also a “PettyBone SOFA sandwich.”

The PettyBone RCT SOFA sandwich:

Input measurement-

“Sepsis was defined according to the Sepsis-3 definition by the presence of a suspected or confirmed infection and an increase in the SOFA score of two points or more.”

Output measurement —

“The primary outcome was the change in the Sequential Organ Failure Assessment (SOFA) score between day 0 and day 7 or date of discharge/death.”

Of course it was all negative but increased bleeding which caused stoppage. (Some of the subjects were harmed) .

(This harm and waste @ESMD is why I am “cognitively stuck”. )

Here is how to do a PettyBone RCT mod.

Find a drug and create a hypothesis
Triage the patients using SOFA. (sepsis 3)
Randomize the triaged patients.
Give drug and placebo.
Measure SOFA as an outcome.

This is the easiest method of RCT performance. It was originally made in the USA. These Brazilians were intellectually colonized to use this pathological science.

Very sad. Harm to the subjects with no hope of success. That’s the PettyBone RCT!

f2harrell · February 24, 2025, 12:27pm

If they had used SOFA as an outcome it would have been a tiny bit better. They did not; they used change in SOFA, which SOFA was not designed to be used for.

llynn · March 3, 2025, 7:45pm

Absolutely and I certainly hope you are willing to do so. Let’s contrast the above aspirin for sepsis trial with the BALANCE trial and then discuss how to avoid the pitfall of the PettyBone RCT mod.

Note the the Aspirin for Sepsis Trial (PettyBone) RCT uses a first triage non-disease specific threshold set of SOFA to capture a second set of different diseases (which are lumped as the synthetic syndrome of “Sepsis”) and then Aspirin is tested using this PettyBone RCT mod. purporting to generate a **single average treatment effect (ATE) of aspirin on this second set of different diseases. (This is generally the way that sepsis and ARDS RCT have been done for 36 years, since Bone’s failed methylprednisolone for SIRS trial in 1989. They have not been reproducible.)

1. “Sepsis was defined according to the Sepsis-3 definition by the presence of a suspected or confirmed infection and an increase in the SOFA score of two points or more.”…
1. “Patients in the ASA group received 200 mg orally or enterally once a day for 7 days, regardless of ICU discharge.”

Contrast that to the BALANCE trial

"1. Patients were eligible for enrollment if they were admitted to a participating hospital at the time a blood culture was reported as positive with a pathogenic bacterium…A full list of inclusion and exclusion criteria is provided in Table S2.…
2. Adequate was defined as antibiotic therapy to which the organism was susceptible according to local laboratory reports;"

Not not only was there an objective diagnosis in the BALANCE (bacteremia) but the treatment was specific to the diagnosis.

So the pitfall is avoided by having a diagnosis or specific measurable targetable homogenous thread in all the patients in the RCT. A set of non-disease specific thresholds, such as SIRS, Sepsis 3 (which is SOFA), or the next threshold set generated by the next Sepsis or ARDS consensus task forces simply cannot do that.

One could argue that BALANCE should have separated the organisms and performed a separate RCT on each and this would have been more in keeping with Bradford Hill’s method. Certainly they had 74 centers so this would have been preferred. As it is we are left wondering if certain more resistant pathogens might not fall within the ATE. In a sense n is artificially high for each specific organism. Yet this RCT mod is profoundly better than a PettyBone RCT mod.

Great to have a discussion. How do you perceive these two RCT mods in comparison with Bradford Hill’s and Fisher’s teachings? Do you agree with my analysis here? What are your views or the next step? Do you think that lumping by non-disease specific threshold set might eventually reveal a common thread?

I look forward to the discussion. I hope others will also contribute.

Lawrence_Lynn · March 9, 2025, 1:29am

@Elias_Eythorsson

Just sending this in case you missed my response to your request for an honest discussion of the comparison of the PettyBone RCT and the Balance trial.

I think many are looking forward to your response and thoughts as this is a very timely and popular thread and topic.

Lawrence_Lynn · March 9, 2025, 1:33am

Corrected reply above should be to @Elias_Eythorsson

Lawrence_Lynn · March 14, 2025, 12:01am

I don’t think @Elias_Eythorsson is coming back for that “honest discussion” since it’s been over 3 weeks but maybe he will. @ESMD and @Doc_Ed both denigrated and summarily bolted. That was not surprising.

I will summarize this thread:

First: By deep review of the history, I identified the 1967 and 1989 combined apical error of a pathological science. This error was the RCT modification called the PettyBone RCT which eliminated the need to diagnose a disease and replaced the diagnostic process with a first set of guessed thresholds to lump (by triage), a second set of different diseases for this new modified RCT.

Second: I showed that this RCT mod is pathological science which has not rendered reproducibly positive results for 35 years despite hundreds of such RCT. Furthermore a one-size-fits-all standard ventilator protocol based on this pathological science caused great harm during the pandemic. This protocol has been abandoned.

This proved that pathological medical science is not only wasteful of money and careers but is harmful to the public.

In any other industry the discovery of a fixable apical error would be an exciting revelation causing action for reform. I was the first to discover that the specific source of the lack of reproducibility of critical care RCT was the modification of the Bradford Hill methodology and, even if unrecognized now, this was a great discovery for the science of critical care.

Indeed critical care scientists have long blamed raw generalized heterogeneity for the failure but failed to go back in history to seek the source. For this reason they failed to see that thier past leaders Petty and Bone had integrated profound heterogeneity into their modified RCT methodology itself by lumping different diseases using a guessed threshold set as triage.

Massive excitement would have been generated in industry responsive to the discovery of a fundamental methodological cause of decades of waste and failure because it would be seen as an amazing opportunity for a new direction and greater productivity.

My father, a chemical engineer in the 1950s, discovered a source of waste in the processing of aluminum. His work was hailed.

In contrast, my discovery of a fixable, apical source of waste in medical science triggered insults and denigration. No one argued it was not pathological science (they could not). Rather they simply did not like the promulgation of it.

I recall this same thing happened to a prominent thought leader (who later was president of the ACCP). She presented evidence over a decade ago at a national meeting that the AHi was not a gold standard for severity of sleep apnea. Rather than being praised for her work and insight, she was accused from the lectern of “euthanizing children”. This public denigration, of course, was said as “tongue in cheek” but it was also a shot across the bow warning her not to disrupt the flow of the spice.

Likewise the denigrating response in this thread to my discovery of the historical onset and source of decades of waste as a function pathological modification of RCT methodology shows that scientists cannot be trusted to police themselves just as they could not be trusted to police the severity standard for sleep apnea.

Any challenge to deep decades old dogma which is rendering a river of grants Is perceived as a challenge to “mother science”. This is why they become verbally denigrating and then quickly run away.

It’s fine to end this thread now but the results of this experiment have made me realize that the “threshold set guessing task forces” must be defunded by the new NIH.

We must cut off the source of the PettyBone RCT mod. or they will simply stay the course.

Without the first guessed threshold set (which , believe it or not, the task force reconvenes to guess anew every decade) this pathological RCT mod will collapse because they won’t have a standard means to triage the patients (to lump the different diseases) for the RCT. They must then turn to the teachings of Bradford Hill and study each disease separately or find a homogeneous thread to identify those included. At the same time the NIH defunds the threshold guessing task forces, the NIH should liberally fund the reform.

Unless anyone has a prolog, goodby all.

This social experiment was fully supportive of my original hypothesis which states:

Scientists will generally seek to discredit any effort which impedes a well established flow of grant funding without regard to the merit of the research.

f2harrell · March 15, 2025, 1:59pm

To reiterate something I said earlier, let’s move towards continuing the discussion with an emphasis on designing future trials.