The Petty/Bone RCT

Absolutely and that has been a direction which some are taking and that may offer one of the greatest early opportunity given the size of the retrospective databases.

The problem is that lumping has been mandated to define the target heterogeneous syndrome to unify or harmonize the worlds research. That consensus is linked to funding. The consensus triage then bakes-in the heterogeneity.

This is why many desire a clean non lumped slate to do the kind of work you are suggesting.

This is a great discussion and I second Erin’s motion that we not pivot to writing about designing better research programs and trials in ARDS and sepsis.

My understanding of Erin’s request was that he was asking for exactly that.

I demurred, as the goal of the talk is general apical error related reform. The specific design issues, as a function of this reform, being best left to the experts.

This discussion needs a reframing or a return to its original frame. It is crucial to apprehend the context when many people engage in asynchronous text exchanges.

RCTs were developed to test interventions within homogenous biological constructs. Petty and Bone proposed RCTs could be used to test interventions within homogenous clinical constructs.

This is no trivial modification from the original method.

I like to use the expression disease model to denote the biological construct that gives a disease its unique taxonomy. Such models must be capable of articulating the clinical presentation, the diagnostic workup, and plausible intervention targets. Clinical constructs are not disease models.

For instance, one may declare that “Strong Headache” is a clinical construct and then enroll 'Strong Headache" patients to test the same intervention in all patients, never caring about common biological mechanisms. This is the “Petty and Bone” approach to headaches.

The Petty and Bone modification is a scientific conjecture per se, on the realm of epistemology.

Refuting a conjecture that failed to provide valid predictions of the empirical world is the unavoidable duty of the scientist.

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Beautifully articulated @Rafael_Leite. Yet this is only the “Petty Apical Error” (the disease lumping dimension) of the pathological RCT.

The 33year old “Bone Apical Error” is the second dimension which teaches “how to lump” .

The Bone technique teaches to derive (as by expert guessing) a set of non-disease specific thresholds and then lump different diseases by using that derived set of thresholds as a triage tool

Combining these apical errors together by a consensus task force creates a “heterogeneous syndrome” which, because it is an artifact we call a “synthetic syndrome”.

Combining Petty error 1 with Bone error 2 a consensus task force generates the latest heterogeneous syndrome which is therefore:

A overarching disease agnostic plurality of sets of a second plurality of sets of different diseases which fall within the scope of set of triage thresholds as amended from time to time by pathological consensus.”

It follows therefore that:

(The PettyBone RCT is an “RCT MIMIC” testing an intervention applied to a heterogeneous syndrome which is a clinical construct comprised of a set of different diseases lumped by a triage set of non-disease specific thresholds).

Contrary to those suggesting in this forum that this Langmuir pathological science is known, there were 3 (THREE) task force meetings using both Petty and Bone’s apical errors together to generate triage threshold sets for lumping diseases for harmonizing worldwide RCT in the past three years. They produced three new heterogeneous syndromes for RCT.

The PettyBone pathological science cannot be known if they are still teaching, funding, intellectually colonizing, and doing it.

However I will close my posts on this subject unless anyone in the future wants to have a substantive debate or discussion related to the actual **math and datamethods **.

Before I close I will provide a brief glossary in another post which explains the terms used to expose the pathological science.

“The mathematics is not there till we put it there.” - Arthur Eddington

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.

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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.

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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 .

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