So lets actually look at a couple of potential “individual responses” to continuous Pulse Oximetry monitoring. **(By the way knowing these things may help you next time the nurse discounts your concern about a loved one’s shortness of breath by pointing out that your loved one’s pulse oximetry readings are satisfactory).
Pulse Oximetry Harm
This is a common harm by classic false sense of security caused by reliance on the pulse oximetry signal as indicative of respiratory stability, since the patient progressively increases ventilation in the Type I pattern moving more air (and therefore more oxygen) into the lungs so the oxygen saturation by pulse oximetry (SpO2) may remain normal till near death.
Here I present a typical Type I Pattern of Unexpected Hospital Death (PUHD). This is a typical relational time series pattern of signals in sepsis, congestive heart failure and other common conditions. Note the SPO2 (oxygen saturation by pulse oximetry actually can rise early in the death process and then can remain stable and normal till close to death.) (This is caused by compensatory response of increasing ventilation volume (Ve) and respiratory rate (RR).
Note the potentially fatal false sense of security provided by the pulse oximeter. Of course, death may not occur, rather there may be complications such as organ injury or prolonged hospital stay due to late detection.
Pulse Oximetry Benefit
In stark contrast (but studied in the same black box RCT) here is a Type II PUHD. Note here pulse oximetry will provide benefit because the SPO2 falls early in the death pattern providing early warning potentially preventing death or complications. (Particularly if the patient is not receiving supplemental oxygen). If the SPO2 falls early
Now the details are different from the @scott example cited by @Stephen but the fundamentals are the same.
There is individual benefit, individual harm, and potential for refusal (which refusal may benefit or harm). The harm or benefit cannot be predicted prior to the study without more knowledge (which might be provided by a prior high density data OS ). The authors are probably unaware that the individual pathophysiology here affects the probability of harm or benefit. The 2 RCT could be done at different centers or on different wards with different pathophysiology sets…
You see how the trialists and statisticians were certain of the validity as long as N was sufficient and compliance was good enough… RCT in black box format (i.e. Does X cause benefit or harm when applied to population Y, as defined by broad and/or capricious, criteria Z?)
Here we see the contrast and consequence of this during the pandemic.
Does dexamethasone improve survival when given to patients with ARDS?
RCT answer-No
Does dexamethasone improve survival when given to patients with ARDS due to COVID?
RCT answer-Yes
How do you reconcile that without deciding “RCT for ARDS” is a pitfall? The answer is the same as for pulse oximetry. Combining the pathophysiologies by using “the perioperative state” as criteria rendered a SET with a mix of individual responses which averaged out to show no harm or benefit for both the pulse oximetry RCT just as occurred with the pathophysiologic mix under ARDS RCT test, as derived from the threshold based nonspecific criteria of the many ARDS RCT. The mix of individual responses in the SET under test determined the average treatment effect of the study. However that ATE may be markedly different then the average treatment effect of another population defined by exactly the same broad criteria. . .
So “individual response”, the focus of this thread, is not just a function of the individual but also a function of the specific pathophysiology affecting the individual, but more importantly it is a function of the percent mix of individual in the SET under test without the fundamental target pathophysiology but which meet the criteria for entry into the RCT.
Finding means to narrow the criteria for the population under test to those with the target pathophysiology is the first step, before deciding if a valid RCT can be reliably performed…
Here, the synergies between OS are RCT are clear. OS, may provide an incorrect answer due to lack of randomization or suitable controls. Yet OS should be performed in complex populations because they provide much greater density of time data, for example time series matrix data from EMR, to render transparent potential individual responses. This was shown in the instant example wherein, before the RCT can be reliably performed, one must learn the lessons of the pathophysiologic basis for pulse oximetry benefit or harm.
During the COVID pandemic most trusting in evidence based medicine were absolutely sure they had RCT evidence that corticosteroids did not work for COVID ARDS and were highly critical of its empiric use. (Given that death was often due to an overwhelming inflammatory response, empiric dexamethasone would have made pathophysiologic sense if the RCT did not exist). The number of lives lost due to that false EBM was likely quite high. We could not have known that, or what to do, but, like the pulse oximetry in Type I pattern of unexpected hospital death, we had a false sense of security that dexamethasone would NOT work. Perhaps clinicians would have been less sure, if everyone was a little more forthcoming about the potential weakness of RCT when applied with broad criteria. This is what failure to consider the heterogeneity of “individual response” as noted by @scott can cause false EBM and harm to the public.
We love RCT based EBM, its our base. Yet lack of reform is robbing EBM of its standing. This article shows the negative drift of the image of EBM, which could be prevented by converting into objective terms the qualities required for entry criteria.
I know I am off track from what the group wants to talk about in this thread and its a great thread and I do not want it to be ended. I will cease so you can get back to it. Regards.
Ref.