Yes. It’s important not to indict the RCT method because some people, historically, haven’t designed them with enough foresight/care.
Assay sensitivity seems to be the key ingredient missing in the design of many of the RCTs Lawrence is concerned about. “Post-operative status” isn’t a disease, so maybe it’s not a great inclusion criterion for an RCT (in contrast to e.g,. acute occlusion MI or gallstone pancreatitis).
Randomly assigning an experimental intervention to subjects who are in a “physiologic state” that can be arrived at by many different biologic pathways, without a deep understanding of the prognostic distribution of untreated subjects, isn’t an ideal approach. If we could turn back the clock to a time before perioperative pulse oximetry became routine, we could maybe imagine a better way to design RCTs to reveal its benefits. For example, a reasonable first step might have been careful analysis of cases involving patients who died suddenly in the perioperative period while not being monitored. Attention to cause of death and measures that might plausibly have averted a bad outcome (e.g., a pulse oximeter alarming), might have identified a patient subset that is more likely to benefit from oximetry. After that, an RCT aiming to corroborate a benefit for oximetry could have been enriched with higher risk patients. Observing more adverse outcomes might have allowed any intrinsic benefit of oximetry to be detected more efficiently. For example, maybe a trial that enrolled only post-op patients with COPD or neuromuscular disease could show a benefit, whereas an RCT involving “all-comers” in the post-op period, would not.
The above process sounds logical enough. But once a medical practice has become firmly established, there will be many who argue that clinical equipoise has been lost. This is especially true if the intervention is cheap and doesn’t use a lot of resources, where downsides to empiric intervention, even without RCT “proof” of benefit, are hard to fathom, and where the potential consequences of not intervening are serious. The second to last point is the real nub of the issue. Often, some stakeholders perceive potential downsides to an intervention, where other stakeholders don’t (see the endless debate re mask mandates during the pandemic). In the case of pulse oximetry, every anesthetist probably can recall a few cases where a pulse oximeter was the first indicator of a patient’s unanticipated abrupt postoperative decompensation- those types of cases probably stick with a person for a very long time…
Finally, it seems important not to start seeing the potential for qualitative interactions everywhere we look. While their presence might be more plausible in a poorly-designed RCT that has lumped a pile of patients together who have no business being part of the same experiment, a well-designed RCT, focusing on patients with more homogeneous disease (e.g., acute occlusion MI) would probably be much less likely to involve important treatment by patient qualitative interactions.
Arguing that EVERY ostensibly neutral RCT plausibly might be “hiding” signals of efficacy that have simply been “obscured” by qualitative interactions, assumes that EVERY treatment we can imagine plausibly has the potential to benefit some patients and harm others- we just need to keep examining people on a more and more granular level in order to distinguish “responders” from “non-responders.” But of course, this argument is susceptible to infinite regress and isn’t a realistic basis for approving new drugs and devices.