I start with the idea that very little or nothing we do works. Bedrest? Bunkum. Daily labs? Nonsense. Paralysis? Poppycock. Therapeutic paracentesis? Tripe. Erythropoesis stimulating agents? Hoopla. A "balloon pump"? Even the name begs derision. This blog has chronicled countless promising therapies that didn't pan out, beautiful scientific underpinnings notwithstanding. So with everything we do, we should start with a personal null hypothesis and accompanying agnosticism about the effects of our interventions. Regardless of how much we learn about pathophysiology, we should assume ignorance about the effects of our interventions, with two notable categories of exceptions:
Category 1. When the observed effect is so robust, dramatic, predictable, and consistent, that denying it would be irrational. Therapies that conform to these qualifications do not really need RCTs to prove them and indeed RCTs may be unethical. The effect size of the intervention is so great that the number needed to treat (NNT) is very small or approaches 1. When I think of such therapies, I'm thinking of cholecystectomy for septic cholecystitis, insulin for DKA, lasix for CHF, angioplasty for AMI, mechanical ventilation for respiratory extremis and ARDS. (In the same vein, I might include paradigm shifts in medical practice that have strong experiential support - such as the reduction in sedation and aggressive physical therapy and mobility in the ICU in the last 10 years. But caution is warranted here - we are prone to getting swept up in any cultural current and carried away. I am more confident in these two "interventions" because they are, in reality, a scaling back of harmful interventions (sedation and paralysis) that have been impeding patients' recovery for decades!)
Category 2. When a trial free from bias demonstrates an unequivocal and repeatable/repeated effect on a meaningful outcome. In this category, I'm thinking of low tidal volume ventilation for ARDS; Aspirin for AMI; ACE inhibitors for CHF; and Statins for cardiovascular disease. Characteristic of this category is the idea that the effect is smaller or takes longer to accrue, so the dramatic obviousness of the first category is absent and longer and closer monitoring is required to document the effect with statistical analyses. The NNT of interventions in this category is larger.