 Frequently, in the biomedical sciences, reliable animal or other non-human models are not available and RCTs on humans are infeasible for ethical or practical reasons. In these and other cases, biomedical hypotheses can be established using observational methods. As we have seen in  Section 5,  evidence-based medicine regards observational methods as generally less reliable than RCTs and other experimental methods. This is because observational studies are subject to a host of confounders and biases that can be controlled when the hypothesis is tested by a—well-designed and well-conducted—RCT. But it is not the case that observational methods cannot deliver reliable results. In fact, it is well possible that the medical knowledge that has been established observationally by far exceeds the knowledge that comes from RCTs. Here are some examples of medical interventions that are widely accepted as effective but whose effectiveness has not been tested using RCTs: penicillin in the treatment of pneumonia, aspirin for mild headache, diuretics for heart failure, appendectomy for acute appendicitis and cholecystectomy for gallstone disease (Worrall 2007a: 986); automatic external defibrillation to start a stopped heart, tracheostomy to open a blocked air passage, the Heimlich maneuver to dislodge an obstruction in the breathing passages, rabies vaccines and epinephrine in the treatment of anaphylactic shock (Howick 2011b, 40).