Natural History RCTs Some Considerations

Often forgotten is the fact that even multiple independent observational studies do not allow an inference of causality, a goal that requires properly conducted RCTs. It is only in relation to concurrent controls that the value of a treatment can be assessed with certainty. This point was exemplified by the recent study of estrogen replacement therapy that failed to demonstrate the expected reduction of cardiovascular risk in postmenopausal women with prior heart disease (34). 

Frequently, RCTs are triple-blind, which means that neither the investigators, patients, nor sponsor has access to study results until the database is completed and locked. Oversight of the natural history RCT 

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