Читать книгу Cobert's Manual Of Drug Safety And Pharmacovigilance (Third Edition) - William Gregory - Страница 59

This is the type of experiment that most people are familiar with. It is an experimental study, not an observational study, because a protocol, used by the investigators, determines who receives what drug treatment. The protocol may differ from the standard practice of medicine. In an observational study, one merely observes and records what happens in the normal course of medical practice and treatment. An observational study may have a protocol, but it does not dictate which treatment a subject will receive, which is left up to the treating physician.

An RCT is prospective in time. It involves two or more groups of subjects who have a disease (or are at risk of a disease) and they receive different treatments. For example, one group may get drug A and the other group may get drug B or placebo. It may be single blinded (the subject does not know what the treatment is) or double blinded (neither the subject nor the investigator knows what the treatment is). The individuals participating may also be randomized between the treatment groups to minimize known and unknown biases (factors other than the drugs tested that may alter or explain the drug effects). These studies are often complex to implement and resource-intensive. They represent the gold standard of clinical research: the double-blind RCT. These studies are usually done during phases I, II, and III of drug development, and for many reasons (ethical, availability of subjects, etc.), may not be feasible after the drug is marketed. The results are usually clear and easily understandable with the calculation of a risk difference between groups. For example, the group receiving drug A had a 4.1% incidence of AEs and the placebo group a 2% incidence of AEs, a difference of 2.1%. These trials, especially before approval for marketing, are usually prepared primarily to examine drug efficacy. The subject numbers and design are done to maximize the likelihood of finding a meaningful clinical and statistical result with the primary efficacy endpoints. The RCTs are usually statistically “powered” to show this one way or another. Statistical power refers to the likelihood that the trial and statistical test will reject a false null hypothesis, or, to put it another way, power is the probability that one will observe a treatment effect in the trial population when such effect would really occur.

The safety data from the trials are rarely sufficient to draw conclusions because rare adverse drug reaction (ADR) will not be observed with only a few hundred to several thousand subjects studied. The studies are not powered to pick up safety information and one might falsely conclude that a drug is “safe” or, more precisely, that doses do not differ from the comparator drug in terms of safety. Thus, the safety information is just presented as tables or listings without statistical tests. This is known as “descriptive statistics”.