Apparent efficacy

Turner, Erick H., Annette M. Matthews, Eftihia Linardatos, Robert A. Tell and Robert Rosenthal, Selective Publication of Antidepressant Trials and Its Influence on Apparent Efficacy , New England Journal of Medicine 358 (2008) 252-60... 

Even if the high background of failure and the variable detection methods are accounted for, a number of factors other than resistance can alter the apparent efficacy of the drug. Firstly,... 

Despite their apparent efficacy, the usefulness of sodium chloride solutions in the treatment of edematous corneas with a traumatized epithelium appears to be limited. The intact corneal epithelium exhibits limited permeability to inorganic ions. In the absence of an intact epithelium the cornea imbibes salt solutions, which reduces the osmotic effect. In the management of corneal edema associated with traumatized epithelium, hypertonic saline solutions may be of limited value due to their increased ability to penetrate the epithelial barrier. 

The major therapeutic use of clonidine (Catapres, others) is in the treatment of hypertension. Clonidine also has apparent efficacy in the off-label treatment of a range of other disorders. Stimulation of ot2-receptors in the G1 tract may increase absorption of sodium chloride and fluid and inhibit secretion of bicarbonate. This may explain why clonidine has been found to be useful in reducing diarrhea in some diabetic patients with autonomic neuropathy. Clonidine also is useful in treating and preparing addicted subjects for withdrawal from narcotics, alcohol, and tobacco. It may help ameliorate some of the adverse sympathetic nervous activity associated with withdrawal from these agents, as well as decrease craving for the... 

Several controlled studies appear to support the use of certain herbal preparations in rational detoxification treatment programs. Exhibit 3 displays findings of selected studies on natural products with apparent efficacy in treating syndromes of substance abuse, withdrawal or addiction. 

Potentiation, the increase in effect produced by a molecule or procedure in a pharmacological preparation. This can be expressed as an apparent increase in efficacy (i.e., maximal response), potency, both. 

The drug has a broad dose range but efficacy in most instances may not be apparent until doses of 400 mg have been reached. An unusually large number of participants drop out because of lack of drug efficacy in some of the major trials (Arvanitis and Miller, 1997). 

The efficacy of the estimation decreases going down this sequence and this is where (but not only where) the weakness of this approach is apparent. 

Although one cannot readily identify any comprehensive, official pronouncement on the topic of development bioequivalency, it is apparent that in many cases FDA officials have adopted a pragmatic and common-sense approach to problems of this type. Obviously, in development bioequivalency our fundamental objective should be, for example, to build an appropriate bridge between F3 and F3 and F2 and F3 such that it is legitimate to use data obtained in clinical trials with F3 and F2 to support a conclusion of safety and efficacy for F3. Depending on how substantial the differences are between Fi and F3 and F2 and F3, the required bridge can be very simple or possibly more elaborate. 

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