Something Old, Something New

The next issue of The Medical Letter (March 31, 2014) includes 2 articles on new formulations of old drugs and one article on an old drug approved for a new indication. New drugs have to demonstrate efficacy and safety to be approved by the FDA, but there is no requirement in the law that they demonstrate an advantage over drugs that are already available, and most of the clinical trials on which FDA approval is based are comparisons with placebo, and not with other active drugs.

So we will review a tumor necrosis factor (TNF) inhibitor that was already approved for treatment of rheumatoid arthritis and now is also approved for ulcerative colitis. It will be the third TNF inhibitor to be approved for its new indication, but the comparative trials that could help us choose among them are nowhere to be found. We do have placebo-controlled trials with results similar to those found earlier with the other 2 TNF inhibitors approved for this indication, but these trials are always somewhat different from each other in their selection of patients, their primary endpoints, and other conditions. The FDA would be among the first to remind us that 2 placebo-controlled trials do not add up to a well-controlled direct comparison.

The other 2 articles in our next issue are on novel formulations of old drugs that come with unique claims of superiority of one kind or another. A long-acting injection of testosterone should be more convenient than shorter-acting injections at shorter intervals, and for this product the FDA’s only demand for proof of efficacy was documentation of an increase in serum testosterone levels. Superiority over placebo in improving symptoms was not required. And the new single-use auto-injector formulation of methotrexate apparently was required only to demonstrate bioavailability similar to that achieved by other injectable formulations of methotrexate. Not unreasonable, really: we all know what methotrexate can do.

So how do we choose between the old and the new, with no comparative trials to guide us? What else should we consider? To answer those questions, I have to refer you to the next issue of The Medical Letter.

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