Famciclovir and Postherpetic Neuralgia

IN RESPONSE:

Bassett and colleagues' calculation of PHN incidence incorrectly assumes that the number of patients included in the “time to loss of PHN” analysis is the total number of patients with “long-term pain” in the entire study sample. In our original paper, the only patients included in the analysis were those who met the predefined study definition of PHN (that is, pain at or after healing). If the point at which lesions healed could not be determined, that patient could not be included in the analysis.

To assess pain prevalence over time in the entire intention-to-treat sample, one must examine the Kaplan-Meier estimates of patients with pain at monthly intervals (Table), as was done in a recently published reanalysis of this trial (1). The proportion of famciclovir recipients with pain does not exceed that of the placebo recipients at any time. Assessment of the relative risk that patients will have pain at monthly intervals after enrollment (placebo compared with famciclovir) also indicates that famciclovir-treated patients have significantly reduced risk for pain 3 to 6 months after rash onset (Table).

Dworkin and colleagues (2) further examined the duration of PHN using the alternative definitions of pain persisting for more than 30 days and more than 3 months after study enrollment. The results support our original PHN analysis and show that famciclovir treatment of acute herpes zoster significantly reduces the duration of PHN. Clearly, famciclovir does not cause PHN.

Bassett and colleagues state that the intent of their letter was to question whether the trial evidence was sufficient to support use of this drug. Famciclovir is approved for the treatment of herpes zoster in more than 70 countries worldwide. When reviewing a marketing application for an investigational drug, regulatory authorities have access to the complete data sets and often perform their own analyses. For example, the analysis performed by the Food and Drug Administration (FDA) using the original data sets supports the conclusion of our original publication—that famciclovir significantly reduces the duration of PHN. The FDA also concluded that the incidence of PHN (defined as pain after rash healing) did not significantly differ between treatment groups (2).

In conclusion, a detailed critical appraisal of a trial can be performed only when the analyst has access to the full data set. Because Bassett and colleagues' analyses were restricted to the information presented in our paper, the authors have misinterpreted the information provided and arrived at an invalid conclusion.

• Copyright ©2004 by the American College of Physicians