Rosacea treatment studies scrutinized by reviewers

February 1, 2005

Leiden, The Netherlands — Cochrane reviewers evaluating published studies of interventions for rosacea concluded there is sufficient evidence demonstrating the efficacy and safety of topical metronidazole and azelaic acid cream used short-term. However, as another important outcome, their analyses also highlighted the need for better-quality studies evaluating treatments for rosacea.

Leiden, The Netherlands - Cochrane reviewers evaluating published studies of interventions for rosacea concluded there is sufficient evidence demonstrating the efficacy and safety of topical metronidazole and azelaic acid cream used short-term. However, as another important outcome, their analyses also highlighted the need for better-quality studies evaluating treatments for rosacea.

Esther van Zuuren, M.D., and her project collaborators sought references published until March 2002 in literature searches that encompassed the Skin Group Specialised Trials Register, the Cochrane Central Register of Controlled Trials, Medline, EMBASE, Biosis and the Science Citation. Fifty-five papers were identified as potentially relevant. However, based on a 15-item checklist for assessing methodological quality, 33 studies considered to be low quality were excluded from further evidence analyses.

"Even then, we found on closer examination that some of the 22 remaining intermediate and high-quality studies suffered from a variety of major flaws," says Dr. van Zuuren, dermatologist, Leiden University Medical Center, The Netherlands, and a clinical assessor, Medicine Evaluation Board.

Aside from finding there was evidence for the efficacy of topical metronidazole and azelaic acid, reviewers concluded there was some evidence indicating oral metronidazole and oral tetracycline are effective.

"However, the fact that we found no evidence to support the efficacy of the other interventions studied should not be interpreted to mean they have no effect," Dr. van Zuuren notes.

Patient perceptions In analyzing the literature on rosacea treatments, the reviewers selected patient-assessed endpoints, i.e., quality of life and self-rated changes in rosacea severity, as the primary outcome measures. Physician ratings, i.e., severity, global improvement, lesion counts, time to improvement, length of remission, and adverse events, comprised the secondary outcome measures.

Upon examining the publications, however, reviewers found that none of the 22 intermediate and high-quality studies assessed quality-of-life changes, while few sought patient opinions of the therapeutic effect.

"Quality-of-life assessment is an important endpoint for rosacea clinical trials because rosacea is a chronic disease associated with significant physical and psychological distress. Failure to assess how a treatment affects the patient's functioning and emotional well-being is an important omission in these studies," says Dr. van Zuuren.

Flaws and omissions The Cochrane reviewers also identified a number of serious flaws in study reporting. For example, in some papers it was unclear how many patients were included, how many dropped out, or what were the baseline demographics of the populations. Randomization procedures were sometimes not described or were unclear, and some results from analyses of continuous measurements did not include standard deviations.

"Without an explanation of the randomization procedure used in a blinded, controlled study, it is impossible to know if treatment assignment was truly random and unknown to the investigators. In addition, failure to report standard deviation or standard error values for continuous measurements makes the data essentially unusable because the variability of the mean is unknown. The distribution of results of two treatments can be very different and yet the mean values may be the same," Dr. Van Zuuren explains.

Other drawbacks of most of the reviewed studies included failure to report times to onset of improvement or duration of remission. In addition, there was an absence of studies investigating the effects of dietary measures or sun protection.

The published literature on rosacea treatments is also characterized by a paucity of studies investigating treatment of ocular rosacea. Among the 22 studies, only two addressed ocular involvement.

"Ocular disease is common - affecting up to 60 percent of patients with rosacea - and it is a cause of significant patient distress. Yet, the literature on this topic is very deficient," Dr. van Zuuren says.

The reviewers also found there were no randomized, controlled trials evaluating other treatments commonly used for rosacea, including doxycycline, minocycline, isotretinoin, laser therapy, erythromycin, dapsone and topical tretinoin.