In our article we addressed 10 issues associated with the clinical application of Periostat (CollaGenex). Our article mainly focused on the data from the phase 3 clinical trial1 and interpreted the scientific findings with regard to their clinical relevance. In addition, general issues related to the application of this therapy were discussed.
We do not agree that our article was inaccurate. The phase 3 trial indicated that, when the efficacy of scaling and root planing was compared with scaling and root planing, or SRP, plus SDD, the results were statistically better with adjunctive subantimicrobial dose doxycycline, or SDD, with respect to reducing probing depths, gaining clinical attachment and reducing the incidence of disease progression.1
Furthermore, it was acknowledged that SDD has not been shown to alter the microflora or induce resistant strains of bacteria.1,2 This was all stated in the article, and the data were accurately cited.
We do not agree that our article was biased. On the contrary, a point/counterpoint format was selected to provide readers contrasting opinions concerning the utility of the drug. In the article, the data were interpreted to indicate that the routine use of SDD in the treatment of chronic periodontitis is not warranted. It also was suggested that the greatest use of SDD may be limited to patients who are highly susceptible to periodontitis, but this concept needs to be validated in other clinical trials.
The bottom line is that the scientific merits of modulating the host response were acknowledged, and interpretations of the data with regard to the clinical application of SDD that do not agree with others’ perceptions are not necessarily biased, but rather reflect a different point of view. The article stands on its own merits, and clinicians can decide for themselves as to the appropriate application of Periostat.
The letter by Dr. Caton and colleagues addressed specific shortcomings of the article and correctly indicated that the serum level of doxycycline was 0.6 to 0.8 micrograms per milliliter and that the article had erroneously stated that this was the level in the gingival crevicular fluid, or GCF. This was an unintentional error, and it does not invalidate the article that addressed the utility of 10 issues concerned with the clinical administration of Periostat.
It is agreed that the article by Sakellari and colleagues3 suggested that the GCF level of tetracyclines would probably be around 70 percent of the serum level, and that, depending on the assay used to monitor GCF, this amount may vary.3 However, there are other articles in the literature that indicated that the concentrations of tetracyclines in GCF were greater than the serum level.4–8
Concerning the citation of the article by Walker and colleagues,2 it is true that the intent of that study was to address the lack of the antimicrobial effect of SDD. However, the authors published their clinical results for 76 patients with regards to clinical parameters associated with microbial sample sites. They stated the following: "No statistically significant differences were detected between the SDD and placebo treatments in the [scaling and root planing] design for either AL (attachment loss) or PD (pocket depth) at any sample period (page 1468)."
Furthermore, the authors did not mention in the article that their analyses lacked statistical power. The results of this study were mentioned in one sentence in our article, and the data were not discussed with regard to their clinical application.
In closing, it needs to be emphasized that focusing on statistical significance avoids the real issue—clinical relevance. Clinicians need to draw conclusions with regard to the clinical meaning of the results (that is, relevant difference between therapies) that have been determined to be statistically significant.9
Too often the reverse has been true, and clinicians have been left to ponder if statistically significant findings are clinically relevant. Accordingly, our intent was to provide a balanced assessment so that clinicians unfamiliar with the data pertaining to the efficacy of Periostat had an opportunity to read more than one point of view regarding the clinical relevance of the scientific data.
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