The unpleasant taste may prevent the normal population from using diluted bleach as a mouthwash. A recent pilot study, which has resulted already in two papers (since pooled microbiological samples had been taken, one might expect at least another paper) in the once prestigious Journal of Periodontal Research, might leave scientists even more skeptical. The published RCT does not mention the CONSORT statement. Apparently, no sample size was calculated. Randomization took place and 15 test patients with untreated periodontitis were asked to rinse twice per week with 0.25% sodium hypochlorite while 15 patients were supposed to rinse twice per week with water [sic] for 3 months. At baseline and after 2 weeks, patients received oral hygiene instructions, and pockets were irrigated with either 0.25% sodium hypochlorite or, well, water. The test solution was prepared by the patients, one teaspoonful Chlorox (6% sodium hypochlorite) on one-half glass of water (5 mL on 120 mL).
It is very much concerning that just 12 out of 30 patients (40%) completed the 3-month trial. While awful taste of Chlorox was actually mentioned by two patients who, for that, missed couple of rinses, according to Galvan et al. concerns of delay of proper periodontal treatment and transportation issues were the main reasons for drop outs.
But what is even more disturbing is how the authors analyzed their data. Although Galvan et al. (2014) claim that the subject was the unit for all statistical analyses, Gonzales et al., in an additional analysis of just 7 test and 5 control subjects who completed the 3-month trial write,
“The individual pockets were treated as independent statistical units, based on nonspecific and wide-ranging antimicrobial action of sodium hypochlorite and the observation that pockets with a large range of depths responded positively to the bleach treatment and that residual bleeding on probing sites showed no tendency to cluster in particular patients or around specific teeth.” (Emphasis added.)
Most of spurious evidence of the 1970s and 1980s in periodontics stems from that misconception, be it clinical responses when pockets with different depths were considered independent in a limited number of patients, or observations made in microbiological samples from numerous sites in certain patients. At least since Larry L. Laster’s paper of 1985, periodontists must be aware of inflated p-values and spurious conclusions.
The picture below displays results as a figure rather than authors’ representation in a table with its numerous hypotheses tested without proper adjustment. What actually happened was that, in the test group, the number of 1-3 mm deep sites increased while bleeding tendency in these sites decreased. In control patients, a few moderately deep sites (4-6 mm) became shallow.
But the paper by Gonzales et al. is more about “progression” of periodontal disease (after just 3 months!), defined as pocket depth increase by 2 mm or more, and its relationship to repeat bleeding on probing. So, in addition numerous hypotheses were tested as to “progression” was more likely if bleeding upon probing was observed at baseline and after 3 months and that this was different in the 7 patients who rinsed with sodium hypochlorite as compared to the 5 patients rinsing with water. Further analyses considered “stable” sites (pocket depths changes between -1 and +1 mm) and “improving” sites (pocket depth reduction of 2 mm or more).
Ignoring that observations made in a certain patient are never independent (in sharp contrast to claims by the authors) must not be regarded good practice. Instead, one might set up a multivariate multilevel model with m=3 outcomes pocket depth “increase” of 2 mm or more, “decrease” of 2 mm or more, and rather “stable” pocket depths (between -1 and +1 mm change), and subject as higher level and site as lower level,
where an additional level below the original level 1 units (sites) is created to define the multivariate structure (Rasbash et al. 2015). Covariates h may then comprise different bleeding on probing patterns (0,0; 0,1; 1,0; 1,1) as well as possible subject and tooth variables. Assumptions for subject residuals uj for all three outcomes include Normal distributions with mean 0 and covariance matrix Omega.
Two further comments. First, progression of periodontal disease manifests itself by attachment loss, not pocket depth increase, and must be considered unlikely to occur within 3 months in 12 patients. It is not clear why authors did not measure attachment loss.
And then, many “progressing sites” (as well as those “improving”) may be due to unknown measurement error. Authors claim that probing force was “about 0.75 N” but no information is given as to how that had been accomplished. That, in the presence of measurement error, deeper sites become more shallow after some time and more shallow sites likely “progress” is due to regression to the mean, a statistical artifact. No word about measurement error in the paper by Gonzales et al.
Authors’ conclusions as regards the strong reduction of bleeding tendency due to twice weekly rinsing with diluted home bleach and, consequently, stop of progression of periodontitis, may in fact be spurious and unjustified. The “pilot study” has not been carefully planned and conducted since 60% participants withdrew after just two weeks. The statistical analysis is faulty and a proper multilevel analysis might not be able to yield a significant result due to the very small sample size.
1 February 2015 @ 10:49 am.
Last modified February 1, 2015.