Evaluating the quality of active-control trials in periodontal research.

AIM: The increasing popularity of randomized-controlled trials (RCTs) has raised the issue of their quality. Frequently overlooked are the differences between superiority and equivalence trials. The purpose of this study was to apply specific methodological criteria to evaluate the quality of active-control trials using studies that compared guided tissue regeneration (GTR) with enamel matrix derivatives (EMD). MATERIALS AND METHODS: Seven RCTs were identified in the literature. Standard methodological criteria and seven additional criteria for trials using active-control groups were used to evaluate the quality of the seven RCTs. RESULTS: Two trials were considered as superiority trials. The remaining five provided no clear statement of their research aim. However, two claimed that EMD and GTR were equally effective, because their results failed to show a significant difference between EMD and GTR. Most trials did not meet the majority of the design criteria. CONCLUSIONS: The general lack of compliance with quality criteria might place doubt on the value of these trials and may render any conclusions questionable. It is therefore important to distinguish clearly between superiority trials and equivalence trials, and to incorporate appropriate additional criteria in the design of future RCTs with active-control groups.

The application of multilevel modeling in the analysis of longitudinal periodontal data--part I: absolute levels of disease.

BACKGROUND: Statistical analyses of periodontal data that average site measurements to subject mean values are unable to explore the site-specific nature of periodontal diseases. Multilevel modeling (MLM) overcomes this, taking hierarchical structure into account. MLM was used to investigate longitudinal relationships between the outcomes of lifetime cumulative attachment loss (LCAL) and probing depth (PD) in relation to potential risk factors for periodontal disease progression. METHODS: One hundred males (mean age 17 years) received a comprehensive periodontal examination at baseline and at 12 and 30 months. The resulting data were analyzed in two stages. In stage one (reported here), the absolute levels of disease were analyzed in relation to potential risk factors; in stage two (reported in a second paper), changes in disease patterns over time were analyzed in relation to the same risk factors. Each approach yielded substantially different insights. RESULTS: For absolute levels of disease, subject-level risk factors (covariates) had limited prediction for LCAL/PD throughout the 30-month observation period. Tooth position demonstrated a near linear relationship for both outcomes, with disease increasing from anterior to posterior teeth. Sites with subgingival calculus and bleeding on probing demonstrated more LCAL and PD, and supragingival calculus had an apparently protective effect. Covariates had more "explanatory power" for the variation in PD than for the variation in LCAL, suggesting that LCAL and PD might be generally associated with a different profile of covariates. CONCLUSION: This study provides, for a relatively young cohort, considerable insights into the factors associated with early-life periodontal disease and its progression at all levels of the natural hierarchy of sites within teeth within subjects.

The application of multilevel modeling in the analysis of longitudinal periodontal data--part II: changes in disease levels over time.

BACKGROUND: The aim of this study was to investigate the longitudinal relationships between the outcome measurements of changes in lifetime cumulative attachment loss (cLCAL) and changes in probing depth (cPD) in relation to potential risk factors or other risk markers for periodontal disease progression from a cohort of 100 young males. In order to account for the hierarchical data structure, and to explore explicitly the site, tooth, and subject levels simultaneously, multilevel modeling was undertaken. METHODS: The analyses were undertaken in two parts. Within a previous article, the absolute levels of disease were analyzed in relation to potential risk factors; within this article, changes in disease are analyzed in relation to these factors. Each analytical approach yielded substantively different insights. RESULTS: Subject-level risk factors had limited predictive value for cLCAL/cPD throughout the 30-month observation period. Tooth position demonstrated a near linear relationship for both outcomes, with disease increasing from anterior to posterior teeth. Supragingival plaque had no significant effect on cLCAL/cPD, while subgingival calculus and bleeding on probing were negatively associated with cLCAL/cPD. In contrast to the outcomes LCAL/PD, supragingival calculus had no significant protective effect on cLCAL/cPD. There was no significant influence of smoking in this cohort. CONCLUSIONS: This study provides, for a relatively young cohort, considerable insights into the factors associated with longitudinal patterns of early-life periodontal disease at all levels of the natural hierarchy of sites within teeth within subjects. Furthermore, it is demonstrated how multilevel modeling can provide considerable insight into some of the inconsistencies and controversies found in the previous periodontal literature.

Mathematical coupling can undermine the statistical assessment of clinical research: illustration from the treatment of guided tissue regeneration.

OBJECTIVES: Previous periodontal literature has shown that there is a strong relationship between treatment effects, such as guided tissue regeneration (GTR), and baseline disease severity. However, relating change to baseline values using correlation or regression is methodologically flawed due to mathematical coupling, where the statistical procedure of testing the null hypothesis-that the coefficient of correlation or slope of regression is equal to zero-becomes erroneous. The aim of this study is to investigate if baseline disease severity is genuinely associated with the treatment outcome of intrabony defects using GTR after adjustment for mathematical coupling. In particular, we seek to demonstrate the potential effect that mathematical coupling has in distorting the results from the statistical analyses of trials of dental treatment, using data from the periodontal literature on GTR. The erroneous results arising from the use of simple correlation and regression techniques to analyse this association will be demonstrated, also the methodological flaw where the statistical procedure tests the null hypothesis-that the coefficient of correlation or the slope of regression is equal to zero. METHODS: Three main periodontal journals were electronically and manually searched to extract the data for the clinical outcomes of pocket probing depth (PPD) and lifetime cumulative attachment loss (LCAL) in the studies using GTR. The relationship between clinical outcomes and baseline measurements were reanalysed using Oldham's method and the variance ratio test. RESULTS: The results of these analyses were compared with those from the papers where the authors used the standard approach of correlation or regression. This shows that mathematical coupling caused spurious correlations between baseline disease severity and treatment effect. Ten out of 12 studies for PPD and nine out of 14 for LCAL initially claimed a significant positive relationship; after using either of the more appropriate statistical methods of adjustment, only three correlations in each group of studies remained significant. CONCLUSIONS: Previous evidence suggesting an association between baseline disease severity and treatment effect for GTR is challenged and therefore needs to be critically reviewed. All future clinical research should avoid using mathematically coupled data in correlation or regression analysis. In seeking to examine the bivariate association between baseline and subsequent change, Oldham's method is recommended.