Claims and denials of clinically relevant effects of, in particular, non-surgical periodontal treatment on markers of diabetic control have not only led to a surge of new randomized clinical trials and systematic reviews thereof. If anybody had hope that the current frenzy has found a happy end with the updated and very comprehensive Cochrane review by Simpson et al. (2015) (s)he has been mistaken. In the June issue of the Australian Dental Journal, Botero et al. (2016) report on an umbrella review in which they systematically reviewed all systematic reviews on the subject, be it with or without meta-analysis, published between 1995 and 2015. The paper has been accepted for publication on January 20, 2016. It has to be emphasized that using the term “umbrella review” is somewhat misleading. In a strict sense, an umbrella review assembles together several systematic reviews on the same condition in the presence of many treatments or many important outcomes.
In a previous post, I have expressed considerable concern about an assumed advertorial in our leading periodontal journal, JCP. Quintessence Publishing was about to launch their fourth installment of “3D” animated, short (each 15-17 min) movies all called Cell-to-Cell Communication, “Oral Health and General Health – The Links between Periodontitis, Atherosclerosis, and Diabetes.” Previous movies have been offered for purchase by QuintPub for a remarkable amount of around $100. Luckily, the new one can now be found on the EFP homepage and accessed by members and non-members for free.
Currently, teachers experience a general problem, a surge of published systematic reviews where slightly modified search criteria have led to slightly different bunch of papers with slightly different results of meta-analyses. Systematic reviews have once been welcomed as valuable tool to either end a story once and forever (if evidence for or against a certain treatment or association was overwhelming), or call for more conclusive randomized controlled trials (RCT) after still open questions had been identified. If, after any new RCT, editors of our professional journals would accept considering a new systematic review for publication, which basically ruminates already published RCT summaries but adds just another study without changing main conclusions, it will in fact become difficult to keep pace with what some call “emerging evidence”.
One main reason why evidence based medicine has to be taught to undergraduate students is to provide future health care workers with proper tools and train specific skills to conduct brief systematic reviews of identified randomized controlled trials themselves. Here on this blog, I had posted a couple of quick examples, see here, here and here.
In particular the latter of the above examples has dealt with the question whether the large multi-center trial by Engebretson et al. (2013), which had reported no effects of periodontal therapy on HbA1c levels in diabetics, would nullify the conclusion (that nonsurgical periodontal treatment may reduce HbA1c levels by about 0.4%) of previous meta-analyses of smaller and mainly single-center RCTs with similar settings.
Engebretson et al. (2013) had listed possible shortcomings of their study. However, that oral hygiene of study participants had not improved was considered by most of our professional leaders scandalous. Further issues for unprecedented criticism included “nearly normal” HbA1c levels at the outset and extreme obesity of participants. Engebretson’s unwelcome results had been reviled by an armada of 21 editors of our key journals, presidents of our main scientific societies, and further periodontal experts. Criticism had culminated in a very strange recommendation.
“Given the inconlusive nature of these data, we recommend that the existing body of evidence in which meta-analyses consistently conclude that successful periodontal therapy appears to improve glycemic control, should instruct us until results from future studies are reported. We urge all interested parties to refrain from using these study results as a basis for future scientific texts, new research projects, guidelines, policies, and advice regarding the incorporation of necessary periodontal treatment in diabetes management.” (My emphasis.)
In other words, forget about Engebretson et al. and continue quoting more favorable results from existing meta-analyses of RCTs on the effect of periodontal therapy on diabetes control. A quick analysis revealed that it won’t nullify a mean HbA1c reduction in diabetics by nonsurgical periodontal therapy, but that considerable heterogeneity was introduced by including Engebretson’s study which may in fact lower the grade of evidence. I had entered meta-data of Engebretson and Kocher 2013 in an amazing tool for meta-analysis and had added findings by Engebretson et al. (2013). That might have been premature, see below.
In an announcement for his talk about periodontal treatment effects on type 2 diabetes at Europerio 8 in London later this year, exasperated Professor Thomas Kocher of Greifswald University in Germany promises to “dissect” the large multicenter trial by Engebretson et al. (2013) who could not find an effect on glycated hemoglobin in type 2 diabtes mellitus. The study had been published in late 2013 in JAMA, not in New England (Journal of Medicine). The large multicenter trial had long been attacked for not yielding the desired results (“a publication which we were really waiting for”).
Kocher was asked to talk in London about “why all the other small studies showed an effect” and he wants to find out “the issues why we [?] couldn’t see anything in the Engebretson study”. Well, it was actually Wenche Borgnakke who had got 20 other “reviewers” aboard who had already dissected the study by Engebretson et al. and has called for censorship.
As noted by Engebretson and Kocher 2013 in one of the numerous previous systematic reviews of RCTs on the effect of nonsurgical periodontal therapy and reported in Table 1 of their article, problems with the design of these small-scale, mainly single-center studies, which included some trials with adjunctive antibiotics, were plentiful. Problems with low and high baseline HbA1c levels and with questionable periodontal outcomes had been reported as well. Engebretson and Kocher (2013) report possible publication bias which means nothing else that studies without an effect on HbA1c might have gone unpublished. Based on this particular and numerous other systematic reviews, the evidence that nonsurgical periodontal therapy in fact has a relevant beneficial effect on HbA1c levels in type 2 diabetics may actually be regarded moderate. The study by Engebretson et al. adds heterogeneity to any meta-analysis which may downgrade this evidence to low. That is what our thought leaders alerts. That’s why censorship.
The large multi-center intervention trial by Engebretson et al. (2013), who had reported lack of any effect of non-surgical periodontal therapy on HbA1c levels in type 2 diabetes mellitus patients after 3 and 6 months, has been harshly criticized because of very moderate clinical improvements as regards pocket depth reduction (from mean 3.26 mm at baseline) of 0.4 mm (95% CI 0.4; 0.5 mm) and reduction of bleeding on probing (from mean 62%) of 19% (95% CI 15.7; 22.4). What was even more concerning was that, 6 months after seemingly intense treatment (at least 160 minutes of scaling and root planing followed by oral hygiene instruction and, for two weeks, twice daily mouthwash with 0.12% clorhexidine digluconate; then, at both 3- and 6-month follow-up examinations, further oral hygiene instructions and scaling/root planing for another hour), bleeding on probing was still seen at an average of 40% sites while, on average, 70% tooth surfaces were still covered by plaque (from 86% at baseline).
These are undeniable problems of the study. Claims that periodontal treatment was insufficient and, as a consequence, periodontal infection still present in most patients after periodontal therapy, may in fact be justified. It is the sheer size of the attack which is so appalling. Each and every editor of our professional journals and numerous further pundits, altogether 21, had joined, well, the public execution of the study’s principle investigator. Because of unwelcome results of a study with the potential of ending a story, or illusion, once and forever. And, absolutely inappropriate attempts of intimidation of scientists when writing,
“Given the inconlusive nature of these data, we recommend that the existing body of evidence in which meta-analyses consistently conclude that successful periodontal therapy appears to improve glycemic control, should instruct us until results from future studies are reported. We urge all interested parties to refrain from using this study results as a basis for future scientific texts, new research projects, guidelines, policies, and advice regarding the incorporation of necessary periodontal treatment in diabetes management.” (Emphasis added.)
So, censorship. This is absolutely unscientific. Meta-analyses are always preliminary and must incorporate new results on a continuous basis.