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.
After my recent comment on the concerted action of 19 eminent and self-proclaimed eminent periodontal scientists spearheaded by Drs. Borgnakke and Chapple (2014) aiming at smashing findings of a large multicenter randomized controlled trial by Engebretson et al. 2013 on HbA1c levels in type 2 diabetics with moderate or severe periodontitis, I had honestly decided not to report any more on the issue unless an updated systematic review by the Cochrane Collaboration was published. A reader of my blog had contacted CC’s Dr. Terry Simpson who promised that, due to “logistical problem[s] including difficulties with authors not supplying vital information [sic!],” they would likely be able to publish it around the turn of the year.
Now, the final paper was published yesterday in the Journal of Evidence-Based Dental Practice with a few editorial amendments. Borgnakke’s, well, rant is remarkable since it assembles (as reviewers who are also listed as authors) in essence all editors and many members of the editorial boards of our core journals in periodontology and implant dentistry as well as the editor of Journal of Dental Research. I had reported on the history of the paper here and had noted that, after a first version had been withdrawn by the authors earlier this year, Panos N. Papapanou was no longer listed as reviewer in the version which went online on 13 August 2014. Instead, Fusanori Nishimora (an editorial board member of Journal of Periodontal Research who is involved in the so-called Hiroshima Study, see below) had joined the group. While the online early version of Borgnakke’s paper had got the title “The randomized controlled trial (RCT) published by the Journal of the American Medical Association (JAMA) on the impact of periodontal therapy on glycated hemoglobin (HbA1c) has fundamental flaws,” a slightly moderated version is now provided: “The Multi-Center Randomized Controlled Trial (RCT) Published by the Journal of the American Medical Association (JAMA) on the Effect (sic!) of Periodontal Therapy on Glycated Hemoglobin (HbA1c) Has Fundamental Problems (sic!).”
In a recent post, I have very briefly tried to add the findings by Engebretson et al. (December 2013) on effects of non-surgical periodontal therapy on HbA1c levels in diabetics with periodontitis to a meta-analysis of Engebretson and Kocher (April 2013) who had identified 9 small-scale single-center studies. In that meta-analysis, a mean reduction of HbA1c of 0.36% was calculated. Low enough but significant. If the results of the large multicenter study by Engebretson et al. (2013) were added, a random effects model revealed still a tiny but significant reduction of HbA1c of -0.28%, 95% confidence interval: -0.45; -0.10.