Abstract
Clinically relevant complex systematic reviews follow the scientific process in the process of identifying, selecting, and evaluating the best available systematic reviews and meta-analyses on any given clinical question specifically in endodontics, and generally in dentistry, as a model of health care. Careful consideration must be given to the tools of quantification of the best evidence and to the process of updating the analysis of the concerted available evidence. The relevance of the research metasynthesis that characterizes clinically relevant complex systematic reviews is discussed in the context of the distinct modes of clinical decision-making in comparative effectiveness vs. evidence-based analysis.
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- 1.
Cf., Baruch Spinoza (1632–1677): a “thing” can be defined in se and per se – in se, meaning that its totality effectively defines what it is, and per se, indicating that it actually can define itself as the concept of itself. That is to say, the product of a research synthesis endeavor is, in its totality, a fundamental primary research product, and it so defines its own essence because it follows the scientific method, the body of scientific techniques we concur to utilize in the pursuit of investigating phenomena, acquiring and creating new knowledge, and of correcting and integrating previous knowledge, as originally crafted by Aristotle (384 A.C.–322 A.C.), and which is the foundation of modern science.
- 2.
Some years ago, I had a dialectical discussion on science and philosophy with a humanist, world-renown for his ground-breaking work in linguistics and literature of the middle ages. His assertion that “biochemistry does not exist as a science” was as grounded on his ignorance of the fundamentals of the science of biochemistry, as the assertion of many that “research synthesis is not a science” rests on their lack of awareness of the rich complexity of the science of research synthesis.
- 3.
This property is indeed not unlike what commonly occurs in the other health sciences: multiple reports by several groups of investigators may be discordant or concordant – hence the need for replicative studies, literature reviews, etc.
- 4.
The term “complex systematic review” to indicate a research meta-analysis paper (i.e., a synthesis of systematic reviews) might suggest that a “systematic review,” a research synthesis paper (i.e., a synthesis of primary research reports) is in some manner or another simple or simplistic, or at least not at all complex and complicated. This statement is misleading and far from the reality of things, and goes to reinforce the points about misconception, misinformation, misunderstanding, and frankly ignorance (cf., footnote 2) about the science of research synthesis and metasynthesis made above.
- 5.
Gestalt – from the German (Berlin School of Psychology, late nineteenth century), meaning the entirety of the essence or being of an entity’s complete form; e.g., the mind, viewed as holistic, parallel, and analog, with self-organizing tendencies.
- 6.
Sequential statistical hypothesis testing is not bound by a predetermined sample. Rather, data are evaluated as they are collected. Sampling is aborted if statistical significance is obtained, based on criteria established at the onset of the study. In other words, the end of a study may be attained at a much earlier stage, with a smaller sample size, and at a lesser overall cost than if the traditional power analysis has estimated the required sample size prior to the onset of the study.
- 7.
Luc de Clapiers Vauvenarques (1715–47) stated in Réflexions et Maximes that …il est plus aisé de dire des choses nouvelles que de concilier celles qui ont étés dites (it is easier to say new things than to reconcile those things that have been said). John William Strutt, 3rd Baron and Lord of Rayleigh (1842–1919), said “The work which deserves, but I am afraid does not always receive, the most credit is that in which discovery and explanation go hand in hand, in which not only are new facts presented, but their relation to old ones is pointed out.”
- 8.
One could conceive of the following: the (simple) design of research synthesis yields the (simple) systematic review by pooling and evaluating primary research (e.g., clinical trials); the (complex) research synthesis, which we have called research metasynthesis, yields the complex systematic review, also termed CRCSR, and results from the pooling and evaluating existing systematic reviews. Yet, a compounded or mixed-form research synthesis would yield a clinically relevant mixed systematic review (CRMSR) and pool and evaluate together both existing systematic reviews and primary research (e.g., clinical trials) that have not yet been incorporated in any existing systematic review. CRMSR promise to be the most arduous and challenging of the research synthesis designs because they will coalesce two fundamentally divergent research entities: primary research reports (e.g., clinical trials) and secondary research reports (i.e., systematic reviews). Study validity issues will be particularly difficult to untangle in CRMSR. Special care must be given not only to the sampling and the measurement processes but as well as to the data analysis component. Case in point, the meta-analysis of a CRMSR will involve a notably greater level of difficulty than even the Bayesian meta-analytical inference required for CRCSR.
- 9.
Vide infra, Part III, 1 and III, 2.
- 10.
Rather than inquisitive.
- 11.
Vide supra, Part I.
- 12.
The “bibliome” is the body of pertinent research literature available for any given systematic review [16].
- 13.
That is, and purely on statistical grounds, if, following acceptable sampling analysis and homogeneity analysis, the number of papers fed into a meta-analysis is less than, say, 2 or 3, one may wonder as to the validity of the generated forest plot.
- 14.
The process of random sampling can be expected to have exactly the same effects when one randomly samples literature in a research synthesis design, as when one obtains a random sample of subjects in an experimental design.
- 15.
Such selection barriers include language, search engine, and library availability, among others.
- 16.
That is, choosing and picking the scientific findings that we want to disseminate because they fit our preferred theory.
- 17.
Cf., Levins R, Lewotin R. The Dialectical Biologist. Harvard University Press, 1985.
- 18.
That is why, even at that very early stage, the National Institutes of Health refers to this research as “clinical research.”
- 19.
Cf., Cochran Q, and its transformation as the I2 test.
- 20.
Not all, it must be emphasized. There exists a school of thought that argues in favor of including all – bad and good – studies in a meta-analysis, akin perhaps to including all – good and bad – materials in the construction of a skyscraper. Should we be surprised if the foundations eventually give, and the edifice crumbles? Should we be surprised if a high proportion of meta-analyses conducted in this manner is likely to evince no statistical significance overall?
- 21.
In the case of repeated t test, this bias lends the analysis increasingly less powerful, by “chipping away” from the level of significance, α, as follows: p(Type I error) = 1 − (1 − α)c, thus when c = 1 (one comparison), then p = 1 − (1 − 0.05)1 = 1 − (0.95)1 = 0.05; but if we were to perform three “cumulative” t tests, then c = 3, and p = 1 − (0.95)3 = 0.14.
- 22.
An attempt toward quantifying clinical recommendations based on R-AMSTAR scores, and translating the outcome into a simple ranking system has been proposed by Kung et al. [16].
- 23.
As noted elsewhere, the research synthesis process for comparative effectiveness typically includes bibliomes composed of cluster randomized controlled trials (CRCT’s), whereas better informed patient-centered clinical decisions about comparative efficacy for evidence-based practice results from systematic reviews that arise from the research synthesis of bibliomes consisting of traditional RCT’s [36]
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Chiappelli, F., Ramchandani, M.H., Phi, L., Brant, X.M.C. (2012). Clinically Relevant Complex Systematic Reviews in Endodontics: Relevance to Comparative Effectiveness Research and Evidence-Based Clinical Decision-Making. In: Chiappelli, F. (eds) Comparative Effectiveness and Efficacy Research and Analysis for Practice (CEERAP). Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-23144-5_3
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