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Copyright © Steffen Mickenautsch and Veerasamy Yengopal
ISBN 978-0-620-68083-7
(All studies reprinted in this book were originally published in open access journals and are reproduced
under the copyright held by the authors as well as in terms of the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work
is properly cited.)
SYSTEM Initiative
Department of Community Dentistry,
Faculty of Health Sciences,
University of the Witwatersrand
7 York Rd., Parktown/Johannesburg
2193, South Africa
2 Glass-ionomers, The SYSTEM Initiative
CONTENTS
Glass-ionomers .................................................................................................................1
The SYSTEM Initiative ...................................................................................................2
Glass-ionomers as tooth restorations
A critique of the laboratory evidence
Executive summary: Laboratory trial results concerning high-viscosity glass-ionomer
versus amalgam tooth restorations not suitable for clinical guidance .......................................... 7
Do laboratory results concerning high-viscosity glass-ionomers versus amalgam for tooth
restorations indicate similar effect direction and magnitude than that of controlled
clinical trials? - A meta-epidemiological study ............................................................................. 9
A critique of the evidence from uncontrolled clinical trials
Executive summary: Common longitudinal studies are unsuitable to guide
clinical restorative dentistry ........................................................................................................ 31
How should competing clinical interventions be compared in dentistry? A simulation-
based investigation ...................................................................................................................... 33
Executive summary: Uncontrolled clinical longitudinal studies provide invalid evidence
concerning claims that high-viscosity glass-ionomers are inferior to silver amalgam ............... 43
Direct contra naïve-indirect comparison of clinical failure rates between high-viscosity
GIC and conventional amalgam restorations. An empirical study .............................................45
Evidence from controlled clinical trials
Executive summary: No evidence that high-viscosity glass-ionomers are inferior to
current gold standard in restorative dentistry .............................................................................. 63
Failure rate of atraumatic restorative treatment using high-viscosity glass-ionomer
cement compared to that of conventional amalgam restorative treatment in primary and
permanent teeth: a systematic review update - III ...................................................................... 65
Evidence synthesis
Are high-viscosity glass-ionomer cements inferior to silver amalgam as restorative
materials for permanent posterior teeth? A Bayesian analysis ................................................ 125
Glass-ionomers as ssure sealants
Retention rate – an invalid predictor for dental caries
Executive summary: New evidence questions ruling quality criterion for pit and
ssure sealants .......................................................................................................................... 139
Retention loss of resin based ssure sealants - a valid predictor for clinical outcome? ........... 141
Retention rate – an invalid surrogate for dental caries
Executive summary: Systematic review result dismisses ssure sealant retention
as valid measure for sealant efcacy ........................................................................................ 155
Validity of sealant retention as surrogate for caries prevention – a systematic review ............ 157
Glass-ionomers as ssure sealants – systematic review evidence
Executive summary: New evidence shows no scientic difference between ruling
ssure sealant options and alternative materials ....................................................................... 175
Caries-preventive effect of glass ionomer and resin-based ssure sealants on permanent
teeth: An update of systematic review evidence ....................................................................... 177
The modied Ottawa method to establish the update need of a systematic review:
glass-ionomer versus resin sealants for caries prevention ........................................................ 203
Glass-ionomers
Glass-ionomers are traditionally considered as unsuitable for placing direct permanent restorations in
posterior teeth regardless the cavity class due to inferior study results in comparison to the current gold
standard (conventional tooth restoration placed with silver amalgam).
In addition, glass-ionomers are traditionally also considered as unsuitable as ssure sealant for dental caries
prevention, due to inferior retention rates in comparison to the current gold standard (resin based sealants).
This book presents new research based on systematic reviews and meta-epidemiological studies conducted
by the SYSTEM Initiative. While these results remain subject to corroboration by future studies they
currently suggest:
Glass-ionomers 1
Concerning tooth restorations:
i. Statements based on laboratory/in-vitro results regarding the clinical inferiority
of high-viscosity glass-ionomers in comparison to the current gold standard
(amalgam); are generally misleading and not t for clinical guidance.
ii. Statements concerning glass-ionomer inferiority to the gold standard are based on
wrong statistical comparison methods;
iii. The currently available clinical data provides no evidence that the success of direct
posterior tooth restorations, placed with high-viscosity glass-ionomers is inferior
to that of the current gold standard;
Concerning pit and ssure sealants:
iv. The currently available clinical data provides no evidence that the caries-
preventive effect of glass-ionomer based pit and ssure sealants is inferior to that
of the current gold standard;
v. Statements concerning glass-ionomer inferiority to the gold standard are based on
a clinically invalid criterion (material retention).
2 Glass-ionomers, The SYSTEM Initiative
best source of evidence to guide clinical decisions
and healthcare policy, and they receive twice
as many citations as non-systematic reviews in
peer-reviewed journals. Furthermore, systematic
reviews are increasingly utilized in appraising
the evidence regarding the cost-effectiveness of
interventions, the costs of guideline dissemination
and implementation or evidence from qualitative
studies.
For these reasons SYSTEM has adopted the use
of systematic reviews in order to achieve its stated
aim.
The work of SYSTEM is focused on conducting
systematic reviews to interrelated aspects per
clinical topic. SYSTEM champions quantitative
above qualitative synthesis as it provides
opportunities for detecting statistically signicant
treatment effects and improves precision of effect
estimation by quantifying their outcomes. Thus
quantitative collation of clinical information from
separate trials (with or without meta-analysis)
covering a particular treatment approach and
comparison of materials used provides a more
objective assessment of the currently available
evidence.
There is still a general lack of randomised control
trials (RCT) in dentistry (as compared to medical
topics) and therefore SYSTEM has departed from
the common approach of strictly considering RCT’s
for review, only. In this way lack of accepted trials
for review and thus lack of information concerning
the current status quo of clinical is avoided.
Instead, SYSTEM has adopted a 2-way approach
regarding the precision and internal validity of
available clinical evidence from controlled trials:
The SYSTEM Initiative
SYSTEM (Systematic Review initiative for Evidence-based Minimum Intervention in Dentistry) is an
initiative that aims to establish an evidence-based body of clinical knowledge in Minimum Intervention
(MI) dentistry. SYSTEM is recognized as a Research Programme by the Faculty Research Committee
(FRC) of the Faculty of Health Science, University of the Witwatersrand. Its objectives are:
• To develop the basis for evidence-based teaching concerning MI related topics;
• To generate evidence-based practice-guidelines for clinical service delivery;
• To provide recommendations for further research.
Minimum Intervention (MI) is a philosophy of
health care consisting of: Disease risk assessment,
Earliest disease detection and Minimally-invasive
treatment.
MI is valid for any type of oral disease and
incorporates aspects of prevention and appropriate
technologies. MI is patient centred and through its
minimally-invasive focus, more patient-friendly
than conventional oral health care. In addition,
MI focuses on disease causes and not on its mere
symptoms.
Despite these benets MI faces, like any innovative
concept, the process of diffusion. During diffusion
of innovation, responses by potential adopters can
vary between adoption, non-adoption or rejection.
Responses are governed by insecurity concerning
uncertainties about the advantages of new ideas
as compared to those of current ones. Doubts
regarding claims of superiority are justied if
these are based on studies containing high degrees
of bias. Bias has been dened as any process at any
stage of inference tending to produce results that
differ systematically from true values.
The problem of bias in studies concerning MI
related topics is best addressed through the use
of systematic reviews. Systematic reviews in
healthcare have been described as providing
objective overviews of all the evidence currently
available on a particular topic of interest. Such
overviews cover clinical trials in order to establish
where effects of healthcare are consistent and where
they may vary. This is achieved through the use
of explicit, systematic methods aimed at limiting
bias and reducing the chance of effect. Systematic
reviews have been recommended as providing the
3
To identify and describe the status quo knowledge
of current clinical knowledge to a specic topic as
precise as possible (i.e. What is known?);
To judge this current body of knowledge on basis
of its internal validity (i.e. How certain is what
is known?) and on this basis to (i) derive from it
any existing limitations that are to be addressed
in future research and (ii) (hopefully) be able to
advise the clinician regarding the current status
quo.
In the judgement of internal validity of RCTs,
SYSTEM’s focus lies on the risk assessment of
selection- performance/detection- and attrition
bias. In regard to assessing selection- performance/
detection bias, SYSTEM has also departed from
the common practice and adopted stricter criteria.
These criteria do include the common focus on
adequacy of reported attempts for bias control but
also includes focus on adequacy of reported results
of attempts for bias control.
In regard to the assessment of attrition bias, the
SYSTEM approach follows the quantitative
method of sensitivity analysis by computation of
assumed worst-case scenarios / clinical outcomes
for study subject that have been lost to follow-up
in the reviewed trials. This method was developed
in collaboration with the help of Prof Paul Fatti
from the School of Statistics & Actuarial Science,
University of the Witwatersrand.
The above stated methods are novel to common
systematic review methodology and have been
applied successfully in SYSTEM’s systematic
review articles that were accepted in international
peer-reviewed dental journals. Besides the
adoption of these novelties, SYSTEM’s
methodology is based on common consensus
for systematic reviews, i.e. as represented by the
Cochrane collaboration and its reporting follows
recommendations of the PRISMA statement.
The SYSTEM Initiative is headed by Prof Dr Steffen Mickenautsch (BDS
Leipzig/Germany; PhD Nijmegen/The Netherlands) and located at the
Department of Community Dentistry, School of Oral Health Science / Faculty
of Health Sciences, University of the Witwatersrand (7 York Rd, Parktown
– Johannesburg, South Africa, Tel +27 11 717 2594 / Fax +27 11 717 2625 /
email: neem@global.co.za / http://www.system-initiative.info/ ).
The SYSTEMS Initiative
4 Glass-ionomers, The SYSTEM Initiative
Glass-ionomers as tooth restorations: A critique of the laboratory evidence 5
Glass-ionomers as tooth restorations
A critique of the laboratory evidence
6 Glass-ionomers, The SYSTEM Initiative
Glass-ionomers as tooth restorations: A critique of the laboratory evidence 7
their joint effect magnitudes and effect direction
statistically compared. While the laboratory trials
indicated inferiority of HVGIC to amalgam, no
signicant differences between both types of tooth
restorations using either material were found in
clinical trials.
For example, the in-vitro measured lower physical
strength of HVGIC in comparison to that of
amalgam might not translated into any clinically
higher fracture rate, because placed glass-
ionomer restorations are generally smaller than
amalgam llings, adhere to the tooth structure
on basis of ion exchange between carboxylate
and phosphate ions and thus do not require the
preparation of macroretention areas in tooth
cavities, like amalgam. Furthermore, HVGIC
placed in tooth cavities may abrade out of contact
due to its potentially lower wear resistance. For
these reasons, HVGIC restoration may not be
exposed to the same extent of daily masticatoric
forces in the oral cavity than amalgam restorations
are. Therefore, while in the laboratory measured
material properties such as compressive strength,
fracture toughness or microleakage of HVGIC
may indeed be inferior to that of silver amalgam,
these may not be sufciently strong enough to
translate into clinically meaningful differences,
due to other inuencing factors that are not present
during laboratory trials.
The established evidence shows that laboratory
results concerning HVGIC versus amalgam for
tooth restorations have no similar effect direction
and magnitude than that of controlled clinical
trials. The reasons remain unclear but may be
due to multifactor inuences and confounding,
particularly due to the lack of clinical factors that
are absent in laboratory trials.
Laboratory Trial results concerning high-viscosity
glass-ionomer versus amalgam tooth restorations
not suitable for clinical guidance
Executive Summary
Results from laboratory studies comparing high-
viscosity glass-ionomer cement (HVGIC) with
amalgam for tooth restorations do not share the
same effect direction and magnitude of results
from controlled clinical trials. Laboratory trial
results may thus not correctly reect clinical
reality and should not be used for clinical guidance
concerning HVGICs in daily dental practice.
A large percentage of evidence concerning dental
interventions is based on laboratory research. The
apparent wealth of laboratory/in-vitro evidence is
sometimes used as basis for clinical inference and
recommendations for daily dental practice.
Traditionally, glass ionomer cements are considered
as unsuitable for clinical use as a permanent lling
material in the posterior dentition due to in-vitro
measured poor mechanical properties. Specically,
in-vitro measured low material strength and wear
resistance have been stated as reasons why glass-
ionomers cannot rival amalgam as truly universal
posterior restorative material.
The SYSTEM Initiative of the Faculty of Health
Sciences, University of the Witwatersrand,
Johannesburg, conducted a systematic search of
the current dental literature for laboratory and
controlled clinical trials that directly compared
the efcacy of high-viscosity glass-ionomer
cement (HVGIC) with amalgam as the current
gold standard for placing tooth restorations. These
trials were identied through the search of main
international data sources, such as CENTRAL
accessed via the Cochrane Library; MEDLINE
accessed via PubMed; Biomed Central; Database
of Open Access Journals (DOAJ); IndMed;
OpenSIGLE and Google Scholar.
After literature search, the laboratory and clinical
results of the identied trials were analysed and
8 Glass-ionomers, The SYSTEM Initiative
Hence, while laboratory trial results may provide valuable explanations for
observed clinical phenomena and may serve during the hypothesis development
process, they appear not be suitable as basis for clinical inference and clinical
recommendations concerning HVGICs in daily dental practice.
The full published report of the ndings are available online for free download:
Mickenautsch S, Yengopal V (2015) Do Laboratory Results Concerning High-
Viscosity Glass-Ionomers versus Amalgam for Tooth Restorations Indicate
Similar Effect Direction and Magnitude than that of Controlled Clinical Trials?
- A Meta-Epidemiological Study. PLoS ONE 10(7): e0132246.
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0132246
Glass-ionomers as tooth restorations: A critique of the laboratory evidence 9
Do laboratory results concerning high-viscosity glass-ionomers
versus amalgam for tooth restorations indicate similar effect direction
and magnitude than that of controlled clinical trials?
A meta-epidemiological study
Steffen Mickenautsch1, Veerasamy Yengopal1
1 Systematic Review initiative for Evidence-based Minimum Intervention in Dentistry/
Department of Community Dentistry, Faculty of Health Sciences,
University of the Witwatersrand - Johannesburg, South Africa
*Corresponding author / email address: neem@global.co.za
Abstract
Background. A large percentage of evidence
concerning dental interventions is based on
laboratory research. The apparent wealth of
laboratory evidence is sometimes used as basis for
clinical inference and recommendations for daily
dental practice. In this study two null-hypotheses
are tested: whether trial results from laboratory and
controlled clinical trials concerning the comparison
of high-viscosity glass-ionomer cements (HVGIC)
to amalgam for restorations placed in permanent
posterior teeth have: (i) similar effect direction and
(ii) similar effect magnitude.
Methods. 7 electronic databases were searched,
as well as reference lists. Odds ratios (OR) and
Standardised Mean Differences (SMD) with
95% Condence intervals were computed for
extracted dichotomous and continuous data,
respectively. Pooled effect estimates for laboratory
and clinical data were computed to test for effect
direction. Odds ratios were converted into SMDs.
SMDs from laboratory and clinical data were
statistically compared to test for differences in
effect magnitude. The analysed results were
further investigated within the context of potential
inuencing or confounding factors using a
Directed acyclic graph. Results. Of the accepted
eight laboratory and nine clinical trials, 13 and
21 datasets could be extracted, respectively. The
pooled results of the laboratory datasets were
highly statistically signicant in favor of amalgam.
No statistically signicant differences, between
HVGICs and amalgam, were identied for clinical
data. For effect magnitude, statistically signicant
differences between clinical and laboratory trial
results were found. Both null-hypotheses were
rejected.
Conclusion. Laboratory results concerning high-
viscosity glass-ionomers versus amalgam for tooth
restorations do not indicate similar effect direction
and magnitude than that of controlled clinical
trials. (Originally published as: Mickenautsch
S, Yengopal V (2015) Do Laboratory Results
Concerning High-Viscosity Glass-Ionomers
versus Amalgam for Tooth Restorations Indicate
Similar Effect Direction and Magnitude than
that of Controlled Clinical Trials? - A Meta-
Epidemiological Study. PLoS ONE 10(7):
e0132246. )
Introduction
A large percentage of evidence concerning dental
interventions is based on laboratory research. A
simple PubMed search (27 August 2014) of the
dental literature published between 2009 - 2014,
using the broad MeSH terms “Dental Amalgam”
and “Glass Ionomer Cements” (S1 File) reveals a
2-3, as well as an over 7 times higher number of
listed citations of laboratory (including in-vitro and
animal based in-vivo) studies than of prospective
clinical studies with control groups (including
randomised controlled trials, non-randomised
controlled trials, split-mouth trials and prospective
2-arm observational studies), respectively.
The apparent wealth of laboratory evidence is
sometimes used as basis for clinical inference
and recommendations for daily dental practice.
10 Glass-ionomers, The SYSTEM Initiative
For example: In 2012, Ilie et al. recommended
that selection of a suitable restorative material
for clinical use in especially stress-bearing
areas should been done with respect to in-vitro
measured material properties, particularly in
relation to its fracture toughness (KIC) [1]. Vichi et
al. (2013) presumed that low in-vitro microleakage
measurements for restorative materials translate
into an adequate marginal seal when such materials
are used for placing tooth restorations in the clinic
[2], and based on laboratory shear bond strength
(SBS) measurements, Ilie et al. (2014) suggested
possible clinical advantages of using owable
bulk-ll resin composites for restoring deep,
narrow cavities, with difcult access angles, and
high-viscosity compounds for easier and faster
restoration of larger tooth cavities [3].
In contrast, studies comparing the ndings of
both laboratory and clinical trials found only little
correlation between the two. Papagiannoulis et
al. (2002) established a lack of any correlation
between in-vivo and in-vitro models in terms of
articial caries experiments and suggested that
these may have only negligible clinical relevance
in predicting the in-vivo effect [4]. Purk et al.
(2004) established that the bonding of resin-
based composite to teeth under in-vivo conditions
yielded much weaker microtensile bond strengths
than did bonding under in-vitro conditions and
that bonding to dentin at the gingival wall under
in-vivo conditions is weaker than that reported in-
vitro studies [5]. In his review of dental literature,
Heintze (2007) established that the quantitative
marginal analysis of Class V llings in the
laboratory was unable to predict the performance
of the same materials in-vivo [6] and Heintze
and Cavalleri (2010) found that retention loss of
Class V tooth restorations in nonretentive cavities
could not be simulated in the laboratory, even after
prolonged water storage and mechanical loading
and thus could not reect the clinical ndings
[7]. In contrast, van Meerbeek et al. (2010) found
some indications for correlation of laboratory bond
strength with clinical retention rates of Class-V
restorations [8]. However, the predictive strength
of the laboratory ndings was only expressed as
linear correlation and not in line with full Prentice
requirements [9], and appeared to be weak and of
borderline signicance (r = 0.5811, p = 0.0475),
only. In addition, Heintze and Zimmerli (2011)
stated that in-vitro dye penetration measurements
have no clinical relevance for the clinical
performance of restorative materials, that marginal
gap analysis in the laboratory is clinically relevant
only to a limited extent and that bond strength tests
are useful as screening tests, only [10].
Traditionally, glass ionomer cements are considered
as unsuitable for clinical use as a permanent lling
material in the posterior dentition due to in-vitro
measured poor mechanical properties [1,11].
Specically, in-vitro measured low material
strength and wear resistance have been stated as
reasons why glass-ionomers cannot rival amalgam
as truly universal posterior restorative material
[12].
However, based on the demonstrated general lack
of any observed correlations between laboratory
and clinical evidence, particularly related to tooth
restorations [6,7,10] the in-vitro measured poor
mechanical properties of glass ionomers, including
high-viscosity glass-ionomers (HVGICs), may not
translate into poor clinical results.
Against this general background, the aim of this
meta-epidemiological study was to test two null-
hypotheses:
H01: The results from laboratory trials
concerning HVGICs versus amalgam indicate
similar effect direction as results from controlled
clinical trials concerning HVGICs versus
amalgam restorations placed in permanent
posterior teeth.
H02: The results from laboratory trials concerning
HVGICs versus amalgam indicate similar effect
magnitude as results from controlled clinical
trials concerning HVGICs versus amalgam
restorations placed in permanent posterior teeth.
Methods
The protocol of this study has been published prior
to its start in an open access journal [13] and is freely
available online (http://www.jmid.org). Although
the methodology of this meta-epidemiological
Glass-ionomers as tooth restorations: A critique of the laboratory evidence 11
study shared many aspects of a systematic review,
its objective was methodological in nature.
Therefore, the study protocol was not eligible for
registration with the International Prospective
Register of Systematic Reviews (PROSPERO)
[14].
Systematic literature search
The following databases: CENTRAL accessed
via Cochrane Library; MEDLINE accessed via
PubMed; Biomed Central; Database of Open
Access Journals (DOAJ); IndMed; OpenSIGLE
and Google Scholar were searched by both authors,
independently using the search strategies for both
laboratory and clinical trials, presented in Table 1.
In addition to the search of databases, reference
lists of accepted trial reports and systematic
reviews, as well as narrative reviews, if found of
importance to the topic, were checked for further
suitable trials.
The identied citations were eligible for possible
inclusion if they followed the inclusion criteria:
(i) Articles published in English;
(ii) Full reports of prospective controlled clinical