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Introduction The presence of secondary or recurrent caries is a common reason for replacing restorations and is often observed after bonding of brackets on the tooth surface during orthodontic treatment. An ideal dental material would have, as one of its properties, the ability to prevent demineralisation and/or promote remineralisation [Mjör and Toffenetti, 2000]. Stud-ies have shown that restoration replacement accounts for 50-70% of the dental care provided in some settings [Donly et al., 1999]. As ionic fluoride in the water supply [McDonagh et al., 2000] and in other vehicles, such as toothpaste [Twet-man et al., 2003], has been shown to reduce the incidence of caries at the population level, considerable attention has been focused on fluoride-containing restorative materials.

The earliest fluoride-releasing restorative material was silicate cement (now superseded). Anecdotal evidence of its

caries-preventive effect was related to the paucity of reports of secondary caries seen in association with silicate cement despite its high intra-oral solubility [Ewoldson and Herwig, 1998]. This observation led to the inclusion of fluoride into restorative materials such as amalgam and resin-based materials, although published evidence of an anti-caries effect was not observed [Wiegand et al., 2007].

Light-cured resin-modified glass-ionomer cements (RM-GIC) were developed as restorative materials, to address the short-comings of conventional glass-ionomer restorative materials (C-GICs) [Nagamine et al., 1997] which, owing to their ability to leach fluoride into the surrounding tooth structure, sig-nificantly influenced the demineralisation-remineralisation cycle and thus produced an anti-caries effect. This effect was observed at the margins of the C-GIC fillings and on adjacent interproximal carious lesions [Jang et al., 2001]. By compari-son with C-GICs, RM-GICs were found to have advantages, such as more resistance to early contamination by moisture, better mechanical properties, less microleakage and better bonding to dentine [Nagamine et al., 1997].

Composite resins (CR) are regarded as the “gold standard” in terms of aesthetic restorative materials and their widespread use can be ascribed to factors such as ease of manipulation and excellent aesthetics [Okida et al., 2008]. CR is also com-monly used for the bonding of brackets onto tooth surfaces during orthodontic treatment. The addition of fluoride ions into CR [Torii et al., 2001] has shown promise both in laboratory [Park and Kim, 1997; Wilson and Donly, 2001] and clinical studies [Andersson-Wenckert and Sunnegårdh-Grönberg, 2006].

This systematic review sought to quantitatively answer the question as to whether RM-GIC, when compared with CR, offers a more significant caries-preventive effect and to review the validity of the available evidence with regard to risk of bias.

materials and methods

Data collection. Five Anglophone databases: Biomed Cen-tral, Cochrane Library, Directory of Open Access Journals, PubMed and Science-Direct were systematically searched for articles reporting on clinical trials up to 29 July 2010. Two strings of MeSH and text search terms, with Boolean operators:

(((‘Tooth Remineralisation’ [Mesh] OR ‘Tooth Demineralisation’ [Mesh])) AND ‘Glass Ionomer Cements’ [Mesh]) AND ‘Composite Resins’ [Mesh], as well as:(((‘Dental Caries’ [Mesh] OR ‘Dental Caries Susceptibil-ity’ [Mesh] OR ‘Root Caries’ [Mesh])) AND ‘Glass Ionomer Cements’ [Mesh]) AND ‘Composite Resins’ [Mesh],

abstractaIm: To determine whether resin-modified glass-ionomer cement (RM-GIC), when compared with composite resins (CR), offers a significant caries-preventive effect. sTuDY DEsIGN: Quantitative systematic review. mETHODs: Five databases were searched until 29 July 2010. Inclu-sion criteria were: relevant to review question related to orthodontic or restorative treatment; published in English; prospective clinical 2-arm study. Exclusion criteria were: no computable data reported; study groups not followed up in the same way. References of included articles were checked. The outcome measure was absence of cari-ous lesions. Dichotomous datasets for both groups were extracted from accepted trials. Trials were assessed for selection-, detection/performance, attrition and publication bias. REsulTs: Of the 11 trials included, 6 were accepted and 24 datasets extracted; 17 datasets showed no differ-ence after 4 weeks to >25 months. There were 7 datasets that favoured (p < 0.05) RM-GIC after 12 – 24 months. The results are limited by risk of selection-, detection-/perfor-mance bias and attrition bias. Risk of publication bias was identified. CONClusIONs: The overall results showed either no difference between the materials, or indicated that RM-GIC has a superior caries-preventive effect. The clinical meaning of this result remains uncertain due to risk of bias. High-quality randomised control trials are needed in order to answer the review question conclusively.

Key words: resin-modified glass ionomers, composite resin, caries, systematic reviewPostal address: Dr. S. Mickenautsch, Division of Public Oral Health, Faculty of Health Sciences, University of the Witwatersrand, 7 York Road, Parktown, Johannesburg, 2193, South Africa.Email: [email protected]

V. Yengopal, S. MickenautschDivision of Public Oral Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.

Caries-preventive effect of resin-modified glass-ionomer cement (Rm-GIC) versus composite resin: a quantitative systematic review

European archives of Paediatric Dentistry 12 (Issue 1). 2011 5

were used in searching the databases. Articles from the search results were selected for review on the basis of their compliance with the inclusion criteria:

l Relevant to review question related to orthodontic or restorative treatment;

l Published in English; l Prospective clinical 2 – (or more) arm study.

Where only a relevant title without a listed abstract was avail-able, a full copy of the article was assessed for inclusion. References of included articles were checked for additional studies suitable for review.

Article review. Only articles that complied with the inclusion criteria were reviewed further. Full copies of articles were reviewed independently by two reviewers (VY and SM). Disa-greements between reviewers were resolved by discussion and consensus.

Articles were excluded if: l No computable data was reported; l Subjects of both groups were not followed up in the same

way.

(For example, the criteria used to assess the absence of caries in a test group should be exactly the same as in the control group. This might sometimes vary, especially in multi-centre trials, where some examiners may use a combination of clinical, visual and radiological aids to check for caries at margins at one centre whilst the other centre may use only visual inspection for caries diagnosis. This lack of consist-ency in the diagnostic criteria is a significant source of bias).

Data extraction from accepted trials. The outcome meas-ure was carious lesion absence. Two reviewers (VY and SM) independently extracted data from the accepted articles. Individual dichotomous datasets for the control- and test group were extracted from each trial. Where possible, miss-ing data were calculated from information given in the text or tables. In addition, in order to obtain missing information, authors of trials were contacted. Disagreements between reviewers during data extraction were resolved through discussion and consensus. It was anticipated that some of the trials eligible for inclusion would be split-mouth in design (quasi-randomised trials). The split-mouth study design is commonly used in dentistry to test interventions and has the advantage of enabling an individual to serve as both subject and control. In this study design one or more pairs of teeth (e.g. primary molars) form the unit of randomisation. These pairs are, strictly speaking, not independent and should be analysed as ‘paired data’ on a per-patient basis. However, as in other similar systematic reviews [Mickenautsch et al., 2009], in order to prevent exclusion of data, split-mouth trials were included and the pairs were analysed independently.

Quality of studies and assessment of potential bias risk. Criteria for quality assessment of trials are listed in Table 1. Quality assessment of accepted trials was undertaken on the basis of availability of evidence indicating successful prevention of selection- and detection/performance bias from the start to end of each trial. If a trial merely reported that randomisation was conducted, reported only the name of the randomisation method used or included a detailed description of the randomisation process without providing any evidence that randomisation was indeed effective throughout the trial, this was regarded as inadequate.

Sensitivity analysis was done, using the RevMan Version 4.2 statistical software of The Nordic Cochrane Centre, The Cochrane Collaboration (Copenhagen; 2003), in order to investigate potential attrition bias risk in trials.

To investigate publication bias, a funnel plot was generated, using the datasets from the included clinical trials. The stand-ard error (SE) of the mean differences was plotted on the Y-axis, and the log of the Relative Risk (RR) on the X-axis, using MIX Version 1.7 meta-analysis software [Bax et al., 2006]. In addition, Egger’s linear regression method [Egger et al., 1997] was used to calculate an intercept with a 95% Confidence Interval (CI), with statistical significance set at α = 0.05.

Statistical analysis. RevMan Version 4.2 statistical software from The Nordic Cochrane Centre, The Cochrane Collabo-ration (Copenhagen, 2003) was used to analyse extracted dichotomous datasets. Differences in treatment groups were computed on the basis of Relative Risk (RR), with 95% con-fidence intervals (CI).

Meta-analysis was considered for datasets only if they complied with criteria for clinical homogeneity. Datasets were considered clinically homogeneous if the CR material contained fluoride and the datasets covered the same type of dentition: type of teeth; study length; type of evaluation method; external fluoride exposure; type of treatment (ortho-dontic or restorative).

Results

Literature search. Figure 1 provides information on the number of articles identified through the search strategy. From 11 articles considered for possible inclusion, 5 were excluded [van Dijken, 2001; Burgess et al., 2004; Kotsanos and Dionysopoulos, 2004; Takeuti et al., 2007; Paradella et al., 2008]. Table 2 provides reasons for the exclusion of these trials. Thus, the results presented were obtained from 6 trials, all of which were split-mouth in design. [Kilpatrick et al., 1996; Chung et al., 1998; Garworski et al., 1999; Fuks et al., 2000; McComb et al., 2002; Andersson-Wenckert and Sunnegårdh-Grönberg, 2006].

V. Yengopal, S. Mickenautsch

European archives of Paediatric Dentistry 12 (Issue 1). 20116

Resin-modified GIC versus composite resin – absence of caries

Table 1. Criteria for quality assessment of trials: A. Selection bias.

Randomisation and concealmentScore Criteria Impact on bias risk

A

(i)Randomisation: Details of any adequate type of allocation method that generates random sequences with the patient as unit of randomisation are reported1 Doubts may still exist whether the trial results are influenced

by selection bias but no indication can be found from the trial report to support such doubt.

(ii)Concealment: Trial provides evidence2 that concealment was indeed effective and that the random sequence could not have been observed or predicted throughout the duration of the trial.

B

(i)Randomisation: Details of any adequate type of allocation method that generates random sequences with the patient as unit of randomisation are reported1

Despite the implementation of method considered to be able to prevent unmasking of the concealed allocation sequence through direct observation and prediction, there are reasons to expect that the concealed allocation sequence may have been unmasked during the cause of the trial.(ii)

Concealment: Trial reports on any adequate method to prevent direct observation3 and prediction4 of the allocation sequence and sequence generation rules

C

(i)Randomisation: Details of any adequate type of allocation method that generates random sequences with the patient as unit of randomisation are reported1 Despite the implementation of method considered to be able

to prevent unmasking of the concealed allocation sequence through direct observation, there are reasons to expect that operators could have predicted the concealed allocation sequence.(ii)

Concealment: Trial reports on any adequate method to prevent direct operator observation of allocation sequence and sequence generation rules3. However, the allocation sequence and sequence generation may have been sufficiently predicted.

D

(i)Randomisation: Details of any adequate type of allocation method that generates random sequences with the patient as unit of randomisation are reported1

Despite the theoretical chance for each patient to be allocated to either treatment group, operator knowledge of the allocation sequence may have lead to patient allocation that favoured the outcome of one type of treatment above the other(ii)

Concealment: The trial report does not include information on how the allocation of random sequence was concealed. The allocation could have been directly observed and/or predicted.

0 Trial does not comply with criteria A – DNo guaranty of equal chance for patients to be allocated to either treatment group, thus allocation may have favoured the outcome of one type of treatment above the other

Baseline data for randomised trials

ABaseline data collected before randomisation and reported for both treatment groups / Data shows no significant differences between both groups

Evidence is given that randomisation has lead to equal groups suggesting little risk of selection bias

BBaseline data collected before randomisation and reported for both treatment groups / Data shows significant differences between both groups but has been statistically adjusted appropriately

Differences have been adjusted, thus the influence of possible selection bias appears to be reduced

CBaseline data collected before randomisation and reported for both treatment groups / Data shows significant differences between both groups without being statistically adjusted

Reported differences may be due to ineffective randomisation , thus indicate risk of selection bias

0 Trial does not comply with criteria A – CNo evidence is given whether randomisation has indeed lead to equal groups with differences beyond chance, thus differences may exists indicating selection bias

1 Excluded are types of allocation methods that are considered as inadequate: cluster randomisation, fixed block randomisation with block size 2, minimization, alternation, randomisation of teeth, use of date of birth or patient record number, ‘quasi’-randomisation, splitmouth

2 E.g. by reporting results of the Berger-Exner Test or any other statistical tests that show that covariates of compared groups were similar at baseline3 E.g. by opening of opaque envelope, obtaining allocation from tables, computer generated or form other sources4 E.g. central randomisation , sequence allocation by other than operator; excluding varied block randomisation



Table 1. Criteria for quality assessment of trials: B. Detection/ Performance bias.

Blinding / MaskingScore Criteria Impact on bias risk

A

(i)Trial reports on any type of method that is known to prevent patient AND operator AND evaluator to discern whether patients are allocated to the test- or the control group (Blinding/Masking)

Evidence is given that the trial results may not have been influenced by detection/performance bias that may have favoured the outcome of one type of treatment above the other

(ii)Trial reports a process with which the effect of Blinding/Masking was evaluated, as well as the results of such evaluation

B


Doubts may still exist whether the trial results are influenced by detection/performance bias but no indication can be found from the trial report to support such doubt. However, no evaluation of the Blinding/Masking effect has been included in the trial, thus no evidence for lack of bias is given (ii)

Trial report does not give reason for doubt that the patient allocation to either the test- or the control group has been unmasked throughout the duration of the trial

C


Despite the implementation of method considered to be able to prevent unmasking, there are reasons to expect that operators/patients could have discovered the allocation.

(ii)Trial report gives reason for doubt that the patient allocation to either the test- or the control group has been unmasked throughout the duration of the trial

0

No process reported or implemented able to blind/mask patients AND operators whether patients where allocated to either the test- or the control group (It is insufficient to report that blinding/masking was done without reporting the details of the process)

Knowledge about the patient allocation may have caused patients/operator to act in a way that may have favoured the outcome of one type of treatment above the other

Table 1. Criteria for quality assessment of trials: C. Attrition bias.

Loss – to follow upScore Criteria Impact on bias riskA Available case analysis, loss-to-follow up reported per treatment

group / Subsequent sensitivity analysis does not indicate a possible risk of bias effect

The trial allows to extract evidence that the loss-to-follow up may have not favoured the outcome of one type of treatment above the other

B Available case analysis, loss-to-follow up reported per treatment group / Subsequent sensitivity analysis indicates a possible risk of bias effect

The trial allows to assess the risk that the loss-to-follow up may have favoured the outcome of one type of treatment above the other

0 Trial does not report number of included participants per treatment group at baseline or give any indication that would allow to ascertain the loss-to-follow up rate per treatment group

The trial carries an unknown risk that the loss-to-follow up may have favoured the outcome of one type of treatment above the other

Table 1. Criteria for quality assessment of trials: D. Trial endpoints

0 The trial reports on secondary of surrogate outcomes as endpoints

Even if the surrogate results would highly correlate with primary (i.e. clinical outcomes) they cannot serve as valid replacements and need to be regarded for hypothesis development, only

A The trial reports on primary outcomes as endpoints Primary outcomes may provide evidence for hypothesis testing

Table 3 describes the characteristics of the included trials and the datasets derived from the results presented in each of them. The Chung et al. [1998] and Gaworski et al. [1999] randomised clinical trials compared RM-GIC and CR mate-rial when used for orthodontic bracket bonding in permanent teeth [Chung et al., 1998; Gaworski et al., 1999]. Both papers regarded the absence of signs of decalcification as indicating caries absence.

Dataset extraction and analysis. There were 24 dichoto-mous datasets extracted from the 6 accepted trials; 17 of them showed no difference between the two materials after test periods lasting from 4 weeks to >25 months (Table 4). Another 7 dichotomous datasets (DS 06, 08, 09, 12-14, 16) were extracted from two trials [McComb et al., 2002; Andersson-Wenckert and Sunnegårdh-Grönberg, 2006] and showed statistically significant results (p < 0.05) in favour of



RM-GIC after 12 to 24 months. One of these datasets with statistically significant results (DS 06) was derived from one trial including CR with fluoride [Andersson-Wenckert and Sunnegårdh-Grönberg, 2006]. The results indicated that pri-mary teeth restored with RM-GIC would have an 11% higher chance of remaining caries-free on their restoration margins than if they were restored with fluoride-containing CR, after 24 months (DS 06: RR 1.11; 95% CI 1.01 – 1.23; p = 0.04).

Results concerning the permanent dentition indicated a 2-3 times higher chance of remaining caries-free on restora-tion margins for teeth restored with RM-GIC, than for teeth restored with CR (not containing fluoride) without external fluoride exposure, after 24 months (DS 14: RR 2.63; 95% CI 1.13 – 6.09; p = 0.02), and with external fluoride exposure, after 18 months (DS 16: RR 2.10; 95% CI 1.04 – 4.24; p = 0.04) [McComb et al., 2002].

Clinical heterogeneity in terms of evaluation criteria, evalu-ation method, type of dentition, as well as fluoride exposure and study period, was observed for all datasets and no meta-analysis was attempted.

Quality assessment of trials and risk of bias

Selection-, Detection-/Performance bias risk. The results of the quality assessment regarding selection- and detection/performance bias are shown in Table 5. None of the accepted trials reported sufficient details of any randomisation process that had indeed given each patient the same chance to be allocated to either the RM-GIC or the CR group and to ensure that direct observation and prediction of the alloca-tion sequences was successfully prevented. Moreover, none of the accepted trials had mentioned baseline data collected before randomisation, and subsequently reported, for both treatment groups. Nor had they statistically compared this data between groups, and none fulfilled the criteria (Table 1) related to successful blinding/masking of patients, operators and trial evaluators.

Attrition bias risk. Sensitivity analysis was used in computing all datasets, under the assumption that either: l All teeth lost to follow-up developed carious lesions;l None of the teeth lost to follow-up developed carious

lesions.

The numbers of teeth lost to follow-up per dataset are shown in Table 3. The results of neither situation changed the con-clusions for most of the datasets. However, a possible risk of attrition bias was identified in the results of four datasets (DS 06, 08-10) extracted from two trials [McComb et al., 2002; Andersson-Wenckert and Sunnegårdh-Grönberg, 2006]. Under the assumption that all teeth lost to follow-up would have developed caries, the results of three datasets (DS 06, 08, 09) would not be statistically significantly in favour of RM-GIC: DS 06 – RR 1.11 (95% CI: 0.90 – 1.38; p = 0.33); DS 08 – RR 1.14 (95% CI: 0.86 – 1.50; p = 0.36) and DS 09 – RR 1.13 (95% CI: 0.66 – 1.91; p = 0.66). The results of one dataset (DS 10) would be statistically significantly in favour of RM-GIC under the assumption that all teeth lost to follow-up would not have developed caries (RR 1.19 – 95% CI: 1.03 – 1.37; p = 0.02).

Publication bias risk. Publication bias was investigated, using one funnel plot (Figure 2). The funnel plot showed an uneven distribution that did suggest publication bias. Egger’s linear regression method for the same datasets showed an intercept of 1.35 (95% CI: 0.49 – 2.21; p = 0.004). The regres-sion result was statistically significant in favour of RM-GIC.

Table 2. Excluded trials with reasons for exclusion in a review of caries-preventive effect of resin-modified glass-ionomer cement (RM-GIC) versus composite resin.

Article Reason for exclusionParadella et al., 2008 No computable data – data presented in quartiles, median onlyBurgess et al., 2004 No computable data – no standard deviation reportedTakeuti et al., 2007 No computable data – number of evaluated restorations after 3 years not reportedKotsanos and Dionysopoulos, 2004 No differentiation of results between composite versus RM-GIC reportedVan Dijken, 2001 No computable data – number of restorations at baseline not reported per group

Figure 1. Flow diagram of trial selection in a review of caries-preventive effect of resin-modified glass-ionomer cement (RM-GIC) versus composite resin. (N = Number of trials; DS = Dataset number).



Table 3. Details of accepted trials

Article DS

Patient charac-teristics

RM-GIC treatment groupComposite resin treatment

group Out-come

measure

Evaluation Dentition/Teeth/

RestorationStudy period

Type of material BSL N n LTF

Type of material BSL N n LTF Criteria Method

Gaworski et al., 1999

01

[1]Fuji

Ortho LC

16 16 6 0

Reli-ance Light Bond

16 16 5 0

Caries absence

No sign of decalcifica-tion around orthodontic

bracket

Visual exami-nation

Permanent – canines

Orthodontic bracket bonding

14 months02 16 16 2 0 16 16 1 0

Permanent – lateral incisors


03 16 16 3 0 16 16 6 0

Permanent – central incisors


Chung et al., 1998 04 [2] Vitremer 25 25 25 0 Right-

On 25 25 21 0 Caries absence

No sign of decalcifica-tion around orthodontic

bracket

Visual exami-nation

Permanent – premolarOrthodontic

bracket bonding

4 weeks

Andersson-Wenckert and Sunnegårdh-Grönberg, 2006

05[3] Vitremer

66 65 63 1 Tetric* Flow

66 62 60 4 Caries absence

Modified USPHS

Visual exami-nation

Primary molar

proximal

12 months

06 66 50 50 16 66 50 45 16 24 months

McComb et al., 2002

07

[4] Vitremer

45 44 43 1

Z100

45 44 39 1

Caries absence

Softness of the surface texture or surface defect

adjacent to the restora-tion is not

greater than 0.5 mm in

diameter

Visual exami-nation

PermanentIndepend-

ent of Fluoride

use

6 months

08 45 34 33 11 45 36 29 9 12 months09 45 19 18 26 45 24 16 21 18 months

10 45 9 8 36 45 18 10 27 24 months

11 24 24 23 0 24 24 19 0Permanent

Non-Fluoride

users

6 months12 18 18 17 0 18 18 9 0 12 months13 11 11 10 0 13 13 5 0 18 months14 8 8 7 0 12 12 4 0 24 months15 20 20 20 0 20 20 20 0

PermanentFluoride

users

6 months16 8 8 8 0 9 9 4 0 12 months17 16 16 16 0 16 16 16 0 18 months

18 1 1 1 0 1 1 1 0 24 months

Kilpatrick et al., 1996 19 [5] Vitre-

bond 80 66 66 14 P-50 80 66 66 14 Caries absence

No visible caries

Visual exami-nation

Permanent – premolar,

molar – Small occlusal cavities

27 months

Fuks et al., 2000

20

[6] Vitremer

40 8 8 32

Z100

38 9 9 27

Caries absence

Modified USPHS

Visual exami-nation

Primary molars Class II

12 months21 40 11 10 29 38 8 8 30 18 months22 40 12 11 28 38 13 13 25 24 months23 40 9 9 31 38 8 6 30 >25 months

24 40 31 29 9 38 32 26 6 X-ray >25 months

DS = Dataset number; BSL = Number of teeth at baseline; N = Number of teeth evaluated; n = Number of teeth with caries, LTF = Loss-to-follow-up; USPHS = United States Public Health Service criteria; RM-GIC = Resin-modified glass-ionomer cement.* Composite resin contains fluoride.Patient characteristics:[1] 16 patients from a teaching institution participated; consecutively selected from individuals seeking orthodontic treatment at Albert Einstein Medical Center in

Philadelphia; maxillary and mandibulary premolar, canine and incisor teeth were bonded allowing up to 20 teeth per patient to be included.[2] 26 patients (11 males, 15 females) with mean age of 13.4 years; all teeth free of decalcification; exposure to fluoride was kept at a minimum during 4 weeks

before treatment and during the treatment; oral hygiene instructions and non-fluoride tooth-paste given during this time; fluoride in drinking water 0.03 ppm; no pre-existing fluoride releasing restorations.

[3] 57 children (30 M and 27 F, with a mean age of 8 years, range 511 years), a total of 66 pairs of restorations were placed; Inclusion criterion: at least 2 proximal carious lesions in primary molars with an expected exfoliation time exceeding 2 years; Exclusion criteria: availability for recall was uncertain, uncooperative, serious health problems, no parental consent; children were treated at their regular appointments and no extra time was reserved for participation in the study; all teeth were vital with no sign of pulpitis.

[4] Inclusion criteria: at least 3 cervical carious lesions in the same arch; all patients had received prior radiation therapy to head and neck; age >18 years; patients were capable to give informed consent; patients xeriostomic.

[5] 67 patients attending the Dept. Child Dental Health at Newcastle Dental Hospital, UK; some older patients had learning difficulties or development delay; of the 58 remaining patients (after drop-out) 25 were female 33 were male; mean age 15 years and 1 month (range 8 years/8 months – 28 years).

[6] 29 schoolchildren, 15 males, 14 females attending the Dental School Clinic pf the University of Sta. Maria, Brazil; Inclusion criteria: age 8-10 years, at least 1 primary molar with interproximal caries with occlusal and proximal contacting adjacent teeth, available for recall every 6 months until shedding teeth, parental consent.



Discussion

This systematic review sought to quantitatively answer the question as to whether RM-GIC, when compared with CR, offers a significant caries-preventive effect. Despite an exten-sive search of the literature, only six articles were included for analysis in this review. A perusal of the Cochrane library, which is regarded as the premier source of systematic reviews, reflects a similar trend, whereby the majority of stud-ies identified for a topic in the search strategy are excluded; mainly because of methodological issues (internal validity) or the manner in which the results (data) are reported /pre-sented. The authors of this review have attempted to address the issue of methodological rigor and data presentation, by setting broad inclusion and exclusion criteria and assessing, in depth, the quality of included trials. This present systematic review did not include trials investigating the caries-preven-tive effect of RM-GIC versus CR-based fissure sealants, as the authors have already assessed the evidence regarding this topic, in another published review [Yengopal and Mick-enautsch, 2010].

However, other aspects in the methodology of this systematic review might may have contributed to limitations in its results: (i) not all relevant publications were listed in the selected databases; (ii) the chosen search terms may not have been broad enough; (iii) not all relevant publications could be found through the reference check; (iv) not all relevant trials may have been published in English.

The primary outcome of interest in this review was the absence of caries. Whilst visual diagnosis of caries presence/absence could be considered acceptable in the Gaworski et al., [1999] Chung et al. [1998] and McComb et al. [2002] trials (as these were orthodontic or Class V cavity placement, respectively), the lack of any radiographic assessment for caries in the Kil-patrick et al. [1996] trial for detection of interproximal caries limits the validity of these results (see Table 3). In terms of the assessment of the restorations post-treatment, only the Andersson-Wenchert et al. [2006] trial provided details of clinicians undergoing a calibration exercise to ensure con-sistency of interpretation of the criteria. Thus, the internal validity of the trials was negatively impacted due to the lack of information provided in the five other included trials.

Selection, Detection/Performance bias risk. All of the accepted trials appear to be limited by risk of selection- and detection/performance bias. Bias or systematic error may affect studies, causing either an over- or under-estimation of the treatment effect of an investigated clinical procedure. Overesti-mation has been observed to be the most common [Chalmers et al., 1977]. Kjaergard et al. [2001] reported a treatment effect overestimation of 48% caused by lack of random sequence allocation and Egger et al. [2003] reported a treatment effect overestimation of 54% and 53% due to lack of allocation con-cealment and lack of evaluator blinding, respectively.

It has been emphasised that selection bias can only be suc-cessfully prevented if the allocation sequence remains truly random and free from potential interference throughout the trial [Berger, 2005; Berger and Alperson, 2009]. Thus, it is

Figure 2. Funnel plot of dataset results (test for publication bias) in a review of caries-preventive effect of resin-modified glass-ionomer cement (RM-GIC) versus composite resin. RR = Relative Risk

Table 4. Results of individual datasets

Article DS RR 95% CI p-value

Gaworski et al., 199901 1.20 0.46 – 3.15 0.7102 2.00 0.20 – 19.91 0.5503 0.50 0.15 – 1.66 0.26

Chung et al., 1998 04 1.19 0.99 – 1.43 0.07Andersson-Wenckert and Sunnegårdh-Grönberg, 2006

05 1.00 0.94 – 1.07 0.9606 1.11 1.01 – 1.23 0.04*

McComb et al., 2002

07 1.10 0.98 – 1.24 0.1008 1.20 1.02 – 1.43 0.03*09 1.42 1.05 – 1.92 002*10 1.60 1.00 – 2.57 0.0511 1.21 0.97 – 1.51 0.09

12 1.89 1.17 – 3.04 0.009*13 2.36 1.16 – 4.82 0.02*14 2.63 1.13 – 6.09 0.02*15 n.e.16 2.10 1.04 – 4.24 0.04*17 n.e.18 n.e.

Kilpatrick et al., 1996 19 n.e.

Fuks et al., 2000

20 n.e.21 0.93 0.71 – 1.21 0.5722 0.92 0.74 – 1.14 0.4423 1.32 0.86 – 2.02 0.2124 1.15 0.95 – 1.39 0.15

DS = Dataset number; RR = Relative risk; CI = Confidence interval; n.e. = Not estimable, data from both treatment groups are essentially the same: p = 1.00. * Statistically significant difference, in favour of RM-GIC.



important that trials should include an effective process for concealing the random allocation sequence and that by the end of each trial this process has indeed prevented direct observation and prediction of the random sequence allocation [Berger, 2005; Berger and Alperson, 2009]. Quality assess-ment in terms of the internal validity of trials should therefore be a measure of the result of random sequence allocation and allocation concealment, and not only of it’s being recorded.

All trials accepted in this systematic review failed to report not only on evidence of successful sequence allocation and allocation concealment results, but also on necessary details about how sequence allocation and allocation concealment were attempted and whether these measures were suc-cessful (Table 5). None of the trials, therefore, provide any guarantee that each patient had an equal chance of being allocated to either treatment group and thus, their allocation may have favoured the outcome of one type of treatment above the other. One measure for testing whether random

sequence allocation has been successful is testing whether covariates differ between treatment groups at baseline [Berger, 2005]. None of the articles had included such a test and reported on its outcome.

From the outset, in all trials successful blinding or masking appeared not to have been possible, owing to the obvious dif-ferences in clinical appearance between GIC and CR fissure sealants. For that reason, allocation to either treatment group was visible to patients, operators and evaluators. However, the difficulties of successful blinding still carry the danger of detection/performance bias, which may thus have affected the trials’ results. Potential knowledge of superiority claims prior to the trial may have led patients to change their oral hygiene habits, operators to place restorations more carefully or evaluators to apply evaluation criteria more subjectively. This in turn may have favoured the outcome of one type of treatment over the other.

Table 5. Results of quality assessment of accepted trials in a review of caries-preventive effect of resin-modified glass-ionomer cement (RM-GIC) versus composite resin.

Article DS

Selection bias

Detection/Performance

bias Attrition bias

Trial outcomeRandomisation Baseline dataBlinding / Masking

Loss-to- follow up

Gaworski et al., 199901 0 0 0 A A02 0 0 0 A A03 0 0 0 A A

Chung et al., 1998 04 0 0 0 A A

Andersson-Wenckert and Sunnegårdh-Grönberg, 2006

05 0 0 0 A A

06 0 0 0 B A

McComb et al., 2002

07 0 0 0 A A08 0 0 0 B A09 0 0 0 B A10 0 0 0 B A11 0 0 0 A A12 0 0 0 A A13 0 0 0 A A14 0 0 0 A A15 0 0 0 A A16 0 0 0 A A17 0 0 0 A A18 0 0 0 A A

Kilpatrick et al., 1996 19 0 0 0 A A

Fuks et al., 2000

20 0 0 0 A A21 0 0 0 A A22 0 0 0 A A23 0 0 0 A A24 0 0 0 A A

DS = Dataset number.



Attrition bias risk. Sensitivity analysis may be used in establishing whether missing data could have affected trial outcomes by assuming that the numbers of restoration lost to evaluation were either failures or successes [Higgins and Green, 2006]. Comparison of the analysis results with reported trial outcomes indicates whether different conclu-sions should be drawn. Sensitivity analysis was conducted for all datasets. The analysis results differed from reported outcomes of four datasets (DS 06, 08-10) extracted from two trials [McComb et al., 2002; Andersson-Wenckert and Sunnegårdh-Grönberg, 2006]. How high the caries rate in the teeth lost to evaluation really was remains unknown. Nev-ertheless, the validity of these datasets can be questioned on grounds of attrition bias. Thus, their results need to be regarded with caution.

Publication bias risk. Publication bias was investigated by generating a funnel plot (Figure 2). Publication bias is present when the results of published research differ from those of all the studies that have been done [Rothstein et al., 2005a]. Funnel plots are scatter graphs showing the sizes of stud-ies on the Y-axis (large studies above; small studies below) and the effect size, observed in these studies, on the X-axis. The effect is that sizes of larger studies tend to cluster near the mean. Small studies have effect sizes that are dispersed across a wider range. Results of both types of study, plotted on a scatter graph, form the shape of an inverted, in absence of publication bias, symmetrical funnel [Rothstein et al., 2005b]. Publication bias results in a concentration of studies on only one side of a funnel plot (asymmetry). Such asym-metry is only created when particular smaller studies showing a larger than average effect are published.

The decision was made to plot results of the 24 extracted dichotomous datasets as units of investigation. These are not all independent from the published trials and this formed a departure from the common application of funnel plots in investigating for publication bias. Despite this departure, the use of datasets (instead of published trials) will also indicate potential publication bias when only datasets that show a larger than average effect are published and other datasets are not. The funnel plot showed an asymmetrical spread of dataset results (Figure 2). As the visual judgement of fun-nel plots is subjective, an intercept (95% CI) was calculated, using Eggers regression [Egger et al., 1997]. The calculated significant intercept confirmed the observations from the fun-nel plot. Both suggest that a potential impact of publication bias in favour of RM-GIC exists regarding this topic.

Analysis of results. Most of the dataset results showed no difference between the two types of material: seven showed as favouring RM-GIC [McComb et al., 2002; Andersson-Wenckert and Sunnegårdh-Grönberg, 2006;] and none was identified as favouring CR above RM-GIC. However, the clini-cal meaning of these results remains uncertain, as all trials identified during this systematic review were limited by risk

of selection- and detection-/performance bias and, for some datasets, attrition bias. In addition, the risk of publication bias was identified.

All six studies included in this review were split-mouth in design. The split-mouth study design is commonly used in dentistry to test interventions and has the advantage of hav-ing an individual serve as both experiment and control. This can increase trial efficiency and, on average, fewer patients are needed [Lesaffre et al., 2007]. However, methodological issues have also been highlighted in recent publications, which must be considered [Lesaffre et al., 2007]. For exam-ple, fluoride that is released from RM-GIC over a period of time into the oral cavity can act as confounding factor. Tantbirojin et al., [1997] have shown that RM-GIC provided caries resistance in bovine enamel located at a considerable distance from the margin of cervical restorations. Thus if a test cavity, filled with RM-GIC, is located near a control cavity filled with CR any caries preventive effect of the CR can be positively confounded by the preventive effect of the fluoride released from the nearby RM-GIC. Such confounding effect may generate equivalence in terms of caries absence. Thus, the split-mouth design may be unsuitable and a randomised controlled trial with a parallel group design more appropriate. In addition, split-mouth studies actively exclude patients, i.e. without at least two equal cavities, [Mejáre et al., 2003] and thus carry by design the risk of selection bias. The true extent of such biases highlighted above remains unknown, which suggests that all trial results need to be regarded with caution and no conclusions in terms of answering the review question can therefore be drawn.

Concluding remarks. Systematic reviews have been reported to provide the highest form of clinical evidence [Mickenautsch, 2010]. However, the internal validity of such evidence can only be as good as the internal validity of the tri-als reviewed. Although the trials accepted in this update may be considered to be less affected by attrition bias, their risk of selection- and detection-/performance bias is high. For that reason, further high quality randomised control trials (RCT) are needed, in order to verify (or disprove) the currently available results. Such RCTs should adopt a parallel group design and include randomisation and allocation conceal-ment methods that can effectively prevent direct observation and prediction of the allocation sequence. For this purpose, the maximum randomisation method has been suggested [Berger, 2005]. Covariates of both treatment groups should be tested as to whether they differ at baseline (after ran-domisation). Recently, use of the Berger-Exner test has been suggested, in order to enable authors of trials to investigate whether selection bias has been introduced into their studies [Berger, 2005; Berger and Alperson, 2009]. Where bias risk has been found, it may be adjusted statistically [Berger, 2005]. Both outcomes should be included in the final trial report. In order to ensure that the lack of blinding may not have led to favouring one treatment over the other, trials should use



and report on procedures and tests employed that may limit, or at least monitor, potential bias risk. Moreover, future tri-als should base their reporting on the CONSORT statement [Moher et al., 2001].

This systematic review identified trials that either (i) showed no difference between the materials or (ii) indicated RM-GIC to be more caries-preventive than composite resin with or without fluoride. However, the clinical meaning of these results remains uncertain, as all trials identified during this systematic review are limited by risk of selection- and detec-tion-/performance bias and, for some datasets, attrition bias. In addition, the risk of publication bias was identified. High-quality randomised control trials are needed in order to answer the review question conclusively.

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