Journal of Dentistry 53 (2016) 12–21

Contents lists available at ScienceDirect

Journal of Dentistry
journal homepage: www.intl.elsevierhealth.com/journals/jden

Review article

Direct versus indirect inlay/onlay composite restorations in posterior

teeth. A systematic review and meta-analysis
Flora Angeletakia , Andreas Gkogkosb , Efstratios Papazoglouc , Dimitrios Kloukosd,e,*
a
Private Practice in Athens, 12 Kousianofski Str, 11525 Athens, Greece
b
Department of Periodontology, 251 Air Force Hospital, 3 P. Kanellopoulou Str, 11527 Cholargos, Athens, Greece
c
Department of Operative Dentistry, Athens Dental School, University of Athens, 2 Thivon str, 11527 Athens, Greece
d
Department of Orthodontics and Dentofacial Orthopedics, University of Bern, Freiburgstrasse 7, CH-3010 Bern, Switzerland
e
Department of Orthodontics, 251 Air Force Hospital, 3 P. Kanellopoulou Str, 11527 Cholargos, Athens, Greece

A R T I C L E I N F O A B S T R A C T

Article history: Objective: To evaluate the long-term clinical performance of direct versus indirect composite inlays/
Received 19 April 2016 onlays in posterior teeth.
Received in revised form 17 July 2016 Data: Screening for inclusion eligibility, quality assessment of studies and data extraction was performed
Accepted 20 July 2016
independently by two authors.
Sources: The electronic databases MEDLINE, EMBASE, Cochrane Oral Health Group’s Trials Register and
Keywords: CENTRAL were searched (14.12.2015), with no restriction to publication date or language. We included
Resin composite
only randomised controlled trials (RCTs) and evaluated them according to Cochrane risk of bias tool. The
Tooth restoration
Inlays
main outcome assessed was the restoration failure, determined by several clinical parameters.
Onlays Study selection: Two studies concerning direct and indirect inlays (82 patients with 248 restorations) and
Direct one study for onlays (157 patients with 176 restorations) satisfied the inclusion criteria. Two trials, one of
Indirect unclear and one of high risk of bias, could be mathematically combined. The meta-analysis indicated no
statistically significant difference in the risk failure between direct and indirect inlays, after 5 years (RR:
1.54; 95% Cl: 0.42, 5.58; p = 0.52) or 11 years of function (RR: 0.95; 95% Cl: 0.34, 2.63; p = 0.92). Only one
parameter, the marginal discoloration, slightly favored direct inlays after 11 years (RR: 0.41; 95% Cl: 0.17,
0.96; p = 0.04). Only one study dealt with onlays; an overall 5-year survival of 87% (95% CI: 81–93%) was
reported.
Conclusion: The difference of the two techniques did not reach statistical significance in order to
recommend one technique over the other. The scarcity of primary studies support the need for further
well-designed long-term studies in order to reach firm conclusions about both techniques.
Clinical significance: Resin composite materials, placed directly or indirectly, exhibit a promising long-
term clinical performance when rehabilitation of posterior teeth is needed. Although many years in
clinical practice, the selection of the best treatment protocol still remains subjective. The available
studies, and their synthesis, cannot provide reliable evidence in this field.
ã 2016 Elsevier Ltd. All rights reserved.

1. Introduction technique selection may be regarded as the key factors that affect
restoration success or failure [2].
Failure of dental restorations presents a major complication in Contemporary dentistry evolves along with patient’s demand
everyday dental practice. It has been reported that about 60% of all for high aesthetics. Even though amalgam and gold have been
operative dental workload refers to placement and replacement of materials with a long history of clinical success and biocompati-
restorations [1]. Correct material manipulation and proper bility, patients often reject these treatment options, as the desire of
a restoration that resembles natural tooth structure, even for
posterior teeth, is high [3].
Conservative restorative dentistry is provided with a wide
* Corresponding author at: Department of Orthodontics and Dentofacial range of techniques and systems for the rehabilitation of posterior
Orthopedics, University of Bern, Freiburgstrasse 7, CH-3010 Bern, Switzerland.
teeth in a minimal invasive way. Resin composite materials, placed
E-mail addresses: flora.angeletaki@gmail.com (F. Angeletaki),
andreasgog@yahoo.gr (A. Gkogkos), papazoglou.dental@otenet.gr (E. Papazoglou), directly or indirectly, are among the best alternative non-metallic,
dimitrios.kloukos@zmk.unibe.ch (D. Kloukos). tooth-colored restorative treatments [4].

http://dx.doi.org/10.1016/j.jdent.2016.07.011
0300-5712/ã 2016 Elsevier Ltd. All rights reserved.
 F. Angeletaki et al. / Journal of Dentistry 53 (2016) 12–21 13

Composite resin materials usually consist of a matrix (organic teeth, with at least 3 years of follow-up after initial restoration.
polymer) and fillers (combination of inorganic particles) of Comparison results relied on the clinical parameters of longevity,
different types. Some of these resinous materials are based on secondary caries, post-operative sensitivity, marginal discolor-
Bisphenol-A (BPA), which is used as a precursor of BPA glycidyl ation and color match between intervention modalities.
dimetha-crylate (Bis-GMA) or BPA dimethacrylate (Bis-DMA). The
BPA structure assembles a bulk, stiff chain that offers low 2. Materials and methods
susceptibility to biodegradation as well as great rigidity and
strength [5]. Clinical, physical and mechanical properties of This systematic review was based on the guidelines of the
composite resins depend on the percentage of fillers in their PRISMA Statement for reporting Systematic Reviews and Meta
volume, the particle size, and load and matrix bonding of the filler. Analyses of studies evaluating health-care interventions [22].
In fact, the more the loading of the filler particle is, the less the
wear resistance [6]. However, these resins are less polishable. Resin 2.1. Protocol and registration
composites have gone through generations of traditional (macro-
filled) composites, microfilled composites, hybrid composites, Not available.
microhybrid composites and nano-composites. Newer resin
formulations of smaller filler particles but higher filler loading 2.2. Selection criteria applied for the review
percentage (approximately 66% inorganic fillers and 33% resin
matrix) have been developed to enhance mechanical character-  Study design: Only randomized clinical trials were eligible for
istics. The submicron-particle fillers provide abrasion resistance, inclusion in this review. Non-randomized or quasi-randomized
more color stability and less polymerization shrinkage, while controlled trials were not eligible for inclusion
increasing flexural and tensile strength. Resins are converted from  Types of participants: Patients of any age who received direct or
monomer to polymer by various methods of polymerization indirect composite inlays/onlays
devices. The controlled degree of polymerization also enhances  Type of intervention: All direct/indirect composite inlays/onlays
tensile strength, wear resistance, fracture toughness and color irrespectively of the resin and bonding material and the type of
stability [7,8]. tooth (molar, premolar)
In direct restorations, light-cured resin composite material is  Outcome: Failure rate of direct and indirect composite inlays/
placed directly into the prepared cavity. The greatest advantage onlays, (restorations which need replacement or repair) and risk
presented by this procedure, is that it permits the maximum ratio of (1) secondary caries, (2) postoperative sensitivity, and (3)
preservation of tooth structure, which collaborates with the marginal discoloration, color match between the two groups
modern concept of a minimal-invasion conservative restorative  Follow-up: At least three years of observation
dentistry. In addition, they are usually performed in one treatment  Exclusion criteria: Animal and in-vitro studies.
appointment, at relatively low costs. However, direct restorations
are associated with polymerization shrinkage and low wear
resistance [9,10]. 2.3. Search strategy for identification of studies
Indirect technique involves fabricating the restoration outside
the oral cavity, using an impression of the prepared tooth. This Detailed search strategies were developed and appropriately
technique overcomes some of the disadvantages of direct resin revised for each database, considering the differences in controlled
composites, such as polymerization shrinkage to the width of the vocabulary and syntax rules. The following elec-tronic databases
luting gap [11]. Furthermore, it provides better physical and were searched: MEDLINE (via Ovid and Pubmed, Appendix A, from
mechanical properties by post-curing the inlay/onlay with light or 1946 to December 14th, 2015), EMBASE (via Ovid), the Cochrane
heat, ideal occlusal morphology, proximal contouring and wear Oral Health Group’s Trials Register and CENTRAL.
compatibility with opposing natural dentition [12,13]. However, Unpublished literature was searched on ClinicalTrials.gov, the
this technique is more time consuming and requires extra cost and National Research Register, and Pro-Quest Dissertation Abstracts
appointments that may, in turn, be out of patient wishes and and Thesis database. The search attempted to identify all relevant
budget. studies irrespective of language. The reference lists of all eligible
As evident in the literature, many in-vitro studies have studies were hand-searched for additional studies.
examined the behavior and durability of direct composite
restorations and indirect composite inlays [14,15]. Although, 2.4. Selection of studies
several studies have verified the long-term in-vivo performance
of those materials separately [16,17], only few have compared Two authors (F.A. and A.G.) of the review independently and in
these techniques [18,19]. In a recent systematic review, Grivas et al. duplicate performed the study selection. The procedure composed
concluded that there was insufficient evidence to make recom- of three stages: title-reading, abstract reading and full-text reading
mendations for the use of indirect composite inlays over direct. In in order to identify studies that potentially met the eligibility
this review, the variety of methodology, the heterogeneity of the criteria. After exclusion of not eligible studies, the full report of
trials – 3 randomized controlled trials (RCTs) and 4 controlled publication was obtained and assessed independently. Any
clinical trials CCT until 2013 were considered eligible- as long as disagreements were discussed and resolved by discussion and
the unlimited observation time could not permit a valid assess- consultation with the other two authors. Reasons of exclusion and
ment on the basis of a meta-analysis regarding the longevity of the all decisions on study identification were recorded.
composite inlays [20]. Even though there is a systematic review
that compares clinical effectiveness of composite versus ceramic 2.5. Data extraction and management
inlays/onlays [21], there is no systematic review apparent in the
literature that has evaluated effectiveness of direct versus indirect Data extraction was performed independently and in duplicate
composite inlays/onlays. by the first two authors. In order to record the desired information,
The aim, therefore, of this systematic review was to provide the following customized data collection forms were used.
updated evidence stemming from randomized controlled trials
comparing direct and indirect composite restorations in posterior  Author/title/year of study
14 F. Angeletaki et al. / Journal of Dentistry 53 (2016) 12–21

 Design of study
 Number/age/gender of patients recruited 2.6. Measures of treatment effect
 Type of restoration, direct or indirect technique
 Number of tooth For continuous outcomes, mean differences and standard
 Composite used deviations were used to summarize the data from each study.
 Bond system used For dichotomous data, number of participants with events and
 Observation period (Follow up of patients) total number of participants in experimental and control groups
 Outcome assessed were analyzed. Regarding meta-analysis for dichotomous data risk
 Failure rate of direct and indirect inlays/onlays ratios (RR) and their 95% confidence intervals (Cls) were calculated.

Table 1
Characteristics of included studies ordered by study design and date.

Reference Assessment No of patients No of restorations Tooth Materials Cement Follow up

type of study criteria
Country Statistical
Operator- analysis
evaluation
Pallesen and Modified USPHS 28 140 88 Briliant Dentin (BD) Cements: 11 y
Qvist [19] Premolars by Coltene. For inlays BD by (2-5-8-11y).
52 Molars and direct Coltene
restorations
RCT X2 and sign test (20 female, 8 28 sets (2 direct, 3 85 MO/DO Estilux Posterior (EP) EP by
male) inlays) (two by Kulzer. For direct Microfil
surfaces restorations Pontic C,
cavities- Heraeus
class II)
Denmark Range: 19–64 84 inlays SR-Iso-sit (ISO) by ISO by
University of years old 56 direct Ivoclar. For indirect Vivadent
Copenhagen (av35) inlays
Operator:One 55 MOD (3
clinician (UP) surfaces
cavities)
Evaluation by Vital teeth
either UP or
UP and VQ

Fennis et al. Authors criteria 157 92 direct 176 hybrid resin Clearfil Mean follow-up time was 5.6 yrs (SD, 0.9
[23] 84 onlays Premolars composite 70% vol, Photobond, yrs; range, 4.5–8.8 yrs) for the direct and
86% wt filler load; Kuraray 6.0 yrs (SD, 1.3 yrs; range, 4.5–8.5 yrs) for
AP-X, Kuraray(direct) the inlays
RCT Kaplan-Meier 77 males, 80 Vital teeth All Class II,
females
Radbound Mean age 54.9 Fracture of Estenia(indirect)
university yrs (range, buccal or
Nijmegen, 35.0–81.0 yrs) palatal
The cusps
Netherlands
Evaluated by
two
clinicians

Cetin et al. [18] Modified 54 108 Molars Indirect: DC for E 5yrs

USPHS, 1.(Estenia [E] inlays
2.Tescera ATL [TATL]) (Panavia)
RCT Statistical 22 males and 41 Indirect inlays 57 Class I Direct: Talt with
analysis fisher 32 females 21(Estenia [E] and 51 Class II 1. Filtek SupremeXT Duo Link
exact test and 20–28yo, 20Tescera ATL [FSXT], (Bisco)
McNemar x2test mean:23yo [TATL]) 2. Tetric Evo Ceram
[TEC
3. AELITE Aesthetic
[AA])
Selcuk Each patient 1 67Direct inlays Vital teeth
university class one and 1 (Filtek SupremeXT
Konya, class II resto- [FSXT], Tetric Evo
Turkey ration Ceram [TEC], AELITE
One clinician Aesthetic [AA])
Evaluation by
two
independent
dentists
(blind)

MO/DO = Mesial Occlusal/ Distal Occlusal.

MOD = Mesial Occlusal Distal.
SD = Standard Deviation.
 F. Angeletaki et al. / Journal of Dentistry 53 (2016) 12–21 15

For continuous data mean difference (MD) and 95% Cls were 2.12. Data synthesis
calculated.
We planned to conduct meta-analyses if there were studies of
2.7. Unit of analysis issues similar comparisons reporting the same outcomes at the same
follow-up periods. Risk ratios were combined for dichotomous
In all cases, the unit of analysis was the restored tooth (number data using fixed-effect models, unless there were more than three
of teeth treated). studies in the meta-analysis, when random-effects models would
have been used.
2.8. Dealing with missing data
3. Results
We contacted study authors via e-mail to request information
where missing. In case of no response, only the available data were 3.1. Description of studies
reported and analyzed. Following our request, Dr. Fennis provided
additional data, concerning the exact time-point that onlays’ A total number of 42 studies were identified as relevant, as
failures had occurred during her trial [23]. screened from the electronic searches and after the specific
inclusion criteria were applied. Many studies concerning direct or
indirect composite inlays separately or in comparison with ceramic
2.9. Assessment of heterogeneity
inlays as well as in-vitro studies and studies assessing veneers were
found, but their outcome was not relevant for this review. After
We assessed clinical heterogeneity by examining the character-
exclusion of all duplicates, the studies were screened and assessed
istics of the studies, the similarity between the types of
for eligibility. 24 studies were discarded after the title-reading
participants, the interventions and the outcomes as specified in
stage and finally 18 abstracts were screened. 4 records met all
inclusion criteria.
eligibility criteria but one was excluded after full text reading,
leaving 3 RCTs (2 regarding direct versus indirect inlays [18,19] and
2.10. Quality assessment 1 regarding direct versus indirect onlays [23]) to be included in this
review (Table 1). The process of study identification is presented in
The methodological quality of RCTs was assessed by two review Fig. 1.
authors, independently and in duplicate, using the Cochrane risk of
bias tool [24]. Risk of bias was assessed and judged for seven 3.2. Quality assessment
separate domains.
The methodological quality of the 3 included RCTs assessed on
 Sequence generation: was the allocation sequence adequately the basis of the Cochrane risk of bias tool is shown in Fig. 2. Only
generated? one study reported an adequate randomization procedure [23].
 Allocation concealment: was allocation adequately concealed? One study was unclear about the randomization method, due to an
 Blinding of participants and investigators: was knowledge of the obvious imbalance between groups and the poor description of the
allocated intervention adequately prevented during the study? restriction methods [19]. One study claimed to having performed
 Blinding of outcome assessors: was knowledge of the allocated randomization after author’s decision and thus it was considered
intervention adequately prevented before assessing the out- as at high risk of bias in this aspect [18]. Allocation concealment
come? was, overall, unclear. Blinding of the clinicians and patients was not
 Incomplete outcome data: were incomplete outcome data always possible due to the nature of the interventions. Losses of
adequately addressed? follow-up were few and if present, they were appropriately
 Selective outcome reporting: were reports of the study free of described. There was no evidence of selective outcome reporting.
suggestion of selective outcome reporting? Two studies, therefore, were classified as at unclear risk of bias
 Other sources of bias: was the study apparently free of other [18,23] and one at high risk of bias [19].
problems that could put it at a high risk of bias?
3.3. Quantitative synthesis of included studies
Each study received a judgment of low risk, high risk or unclear
risk of bias (indicating either lack of sufficient information to make Substantial differences in the interventions, participants, and
a judgment or uncertainty over the risk of bias) for each of the outcomes among studies were observed. Since only one trial
seven domains. Studies were finally grouped into the following concerned onlays [23], quantitative analysis was only feasible
categories: between two studies, regarding direct composite inlays versus
indirect composite inlays [18,19]. Moreover, some variations with
 Low risk of bias (plausible bias unlikely to seriously alter the respect to the type of the cavity, the number of participants and the
results) if all key domains of the study were at low risk of bias. observation period with in the studies included in the meta-
 Unclear risk of bias (plausible bias that raises some doubt about analysis were also evident.
the results) if one or more key domains of the study were
unclear. 3.3.1. Effects of interventions
 High risk of bias (plausible bias that seriously weakens Two trials could be mathematically combined for this
confidence in the results) if one or more key domains were at comparison [18,19]. The inlays compared, were direct or indirect
high risk of bias. placed and made of different composite resin materials. For direct
inlays, Pallesen and Qvist [18] used Brilliant Dentin (BD) and Estilux
Posterior (EP) and for indirect, Brilliant Dentin (BD), Estilux Posterior
2.11. Assessment of reporting bias (EP) and SR-Isosit (ISO). Cetin [19] selected three nanofilled
composite restorative systems (Filtek Supreme XT [FS], 3 M ESPE,
In the presence of more than 10 studies in a meta-analysis, the St. Paul, MN, USA; Tetric EvoCeram [TEC], Ivoclar Vivadent, Schaan,
possible presence of publication bias was investigated. Liechtenstein; AELITE Aesthetic [AA], Bisco, Schaumburg, IL, USA) and
16 F. Angeletaki et al. / Journal of Dentistry 53 (2016) 12–21

Fig. 1. Study flow diagram.

two indirect inlay restorative systems (Estenia [E], Kuraray, Tokyo, restorations scored A (Alpha), B (Bravo), C (Charlie), D (Delta) and
Japan; Tescera ATL [TATL], Bisco, Schaumburg, IL, USA) in his study. results were given in percentage (%) with no detailed number of
The duration of the studies was 5 [19] and 11 years [18]. Clinical patients with missing outcome data.
outcomes were assessed at baseline, 1 and 5 years and at baseline, Since the outcome was measured on individual teeth and not on
2, 5, 8 and 11 years respectively. For both studies included in the patients (clusters), clustering needed to be taken into account for
meta-analysis, clinical outcome assessment involved the modified the meta-analysis. We implemented Generic Inverse Variance
USPHS (United Stated Public Health) criteria [26]. In the Pallesen (GIV) with adjusted standard error. We inflated the variance of the
and Qvist study [18] the clinical aspects evaluated were: anatomic estimate by an amount equal to (1 + (m-1)* ICC), where m is the
form, marginal adaptation, color match, marginal discoloration, average cluster size and ICC the interclass correlation coefficient. A
surface discoloration, cracks and secondary caries. Post-operative conservative value of 0.1 for the ICC was used since we could not
sensitivity symptoms were performed after 1 month, then 6 find an ICC from this or any similar trial. Average cluster size (m)
months and at two years recall. In the Cetin et al. trial [19], the was calculated to be 3.5. Design effect was, therefore, 1.25.
clinical aspects assessed were: surface texture, marginal integrity, Standard Error was, in turn, inflated by the square root of design
marginal discoloration, gingival adaptation, postoperative sensi- effect (1.25), thus by 1.118.
tivity, color match, retention and secondary caries. The numbers of In the Fennis et al. study [23], the onlays compared, were direct
events (direct and indirect composite inlays that received the or indirect composite cuspal restorations made of two composite
worst grades) by the four common criteria (marginal discoloration, resin materials. For direct onlays, Fennis applied a highly filled
color match, post-operative sensitivity, secondary caries) reported hybrid resin composite 70% vol, 86% wt filler load; AP-X, Kuraray
by both studies are presented in Figs. 3–6. and for indirect 82% vol, 92% wt filler load; Estenia, Kuraray. Mean
The Pallesen and Qvist study [18] reported assessment grades follow-up time was 5.6 years (SD: 0.9 years; range, 4.5–8.8 years)
using the 4-step USPHS rating system which reflects absolute for the direct technique and 6 years (SD: 1.3 years; range, 4.5–8.5
differences (restorations scored optimal/acceptable or unaccept- years) for the indirect. Clinical outcome assessment was recorded
able with detailed number of patients and restorations) after 2, 5, 8 on the basis of authors’ predefined criteria and considered as
and 11 years. The Cetin et al. study [19] reported 5-year grades as reparable and complete failure.
 F. Angeletaki et al. / Journal of Dentistry 53 (2016) 12–21 17

3.3.2. Secondary caries

In the Pallesen and Qvist study [18], a relatively low frequency
of secondary caries was detected for the direct and indirect
composite restorations. More specifically, two direct restorations
(4%) had been detected with secondary caries in the proximal
gingival area at 5 and 9.2 years. Four indirect inlays (6%) in four
teeth were diagnosed with secondary caries at 6.5, 6, 8 and 8.8
years respectively. Cetin et al. in his RCT [19] required replacement
of only one direct composite restoration (member of TEC group)
due to secondary caries, after three years. The meta-analysis
indicated no statistically significant differences in the risk ratio
between direct versus indirect composite inlays in this aspect (RR:
0.93; 95% Cl: 0.21, 4.04; p = 0.92), (Fig. 3). Cluster analysis was not
performed for this parameter, as in Cetin et al. study [19] only one
event was present. Finally, in the Fennis et al. study [23], secondary
caries has been reported at only one indirect inlay.

3.3.3. Postoperative sensitivity

Regarding postoperative sensitivity, Cetin et al. [19] reported
sensitivity to 4% of the restorations (three indirect, one direct);
however only one indirect inlay required canal treatment and
replacement after two years. Similarly, Pallesen and Qvist [18]
found 7% and 10% of post-operative sensitivity for direct and
indirect inlays respectively. The findings suggest that there is
insignificant difference between the two methods and meta-
analysis risk ratio results also confirm that (RR: 0.60, 95% Cl: 0.19,
Fig. 2. Risk of bias summary for included RCTs: the plus sign indicates low risk of 1.90; p = 0.38), (Fig. 4). According to Fennis et al. [23], one direct
bias; the circle with question mark indicates unclear risk of bias; the minus sign onlay restoration had to be replaced due to post-operative
indicates high risk of bias. sensitivity and was considered failed.

As failures, were considered restorations, in need of repair or 3.3.4. Esthetic quality

replacement. Type and time they occurred are described in Regarding color match and marginal discoloration, a detailed
Tables 2a and 2b. Regarding inlays, the random-effects meta- report was given by Pallesen and Qvist [18], where inlays scored
analysis indicated no statistically significant difference in the risk better than fillings. Color match and discoloration of the margin
failure between direct versus indirect inlays, after 5 years of were 44%–50% respectively for indirect inlays and 33%–26% for
function (RR: 1.54; 95% Cl: 0.42, 5.58; p = 0.52) (Fig. 7), although fillings which is reported as a significant difference only for
results turn slightly in favor of indirect. However, when the marginal discoloration, in favor of fillings. In the Cetin trial [19], at
observation time exceeds to 11 years, results are gravitated five-year evaluation, color match was predominately scored as
towards direct composite restorations, although no statistical Alpha for all groups. At the same time marginal discoloration was
significant difference was observed (RR: 0.95; 95% Cl: 0.34, 2.63; scored as Alpha for both direct and indirect composite restorations
p = 0.92) (Fig. 8). The degree of heterogeneity between studies was but there was statistical significant differences between two direct
found to be overall low (I2 = 0%). Statistical analysis of the materials (AA 64%: AELITE Bisco, Schaumburg, IL, USA and TEC 95%
publication bias was not possible, as only two studies were Tetric Evo Ceram). The meta-analysis of Pallesen & Qvist and Cetin
included in the quantitative synthesis. trials [18,19], indicated no statistically significant differences in the
Regarding onlays, the distribution of failure categories is shown risk of color match between the two techniques (RR: 0.62; 95%Cl:
in Table 2b. The mean follow up time of failures was 35.4 months 0.26, 1.47; p = 0.28), (Fig. 6). However, overall marginal discolor-
(SD, 20.9 months) for the direct technique and 37.4 months (SD, ation risk ratio was statistically in favor of direct inlays (RR: 0.41;
14.4 months) for the indirect technique. An overall five-year 95% Cl: 0.17, 0.96; p = 0.04), (Fig. 5). No information was reported by
survival of 87% (95% CI = 81–93%) of Class II cavity and a missing Fennis et al. in their RCT [23] regarding those parameters.
cusp restorations was obtained (pooled Kaplan-Meier analyses).
Five-year survival rate was higher for direct than indirect 4. Discussion
restorations for both repairable (89.9% vs 83.2%) and complete
failures (91.2% vs 83.2%), however differences were not statistically The aim of the present systematic review was to search the
significant (reparable failure 95% CI = 5.1–18.5%, p = 0.23, com- relevant literature for RCTs assessing the long-term clinical
plete failure, 95% CI = 3.6–19.6%, p = 0.15). behavior of direct and indirect composite inlays/onlays as well

Fig. 3. Forest plot of comparison of direct vs indirect inlays regarding secondary caries during 11 years.
18 F. Angeletaki et al. / Journal of Dentistry 53 (2016) 12–21

Fig. 4. Forest plot of comparison of direct vs indirect inlays regarding post-operative sensitivity (Cluster level analysis).

Fig. 5. Forest plot of comparison of direct vs indirect inlays regarding marginal discoloration during 11 years (Cluster level analysis).

Fig. 6. Forest plot of comparison of direct vs indirect inlays regarding color match during 11 years (Cluster level analysis).

Table 2a
Types and time of failure (Inlays).

Study Pallesen and Qvist [18] Cetin et al. [19]

Direct Indirect Direct Indirect
Failures N Years N Years N Years N Years
Secondary caries 2 5; 9.2 4 6; 8; 8.8 1 3 0
(replaced) (replaced) (replaced)
6.5 (repaired)
Loss of proximal contact 2 1; 1 (replaced) 0 0 0
Occlusal Fracture 4 5; 5; (repaired) 1 5 (replaced) 0 0
9.9; 10 (replaced)
Fracture of the marginal ridge 0 4 1.5; 7; 10.1 (replaced) 0 0
5 (repaired)
Debonding of the restoration 0 1 2.7 (replaced) 0 0
Cusp Fracture 0 2 7; 8 (replaced) 0 0
Endodontic treatment 1 2
(replaced)

Table 2b
Types and time of failure (Onlays).

Study Fennis et al. [23], after e-mail communication

Direct Indirect

Failures N Years N Years

Secondary caries 0 1 2.6 (replaced)
Debonding of the restoration 1 3.8 (replaced) 4 1.8; 2.3; 2.5 (repaired)
3.2 (replaced)
Cusp Fracture 3 1.8; 3.7; 4.2 (replaced)
Cohesive failure 2 0.6 (replaced) 1 0.6 (replaced)
4.1 (repair)
Dislodgement and cohesive failure 3 2.8; 4; 4.4 (replaced)
Endodontic treatment 2 2.2; 3.1 (replaced)
 F. Angeletaki et al. / Journal of Dentistry 53 (2016) 12–21 19

Fig. 7. Forest plot of comparison of direct vs indirect inlays, regarding restorations’ failure (restorations in need of repair or replacement at 5 years), (Cluster level analysis).

Fig. 8. Forest plot of comparison of direct vs indirect inlays, regarding restorations’ failure (restorations in need of repair or replacement at 11 years), (Cluster level analysis).

to identify factors that influence the risk of failure. To our There are only few clinical studies in the literature that compare
knowledge, a similar systematic review has yet not been published. direct and indirect composite restoration and these are mostly
The review examined reports of 3 randomized controlled trials short-term [4,29,30]. According to the results of a review by Hickel
[18,19,23]. Only one study, by Fennis et al. [23], dealt with onlays, and Manhart in 2001 [31], annual failure rate of composite inlays
and couldn’t, therefore, be part of a quantitative analysis. An and onlays ranged from 0% to 11.8%. Individually, concerning direct
overall five-year survival of 87% (95% CI = 81–93%) of Class II cavity posterior composite restorations, it has been reported by Manhart
and a missing cusp restorations was obtained. That reveals high et al. annual failure rates from 0,3% to 4.5%, in an observation
survival rates of composite restorations in premolars for both period of 3–17 years [32]. Regarding indirect composite inlays,
techniques (direct or indirect). These results are in agreement with different studies have shown annual failure rates from 1.6% to 4.8%
other studies, supporting that both direct [16,17] and indirect after 5–11 years [16,33,34]. In the Pallesen and Qvist study [18]
onlays composite restorations [25,26] offer a predictable and annual failure rate of direct/indirect inlays after 11 years was 1.5%
successful treatment modality in combination with preservation of (range 1–2%) and in the Cetin et al. study direct/indirect restoration
sound tooth tissue. Furthermore, the minimally cavity prepara- annual failure rate was 1.6% and 2.5% respectively, which is within
tions applied for both techniques and the possibility of repair, as the range of the published data.
the nature of the material permits it, makes direct and indirect Regarding aesthetic aspects, in Pallesen and Qvist study [18],
composite onlays equal recommendable. 44% of indirect inlays and 33% of direct inlays showed optimal or
Five-year failure rate was higher for indirect onlays than direct. acceptable color match and BD filling material showed better color
However, differences were not statistically significant (reparable match than BD inlay material (p < 0.05). Additionally, in Cetin et al.
failure, 95% CI = 5.1 to 18.5%, p = 0.23 complete failure, 95% study color match was 100% A for the 2 direct composite materials
CI = 3.6 to 19.6%, p = 0.15). The reason of failure was predomi- (FS, TEC) and for one indirect (E) but 95% A for 1 indirect (TATL) and
nantly fracture and cohesive restoration failure for direct restora- one direct (AA) at 5 years. The meta-analysis of Pallesen & Qvist
tions and dislodgment together with cohesive failures for indirect. and Cetin trials [18,19], indicated no statistically significant
Secondary caries was reported at only one indirect onlay. One differences in the risk ratio of color match between the two
direct onlay restoration had to be replaced due to post-operative techniques (RR: 0.62; 95%Cl: 0.26, 1.47; p = 0.28), (Fig. 6) after five
sensitivity. Although baseline and five years clinical evaluation of to eleven years. A decreased, but insignificant frequency of perfect
the two techniques revealed no statistical significant difference, color match has been reported for both techniques in studies with
direct technique seems to be the most favorable mostly due to the an observation period up to 10 years [16,35].
lower treatment time and less cost [27]. A similar short-term RCT Another parameter than has been evaluated is that of marginal
[28] reported that the indirect and direct cusp-replacing composite discoloration. Pallesen and Qvist [18], reported discoloration of the
resin restorations provided comparable results for proximal and margin for 50% of indirect inlays and 26% of direct. The least
occlusal contacts, post-operative sensitivity and color. Neverthe- marginal discoloration was found in BD and EP direct materials,
less, there is a lack of evidence in the literature concerning the although no statistical significant difference was observed. ISO
selection of direct or indirect resin composite onlay technique. material for direct and indirect inlays was found at the highest
Regarding inlays, two studies met all eligibility criteria for frequency of marginal discoloration with 45% and 67% respectively.
inclusion in this review [18,19]. Failures necessitating restoration Same results concerning ISO inlay material have been reported by
with replacement or repair were well reported for both studies. Hannig in 1996 after 7 years [36]. In the Cetin et al. study [19],
Failure data for inlays were combined: the resulting overall 5-year marginal discoloration was scored as Alpha for both direct and
failure risk ratio was 1.54 (95% Cl: 0.42, 5.58; p = 0.52) (Fig. 7) in indirect composite restorations but there were statistically
favor of indirect. The 11-year failure risk ratio was 0.95 (95% Cl: significant differences between two direct materials (AA 64%:
0.34, 2.63; p = 0.92) (Fig. 8) in favor of direct composite inlays, AELITE Bisco, Schaumburg, IL, USA and TEC 95% Tetric Evo Ceram/
although no statistically significant difference was observed at Ivoclar). The overall marginal discoloration risk ratio was statisti-
both time-points. However, it should be noted that these results cally in favor of direct inlays (RR: 0.41; 95% Cl: 0.17, 0.96; p = 0.04),
were generated by combining only two trials with a relatively small (Fig. 6) after five to eleven years. A major reason of marginal
sample size and at questionable risk of bias. discoloration of indirect inlays was the loss of cement due to wear
20 F. Angeletaki et al. / Journal of Dentistry 53 (2016) 12–21

[32,37]. Contrary, a higher rate of marginal discoloration in favor of Finally, the observation time differed between the studies (5 versus
direct composite inlays has been reported from other studies 11 years) and the composite restorative materials utilized were
[16,30,34], but with insufficient significant differences. However, it various. Nevertheless, the statistical analysis, tried to minimize
is not surprising to see controversial results between studies as the these imbalances, and, indeed, was performed at a great extent in a
materials and techniques used from authors varied. Nevertheless, homogeneous sample and materials assessing common outcomes
it has to be noted that inadequate blinding of outcome assessment at common time-points, taking clustering into consideration, as
has much higher risk for introducing bias, in parameters like well.
marginal discoloration which may considered a subjective
outcome [37]. 4.2. Implications for research
Many studies have verified that main reasons for failure of
composite inlays include secondary caries and postoperative The control of multiple variables necessary for such RCTs makes
sensitivity [11,16,18,38]. In the present review, secondary caries the designing of new studies difficult. Moreover, the strict
was the principal reason of failure. In the Pallesen and Qvist study, inclusion criteria needed and the lack of patients with specific
two direct restorations (4%) had been detected with secondary characteristics willing to participate in a study make it difficult to
caries in the proximal gingival area at 5 and 9,2 years and four achieve a proper sample size. These reasons, as well as the long
indirect inlays (6%) in four teeth were diagnosed with secondary follow-up observation period that is often required for such
caries at 6.5, 6, 8 and 8.8 years. Cetin et al. in their RCT [19] required studies, may explain the scarcity of research in the field.
replacement of only one direct composite restoration (member of Consequently, greater attention to the design and reporting of
TEC group) due to secondary caries, after three years. The low studies should be given in order to improve the quality of clinical
incidence of secondary caries at Cetin et al. trial may be explained trials on composite inlays/onlays. In our review, the minimum
by the newer generation bonding agents in combination with all- follow-up period accepted was 3 years for the analysis of the long-
enamel margins restorations included in the study. The meta- term behavior of those techniques, as this may represent better the
analysis indicated no statistically significant differences in the risk patients’ interests. Thus, more long-term RCTs are required.
ratio between direct versus indirect composite inlays (RR: 0.93;
95% Cl: 0.21, 4.04; p = 0.92), (Fig. 3) in this aspect, after five to eleven 5. Conclusions
years. However in Pallesen and Qvist study [18] it is mentioned
that the actual study population showed low to moderate caries Overall, there is insufficient evidence to make strict recom-
activity and in Cetin et al. trial that the restorations were carried mendations in favor of direct over indirect technique. The results of
out by excellent clinicians under optimal conditions, while patients our review and meta-analysis derive from studies with unclear and
were specifically selected for good compliance. Thus, these high risk of bias. Certainly, further well-designed long-term
parameters are likely to have an important impact on our studies should be undertaken in order to make more meaningful
confidence in the estimate effect and may change the estimate comparisons or recommendations about both techniques.
in ‘real-life’ circumstances.
In the evaluation of the criterion hypersensitivity, Pallesen and Funding
Qvist trial [18] showed better results for direct (7%) than indirect
(10%) inlays while Cetin et al. [19] reported sensitivity for five teeth No funding was obtained for this review.
at baseline and one indirect inlay that required canal treatment;
Meta-analysis on clusters (RR: 0.60, 95% Cl: 0.19, 1.90; p = 0.38), Conflict of interest
(Fig. 4) suggested that there is insignificant difference between the
two methods after five to eleven years, although results were in The authors declare no conflict of interest on relevant
favor of direct inlays. Postoperative hypersensitivity is usually an composite resin materials.
early complication of dental restorations, often encountered after
the luting of the adhesive restoration [33,39]. The high incidence of Appendix A.
post-operative sensitivity at the Pallesen and Qvist study [18]
compared to Cetin et al. [19] can be attributed to the older bonding
agents and resin cements available at that time. Lastly, the isolation Medline via Pubmed, search date: 14.12.2015.
method of the operative field (cotton rolls but no rubber dam used
in any of the studies) was found not to influence the failure rate. #1 dental inlay 3828
That was in agreement with the study of Raskin et al., where in a #2 dental onlay 3762
ten-year evaluation of posterior composite restorations, no #3 (dental onlay) OR dental inlay 4151
significant differences were observed between these two isolation #4 (((dental onlay) OR dental inlay)) AND indirect[Title/Abstract] 450
methods [40]. #5 (((dental onlay) OR dental inlay)) AND direct[Title/Abstract] 350
#6 (((((dental onlay) OR dental inlay)) AND direct[Title/Abstract])) 608
OR ((((dental onlay) OR dental inlay))
4.1. Quality of the evidence AND indirect[Title/Abstract])
#7 (((((dental onlay) OR dental inlay)) AND direct[Title/Abstract])) 33
The present systematic review is not free of limitations. The OR ((((dental onlay) OR dental inlay)) AND indirect[Title/
Abstract]) Filters: Randomized Controlled Trial
number of the studies included (2 RCTs for inlays and one RCT for
#8 ((posterior[Title/Abstract]) AND restoration*[Title/Abstract]) 521
onlays) and the sample size (157 patients with 176 restorations for AND (direct[Title/Abstract] OR indirect[Title/Abstract])
direct/indirect onlays and 82 patients with 248 restorations for #9 ((posterior[Title/Abstract]) AND restoration*[Title/Abstract]) 29
direct/indirect inlays) may be regarded as relatively small. The AND (direct[Title/Abstract] OR indirect[Title/Abstract])
included studies, moreover, were found to be at unclear or high risk Filters: Randomized Controlled Trial
#10 (((((((dental onlay) OR dental inlay)) AND direct[Title/Abstract])) 14
of bias. Additionally, included trials concerning inlays, had some
OR ((((dental onlay) OR dental inlay))
methodological issues: although both trials [18,19] presented low AND indirect[Title/Abstract]))) AND (failure OR success)
heterogeneity regarding the cavity size, tooth type was different; Filters: Randomized Controlled Trial
only molars were restored in Cetin et al. study [19], whereas molars #11 (((((((dental onlay) OR dental inlay)) AND direct[Title/Abstract])) 1
OR ((((dental onlay) OR dental inlay))
and premolars were restored in Pallesen and Qvist study [18].
 F. Angeletaki et al. / Journal of Dentistry 53 (2016) 12–21 21

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