Appendix
Appendix 1. Search strategy for MEDLINE via PubMed
Appendix 2. Articles excluded from this review
Appendix 3. Risk of bias in included studies
Appendix 4. Grade profile table
1
Appendix 1. Search strategy for MEDLINE via PubMed
#1
"tooth remineralization"[MeSH]
#2
"tooth demineralization"[MeSH]
#3
“dental caries”[MeSH]
#4
“white spot lesion” OR “white spot”[Title/Abstract]
#5
“biofilm” OR “biofilms”[MeSH]
#6
“dental plaque”[MeSH]
#7
“decay, dental”[MeSH]
#8
#1 or #2 or #3 or #4 or #5 or #6 or #7
#9
“arginine”[Title/Abstract]
#10 “cavistat”[Title/Abstract]
#11 #9 or #10
#12 #8 and #11
2
Appendix 2. Articles excluded from this review
Article
Reason for exclusion
Santarpia III RP, Lavender S, Gittins E, Vandeven M, Cummins D, Sullivan R: Focused on the effect
A 12 week clinical study assessing the in vivo effects on plaque metabolism of of arginine on plaque
a dentifrice containing 1.5% arginine, an insoluble calcium compound and 1450 metabolism
ppm fluoride.
Shapira J, Sgan-Cohen HD, Stabholz A, Sela MN, Schurr D, Goultschin J: Focused on the effect
Clinical
and
microbiological
effects
of
chlorhexidine
and
arginine of arginine on plaque
sustained-release varnishes in the mentally retarded. Special care in dentistry metabolism, and
1994;14:158-163
patients were
intellectually disabled
Vuletic L, Spalj S, Rogic D, Ruzic L, Alajbeg I: Effect of L-arginine dietary Focused on the effect
supplementation on salivary urea concentration and pH in physically active of arginine on plaque
individuals. Australian Dental Journal 2013;58:491–497
metabolism
Wolff M, Corby P, Klaczany G, Santarpia P, Lavender S, Gittins E, Vandeven Focused on the effect
M, Cummins D, Sullivan R: In Vivo Effects of a New Dentifrice Containing of arginine on plaque
1.5% Arginine and 1450 ppm Fluoride on Plaque Metabolism. J Clin Dent metabolism
2013;24[Spec Iss A]:45–54.
Burne RA, Marquis RE: Alkali production by oral bacteria and protection Review article
against dental caries. FEMS Microbiology Letters 2000;193:1-6.
Burne RA, Zeng L, Ahn SJ, Palmer SR, Liu Y, Lefebure T, Stanhope MJ, Review article
Nascimento MM: Progress dissecting the oral microbiome in caries and health.
Advances in Dental Research 2012;24:77-80.
Cummins, D: Dental caries: a disease which remains a public health concern in Review article
the 21st century--the exploration of a breakthrough technology for caries
prevention. Journal of Clinical Dentistry 2013;24[Spec Iss A]:1–14.
Liu,
Ya-Ling,
Nascimento
Marcelle,
Burne,
RA:
Progress
toward Review article
understanding the contribution of alkali generation in dental biofilms to
inhibition
of
dental
caries.
International
Journal
Of
Oral
Science
2012;4:135-140.
3
Reyes Beltrán Évelyn, Martín Casielles Javier, Yevenes López Ismael, Neira Review article
Jara Miguel, Palma Fluxá Patricia, Gordán Veiga
Valeria, Moncada Cortés
Gustavo: Activity and effects of urease and arginine deiminase in saliva and
oral human biofilm. Revista Facultad de Odontología Universidad de Antioquia
2012;23:343-352.
Ten Cate J M, Cummins D: Fluoride toothpaste containing 1.5% arginine and Review article
insoluble calcium as a new standard of care in caries prevention. Journal of
Clinical Dentistry 2013;24:79-87.
Vranic L. Granic P, Rajic Z: Basic amino acid in the pathogenesis of caries. Review article
Acta stomatologica Croatica 1991;25:71-76.
Cummins D: The development and validation of a new technology, based upon Review article
1.5% arginine, an insoluble calcium compound and fluoride, for everyday use
in the prevention and treatment of dental caries. Journal of Dentistry 2013;41
Supplement 2:S1-11.
Scannapieco FA: Monitoring the Efficacy of Plaque Control Method. Review article
Periodontology 2000 1995;8:24-41.
Ellwood R: Benefits of a dentifrice containing 8% arginine, calcium carbonate, Review article
and sodium monofluorophosphate on enamel erosion. Journal of Clinical
Dentistry 2014;25(1 Spec No A):A1-2.
Acevedo A M, Chatterjee R., Kleinberg, I: Calcium arginine phytates, a series Meeting abstract
of
multi-factorial
anti-caries
agents.
Journal
Of
Dental
Research
1998;77:257-257.
Acevedo M, Machado C, Wolff MS, Kleinber I: Initial examination of a Meeting abstract
CaviStat (R)-containing dentifrice on caries development in Venezuelan
children. Journal Of Dental Research 2003;82:354-354.
Bretz Walter A: Arginine Metabolism in Dental Plaque Is Associated With Not RCT
Tooth Surface Dental Caries Status. Journal of Evidence Based Dental Practice.
2014;14:42-43.
Nascimento MM, Browngardt C, Xiaohui X, Klepac-Ceraj V, Paster BJ, Burne Not RCT
RA: The effect of arginine on oral biofilm communities. Molecular Oral
4
Microbiology 2014;29:45-54.
Nascimento MM, Gordan VV, Garvan CW, Browngardt CM, Burne RA: Not RCT
Correlations of oral bacterial arginine and urea catabolism with caries
experience. Oral Microbiology And Immunology 2009;24:264-264.
Abelson DC, Vratsanos S M, Mandel ID: Modification of dental plaque by Not RCT
arginine-urea to resist pH fall in vivo. Clinical Preventive Dentistry
1986;8:7-10.
Acevedo AM, Machado C, Rivera LE, Wolff M, Kleinberg I: The inhibitory Not RCT
effect of an arginine bicarbonate/calcium carbonate CaviStat-containing
dentifrice on the development of dental caries in Venezuelan school children.
Journal of Clinical Dentistry 2005;16:63-70.
Sullivan R, Rege A, Corby P, Klaczany G, Allen K, Hershkowitz D, Goldder Not RCT
B, Wolff M: Evaluation of a dentifrice containing 8% arginine, calcium
carbonate, and sodium monofluorophosphate to repair acid-softened enamel
using an intra-oral remineralization model. Journal of Clinical Dentistry
2014;25(1 Spec No A):A14-9.
5
Appendix 3. Risk of bias in included studies
A．M Acevedo/2008
Item
Authors’
Description
judgement
Random
Unclear
Comment: Insufficient information is provided regarding the sequence
sequence
generation process.
generation
Quote: “A double-blinded, randomized and controlled clinical trial of one
year’s duration was initiated in children… Children entered into the study
were randomly divided into two groups (A and B), with distribution being
performed on the basis of matching the DMFS (decayed, missing, filled
surfaces) levels of their first permanent molars as closely as possible.”
Allocation
Unclear
Comment: The method of concealment is not described.
Unclear
Comment: Whether the personnel were blinded is unclear.
concealment
Blinding of
participants
Quote: “A double-blinded, randomized and controlled clinical trial of one
and personnel
year’s duration was initiated in children.” “Packaging and appearance of
both types of mints were identical, except for their A and B designations.”
Blinding of
Yes
Quote: “The examiner performing the clinical examinations did not know
outcome
which group was which, or which of products A and B contained CaviStat.
assessment
Dental radiographs were not taken.”
Incomplete
Unclear
Comment: No reasons for missing data are provided.
outcome data
Quote: “Out of the 200 children selected, 195 ultimately finished the
addressed
one-year study with complete data.”
Free of
No
Comment: The total number of initial lesions is not reported.
selective
Quote: “The caries experience was expressed as DMFS, and the total number
reporting
of initial lesions was calculated only for the first permanent molars by
summing the total number of such demineralization lesions detected before
and after drying the enamel surface.”
Losses to
follow-up less
Yes
Quote: “Out of the 200 children selected, 195 ultimately finished the
one-year study with complete data.”
than 20%
6
Diagnosis
Yes
reliability
Quote: “Re-examination of 10% of the subjects was done by the single
examiner, and the data were used to determine her consistency by Cohen
Kappa analysis. 10 Subjects were randomly selected at different times in the
study for this re-examination. The Kappa value obtained before the final
examination (January, 2006) for the first group of subjects was 0.99, and for
the second group (May, 2006) it was 0.99 as well.”
Baseline
Yes
Quote: “These numbers were essentially the same, because the matching of
characteristics
the two groups of subjects at baseline was performed to try to distribute
balance
subjects evenly.”
Free of
Unclear
contamination
Comment: No strategies for avoiding contamination between groups are
mentioned.
R. Cantore/2013
Item
Authors’
Description
judgement
Random
Unclear
Comment: Insufficient information is provided regarding the sequence
sequence
generation process.
generation
Quote: “Each study utilized a randomized, double-blind, crossover design,
with a balanced order presentation to further minimize potential carryover
effects.”
Allocation
Yes
concealment
Quote (via email): “Subjects were assigned their number based on the order
of the screening to see whether or not they could participate. Subjects did not
know their number nor did they know of treatment sequence in advance of
the study. A person not involved in the study kept the code for the treatment.
The code was broken after the statistical analysis was complete” ”
Blinding of
Yes
Quote (via email): “Each study utilized a randomized, double-blind,
participants
crossover design. All of the dentifrices were over-wrapped and coded to
and personnel
blind the studies. A person not involved in the study kept the code for the
treatment. The code was broken after the statistical analysis was complete”
Blinding of
outcome
Yes
Quote (via email): “A person not involved in the study kept the code for the
treatment. The code was broken after the statistical analysis was complete”
7
assessment
Incomplete
Yes
Comment: Reasons for missing outcome data unlikely to be related to true
outcome data
outcome, and plausible effect size (difference in means or standardized
addressed
difference in means) among missing outcomes is likely insufficient to have a
clinically relevant impact on observed effect size.
Quote: “The inability of one subject to complete the study was not related to
product use, rather a result of personal reasons unrelated to the study.”
Free of
Yes
selective
Comment: Average mineral changes in the enamel-thin sections from
micro-radiography are reported.
reporting
Losses to
Yes
Quote: “Twenty-nine of thirty panelists successfully completed the study.
follow-up less
The inability of one subject to complete the study was not related to product
than 20%
use, rather a result of personal reasons unrelated to the study.”
Diagnosis
Unclear
reliability
Baseline
Comment: Number of examiners and the inter/ intra-examiner reliability are
not reported.
Unclear
characteristics
Comment: No detailed information is provided regarding the baseline caries
level of the subjects.
balance
Free of
Unclear
contamination
Comment: No strategies for avoiding contamination between groups are
mentioned.
D.Y. Hu/2013
Item
Authors’
Description
judgement
Random
Unclear
Comment: Insufficient information is provided regarding the sequence
sequence
generation process.
generation
Quote: “This six-month study was a randomized, controlled, double blind
clinical trial...Subjects meeting the screening criteria were recruited and
randomly allocated to groups.”
Allocation
concealment
Unclear
Quote (via email): “Study personnel received 3 kinds of toothpaste labeled
A, B and C from the Colgate-Palmolive Company, but they did not know
8
what exactly those toothpaste were. The formulation of each toothpaste was
not broken until the trial was finished.”
Blinding of
Unclear
Comment: Insufficient information is provided regarding the blinding of
participants
personnel.
and personnel
Quote: “This six-month study was a randomized, controlled, double blind
clinical trial...The tubes were individually labeled for each study participant,
and supplied in plain white containers to conceal the identity of the product.
Blinding of
Yes
Quote: “This six-month study was a randomized, controlled, double blind
outcome
clinical trial” “The examiners did not know the product content for each
assessment
participant until the trial was finished.”
Incomplete
Yes
Comment: Missing outcome data are balanced in number among intervention
outcome data
groups, with similar reasons (provided in Figure 2) for missing data among
addressed
groups.
Quote: “At the three-month examination, sixteen subjects were lost from the
study, and by the six-month examination, a further sixteen subjects were lost
(Figure 2). ”
Free of
Yes
selective
Comment: Clinical hardness and the mean electrical caries monitor
resistance values were reported at baseline and after three and six months.
reporting
Losses to
Yes
Quote: “Of these subjects, 444 satisfied the inclusion and exclusion criteria,
follow-up less
had a baseline examination, and were recruited into the study. At the
than 20%
three-month examination, sixteen subjects were lost from the study, and by
the six-month examination, a further sixteen subjects were lost (Figure 2).”
Diagnosis
Yes
reliability
Quote: “The Kappa value for intra-examiner reproducibility for the hardness
scores was 0.92. The Intra Class Correlation Coefficient was calculated from
the log10 ECM value of lesions and sound tissues around lesions. The ICC
values were 0.89 for lesions and 0.92 for sound tissues.”
Baseline
Yes
Quote: “Overall these data demonstrate excellent baseline balance between
characteristics
the study groups, with no statistically significant differences identified for
balance
any of the paired comparisons (p > 0.05).”
9
Free of
Yes
contamination
Quote: “Only one type of toothpaste was assigned per family, and additional
tubes of toothpaste were available upon request from participants. To help
ensure the products were being used by the study participants, at both the
three- and six-month examinations, empty and partially used tubes were
returned to the study site before additional toothpaste was supplied.”
P. Kraivaphan/2013
Item
Authors’
Description
judgement
Random
Yes
Quote: “Qualified subjects were randomly assigned to one of the three study
sequence
treatments using a randomization table generated centrally by the study
generation
statistician.”
Allocation
Unclear
Comment: The method of concealment is not described.
Unclear
Comment: Whether the personnel were blinded is unclear.
concealment
Blinding of
participants
Quote: “This six-month study was a randomized, controlled, double blind
and personnel
clinical trial…The tubes of dentifrice were completely wrapped in white tape
so that neither the examiners nor the subjects were aware of the identity of
the product they were using.”
Blinding of
Yes
Quote: “The tubes of dentifrice were completely wrapped in white tape so
outcome
that neither the examiners nor the subjects were aware of the identity of the
assessment
product they were using.”
Incomplete
Yes
Comment: Missing outcome data are balanced in number among intervention
outcome data
groups, with similar reasons (provided in Figure 1) for missing data among
addressed
groups.
Quote: “6,000 were assigned to one of the three study groups, whereas 90
who were unavailable for examination were excluded from the study (Fig.
1).”
Free of
selective
Yes
Comment: Clinical examinations with DMFT and DMFS scores at baseline
and after 1 and 2 years are reported.
reporting
10
Losses to
Yes
Quote: “6,000 were assigned to one of the three study groups, whereas 90
follow-up less
who were unavailable for examination were excluded from the study (Fig.
than 20%
1).”
Diagnosis
Yes
reliability
Quote: “The kappa statistics for inter- and intra-examiner reproducibility of
DMFT and DMFS were all >0.83, indicating a high level of agreement
within and between the three examiners.”
Baseline
Yes
Quote: “No statistically significant differences in either DMFT or DMFS
were indicated among the three groups (table 2 ).”
characteristics
balance
Free of
Yes
contamination
Quote: “School nurses monitored the tooth brushing of subjects by interview,
collection of used toothpaste tubes and assessment of oral hygiene. When the
subjects received new supplies of dentifrice and toothbrushes, the clinical
team checked and reviewed returned/used dentifrices to help ensure
compliance.”
M.L.R. Souza/2013
Item
Authors’
Description
judgement
Random
Unclear
Quote: “Participants were allocated to one of two groups using a sequence of
codes randomly generated by the study administrator.”
sequence
generation
Allocation
Yes
concealment
Quote (via email): “The tubes were individually labeled for each study
participant and supplied in plain white containers to conceal the identity of
the product. Product allocation was conducted blind to the examining dentist.
The allocation sequence was developed by the study statistician separate to
those doing the allocation.”
Blinding of
Unclear
Comment: Whether the personnel were blinded is unclear.
participants
Quote: “The tubes were individually labeled for each study participant and
and personnel
supplied in plain white containers to conceal the identity of the product.”
Blinding of
outcome
Yes
Quote (via email): “The study was conducted under blind conditions for the
subjects and examiners.”
11
assessment
Incomplete
Yes
Comment: Missing outcome data are balanced in number among intervention
outcome data
groups, with similar reasons (provided in Figure 1) for missing data among
addressed
groups.
Quote: “A total of 129 of 144 subjects were included in the final statistical
analysis for the experimental group and 124 of 140 in the positive control
group. Reasons for loss from the study are tabulated in Fig. 1.”
Free of
Yes
selective
Comment: Clinical hardness at baseline and after three and six months is
reported.
reporting
Losses
to Yes
Comment: Two hundred and eighty-four subjects entered the study, and 38
follow-up less
subjects were lost during follow-up. The dropout rates of the experimental
than 20%
and control groups were 13.2% and 13.6%, respectively.
Diagnosis
Unclear
reliability
Baseline
Comment: The number of examiners and the inter/intra-examiner reliability
are not reported.
Yes
Comment: Slight baseline imbalance was present but unlikely to lead to
characteristics
exaggerated effect estimates.
balance
Quote: “It can be seen that there was some evidence of baseline imbalance
with lesions tending to be larger in area (p=0.022) in the arginine-containing
dentifrice group than in the positive control group. The results of the logistic
regression analysis, show in Table 3, indicate that these differences would
increase the probability that a lesion would not become hard for the
arginine-containing dentifrice group compared to the positive control.”
Free of
Yes
contamination
Comment: Only one type of toothpaste was assigned per family, and
additional tubes of toothpaste were available upon participant request. To
help ensure that the products were being used by the study participants, at
both the 3- and 6-month examinations, empty and partially used tubes were
returned to the study site before additional toothpaste was supplied.
P. Srisilapanan/2013
Item
Authors’
Description
12
judgement
Random
Unclear
Quote: “Students meeting the inclusion criteria were centrally, randomly
sequence
allocated to study group by the study administrator using a randomly
generation
generated series of numbers.”
Allocation
Yes
concealment
Quote (via email): “All dentifrices were supplied in identical white laminated
tubes and the products were identical in terms of taste and consistency.
Product allocation was conducted blind to the examining dentist. The
allocation sequence was developed by the study statistician separate to those
doing the allocation.”
Blinding of
Yes
Quote: “This study was a randomized, double-blind controlled clinical
participants
trial…All dentifrices were supplied in identical white laminated tubes and
and personnel
the products were identical in terms of taste and consistency.”
Blinding
Quote (via email): “The study was conducted under blind conditions for the
of Yes
subjects and examiners.”
outcome
assessment
Incomplete
Yes
Comment: Missing outcome data are balanced in number among intervention
outcome data
groups, with similar reasons for missing data among groups.
addressed
Quote: “Between the baseline and 3-month examination, six students were
lost from the study as they had moved to other schools. Between the 3- and
6-month examinations, a further four children were lost from the study for
the same reason.”
Free of
Yes
Comment: The mean subject △Q at the 6-month examination is reported.
Yes
Quote: “Of the consenting students, 341 children satisfied the inclusion
selective
reporting
Losses to
follow-up less
criteria and were recruited into the study…A total of 331 students completed
than 20%
the study of which 166 used the test dentifrice containing 1.5% arginine, and
165 used the positive control dentifrice with fluoride alone.”
Diagnosis
reliability
Yes
Quote: “All images were taken by the same examiner. For 34 subjects,
duplicate baseline images were captured without the video repositioning
13
function to assess the reproducibility of the method. For DQ, the Intra Class
Correlation Coefficients (ICC) at the baseline, 3- and 6-month examinations
were, respectively, 0.95, 0.95 and 0.94 between the original and duplicate
image sets.”
Baseline
Yes
Quote: “For both groups, the mean values for all parameters were not
statistically significant different indicating good baseline balance.”
characteristics
balance
Free of
Unclear
contamination
Comment: No strategies for avoiding contamination between groups are
mentioned.
W. Yin/2013 a
Authors’
Item
Description
judgement
Random
Unclear
Comment: Insufficient information is provided regarding the sequence
sequence
generation process.
generation
Quote: “This six-month study was a randomized, controlled, double-blind
clinical trial…Subjects meeting the screening criteria were randomly
allocated to groups by the study administrator.
Allocation
Unclear
concealment
Quote (via email): “Study personnel received 3 kinds of toothpaste labeled
A, B and C from the Colgate-Palmolive Company, but they did not know
what exactly those toothpaste were. The formulation of each toothpaste was
concealed until the trial was finished.”
Blinding of
Yes
Quote: “This six-month study was a randomized, controlled, double-blind
participants
clinical trial…The tubes were individually labeled for each study participant
and personnel
and supplied in plain white laminated tubes to conceal the formulation.
Blinding
Quote: “The examiners did not know the product content for each participant
of Yes
until the trial was finished.”
outcome
assessment
Incomplete
Yes
Comment: Missing outcome data are balanced in number among intervention
outcome data
groups, with similar reasons (transfer to another school) for missing data
addressed
among groups.
14
Quote: “At the three-month examination, two subjects were lost from study,
and by the six-month examination, a further two subjects were lost.”
Free of
Yes
Comment: The mean subject △Q at the 6-month examination is reported.
selective
reporting
Losses
to Yes
Quote: “Four-hundred fifty (450) satisfied the inclusion and exclusion
follow-up less
criteria and were recruited into the study… A total of 446 subjects completed
than 20%
the study.”
Diagnosis
Yes
reliability
Quote: “Prior to the baseline examination, 20 subjects were randomly
selected for repeat examinations after 24 hours without using the video
repositioning (Vidrep) function of the QLF software. After analysis, the △Q
values of the same subjects were used to calculate an Intra-Class Correlation
coefficient (ICC) which was 0.92. In addition, 40 subjects were randomly
selected to be analyzed for repeat image analysis after a one-week interval.
An ICC value of 0.86 was reached for the △Q values.”
Baseline
Yes
Quote: “There were no statistically significant differences between the three
study groups for any of the baseline measurements.”
characteristics
balance
Free of
Unclear
contamination
Comment: No strategies for avoiding contamination between groups are
mentioned.
W. Yin/2013 b
Item
Authors’
Description
judgement
Random
Unclear
Comment: Insufficient information is provided regarding the sequence
sequence
generation process.
generation
Quote: “This study was a randomized, controlled, double blind clinical trial
of 6 month’s duration… Subjects meeting the screening criteria were
randomly allocated to groups by the study administrator.”
Allocation
concealment
Unclear
Quote (via email): “Study personnel received 3 kinds of toothpaste labeled
A, B and C from the Colgate-Palmolive Company, but they did not know
15
that exactly those toothpaste were. The formulation of each toothpaste was
concealed until the trial was finished.”
Blinding
of Yes
Quote: “This study was a randomized, controlled, double blind clinical trial
of 6 month’s duration…two individually labelled white laminated tubes…
participants
and personnel
Blinding
of Yes
Quote: “The examiners did not know the product content for each participant
until the trial was finished.”
outcome
assessment
Incomplete
Yes
Comment: Missing outcome data are balanced in number among intervention
outcome data
groups, with similar reasons for missing data among groups.
addressed
Quote: “At the 3-month examination, sixteen subjects were lost from study.
Of these, five transferred to another school; for eleven subjects, images could
not be captured at the time of each scheduled assessment. At the 6-month
examination, a further nine subjects, who transferred to another school, were
lost from the study.”
Free
of Yes
Comment: The mean subject △Q at the 6-month examination is reported.
to Yes
Quote: “Of these 463 satisfied the inclusion and exclusion criteria and were
selective
reporting
Losses
follow-up less
recruited into the study. At the 3-month examination, sixteen subjects were
than 20%
lost from study…At the 6-month examination, a further nine subjects…were
lost from the study.”
Diagnosis
Yes
reliability
Quote: “At the baseline examinations, 27 randomly selected children were
examined using the QLF system and repeat examinations were conducted 24
h later without using the video repositioning (Vidrep) function. The
Intra-class Correlation Coefficient (ICC) between the two examinations was
0.95. In addition, to check the reproducibility of the software analysis, 32
subjects were randomly selected and a repeat analysis conducted after a
1-week interval. An ICC value of 0.93 was reached for the △Q values”
Baseline
Yes
Quote: “At the baseline examination, the three study groups were well
16
characteristics
balanced with respect to all QLF metrics with no statistically significant
balance
differences between the groups.”
Free of
Unclear
contamination
Comment: No strategies for avoiding contamination between groups are
mentioned.
P.E. Petersen/2015
Authors’
Item
Description
judgement
Random
Unclear
Comment: Insufficient information is provided regarding the sequence
sequence
generation process.
generation
Quote: “This study was an examiner blind, parallel group, two intervention
community-(school-) based randomized controlled clinical trial…Schools
were selected randomly to take part in the study.”
Allocation
No
concealment
Blinding
Comment: There was no need for allocation concealment because the two
group treatments were obviously different.
of No
Quote: “In the first or control group, children in principle followed the policy
participants
of tooth brushing…This policy was unstructured with weak or often no
and personnel
supervision by teachers...In the second or intervention group, supervised
tooth brushing was carried out in the school after lunch…The intervention
group also benefited from an enhanced oral hygiene program and
classroom-based health education.”
Blinding
of Yes
Quote: “This study was an examiner blind… randomized controlled clinical
outcome
trial. Clinical examination of the study participants was conducted by an
assessment
examination team of five dentists independent of the health promotion team
to help maintain objectivity.”
Incomplete
outcome data
Unclear
Comment: Missing outcome data are not balanced in number among
intervention groups, and the plausible effect size among missing outcomes
may have had a clinically relevant impact on the observed effect size.
Quote: “Overall 8 schools with 1,766 pupils were assigned to the control
groups and 7 schools with 1,940 pupils to the intervention group. At the 24
month examination, 915 of these pupils were not examined: 380 from the
17
control group, 535 from the intervention group. Reasons for loss to follow up
included absence on the day of examination and moving to other schools.”
Free
of Yes
Comment: The DMFS and DMFT scores are reported.
to No
Quote: “Overall 8 schools with 1,766 pupils were assigned to the control
selective
reporting
Losses
follow-up less
groups and 7 schools with 1,940 pupils to the intervention group. At the 24
than 20%
month examination, 915 of these pupils were not examined: 380 from the
control group, 535 from the intervention group.”
Diagnosis
Yes
reliability
Quote: “Four examiners were calibrated against one trained examiner. To
qualify to conduct the examinations examiners had to achieve Kappa scores
greater than 0.7.”
Baseline
Yes
Quote: “At baseline there was good balance between the study groups with
respect to age, gender and clinical measures (Figure 1 and Table 1).”
characteristics
balance
Free of
Yes
contamination
Quote: “Schools were randomly assigned to intervention and control
groups...A soft bristled toothbrush and fluoridated tooth paste were supplied
to every child and kept in school.”
X. Li/2015
Authors’
item
Description
judgement
Random
Yes
Quote: “Qualified subjects were randomly assigned to one of the three study
sequence
treatments using a randomization table generated centrally by the study
generation
statistician.”
Allocation
Unclear
Comment: The method of concealment is not described.
concealment
Blinding
of Unclear
Comment: The blinding of personnel is not described.
participants
Quote: “This double blind, randomized parallel group investigation was
and personnel
conducted in…” “The tubes of dentifrice were completely over-wrapped
with white tape so that neither the examiners nor the subjects were aware of
18
the identity of the product they were using.”
Blinding
of Yes
Quote: “The tubes of dentifrice were completely over-wrapped with white
outcome
tape so that neither the examiners nor the subjects were aware of the identity
assessment
of the product they were using.”
Incomplete
Yes
outcome data
Comment: Missing outcome data are balanced in number among intervention
and control groups, with similar reasons for missing data among groups.
Quote: “6,285 consented and 6,074 met the inclusion criteria and were
assigned to one of the three study groups (Figure 1). A total of 5,669 students
completed all phases of the study.”
Free
of Yes
Comment: The mean DMFT and DMFS scores are reported for each group.
to Yes
Quote: “6,285 consented and 6,074 met the inclusion criteria and were
selective
reporting
Losses
follow-up less
assigned to one of the three study groups (Figure 1). A total of 5,669 students
than 20%
completed all phases of the study.”
Diagnosis
Yes
reliability
Quote: “The overall Kappa statistic for inter and intra-examiner
reproducibility of DMFT and DMFS was 0.82, which indicates a high level
of agreement within and among the three examiners.”
Baseline
Yes
Quote: “No statistically significant (p > 0.05) differences in either DMFT or
DMFS were indicated among the three groups at baseline (Table 2).”
characteristics
balance
Free of
contamination
Yes
Quote: “Children residing in the same household were assigned the same
dentifrice to use at home.” “When the subjects received new supplies and
toothbrush, the clinical team checked and reviewed returned/used dentifrices
to help ensure compliance.”
19
Appendix 4. Grade profile table
4.1 QUESTION: 1.5% arginine/1,450 ppm F versus 1,450 ppm F for primary root caries
Settings: 36- to 70-year-old population
Quality assessment
No of patients
Effect
1.5%
No of
Risk of
Design
studies
Other
Inconsistency Indirectness Imprecision
bias
Quality
arginine/1,450
Relative
Control
considerations ppm F versus
Absolute
(95% CI)
1,450 ppm F
Lesion hardness after 6 months follow-up (follow-up mean 6 months)
randomized serious1 no
2
trials
serious no
inconsistency
serious no
indirectness
serious reporting bias
2
imprecision
178/270
(65.9%)
91 more

(1.01 to
per 1000
LOW
1.33)
(from 6
147/258 RR 1.16
(57%)
more to 165
more)
CI, confidence interval; RR, risk ratio
1
Both studies were rated as having an unclear risk of bias.
2
The trials were sponsored by the same company and conducted by the same author group.
4.2 QUESTION: 1.5% arginine/1,450 ppm F versus 1,450 ppm F for early coronal caries
Settings: General child population
Quality assessment
No of patients
Effect
1.5%
Quality
Relative
No of
Risk of
Design
studies
Other
arginine/1,450
Inconsistency Indirectness Imprecision
bias
Control (95%
Absolute
considerations ppm F versus
CI)
1,450 ppm F
mean subject △Q (follow-up mean 6 months; Better indicated by lower values)
3
randomized serious1 no
trials
serious no
inconsistency
serious no
indirectness
serious reporting bias
2
imprecision
457
460
-
MD 4.67

lower (6.34 LOW
to 3.01
lower)
CI, confidence interval; MD, mean difference.
1
All three studies were rated as having an unclear risk of bias.
2
The trials were sponsored by the same company and conducted by the same author group.
20
4.3 QUESTION: 1.5% arginine/1,450 ppm F/Dical versus 1,450 ppm F for cavitated caries
Settings: General child population
Quality assessment
No of patients
Effect
1.5% arginine/1,450
No of
Risk of
Design
studies
Quality
Relative
Other
Inconsistency Indirectness Imprecision
bias
ppmF/Dical versus Control (95%
Absolute
considerations
1,450 ppm F
CI)
mean subject △Q (follow-up mean 6 months; Better indicated by lower values)
randomized serious1 no
2
trials
serious no
inconsistency
serious no
serious reporting bias
3559
3592
MD 0.09 
-
2
indirectness imprecision
lower
LOW
(0.13 to
0.06
lower)
CI, confidence interval; MD, mean difference.
1
Both studies were rated as having an unclear risk of bias.
2
The trials were sponsored by the same company and conducted by the same author group.
4.4 QUESTION: 1.5% arginine/1,450 ppm F/calcium carbonate versus 1,450 ppm F for cavitated caries
Settings: General child population
Quality assessment
No of patients
Effect
1.5% arginine/1,450
Quality
Relative
No of
Risk of
Design
studies
Other
ppm F/ calcium
Inconsistency Indirectness Imprecision
bias
Control (95%
Absolute
considerations carbonate versus
CI)
1,450 ppm F
mean subject △Q (follow-up mean 6 months; Better indicated by lower values)
2
randomized serious1 no
trials
serious no
inconsistency
serious no
serious reporting bias
2
indirectness imprecision
3574
3592
-
MD 0.09 
lower
LOW
(0.13 to
0.05
lower)
CI, confidence interval; MD, mean difference.
1
Both studies were rated as having an unclear risk of bias.
2
The trials were sponsored by the same company and conducted by the same author group.
21