2. A Protocol
is to be adopted prior to the start of the trial. Pre-approval
of the protocol by VOHC is not required; however it is recommended,
particularly when a company has not made a recent submission to
VOHC. Parallel or cross-over trial designs are acceptable.
3. Population.
Dogs or cats in both trials are to be to be of
similar body weight, head type, and age. General health is to
be assessed by physical examination, CBC, chemistry panel, and
urinalysis, or assured by the veterinarian of record. Trials in
dogs of different sizes are encouraged; the requirement for similarity
of body weight in the two trials submitted for VOHC review is
to ensure validation of the statistical result.
4. Use
of Product. During the VOHC trial, the product
is to be used as recommended by the manufacturer on the packaging
and advertisements of the marketed product.
5.
Control Diet. For the duration of the trial, the
dogs or cats are to be fed a control diet, either in both the
product and control groups, or in the control group if the product
is a diet that meets AAFCO nutritional standards. The control
diet is defined as a commercially available dry dog food or dry
cat food, fed dry, that meets AAFCO requirements for all life
stages.
7. Clean
Tooth Model. The teeth are to be scaled and polished
on day zero so that the plaque and calculus scores are zero at
the start of the trial. Minimum trial period: Plaque 7 days, unless a scoring method validating a shorter period has been previously approved by Council. Calculus
21 days. Note: these are the minimum trials periods. Trials of
longer duration are encouraged; however, VOHC recognizes that there
is sufficient documentation available to accept that differences
obvious at 1 week (for plaque) and 3 weeks (for calculus) are
indicative of longer-term clinical relevance and safety.
8. Plaque
Claim. Plaque Index is to be recorded after staining
with a plaque disclosing agent and gently rinsing the tooth surface.
A combination index incorporating extent of coverage and thickness
of coverage may be used. Describe and reference the Plaque Index;
if a novel plaque assessment is used, include a detailed referenced
statement justifying the assessment method. For a submission supporting
a product that incorporates a chemical anti-plaque agent, see
Chemical Protocol for additional requirements. For a submission
supporting a product with a mechanical anti-plaque effect, see
Mechanical Protocol for additional requirements. See
also Division of the Crown into Segments for
Scoring. VOHC will consider submissions in which the GCPI plaque scoring system (Journal of Veterinary Dentistry volume 24, pages 14-20, 2007) is used in the trials, provided that the plaque score and calculus score in each dog on day 0 is zero.
9. Tartar
(Calculus) Claim. The indexing method must be
selected prior to the trial and used consistently. The Calculus
Index is to be recorded after air-drying the tooth surface. A
combination index incorporating extent of coverage and thickness
of coverage may be used. Whether or not a dental explorer is used
to determine the edges of calculus deposits is not mandated. Describe
and reference the Calculus Index; if a novel calculus assessment
is used, include a detailed referenced statement justifying the
assessment method. For a submission supporting a product with
a chemical anti-calculus agent, see Chemical Protocol for more
information. For a product designed to have a mechanical anti-calculus
effect, see Mechanical Protocol for additional information. See
also Division of the Crown into Segments for
Scoring.
10. Scoring.
14. Statistical
Analysis Information
Statistical Presentations for Inclusion in VOHC
Submissions
One of the
most common reasons for concerns being raised about a submission
during review by the VOHC Council and Statistical Consultant is
failure to use and adequately describe appropriate study design
and analysis procedures to demonstrate that the VOHC statistical
hurdles have been met.
Use of inappropriate study design and/or analysis criteria can
be an expensive mistake if the trial has to be repeated. VOHC
strongly suggests pre-trial consultation with a qualified statistician.
It is the responsibility of the sponsor to ensure that appropriate
methods are used.
Requirements for the statistical methods and results sections
in the submission:
1. Provide a clear description of the statistical analysis methodology
employed, with justification for choice of the specific tests
used. The tests used must be appropriate for the type(s) of data
(categorical, ordinal [ranks] or continuous [actual metric]) analyzed.
2. Note that there is a risk when using a small sample size (fewer
than 30 animals per group, as is typical in VOHC trials) that
the data may not be amenable to parametric analysis. Again, for
small samples (as just defined), if the group sample variances
are greatly disparate (ratio > 2:1), assume the data are not
treatable by a parametric approach and apply a non-parametric
test (such as Wilcoxon Rank-Sum test) instead of the t-test. Note:
there are rank tests for several groups, even when stratified
or blocked, to replace ANOVA when necessary.
3. Use a two-tail test when determining p-level.
4. Randomization of subjects to treatment groups is required.
The randomization method must be described, and can be used to
your advantage. For example: if subjects are assigned to treatments within a blocking structure (to reduce
variability), the blocks can be included in the analyses to reduce
the size of the residual error term (i.e.: the denominator of
the F-Test).
5. Tabulation of the results of the statistical analyses is required
in order to assess the validity of the claim made in the submission.
For example: when analyses of variance are used, ANOVA tables
are to be presented, including mean squares, F- tests and p-levels.
When multi-way layouts are used (for example when various centers
are used) the interaction of treatments with the other levels
used must be evaluated to insure additivity (that the treatments
compared are consistent across the other levels employed in the
design).
6. Where several groups are compared, adjustment for type-error
must be applied, i.e.; for multiple comparisons.
7. In trials using a cross-over design, effects for carry-over
(sequence effect) and period must be included and evaluated in
the applicable ANOVA tables. In the event of a statistically significant
sequence effect in a 2 period cross-over, only the first period
data can then be used in a parallel analysis – the second period
data must be ignored. In cases of cross-over designs with 3 or
more periods, statistical protocols are available to adjust for
carry-over effects detected in the analysis.
8. A descriptive summary table with sample sizes, means with standard
deviation and standard error, percentages differences in means
of the analyzed variable (e.g. plaque or calculus [tartar]) and
where applicable, p-levels for the statistically significant findings,
must be included.
9. An electronic copy of the raw data in spreadsheet format (including
a clear explanation of the data formatting) is to be included.
Including the individual tooth data in the main submission document
is not required – in the main submission document, include only
the data and analysis information required in items 1-8 above.
Division
of the Crown Into Segments for Scoring:
Plaque
or calculus scoring systems that utilize division of the crown
of the scored teeth into segments are acceptable if:
• For ‘vertical’ division (i.e. from gingival margin to the tip
of the crown), include no more than two vertical segments (mesial
part of buccal surface and distal part of buccal surface), include
a clear description of the anatomical markers used to assign ‘vertical’
sections, and include scores from each vertical segment to calculate
a mean tooth score for use in the statistical analysis.
• For ‘horizontal’ division (i.e. parallel to the gingival margin),
the anatomical locations for visualizing the ‘horizontal line’
are to be clearly stated and only the gingival segment is scored.
• The division cannot be made e.g. vertically for calculus index
and horizontal for plaque index in the same trial.
Relevant
Literature:
Review of Studies Assessing Plaque Accumulation and Gingival Inflammation
in Dogs. Hennet P: J Vet Dent 16(1); 23-29, 1999.
Summary: Periodontal disease is difficult to measure objectively
Many indices measuring plaque accumulation and gingivitis have
been designed for humans, the Silness and Löe plaque index
and Turesky modification of the Quigley and Hein plaque index
being examples of well-accepted systems. It may, however; be beneficial
to consider new or modified measurement systems for dogs, and
such veterinary modifications need to be supported and clearly
identified. This article reviews the origins of clinical periodontal
indices now in common use in studies that examine the effectiveness
of oral hygiene products.
Shape and
Size of Teeth of Dogs and Cats-Relevance to Studies of Plaque
and Calculus Accumulation. Harvey CE: J Vet Dent 19(4); 186 -195,
2002.
Summary: Crown width, height and buccal surface areas were measured
on heads or skulls of four dogs and four cats, and were compared
with similar measurements on models of human dentition. Buccal
surface area variability was greater in dogs and cats than in
humans, and teeth of cats were smaller. Horizontal (gingival and
occlusal halves) and vertical (mesial, middle, and distal thirds)
buccal surface area variability was also greater in canine and
feline teeth compared with human teeth. This increased variability
suggests the need for testing of reliability and repeatability
of scoring when using plaque and calculus indices based on horizontal
or vertical segmentation. Buccal surface area variability between
teeth also prompts questioning the validity of equal weighting
of smaller, irregularly-shaped teeth when calculating a mean mouth
score. Whether equal or more reliable results would be obtained
from scores of whole teeth in comparison with segmentation indices
used currently has yet to be determined.
Evaluation
of the Logan and Boyce Plaque Index for the Study of Dental Plaque
Accumulation in Dogs. Hennet P, Servet E, Salesse H, Soulard Y:
Res Vet Sci, 80, 175-180, 2006.
Summary: The objectives of this study were to assess intra-examiner
(experienced examiner) and inter-examiner agreements (experienced
versus non-experienced examiners) of scores assessed with the
Logan & Boyce plaque index and to evaluate whether a modification
of this index, where anatomical landmarks are used for horizontal
division [mod L&B-AL] and dye references are used for assessing
intensity of dye (plaque thickness) [mod L&B-DR], would improve
repeatability. The Logan & Boyce index was found to be inaccurate
when scoring plaque coverage as it underestimated the total crown
surface. The contribution of the gingival part to the total tooth
score was minimized by the Logan & Boyce index compared to
the mod L&B-AL/DR. Precision of global plaque scorings was
significantly improved by the mod L&B-AL/DR. Intra-examiner
agreement of plaque thickness and plaque coverage scorings on
the gingival part of the tooth was significantly improved by the
mod L&B-AL/DR. Studies evaluating plaque accumulation in dogs
should therefore use the mod L&B-AL/DR rather than the Logan
& Boyce index.
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Mechanical
Additional
Requirements for Products Designed to Have a Mechanical Anti-Plaque
or Anti-Calculus Effect.
The
General Requirements
Applicable to All Submissions
apply to products with a mechanical anti-plaque or anti-calculus
effect, with the following additions:
1. Presence or absence of inflammation, ulceration or laceration
anywhere in the oral cavity is to be recorded for each dog or
cat both at time zero and at the time of the final examination.
2. Owner-applied Mechanical Products.
Trials of brushes or similar mechanical dental devices designed
to be applied by owners in dogs are to include:
4.
The minimal requirement for acceptability is that the mouth
mean plaque score in the treated vehicle group is to be statistically
different from the means in the control diet and the untreated
vehicle groups, and have a minimum reduction in mean plaque
score of 20% in each of the two trials compared
with the control diet group mean.
5.
No specific microbial testing is required. Supporting data documenting
the antimicrobial effectiveness and safety of the active agent
may be provided by the submitting company, but is not required.
Supporting data is particularly recommended for products containing
compounds that have yet to be awarded ADA recognition as anti-plaque
agents.
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Policy on Revision of
VOHC Requirements
VOHC
will consider submissions containing results of trials conducted
according to VOHC requirements that were in place at the time
the trial was commenced, even if a change in VOHC protocol requirements
was made subsequent to the commencement date of the trial.
Safety and Regulatory Issues
Please
read the 'Meaning of the VOHC Seal' on the VOHC web Home
page.
VOHC
requires that the sponsor of a product that is the subject of
a submission to VOHC certifies at the time of submission that
it has complied with all safety and regulatory requirements in
the jurisdictions where the product is marketed, that there is
no information at the time of the VOHC submission that the product
is unsafe, and that it will promptly inform VOHC of any reports
or regulatory actions concerning the safety of the product.
'Safety ' in the VOHC context includes:
A. Major extra-oral or body-wide issues such as toxicity, esophageal or gastro-intestinal obstruction or perforation, or gross nutritional imbalance;
B. Trauma to oral tissues, such as fracture of teeth or laceration or penetration of oral mucosa.
Complaints from consumers that relate to any of the product safety issues mentioned above are to be promptly copied to VOHC, and annual confirmation of continuation of use of the VOHC Accepted Seal is contingent on affirmation that no safety complaints that have not already been brought to VOHC's attention have been received by the product sponsor.
