General
Requirements Applicable to All Protocols
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1.
Two trials Two
trials are required. The dogs/cats included in one trial cannot
be included in the second trial. For products in a “Product Line”,
such as the same product in different sizes, or dietary products
with a common anti-plaque or anti-calculus mechanism but with different
nutrient profiles, see Product Line
requirements.
2. A Protocol
is to be adopted prior to the start of the trial. Pre-approval
of the protocol by VOHC is required for trials conducted after January 1, 2012. 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.
Use of Client-Owned Animals in VOHC Trials
An information/informed consent document (‘Owner document’) is to be signed by the owners before entry of the subject into the trial. A blank copy of the Owner document is to be included in the submission.
The Owner document is to include a requirement that the owners complete a daily compliance log, and copies of the completed owner’s daily compliance logs are to be included in the submission. Out-of-protocol events reported by the owners are to be described and comments by the sponsor on significance of the out-of-protocol events are to be provided in the submission.
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.If the product is a toothbrush or is applied with a toothbrush, the VOHC Toothbrush Policy is to be followed.
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.
6. Teeth Scored. All
teeth listed are to be present and intact, with normal occlusion
for a dog or cat of that head shape. The teeth listed were selected
on the basis of functional importance, likelihood of accumulation
of plaque and calculus, likelihood of being present in the mouth
in the face of moderate periodontal disease, and size for ease of
recording. Score the buccal surfaces of the teeth on both sides
of the mouth (unless a split-mouth study design is used for a trial
of e.g. a tooth brush):
Dog:
Upper Jaw - I3, C, P3, P4, Ml. Lower Jaw - C, P3, P4, Ml.
Cat: Upper Jaw - C, P3, P4. Lower Jaw - C, P3, P4, Ml.
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. The animals are to be anesthetized and intubated during the scaling procedure.
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.
A. Plaque
and calculus indices are to be scored with the dog or cat under
sedation or short-acting anesthesia, unless a detailed referenced
statement is included supporting use of a scoring system suitable
for non-sedated dogs or cats. See also Division
of the Crown into Segments for Scoring
B.
Training and experience of the scorer is to be described in the
submission material. The scorer is to be blinded to the group
assignments during the entire study period. The same scorer is
to score plaque and/or calculus indices at each examination.
11.
Randomization into
trial groups. The dogs or cats are to be assigned to product or
control groups randomly. VOHC strongly recommends stratification
prior to randomization, to reduce variability between groups, and
recommends that randomization by blocking on stratification of the
substrate (plaque or calculus) under study is based on blocks equal
to the number of arms or legs in the trial. There is no minimum
required number of animals in each group. Full consideration of
possible carry-over effects must be included in analyses of cross-over
design trials.
12. Required
Group Differences. Effective Janaury 1st, 2011, the Required Group Difference was changed.
The requirement from January 1st, 2011 is:
The minimum difference required
between changes in "mouth mean score" (mean of all tested
teeth for all animals in the group) comparing the product group
with the negative control group is 15% reduction in the plaque
or calculus score in each trial and 20% in the mean of the two trials, with a statistically significant
difference (p<0.05) in each trial. Data are to be reported
as means ± SD. Statistical significance is to be determined
using a two-tailed test.
Reduction (VOHC efficacy %) is defined as:
([Control group mouth mean] minus [Test group mouth mean]) divided by (Control group mouth mean) x 100
The requirement prior to January 1st, 2011 was:
Minimum difference required between changes in "mouth mean score" (mean of all tested teeth for all animals in the group) comparing the product group with the negative control group is 10% reduction in the plaque or calculus score in each trial (20% for a product containing a chemical anti-plaque agent), AND a statistically significant difference (p<0.05) in each trial. Data are to be reported as means ± SD. Statistical significance is to be determined using a two-tailed test.
Products awarded the VOHC Accepted Seal based on trials that were conducted prior to Janaury 1st, 2011, and for which the trial data met the pre-January 2011 standard but do not meet the post-January 2011 standard will be permitted to continue to use the VOHC Accepted Seal for five years from January 1st, 2011.
13. Miscellaneous.
A. Drugs
or locally applied or lickable antiseptics other than the tested
product may not be used for 14 days pre-trial, during the trial
or during the rest period between trial legs in cross-over trials.
B. VOHC
recognizes that there is need for flexibility in measuring efficacy.
Alternative but credible methods of demonstrating efficacy will
be considered by VOHC, provided that detailed justification
is provided for novel or non-referenced methods.
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:
The following policy was approved by VOHC COuncil members and the Board of Directors of the American Veterinary Dental College in April 2013, for publication in the News section of the Journal of Veterinary Dentistry for public comment. It will become effective October 1st, 2013 unless revised as a result of public comments.
VOHC Policy on Segmentation of Teeth During Scoring
Use of vertical segmentation will not be accepted in VOHC trials.
Either whole tooth or horizontally segmented tooth surfaces can be used for scoring. Only the scores from the gingival half of the tooth are to be considered in the analysis when horizontal segmentation is used.
The specific VOHC Recommendation is:
Dogs: Score only the gingival half of all of the scored teeth.
Cats: Score only the gingival half of the canine teeth, and the whole surface of all other teeth in the VOHC set.
References:
1. 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.
2. 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:
A. Negative
control group (dry food diet, fed dry).
B. Positive
control group (dry food diet, fed dry, plus daily brushing
using a flat profile, soft bristle manual toothbrush comparable
to the Oral B 30 brush).
C. Product
group (dry food diet, fed dry).
A
split mouth design may be used, provided that assignment to
left or right side is randomized.
The mean score for the tested product group is to be statistically
“at least as good as” the positive control group and statistically
significantly better than the negative control group (p<0.05),
and with a minimum 20% reduction compared with the negative
control group.
Brushing Policy
VOHC Policy on testing of toothbrushes or for trials of products that are applied with a tooth brush. Click VOHC Brushing Policy for Dogs or VOHC Brushing Policy For Cats for details.
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Chemical
Additional
Requirements Applicable to Products Containing Chemical Anti-Plaque
and Anti-Calculus Agent(s).
The
General Requirements
Applicable to All Submissions
apply to products with a chemical anti-plaque or anti-calculus
effects, with the following additions:
If
the product contains a chemical anti-plaque or anti-calculus
agent, the submission is to demonstrate that either:
A. The chemical agent is on the Generally Regarded As Safe (GRAS)
list as an ingredient in a pet food, treat or device at the
concentration used in the product submitted for VOHC review,
OR
B. If the chemical agent is a novel agent (not previously used
as an ingredient in a pet food, treat or device), it has been
reviewed and accepted as safe by US-FDA (or equivalent regulatory
agency if the product is to be marketed only in a non-North
American country), and confirmation of safety is to be included
in the submission.
Two-arm (or two-leg for cross-over design) trials (control diet
fed dry; Product as diet or used as a treat or device with the
control diet), demonstrating the standard VOHC statistically
significant difference from control, will be sufficient if A
or B above has been met.
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, provided that a pre-trial protocol review was provided by VOHC, 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.
