Silver Diamine Fluoride and Papain-Based Gel for Management of MIH-affected Molar in Paediatric Patients: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Silver Diamine Fluoride and Papain-Based Gel for Management of MIH-affected Molar in Paediatric Patients (NCT04710927), a randomized na study. The primary outcome is Clinical Outcome Based on Success After Intervention on MIH Affected Molar at 6 Months.

2. Clinical Question

The clinical question is about the count of molars meeting a composite definition of success, rather than a single symptom or a participant-level outcome. The registry record says that a participant could have more than one tooth assigned to one or more intervention groups. Consequently, molar counts and participant counts are not interchangeable, and a participant-level interpretation of the outcome counts would be inappropriate without further information.

The posted results give successful molar counts of 17.0 for HVGIC, 18.0 for SDF plus HVGIC, and 17.0 for papain-based gel plus SDF and HVGIC. These are descriptive counts. The registry does not report a statistical comparison among the groups, an effect estimate, or uncertainty intervals for the differences. The counts therefore describe what was recorded at the specified follow-up; they do not establish whether one approach performed better than another.

3. Trial Design

This was a randomized, parallel-group trial listed as completed in the registry. The registry reports enrollment of 38 and identifies the sponsor as the University of Malaya. The study began on 2019-12-01, and primary completion is listed as 2021-05-31. The phase is recorded as NA. The registry identifies the masking as single, but who was masked is not reported in the registry record.

Participants were assigned to one of three treatment groups: HVGIC alone; SDF followed by HVGIC; or papain-based gel followed by SDF and HVGIC. These groups allow descriptive consideration of the approaches as recorded, but the registry does not report a formal statistical comparison. In particular, it does not state whether the principal intended comparisons were each SDF-containing approach against HVGIC alone, the two SDF-containing approaches against each other, or another set of contrasts.

The primary outcome is recorded at 6 months as the number of successful MIH-affected molars. The outcome description emphasizes that the molar, rather than the participant, is the unit represented in the descriptive frequency analysis, because participants could contribute more than one tooth and teeth could be allocated across intervention groups. The posted arm entries list 15.0, 16.0, and 16.0, while the successful molar counts are 17.0, 18.0, and 17.0, respectively. The record does not explain the relationship between those arm entries and the number of molars assessed, so they should not be treated as denominators for calculating success rates.

The registry does not report the randomization procedure, allocation concealment, the identities of masked parties, or details of treatment delivery and follow-up beyond the outcome timeframe. It also does not report a sample-size justification or a prespecified analysis plan. These absences limit assessment of how the planned design relates to the posted descriptive results.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Before assignment: For this study, Molar Incisor Hypomineralisation (MIH) affected molar was used as unit prior assignment to intervention groups. The reason for this, data collections were affected by the peak of Coronavirus disease (COVID-19) pandemic with movement control orders enforcement for months in Malaysia. Due to this problem, one participants may had one to four molars (teeth) affected with MIH and be assigned into more than 1 intervention groups. Total participants for this study was 38 participants.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Descriptive analysis of frequency was used. MIH affected molars represents as participants. This is because one participants may have more than 1 tooth assigned into one or more intervention groups.

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

Population: MIH affected molars represent the number of participants analysed for each treatment interventions.This is because one participant can have more than one MIH affected molars assigned into the same or different treatment groups. The total number of participants involved in this study was 38 with 63 MIH affected molars involved. Total number of participants at baseline (1 participants may have \>1 MIH molars into same or different group) assigned into all interventions was 57.

6. Primary Endpoint

The registry lists the primary outcome as Clinical Outcome Based on Success After Intervention on MIH Affected Molar at 6 Months, measured over 6 month.

The primary endpoint counts treated MIH-affected molars that met all the registry’s criteria for success at 6 months. A molar qualified as successful only if the stated criteria were all fulfilled: no pain related to the treated tooth, no tenderness to percussion, no swelling of supporting soft tissue or sinus tract, no enamel breakdown or caries along the restoration margin, and a Schiff Cold Air Sensitivity Scale score of 0 or 1.

This composite endpoint brings together symptoms, clinical signs, restoration-margin findings, and a sensitivity score. A combined definition can describe a broader clinical status than any one component alone. It also means that the count does not show which criteria were met or missed for individual molars. Component-level results are not reported in the registry record.

The registry describes the outcome as a number of successful molars and says the analysis was a descriptive frequency analysis. It explicitly notes that one participant could contribute more than one molar and that a participant could have teeth assigned to one or more intervention groups. Therefore, the outcome unit is the treated molar, not necessarily an independent participant. The reported counts should be read as molar counts, not as the number or proportion of participants who experienced success.

Success counts were 17.0 for HVGIC, 18.0 for SDF plus HVGIC, and 17.0 for papain-based gel plus SDF and HVGIC. The total number of molars assessed in each group, a complete accounting of missing follow-up outcomes, and component-specific findings are not reported in the registry record. Without those details, the counts alone do not provide a rate of success or a measure of comparative precision.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registered primary outcome is a count, not a continuous measurement or a time-to-event outcome. The count refers to MIH-affected molars satisfying a composite success definition at the 6-month assessment. The registry says descriptive frequency analysis was used. That approach reports how many outcome units met a definition; by itself, it does not quantify the uncertainty around a group difference or test a hypothesis.

What does a descriptive count tell the reader?

A count answers how many molars were recorded as successful in a group. It does not, on its own, show how often success occurred unless the corresponding number of molars assessed is clear. A rate requires a numerator and a denominator that refer to the same outcome unit and assessment. The record lists successful molar counts and arm n entries, but also explains that participants may have more than one molar. It does not make clear that the arm entries are the total molars assessed. A success rate should therefore not be derived from those figures.

A count also does not give a direct comparison between groups. A comparative analysis would need to define the relevant contrast and account for the outcome structure. The registry record does not identify a primary contrast or report a comparison estimate. No p-value or confidence interval is reported for the primary result. A reader cannot infer a formal treatment comparison from the counts alone.

Why does the unit of analysis matter?

The outcome is recorded for molars, while treatment is assigned in a study involving participants. The registry notes that one participant may contribute more than one tooth and may have teeth assigned to one or more intervention groups. Multiple molars from the same participant can share characteristics and are not necessarily statistically independent. General statistical reasoning indicates that this clustering can affect the uncertainty of an estimate. An analysis may need to account for the fact that teeth are grouped within participants rather than treating each tooth as unrelated.

The registry describes descriptive frequency analysis but does not explain whether the analysis accounted for clustering or how it handled participants with multiple treated teeth. It also does not report a participant-level analysis. The analysis population and the handling of repeated or multiple tooth observations are not reported in the registry record. Thus, no claim about the statistical independence of molar outcomes is warranted.

What would a confidence interval contribute?

General explanation: a confidence interval expresses the statistical uncertainty around an estimated quantity, such as a rate or a difference between groups, under the assumptions of the analysis. A narrower interval indicates greater precision, while a wider interval indicates less precision. An interval for a group contrast would help readers judge which effect sizes remain compatible with the data and analysis. No such interval is reported for this primary outcome, so the precision of a comparative effect cannot be assessed from the registry results.

How should a hypothesis test be understood?

General explanation: a hypothesis test evaluates data against a specified null hypothesis using a statistical model and assumptions. A p-value, if reported, would describe how unusual the observed data or more extreme data would be under that null model; it would not measure the probability that a treatment works, nor would it establish clinical importance. The registry record does not report a p-value or the hypothesis being tested for the primary outcome. No inferential conclusion should be attributed to the posted counts.

What information is missing about the analysis?

The registry does not report the statistical analysis plan, the intended contrasts, a sample-size justification, or the method used to handle multiple molars per participant. It does not provide a clear molar denominator for each group, component-level results for the composite endpoint, or a complete account of missing endpoint observations. The record’s description that descriptive frequency analysis was used is the available characterization of the primary analysis. More specific methods, including adjustment for covariates or clustering, are not reported in the registry record and should not be assumed.

General explanation: over-dispersion can matter in count data when observed variability exceeds what a chosen count model expects. It can lead to uncertainty estimates that are too small if the model fails to allow for that extra variability. In this trial, however, the registry reports a descriptive analysis and no fitted count model, dispersion estimate, or model-based comparison. Over-dispersion is therefore a general consideration, not a reported finding about this trial.

These methodological details determine how far the result can be interpreted. The posted information supports reporting the three successful molar counts at the specified follow-up. It does not support reconstructing a formal comparison, estimating precision, or evaluating model assumptions.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists two outcome measures but reports no secondary outcome results. Details of any secondary outcome definitions, analyses, or results are not reported in the registry record. The primary outcome has no reported inferential comparison, and the record does not specify a multiplicity strategy for testing multiple groups or outcomes.

Multiplicity is a general statistical concern when several outcomes or contrasts are tested. Testing multiple hypotheses can increase the chance of obtaining a nominally significant result by chance, so a prespecified plan may define a primary comparison or adjust interpretation for multiple testing. Here, the intended group contrasts and any adjustment approach are not reported in the registry record. There is no reported p-value for the primary outcome to interpret in light of multiplicity.

The registry’s primary outcome is a composite. The posted endpoint description lists several clinical requirements but does not give results for each component separately. Whether component outcomes were analyzed, or whether any such analyses were prespecified, is not reported in the registry record. The registry also does not provide a missing-data plan, the number of molars with unavailable 6-month assessments, or an account of how missing outcomes were handled.

The analysis population is not described beyond the outcome’s descriptive frequency analysis. It is not reported whether all randomized participants or all treated molars were included, whether any participants or teeth were excluded after assignment, or how allocation to one or more intervention groups was represented in analysis. These omissions prevent assessment of how missing information or analysis-population choices might influence the reported counts.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

The registry reports serious adverse events, other adverse events, and deaths by group. For HVGIC, the at-risk count is 18 and the recorded affected counts are 0 for serious events, 0 for other events, and 0 deaths. For SDF plus HVGIC, the at-risk count is 19, with 0 serious events, 0 other events, and 0 deaths. For papain-based gel plus SDF and HVGIC, the at-risk count is 20, with 0 serious events, 0 other events, and 0 deaths.

These figures describe the adverse-event entries in the registry record. They should not be interpreted as proof that no event of any kind occurred. The record does not report how adverse events were collected, the observation period for safety, event definitions beyond the serious and other categories, or whether the at-risk counts represent the same population as the primary endpoint.

No serious adverse-event terms are listed. The absence of listed terms means there are no terms to describe in the posted record; it does not supply information about unrecorded events or the sensitivity of event monitoring. The posted counts are descriptive and do not provide a comparative safety estimate or uncertainty interval.

12. What the Result Does, and Does Not, Mean

The registry result supports a limited descriptive statement: at 6 months, the record lists 17.0 successful MIH-affected molars for HVGIC, 18.0 for SDF plus HVGIC, and 17.0 for papain-based gel plus SDF and HVGIC. Success required every stated criterion in the composite definition to be met. The registry also lists zero serious adverse events, zero other adverse events, and zero deaths in each group.

These findings do not, by themselves, show that one approach is better or worse than another. The registry does not report a comparative effect estimate, a confidence interval, a p-value, or a formal test for the primary endpoint. It also does not provide clearly matched molar denominators for the success counts. The arm n entries cannot safely be treated as numbers of molars assessed because the registry says that participants could contribute more than one tooth.

The counts do not show which specific success criteria were satisfied or failed, and component-specific outcome results are not reported in the registry record. They also do not establish the proportion of participants with a successful outcome. The outcome unit is the molar, and multiple molars from one participant may be correlated. The analysis description does not explain how that structure was handled.

Likewise, the adverse-event entries do not establish that there were no possible harms. They record no events in the listed categories, but the registry does not describe event ascertainment or the duration and completeness of safety follow-up. The record also does not provide enough information to judge the precision of the safety comparison.

In general, a clinical result is most informative when outcome definitions, denominators, missing-data handling, and comparative uncertainty are clear. The registry record supplies the outcome definition and descriptive counts but leaves important comparative and analysis details unreported. The appropriate interpretation is therefore bounded by what is posted: counts at the specified follow-up, not proof of equivalence, superiority, or absence of risk.

13. Why This Trial Matters Statistically

This trial raises statistical issues that commonly arise when clinical outcomes are measured on teeth but treatment is studied in participants. A participant may contribute more than one molar, and the registry says teeth from one participant could be allocated to one or more groups. That structure matters because repeated outcomes from one person may be related. The analysis needs to distinguish the number of outcome units from the number of independent participants and to address any within-participant dependence when estimating uncertainty.

The endpoint is also a composite: a molar must meet every listed success condition to count as successful. This produces a single clinically framed summary, but it can conceal whether group patterns differ across pain, percussion tenderness, soft-tissue findings, restoration margins, or sensitivity. Component results would help explain the composite classification, but they are not reported in the registry record.

Finally, counts alone are not enough for a sound comparison when denominators and uncertainty estimates are unclear. The registry lists successful molar counts but does not report a comparative estimate or interval. Its arm n entries do not resolve the molar denominators, given the stated possibility of multiple teeth per participant. The record therefore illustrates why clear outcome units, denominators, analysis populations, and methods for clustering are essential for interpreting randomized clinical data.

14. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

Several limitations specific to this record constrain interpretation. The primary results are successful molar counts, but the number of molars assessed in each group is not clearly reported. The arm n entries of 15.0, 16.0, and 16.0 are not explained as molar denominators, while the endpoint description states that participants could contribute more than one tooth. Success rates should not be inferred from those entries.

The registry does not report confidence intervals, p-values, or a formal comparison among the three groups. The intended contrasts and statistical analysis plan are also not reported. Since the endpoint is measured per molar and multiple molars may come from one participant, the lack of information about handling within-participant correlation is a particular limitation.

There are no component-level results for the composite success definition, no clear account of missing 6-month outcomes, and no description of the analysis population. The registry does not report whether all assigned participants or teeth were included, or how any unavailable outcomes were handled. The identities of those masked in the single-masked design, the randomization procedure, and allocation concealment are not reported in the registry record.

For safety, the posted event counts are zero in each category, but event collection methods and safety follow-up details are not reported. These omissions mean the counts cannot be interpreted as a complete assessment of all possible adverse events. The limits reflect what is documented in the registry record; additional protocol or trial-report details are not reported there.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Silver Diamine Fluoride and Papain-Based Gel for Management of MIH-affected Molar in Paediatric Patients — NCT04710927.
• Registry record last updated 2023-07-20; status last verified 2023-06.
• Results first posted 2023-07-20.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

18. Record Summary

The registry describes a completed randomized, parallel-group trial sponsored by the University of Malaya, with enrollment of 38. The study compared HVGIC alone, SDF plus HVGIC, and papain-based gel plus SDF and HVGIC in paediatric patients with MIH-affected molars. It is listed as single-masked; the masked party is not reported in the registry record.

The primary outcome was the count of molars meeting a composite success definition at 6 months. Posted successful molar counts were 17.0, 18.0, and 17.0 across the respective groups. The registry reports descriptive frequency analysis and does not report a comparative estimate or uncertainty interval. It also lists zero serious events, zero other events, and zero deaths in each group.

Interpretation is limited by unclear molar denominators, possible multiple molars per participant, and missing details on analysis methods, missing outcomes, and adverse-event collection. These details are not reported in the registry record.