This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Efficacy and Safety of Tenoten for Children in the Treatment of Specific Developmental Disorders of Scholastic Skills in Children (NCT03159104), a randomized phase 3 study. The primary outcome is Mean Total Scholastic Skills Score (a Sum of Three Scales: Reading, Spelling, and Counting)..
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT03159104 |
| Phase | Phase 3 |
| Condition | Specific Developmental Disorders of Scholastic Skills |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Quadruple |
| Enrollment | 240 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Materia Medica Holding |
| Results posted | Yes |
2. Clinical Question
Population
Children with specific developmental disorders of scholastic skills. The registry record does not report further eligibility details or a demographic description of the enrolled children.
Intervention
Tenoten for children, described as 1 tablet three times daily. The tablets were to be held in the mouth until complete dissolution, without a meal.
Comparator
Placebo, described with the same administration schedule: 1 tablet three times daily, held in the mouth until complete dissolution, without a meal.
Primary question
The trial set out to evaluate efficacy and safety using the mean total scholastic skills score, a sum of reading, spelling, and counting scales, at Day 1 and after 12 weeks of therapy. The registry record does not report a single comparison of change or endpoint scores between the treatment groups.
The clinical question is whether the assigned treatment groups differed in scholastic skills during the trial, as assessed by the stated score, and what safety events were recorded. The score combines three areas rather than measuring only one academic skill. That makes it a broad outcome, but the combined result alone would not show which component contributed most to any difference.
The registry identifies a randomized, parallel-group comparison with placebo and quadruple masking. These design features describe how the comparison was organized, but the record does not provide enough information to assess how randomization was generated or maintained, or how masking was implemented. The primary outcome is named and its measurement time is specified; the outcome data and analysis needed to answer the group-comparison question are not reported in the registry record.
3. Trial Design
The registry describes a phase 3, randomized, quadruple-masked, parallel-group, placebo-controlled clinical trial sponsored by Materia Medica Holding. Its listed condition is specific developmental disorders of scholastic skills. Enrollment is recorded as 240, and the trial status is completed. The start date is 2015-08-25, and the primary completion date is 2019-02-18.
Children were assigned to Tenoten for children or placebo. Both arm descriptions specify 1 tablet three times daily, held in the mouth until complete dissolution, without a meal. Using the same administration schedule in both groups is consistent with a placebo comparison in which the assigned study treatment is the intended contrast. The registry does not report details of tablet appearance, adherence monitoring, treatment changes, or concomitant care.
Randomization and masking are important design features because they can limit systematic differences between groups and reduce the influence of expectations on trial conduct or assessment. However, the registry record does not report the randomization sequence method, allocation concealment, who was included in the masking designation, or whether masking was assessed. Those details cannot be inferred from the labels “randomized” and “quadruple.”
The primary outcome is the mean total scholastic skills score, assessed on Day 1 and after 12 weeks of therapy. The registry also lists reading, spelling, and counting scores, the percentage of children with an increase in the total score, and an efficacy index according to the Clinical Global Impression Scale as secondary outcomes. The posted primary outcome is not reduced to one comparison because it has several categories or time points. Thus, although the trial design and outcome framework are described, the registry record does not report a primary between-group estimate or its uncertainty.
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.
Overall Study
| Stage | Tenoten for Children | Placebo |
|---|---|---|
| STARTED | 122 | 118 |
| COMPLETED | 121 | 116 |
| NOT COMPLETED | 1 | 2 |
Reasons for not completing this period:
| Reason | Tenoten for Children | Placebo |
|---|---|---|
| Violation of inclusion criteria | 1 | 2 |
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.
| Characteristic | Unit | Tenoten for Children | Placebo | Total |
|---|---|---|---|---|
| Participants analysed | 121 | 116 | 237 | |
| Age, Categorical: <=18 years | Participants | 121 | 116 | 237 |
| Age, Categorical: Between 18 and 65 years | Participants | 0 | 0 | 0 |
| Age, Categorical: >=65 years | Participants | 0 | 0 | 0 |
| Age, Continuous | years | 8.5 (SD 0.7) | 8.6 (SD 0.6) | 8.6 (SD 0.7) |
| Sex: Female, Male: Female | Participants | 49 | 46 | 95 |
| Sex: Female, Male: Male | Participants | 72 | 70 | 142 |
| Race and Ethnicity Not Collected | Participants | — | — | 0 |
| Region of Enrollment: Russia | participants | 121 | 116 | 237 |
6. Primary Endpoint
The registry lists the primary outcome as Mean Total Scholastic Skills Score (a Sum of Three Scales: Reading, Spelling, and Counting)., measured over On Day 1 and after 12 weeks of the therapy.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Standard Deviation |
| Unit | score on a scale |
| Endpoint classification | Continuous Endpoint |
The primary endpoint is the mean total scholastic skills score, a continuous score formed by adding reading, spelling, and counting skill scales. Its stated range is 0 to 110 points, with higher scores indicating better results. Reading is assessed using subscales for reading speed, method or understanding, and accuracy; spelling uses a scale with listed score levels; counting uses the Arithmetic subtest of the Wechsler Intelligence Scale for Children. The record gives separate maximum and minimum values for the component scales.
A combined endpoint can represent performance across several related scholastic domains in a single measure. It may be useful when the trial question concerns overall scholastic skills rather than one component alone. At the same time, a total can conceal different patterns across its components: a similar total could reflect different reading, spelling, or counting profiles. Component outcomes can help describe those patterns, but they do not replace a clearly defined primary comparison.
The registry states that the score was assessed on Day 1 and after 12 weeks of therapy. It does not report the group means, standard deviations, change scores, an adjusted or unadjusted contrast, or confidence intervals for those measurements. The posted record therefore describes what the endpoint is intended to measure, but does not provide the numerical result needed to quantify a difference between the assigned groups or its precision.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record establishes that the trial was designed to compare Tenoten for children with placebo and identifies a continuous primary outcome. It does not report the primary endpoint values or a single primary comparison. As a result, the magnitude and direction of any group difference, and the precision with which it was estimated, are not reported in the registry record. This is an absence of a reported estimate, not evidence that the groups were equal.
The primary endpoint is recorded at Day 1 and after 12 weeks. A comparison could be framed using endpoint scores, within-group changes, or a model that accounts for baseline score, but the registry does not state which approach was used. These approaches can target different quantities, especially when baseline values vary. Without the reported analysis method and result, there is no basis for choosing among them or interpreting an effect estimate.
The score is a sum across reading, spelling, and counting. A group contrast in the total, if reported, would describe the combined scale and would need to be interpreted in the score’s units and in light of its uncertainty. It would not by itself establish that each component changed in the same way. The registry lists component measures among secondary outcomes, but their numerical results are not reported in the record.
Confidence intervals are a general statistical way to express the uncertainty around an estimated contrast. A narrower interval indicates greater precision under the analysis assumptions; an interval that includes values on both sides of no difference can leave the direction and size of the underlying contrast uncertain. No primary confidence interval is reported in the registry record, so the precision of the primary comparison cannot be assessed.
The safety listing records serious adverse events in the two arms and also gives counts for other adverse events and deaths. Those counts are descriptive safety information. The record does not supply a statistical comparison of these events, details of event ascertainment, or a complete narrative describing each event’s timing and relationship to treatment. The small set of reported counts should not be treated as a complete characterization of safety.
Overall, the registry provides a trial framework, a defined primary score, and selected safety counts, but not the main efficacy result. Conclusions about the observed primary outcome contrast cannot be drawn from the record because the relevant group results and analysis are not reported.
9. Statistical Methods Explained
The design labels identify the broad structure of the experiment: randomized assignment, a parallel-group comparison, placebo control, and quadruple masking. These features are relevant to how a treatment contrast might be interpreted, but do not by themselves specify the statistical model or establish that bias was absent. The registry record does not report the detailed analysis plan, randomization procedure, or masking procedures.
What does a mean describe?
For a continuous outcome, a mean describes the arithmetic average of the observed scores in a group. The primary endpoint is a mean total scholastic skills score, and the listed dispersion measure is the standard deviation. In general, the standard deviation describes how spread out individual scores are around the group mean. It is not the same as the uncertainty in the estimated mean or in a difference between group means.
A mean can be informative when the outcome has meaningful numerical units and a group average is relevant to the clinical question. It can also conceal variation among individuals, including whether changes are concentrated in a subset or distributed across the group. The registry record does not report the score distributions, group means, or standard deviations at the stated assessment times, so those features cannot be evaluated for this trial.
What would a group contrast mean?
A between-group contrast compares outcomes under the two randomized assignments. A contrast in endpoint means would describe the difference in average score at the chosen assessment, while a contrast in changes would describe how the group averages moved from baseline. An adjusted analysis might account for baseline outcome values or other prespecified variables. These are general analysis options, not claims about the method used in this trial. The registry record does not report which contrast was selected or provide an estimate.
Randomization supports comparison by assignment because, in general, it aims to make groups comparable in expectation at the outset. It does not guarantee identical baseline characteristics in a particular trial. A report of baseline outcomes and characteristics can help readers understand the starting point and the analysis, but those details are not reported in the registry record. The randomized label alone is not enough to reconstruct the treatment effect or its uncertainty.
How should uncertainty be understood?
A confidence interval is a general method for expressing sampling uncertainty around an estimate. Its width reflects both the variability in the data and the amount of information available, subject to the model and assumptions used. The interval is useful alongside the point estimate because the same estimate can be compatible with different degrees of precision. The registry record does not report a confidence interval for the primary outcome.
A p-value, in general, describes how incompatible the observed data are with a specified null model, assuming that model and the analysis assumptions hold. It does not give the probability that a treatment is effective, and it does not describe the size or practical importance of an effect. No primary p-value or primary comparison is reported in the registry record. Therefore, statistical significance cannot be assessed from the primary outcome information recorded.
Why does the score structure matter?
The total score combines reading, spelling, and counting. As a composite, it can summarize performance across these domains, but the construction can make interpretation less direct than for a single skill. The total score’s range is stated as 0 to 110 points, and a higher value is described as better. Whether a particular difference is educationally meaningful is not established by the scale range alone; the registry record does not report a threshold for meaningful change or validation details sufficient to interpret such a threshold.
The registry lists separate reading, spelling, and counting outcomes, along with a percentage with an increase in the total score and an efficacy index according to the Clinical Global Impression Scale. These additional outcomes could offer complementary descriptions. Their presence also means that interpreting the full set of findings would require clarity about the analysis plan and multiplicity. The record does not report a complete set of numerical results or a statistical plan for these outcomes.
What is over-dispersion, and is it relevant?
Over-dispersion is a general concern for some count outcomes when observed variability exceeds what a simple probability model assumes. It can make standard errors too small if the extra variability is ignored. The primary outcome in this trial is described as a continuous mean score, not a count outcome, so over-dispersion is not the central issue for interpreting that endpoint. The registry record does not report a model that would permit a more specific assessment of distributional assumptions.
For continuous outcomes, analysts commonly consider whether residual variation and model assumptions are appropriate, and whether the measurement behaves comparably across groups and assessment times. These are general considerations, not documented methods for this trial. The registry does not report diagnostic checks, transformations, or a model specification.
What can the planning illustrations establish?
In general, sample-size planning calculations describe how much information a future design might need under stated assumptions; they do not show the probability that this completed trial detected an effect. The registry’s planning assumptions describe a two-sided significance level of 0.05, equal allocation, a normal approximation, and an effect expressed as a fraction of an observed effect. The registry labels such calculations as planning illustrations rather than the trial’s own design justification. No planning result should be interpreted as observed power, and the registry record does not report the trial’s own sample-size justification.
10. Multiplicity, Missing Data and Analysis Populations
Multiplicity arises when several outcomes, time points, or analyses are examined. In general, making many inferential comparisons can increase the chance that at least one appears notable by chance if no adjustment or prespecified hierarchy is used. A statistical plan may address this through a designated primary comparison, adjustment methods, or a structured testing sequence. The registry record does not report such a plan or a multiplicity adjustment.
The primary outcome is described at Day 1 and after 12 weeks, and the registry notes that it has several categories or time points and is not reduced to one comparison. The record also lists secondary measures for reading, spelling, counting, an increase in the total score, and an efficacy index. Without a clear definition of the primary contrast and the handling of the additional outcomes, the inferential status of any individual result would be difficult to assess. The registry does not report a single primary result or numerical results for the listed outcomes.
Missing-data methods are also not reported in the registry record. The record does not state how many outcome observations were available at each assessment, whether missingness occurred, why observations might be missing, or how any missing values were handled. In general, missingness can affect interpretation when the likelihood of an outcome being recorded is related to participants’ status or treatment experience. The direction and scale of any such influence cannot be inferred without details.
The analysis populations are not reported in the registry record. It is therefore not possible to determine from this information whether the primary analysis included all randomized participants, only those who completed treatment, or another defined group. The registry identifies randomized assignment and enrollment, but those details do not establish the population used for a particular analysis. No assumptions about intention-to-treat, per-protocol, or safety populations should be made from the available record.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Tenoten for Children | 0 | 122 | 0.0% |
| Placebo | 2 | 118 | 1.7% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Tenoten for Children | 0 of 122 |
| Placebo | 0 of 118 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Tenoten for Children | 42 of 122 |
| Placebo | 29 of 118 |
Most frequent serious adverse event terms
| Event term | Organ system | Tenoten for Children | Placebo |
|---|---|---|---|
| Phlegmonous appendicitis | Infections and infestations | 0 of 122 | 1 of 118 |
| Bacterial pneumonia | Infections and infestations | 0 of 122 | 1 of 118 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Tenoten for Children | Placebo |
|---|---|---|---|
| ARVI | Infections and infestations | 14 of 122 | 6 of 118 |
| ARI | Infections and infestations | 7 of 122 | 4 of 118 |
| Headache | Nervous system disorders | 4 of 122 | 5 of 118 |
| Abdominal pain | Gastrointestinal disorders | 2 of 122 | 5 of 118 |
| Nasopharyngitis | Infections and infestations | 2 of 122 | 5 of 118 |
| Diarrhea | Gastrointestinal disorders | 2 of 122 | 4 of 118 |
| Allergic dermatitis | Skin and subcutaneous tissue disorders | 5 of 122 | 1 of 118 |
| Pharyngitis | Infections and infestations | 3 of 122 | 2 of 118 |
| Rhinitis | Infections and infestations | 4 of 122 | 1 of 118 |
| Nose bleed | Respiratory, thoracic and mediastinal disorders | 0 of 122 | 3 of 118 |
Serious events with the highest arm-level rate: phlegmonous appendicitis (0.8%), bacterial pneumonia (0.8%).
The registry lists serious adverse events and other adverse events separately for Tenoten for Children and placebo. In the Tenoten arm, the serious adverse-event count is 0 among 122 at risk, and the other adverse-event count is 42 among 122 at risk. In the placebo arm, the serious adverse-event count is 2 among 118 at risk, and the other adverse-event count is 29 among 118 at risk. The registry records 0 deaths in each arm.
These are descriptive counts in the registry record, not a comparative analysis. They do not, by themselves, establish whether the groups differed in risk or whether an event was caused by the assigned treatment. The record does not report a statistical comparison, confidence intervals, event timing, exposure-adjusted summaries, or a detailed account of how events were collected and classified.
The record lists phlegmonous appendicitis and bacterial pneumonia among the top serious terms, each with 0.8%. The group attribution of these listed terms is not specified in the available record. Serious and other adverse-event counts should be read as distinct categories as presented; the registry does not provide enough detail to reconstruct individual event histories or determine whether people could contribute to more than one category.
12. What the Result Does, and Does Not, Mean
The trial record describes a randomized comparison of Tenoten for children with placebo in children with specific developmental disorders of scholastic skills. It specifies a combined scholastic skills score and a 12-week assessment, and it records selected adverse-event counts. These details explain what the trial set out to study and some of what was recorded.
The record does not report the primary outcome values, a between-group estimate, a confidence interval, or a primary p-value. Therefore, it does not establish the direction, magnitude, or precision of the primary contrast. A missing reported result must not be interpreted as a finding of no difference, just as the design labels cannot be treated as evidence of a particular outcome.
The total score combines reading, spelling, and counting. Even if a total-score contrast were available, interpretation would depend on its size, uncertainty, analysis method, and the relevance of the scale units. A composite result would not alone show how each component behaved. The record does not report a threshold for meaningful change, so the scale’s numerical range is not enough to label a difference important or unimportant.
The safety information likewise has limits. Counts of serious and other adverse events and deaths provide a description of recorded events, but do not establish causality or provide a full comparison of risks. The record does not report event-level detail or a statistical safety analysis.
In general, a trial’s conclusion depends not only on its design but also on transparent reporting of outcomes, analyses, uncertainty, and missing data. Those elements are not reported for the primary comparison in this registry record. Accordingly, the available information supports a description of the intended comparison and the recorded safety counts, but not a conclusion about the primary efficacy result.
13. Why This Trial Matters Statistically
This trial is statistically notable as a randomized, placebo-controlled comparison using a composite continuous outcome. Its primary score brings reading, spelling, and counting into a single measure, which raises a common interpretive question: whether the overall score is the most informative summary for the intended research question, and how its components should be understood alongside it.
The design labels also illustrate why knowing that a study is randomized and masked is only part of statistical appraisal. Readers also need the definition of the target contrast, details of the analysis population, treatment of missing outcomes, and estimates with uncertainty. Those items help connect the design to the result and show how much confidence the data support. The registry record does not report these details for the primary comparison.
The outcome is specified at Day 1 and after 12 weeks, while several additional scholastic and clinical outcomes are listed. Multiple outcomes and assessment times make a clear prespecified analysis plan important in general. Without a reported plan, readers cannot determine how the primary comparison was prioritized or how secondary findings should be interpreted relative to it.
The record’s safety counts provide another statistical teaching point: raw counts are not a complete risk comparison. Interpretation requires context about the event definitions, the analysis population, ascertainment, follow-up, and uncertainty. These details are not reported in the registry record.
For clinical researchers and biostatisticians, the central lesson is that a detailed trial design and a named endpoint do not substitute for a reported treatment-effect estimate. Statistical interpretation requires both the design context and transparent results. Here, the design and measurement framework are described, but the primary numerical comparison is not reported in the registry record.
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.
The principal trial-specific limitation of the registry information is that it does not report the primary outcome data or a single primary comparison. Although the endpoint definition and assessment timing are described, there are no reported group means, standard deviations, effect estimate, confidence interval, or primary p-value. The efficacy question therefore cannot be resolved from the registry record.
The record does not describe the methods used to generate or conceal the randomization sequence, the people covered by quadruple masking, or whether masking was maintained. It also does not report baseline characteristics, outcome completeness, adherence, protocol deviations, or the analysis populations. These omissions limit assessment of the conduct and analysis, without showing that any particular problem occurred.
The primary measure is a sum across reading, spelling, and counting. The score range and direction are stated, but the record does not report a threshold for meaningful change or provide the results for the separate skill components. Consequently, the scale definition alone cannot establish the practical interpretation of a potential total-score difference.
The registry lists secondary outcomes but does not report their numerical results or the strategy for handling multiple outcomes and time points. It also does not report missing-data methods or a complete statistical analysis plan. These are important limitations for judging selective reporting and the robustness of any analysis.
The adverse-event listing is limited to selected counts and terms. The record does not provide a detailed event-level account, comparative statistical analysis, or further information on event assessment. These limits apply to what can be concluded from the registry information; they are not evidence that unreported methods or outcomes were absent from the full trial materials.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Efficacy and Safety of Tenoten for Children in the Treatment of Specific Developmental Disorders of Scholastic Skills in Children — NCT03159104.
- Registry record last updated 2023-08-21; status last verified 2021-10.
- Results first posted 2023-08-21.
- 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.
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18. Record Summary
The registry record describes a completed phase 3, randomized, quadruple-masked, parallel-group, placebo-controlled trial sponsored by Materia Medica Holding. Enrollment is recorded as 240. The listed condition is specific developmental disorders of scholastic skills.
The intervention and placebo descriptions specify the same schedule: 1 tablet three times daily, held in the mouth until complete dissolution, without a meal. The primary outcome is the mean total scholastic skills score, combining reading, spelling, and counting, assessed on Day 1 and after 12 weeks of therapy.
The record lists secondary scholastic and clinical outcomes and provides selected adverse-event counts. It does not report a single primary comparison, the numerical primary outcome results, the analysis plan, missing-data methods, or analysis populations. The registry information therefore describes the trial’s design and measures but does not provide the primary efficacy estimate or its precision.