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 Safety and Efficacy Study of Oral Glycopyrrolate Liquid for the Treatment of Pathologic (Chronic Moderate to Severe) Drooling in Pediatric Patients 3 to 18 Years of Age With Cerebral Palsy or Other Neurologic Conditions (NCT00491894), a non-randomized phase 3 study. The primary outcome is Proportion of Responders According to the Modified Teacher's Drooling Scale (mTDS).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00491894 |
| Phase | Phase 3 |
| Condition | Cerebral Palsy, Neurological Conditions, Mental Retardation |
| Allocation | Non-Randomized |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 137 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Shionogi |
| Results posted | Yes |
2. Clinical Question
The study asked whether pediatric patients with chronic moderate to severe drooling who received oral glycopyrrolate liquid would meet a prespecified responder definition at Week 24. The registry record describes patients aged 3 to 18 years with cerebral palsy or other neurologic conditions. The primary endpoint classified a patient as a responder if the mean Modified Teacher’s Drooling Scale (mTDS) rating decreased by at least 3 points from baseline to Week 24.
The study also collected parent or caregiver assessments of drooling using a visual analog scale and global assessments of treatment, as well as an investigator global assessment. The record lists these as secondary outcomes, though it does not report their numerical results. The central question was therefore about change in a drooling rating during treatment, rather than a comparison of glycopyrrolate against a control treatment.
Population
Patients aged 3 to 18 years with chronic moderate to severe drooling and cerebral palsy or other neurologic conditions.
Intervention
Oral glycopyrrolate liquid, titrated toward an individualized dose during the study.
Comparator
No separate comparator group is described. The study used a single-group, non-randomized design.
Primary question
What proportion of participants met the mTDS responder definition at Week 24?
The registry record does not report the observed number or proportion of responders. Consequently, it does not provide the numerical answer to the primary question. The study design can describe outcomes among enrolled participants, but without a concurrent control group it cannot isolate treatment-associated change from other influences on ratings over time.
3. Trial Design
This was a Phase 3, open-label, non-randomized, single-group study. The official title describes a six-month, multicenter study, and the registry lists an enrollment of 137. Participants received oral glycopyrrolate liquid; no control arm or masking is described. The study status is completed, with a start date of 2007-03 and primary completion date of 2008-05.
The brief summary describes a washout, screening, and 2-day baseline period, followed by a 4-week dose-titration period. Titration began at 0.02 mg/kg per dose three times a day, with sequential increases in 0.02 mg/kg per dose increments every 5-7 days during the first four weeks. The dose could be increased until an individualized optimal response was reached or the stated maximum was reached: 0.1 mg/kg three times a day, not exceeding 3 mg three times a day or Dose-level 5, whichever was lesser. The record describes the optimal dose as one balancing greatest improvement in drooling with minimum side effects. Study duration is described as 24 weeks, and the primary endpoint timeframe is 6 months.
Because the study was open-label, participants, caregivers, and investigators were not masked to treatment according to the registry design fields. The design does not include random allocation or a like-for-like control group. Changes in mTDS ratings are therefore within-participant changes over time, not an estimate of the difference between treatment and control groups.
The registry record does not report the protocol’s sample-size justification, detailed operational procedures beyond the summary, or a statistical analysis plan. The enrollment figure describes the number enrolled; it does not, by itself, establish how many contributed data at Week 24 or to each analysis.
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: After a washout and screening period, and 2-day baseline period, patients were enrolled in a 4-week dose titration period which commenced with the goal of identifying an optimal 3 times daily maintenance dose for each patient. The resulting individualized optimal maintenance dose was to be administered for the remainder of the 24-week study
Overall Study
| Stage | Patients With Chronic Drooling |
|---|---|
| STARTED | 137 |
| COMPLETED | 103 |
| NOT COMPLETED | 34 |
Reasons for not completing this period:
| Reason | Patients With Chronic Drooling |
|---|---|
| Adverse Event | 14 |
| Withdrawal by Subject | 5 |
| Death | 3 |
| Lost to Follow-up | 3 |
| Lack of Efficacy | 2 |
| Other-Failed to meet any criteria | 2 |
| Physician Decision | 2 |
| Protocol Violation | 2 |
| Other-Intake of prohibited medication | 1 |
Analysis population for the primary outcome, as defined in the registry: The analysis was done by intention to treat method. For purposes of statistical estimation, patients who dropped out due to lack of efficacy had their worst observation carried forward. Patients who dropped out for reasons other than lack of efficacy had their last observation carried forward
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 | Patients With Chronic Drooling |
|---|---|---|
| Participants analysed | 137 | |
| Age, Categorical: <=18 years | Participants | 137 |
| Age, Categorical: Between 18 and 65 years | Participants | 0 |
| Age, Categorical: >=65 years | Participants | 0 |
| Age Continuous | years | 11.0 (SD 4.35) |
| Sex: Female, Male: Female | Participants | 60 |
| Sex: Female, Male: Male | Participants | 77 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 15 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 121 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 1 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 1 |
| Race (NIH/OMB): Asian | Participants | 4 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 |
| Race (NIH/OMB): Black or African American | Participants | 29 |
| Race (NIH/OMB): White | Participants | 98 |
| Race (NIH/OMB): More than one race | Participants | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 5 |
6. Primary Endpoint
The registry lists the primary outcome as Proportion of Responders According to the Modified Teacher's Drooling Scale (mTDS), measured over 6 months.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | Participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint was the proportion of participants classified as responders according to the Modified Teacher’s Drooling Scale (mTDS). The registry describes response status as based on the change from baseline to Week 24, with a responder defined as having at least a 3-point decrease in the mean mTDS rating. Thus, the endpoint reduces a change in a rating scale to a binary classification: responder or non-responder.
In general, a responder definition can make an outcome easier to interpret as the share of participants reaching a prespecified threshold. It also discards information about the size of changes beyond the threshold and treats changes on either side of the cutoff differently, even if they are close. The rating-scale change and the responder proportion answer related but distinct questions.
The registry record does not report the observed responder count, responder proportion, or an uncertainty interval for that proportion. It therefore documents how response was defined but does not provide the numerical primary efficacy result. The record also does not report the distribution of mTDS changes or the baseline and Week 24 ratings needed to describe the scale outcome in more detail.
In general, an endpoint is useful when it gives a clear, prespecified way to characterize the outcome of interest. Interpretation still depends on the quality and completeness of measurements, the relevance of the threshold, and the study design. In this single-group open-label study, the responder endpoint describes observed change during follow-up; it does not establish how outcomes would have differed under a separate comparator.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record supplies the primary endpoint definition, enrollment, study design, and adverse-event counts, but it does not report the primary responder result. There is no posted number or proportion of participants meeting the mTDS definition, and no confidence interval or test result for that endpoint. The evidence available in the record therefore does not allow a numerical assessment of the primary efficacy outcome or its precision.
The design also limits the type of inference available. Participants received study drug in a single group, without randomization or a concurrent control. A change from baseline to Week 24 can describe the course of ratings among participants, but change alone cannot distinguish treatment-associated effects from natural fluctuation, concurrent care, changes in observer expectations, or other influences. These are general interpretive considerations for uncontrolled before-and-after studies, not additional findings reported for this trial.
The outcome relied on ratings, and the study was open-label. In general, knowledge of treatment can affect expectations or assessments, particularly for outcomes involving caregiver or investigator judgments. The registry record does not describe masking procedures or an independent blinded assessment. It also does not report the results of the listed caregiver and investigator global assessments or visual analog scale assessments.
The registry reports 137 participants enrolled and describes an intention-to-treat analysis for the primary efficacy endpoint. It states that participants who dropped out due to lack of efficacy had their worst observation carried forward, while participants who dropped out for reasons other than lack of efficacy had their last observation carried forward. The number of participants with missing Week 24 data and the number handled under each rule are not reported in the registry record. Those details matter because the endpoint depends on follow-up ratings and because carried-forward values rely on assumptions about outcomes after dropout.
Adverse-event counts are reported for 137 participants at risk: 14 participants with serious adverse events and 122 with other adverse events. These are descriptive counts in a single treatment group; the record does not establish that each event was caused by study drug. The listed serious-event terms include pneumonia, nystagmus, convulsion, hydrocephalus, anoxic encephalopathy, and urinary tract infection, with the registry percentages stated for each. The death count is not reported in the registry record.
Overall, the registry supports a description of the planned endpoint, study conduct, and recorded safety counts. It does not provide the numerical primary efficacy result, an estimate of comparative treatment effect, or the precision of an efficacy estimate. Any stronger conclusion would require information not reported in the registry record.
9. Statistical Methods Explained
The statistical methods described in the registry record are limited. It defines a binary primary outcome, identifies an intention-to-treat analysis, and specifies how certain missing observations were carried forward. The record does not report a full statistical analysis plan, model specification, inferential results, or a sample-size justification. The explanations below distinguish general statistical concepts from methods specifically documented for this study.
What does a responder proportion represent?
The mTDS primary endpoint classified each participant as a responder or non-responder based on a decrease of at least 3 points from baseline to Week 24. In general, a proportion describes the share of an analyzed group meeting a specified condition. It is interpretable in terms of the chosen threshold, but it does not show how far each person’s rating changed. A participant just meeting the cutoff and one with a larger decrease both count as responders under this definition.
The record does not report the responder count or proportion. Without those values, it is not possible to describe the observed response frequency, calculate its uncertainty, or assess whether the estimate is precise. No new estimate can be recovered from enrollment alone.
How should an uncertainty interval be understood?
In general, a confidence interval expresses the range of estimates compatible with the observed data under a specified statistical procedure. A narrow interval indicates greater precision than a wide interval, while neither interval by itself resolves limitations in study design or measurement. The registry record does not report a confidence interval for the primary endpoint. It also does not report an inferential test or a model-based estimate for the primary outcome.
What does the single-group design imply?
With one treatment group, the primary endpoint can describe the proportion classified as responders among participants included in the analysis. There is no randomized control group to estimate what would have happened over the same period without the study treatment or under another intervention. In general, randomization helps balance measured and unmeasured factors between comparison groups, while masking can reduce some expectation-related influences on assessment. Neither a randomized comparator nor masking is described in this record.
Within-participant baseline-to-follow-up change can still be described, but it is not equivalent to a controlled treatment contrast. General factors such as changes over time, regression to the mean, co-interventions, and observer expectations can influence before-and-after outcomes. Their contribution in this trial is not reported in the registry record.
What is the role of the intention-to-treat approach?
The primary efficacy analysis is described as intention to treat. In general, an intention-to-treat approach aims to analyze participants according to the group to which they were assigned, preserving the benefits of random allocation when a randomized design has been used. This study is non-randomized and single-group, so the phrase does not create a randomized comparison. The record does not provide further details about which enrolled participants were included in the primary analysis or how the analysis population was operationalized.
What assumptions accompany carried-forward observations?
For participants who dropped out due to lack of efficacy, the record says the worst observation was carried forward. For dropouts for other reasons, it says the last observation was carried forward. In general, carrying a prior or selected observation forward substitutes an assumed follow-up value for an unobserved one. This can make an analysis possible, but it treats the carried value as a stand-in for the missing outcome and may not reflect what would actually have been observed at Week 24.
The direction and size of any resulting bias depend on why data are missing and how outcomes would have changed after dropout. The record does not report the number of dropouts, their reasons, the number of carried-forward values, or sensitivity analyses using alternative assumptions. Consequently, the effect of missing data on the primary endpoint cannot be evaluated from the registry record.
Why can over-dispersion matter in general?
For count outcomes, a statistical model may assume that the variability follows a particular relationship to the mean. Over-dispersion means observed variation is greater than that assumption allows; if unaddressed, uncertainty can be understated. This general issue is not identified as a method used in this study. The primary endpoint is recorded as a binary responder outcome, and the registry does not report a count-outcome model or an over-dispersion assessment.
What can planning calculations tell readers?
In general, sample-size planning calculations describe how many participants might be required under stated assumptions about an effect, allocation, significance level, and statistical model. They are not a measure of the probability that a completed study found a real effect, and they are not observed power. The registry record does not report the trial’s own sample-size justification. Any planning illustration based on an observed effect is a separate hypothetical calculation, not evidence that the trial was designed around that effect or that a particular effect was observed.
The record gives no primary efficacy estimate to interpret, and it does not report the underlying analysis outputs needed to evaluate model choices or precision. Statistical interpretation is therefore limited to the endpoint definition, design, stated missing-data rules, enrollment, and reported adverse-event counts.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists secondary outcomes that include parent or caregiver visual analog scale assessments of drooling, a parent or caregiver global assessment of treatment, and an investigator global assessment of treatment. The visual analog scale assessment appears twice in the outcome listing, with slightly different wording. The record does not report numerical results for these measures or explain how their analyses were prioritized relative to the primary endpoint.
When a study evaluates multiple outcomes or performs multiple statistical tests, the chance of at least one apparently notable result can increase. In general, multiplicity procedures or a prespecified hierarchy can help control how results are interpreted. The registry record does not report whether multiplicity was addressed, whether secondary outcomes were confirmatory or exploratory, or whether any interim analyses were planned or conducted. These details are not reported in the registry record.
For the primary endpoint, the stated analysis population was intention to treat. The record’s missing-data rule assigns the worst observation carried forward to participants who dropped out due to lack of efficacy and the last observation carried forward to participants who dropped out for other reasons. The number of participants with missing outcomes, the timing of dropout, and the number handled by each rule are not reported. The record does not describe sensitivity analyses that would show whether conclusions depended on those assumptions.
The registry does not report how missing data were handled for the secondary outcomes, whether participants with incomplete measurements were excluded from particular analyses, or whether analysis populations differed across outcomes. These omissions limit evaluation of completeness and potential bias. They also prevent assessment of whether the stated intention-to-treat approach included all enrolled participants in practice.
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 |
|---|---|---|---|
| Patients With Chronic Drooling | 14 | 137 | 10.2% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 3% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Patients With Chronic Drooling | 122 of 137 |
Most frequent serious adverse event terms
| Event term | Organ system | Patients With Chronic Drooling |
|---|---|---|
| Pneumonia | Infections and infestations | 3 of 137 |
| Nystagmus | Nervous system disorders | 1 of 137 |
| Convulsion | Nervous system disorders | 1 of 137 |
| Hydrocephalus | Nervous system disorders | 1 of 137 |
| Anoxic encephalopathy | Nervous system disorders | 1 of 137 |
| Urinary tract infection | Infections and infestations | 1 of 137 |
| Otitis media | Infections and infestations | 1 of 137 |
| Esophageal candidiasis | Infections and infestations | 1 of 137 |
| Cellulitis | Infections and infestations | 1 of 137 |
| Tonsillar hypertrophy | Respiratory, thoracic and mediastinal disorders | 1 of 137 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Patients With Chronic Drooling |
|---|---|---|
| Constipation | Gastrointestinal disorders | 28 of 137 |
| Diarrhea | Gastrointestinal disorders | 24 of 137 |
| Vomiting | Gastrointestinal disorders | 24 of 137 |
| Pyrexia | General disorders | 20 of 137 |
| Dry mouth | Gastrointestinal disorders | 15 of 137 |
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | 15 of 137 |
| Flushing | Vascular disorders | 15 of 137 |
| Otitis media | Infections and infestations | 11 of 137 |
| Upper respiratory tract infection | Infections and infestations | 11 of 137 |
| Rash | Skin and subcutaneous tissue disorders | 11 of 137 |
Serious events with the highest arm-level rate: pneumonia (2.2%), nystagmus (0.7%), convulsion (0.7%), hydrocephalus (0.7%), anoxic encephalopathy (0.7%).
The registry reports that 14 of the 137 participants at risk had serious adverse events. It also reports that 122 of the 137 participants at risk had other adverse events. These are participant counts in the study group, not comparisons between treatment and control groups. The record does not report a control group, so these figures cannot estimate a difference in event frequency relative to an untreated or alternative-treatment group.
The listed serious adverse-event terms and their registry percentages are pneumonia (2.2%), nystagmus (0.7%), convulsion (0.7%), hydrocephalus (0.7%), anoxic encephalopathy (0.7%), and urinary tract infection (0.7%). These percentages are reported as listed; the record does not provide further detail in this summary about event timing, recurrence, severity beyond the serious-event classification, or attribution.
An adverse event occurring during a study is not, by itself, proof that the study drug caused it. Causal interpretation requires consideration of timing, clinical context, background risks, and comparison information. The death count is not reported in the registry record, so it should not be interpreted as zero. The reported counts describe safety observations during the study but do not establish comparative safety.
12. What the Result Does, and Does Not, Mean
The registry record documents a completed, open-label, single-group study of oral glycopyrrolate liquid in pediatric patients with chronic moderate to severe drooling. It specifies a primary responder definition based on a decrease of at least 3 points in mean mTDS rating from baseline to Week 24. It also states the planned analysis population and the method used to carry forward observations for certain dropouts.
However, the record does not report how many participants met the responder definition, the proportion who responded, or an uncertainty interval. It therefore does not show the numerical primary efficacy result or how precisely that result was estimated. The secondary outcomes are listed, but their numerical results are not reported in the registry record.
Even if a within-group change were available, the design would not support a direct estimate of how outcomes compared with a control condition. Participants were not randomized to separate groups, and no comparator arm is described. In general, an uncontrolled change over time can reflect several influences, including treatment, changes in the underlying condition, other care, measurement variability, and expectations. The registry record does not quantify these influences.
The adverse-event data indicate that serious and other adverse events were recorded among study participants. Those counts are useful for describing what the registry reports during the study, but a single-group record does not establish whether events were caused by the study drug or how event frequencies compare with another treatment or no treatment.
Accordingly, the record supports an account of the study’s design, endpoint definition, missing-data approach, and reported safety counts. It does not support a numerical conclusion about the primary efficacy outcome, a controlled treatment-effect estimate, or a comparative safety assessment. Those distinctions separate what the record documents from questions it does not answer.
13. Why This Trial Matters Statistically
This study illustrates why an endpoint definition and an endpoint result are different pieces of evidence. The registry specifies a concrete responder threshold for the mTDS, which makes clear what would count as response. Yet without the observed responder count or proportion, readers cannot assess the frequency of response or its statistical precision. A detailed definition cannot substitute for a reported result.
The design also makes the estimand important. A single-group study can characterize outcomes among participants receiving the intervention, but it does not directly estimate a contrast against a control. This distinction is central when interpreting change from baseline: a measured change is descriptive of the observed course, while a comparative effect asks how outcomes differ under alternative conditions. The registry record describes the former design and not the latter.
Missing-data rules are another important statistical feature. The record distinguishes dropouts attributed to lack of efficacy from dropouts for other reasons and assigns different carried-forward values. In general, such choices encode assumptions about unobserved outcomes. The absence of counts and sensitivity analyses means the influence of those assumptions cannot be judged from the registry record.
Finally, safety counts need a denominator and a suitable comparison for comparative interpretation. The record gives counts among 137 participants at risk, but does not describe a control group. That permits a descriptive account of recorded events, not an estimate of excess risk or causal attribution.
Taken together, these features show why statistical interpretation requires more than a study label or a prespecified endpoint. Design, analysis populations, missingness, uncertainty, and availability of results all shape what can reasonably be concluded. In this case, the registry record leaves the primary numerical outcome and several analysis details unreported.
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 main limitation for interpreting efficacy is that the registry record does not report the primary responder result. It gives the mTDS definition but no observed count or proportion, no confidence interval, and no test result. The listed secondary outcomes also lack numerical results in the record. Thus, the record cannot support an assessment of the magnitude or precision of efficacy outcomes.
The study was non-randomized, open-label, and single-group, with no comparator described. This limits causal interpretation of changes from baseline and prevents a controlled comparison. Since the primary outcome is rating-based and the study was unmasked, expectation-related influences are a general concern; the registry record does not report any blinded assessment process.
The record describes carried-forward rules for missing primary outcome data but does not report how many observations were missing, how many participants dropped out, or the reasons and timing of all withdrawals. It also does not report sensitivity analyses. These gaps make it difficult to assess the impact of missing outcomes or the robustness of the primary analysis.
The registry record does not report a full statistical analysis plan, a sample-size justification, multiplicity procedures, or details of interim analyses. It also does not provide enough detail to evaluate how the listed secondary outcomes were analyzed or how the intention-to-treat population was implemented. These items are not reported in the registry record, rather than evidence that a particular procedure was or was not used.
For safety, the reported counts lack a concurrent comparison group, and the death count is not reported in the registry record. Event counts therefore provide descriptive information only and do not establish causation or comparative risk.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Safety and Efficacy Study of Oral Glycopyrrolate Liquid for the Treatment of Pathologic (Chronic Moderate to Severe) Drooling in Pediatric Patients 3 to 18 Years of Age With Cerebral Palsy or Other Neurologic Conditions — NCT00491894.
- Registry record last updated 2012-07-09; status last verified 2012-04.
- Results first posted 2012-07-09.
- 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, multicenter, open-label, non-randomized, single-group study sponsored by Shionogi. Enrollment was 137. Participants aged 3 to 18 years with chronic moderate to severe drooling associated with cerebral palsy or other neurologic conditions received oral glycopyrrolate liquid, with a titration period and study duration described as 24 weeks.
The primary endpoint was responder status on the mTDS at Week 24, defined as at least a 3-point decrease from baseline. The primary analysis was described as intention to treat, with different carry-forward rules for dropouts according to reason. The observed primary efficacy result and numerical results for secondary outcomes are not reported in the registry record.
The registry reports 14 participants with serious adverse events and 122 with other adverse events among 137 at risk. The death count is not reported in the registry record. With no comparator group described, these safety counts are descriptive and do not establish treatment causation or comparative risk.