Long-term Treatment of Moderate to Severe Glabellar Lines and Lateral Canthal Lines: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Long-term Treatment of Moderate to Severe Glabellar Lines and Lateral Canthal Lines (NCT04225260), a na phase 3 study. The primary outcome is Percentage of Subjects Who Achieve Grade/Level 0 or 1 on the GL Investigator Scales at Maximum Frown.

2. Clinical Question

3. Trial Design

This was a phase 3, multicenter, open-label study of QM1114-DP for moderate to severe glabellar lines and lateral canthal lines. The registry lists a single-group model, no masking, and allocation as not applicable. Enrollment was 902. The study status is completed; the recorded start date is 2020-01-27 and the primary completion date is 2021-04-12.

The intervention is described as a botulinum toxin neuromodulator, with the investigational product identified as QM1114-DP, a BoNT Type A. At each treatment, a total dose was to be administered in the glabellar and lateral canthal line areas. The amount of that dose, number of treatments, intervals between treatments, and total follow-up schedule are not reported in the registry record.

The primary outcome concerns the proportion of participants reaching Grade/Level 0 or 1 on the glabellar-line investigator scales at maximum frown at Week 4. The registry describes the scale as a 4-point scale and identifies the analysis population as FAS. It does not provide a definition of FAS. Although the study summary emphasizes long-term safety, the recorded primary endpoint is a Week 4 glabellar-line assessment.

With one study group and no masking, the design can describe outcomes among participants receiving QM1114-DP, but it does not support a randomized treatment contrast. The registry record does not report a control group, a blinding procedure, or an allocation sequence. Details of eligibility criteria, treatment adherence, and the reasons participants may have left the study are not reported in the registry record.

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

Analysis population for the primary outcome, as defined in the registry: FAS

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.

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Subjects Who Achieve Grade/Level 0 or 1 on the GL Investigator Scales at Maximum Frown, measured over Week 4.

The primary endpoint is titled as the percentage of participants who achieve Grade/Level 0 or 1 on the glabellar-line investigator scales at maximum frown. Its recorded timeframe is Week 4, and the scale is described as a 4-point scale. The registry outcome entry uses participants as the unit and describes the measure as a count of participants, but it does not report the observed count or percentage.

In general, a threshold-based endpoint classifies participants according to whether they meet a specified response level. Reporting the proportion meeting that threshold can make a clinical scale easier to interpret than reporting only an average score, because it describes how many participants reached a defined category. That interpretation depends on knowing the scale and threshold; the registry record supplies the threshold as Grade/Level 0 or 1 but does not give further scale definitions.

The endpoint is specific to glabellar lines and investigator assessment at maximum frown. It does not, by itself, report the corresponding outcome for lateral canthal lines, long-term response over repeated assessments, or safety. Those questions would require separately reported outcomes. No endpoint estimate, uncertainty interval, or statistical test result is reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Study structure. This is a single-group study, rather than a randomized comparison. In general, a single-group design can describe what was observed among participants receiving an intervention. Without a concurrent comparator, it cannot directly estimate how outcomes would differ under another intervention or under no intervention. The registry lists allocation as not applicable and masking as none, consistent with the recorded open-label design.

What a response proportion means. The primary endpoint is framed as the percentage achieving Grade/Level 0 or 1 on the glabellar-line investigator scales at maximum frown at Week 4. In general, a binary endpoint separates participants into those who meet a criterion and those who do not. The count meeting the criterion and the number assessed are needed to calculate a proportion. Although the registry identifies the unit as participants and the measure as a participant count, it does not report the endpoint count, percentage, or denominator assessed.

Precision and uncertainty. A confidence interval is a statistical way to express uncertainty around an estimated quantity. For a response proportion, it communicates how imprecisely the proportion is estimated, conditional on the data and method. A point estimate alone would not show that uncertainty; conversely, an interval would not address design limitations such as the absence of a control group or possible influences on unmasked assessment. No confidence interval for the primary outcome is reported in the registry record.

Tests and comparisons. A p-value is generally used to assess how compatible observed data are with a specified null hypothesis under a statistical model. Its meaning depends on the question, analysis, and assumptions. In a single-group study, a test might address a prespecified benchmark or within-group change, but the registry record does not report such a benchmark, an analysis plan, or a test for the primary endpoint. It reports zero analyses. No p-value or inferential result for the primary endpoint is reported.

Model assumptions. Statistical models rely on assumptions appropriate to the outcome and design. For a binary response, an analysis might model the probability of meeting the response threshold; repeated observations may require methods that account for within-participant dependence. These are general methodological considerations, not descriptions of methods documented for this study. The registry record does not report the statistical model, handling of repeated assessments, covariate adjustment, or assumptions used in an analysis.

Planning illustrations versus observed evidence. A sample-size planning illustration based on an observed effect is conceptually different from the trial’s original design calculation. The stated illustration assumptions use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect expressed as a fraction of the observed effect. Such calculations are planning illustrations, not observed power, and do not establish that this single-group study was designed as a two-arm trial. The registry record does not report a trial-specific sample-size justification or the observed effect needed to interpret such an illustration.

Over-dispersion and count outcomes. In general, over-dispersion occurs when count data vary more than a statistical model expects. If present, it can make standard errors from a model too small and confidence intervals too narrow unless the analysis accounts for the extra variation. This study’s recorded primary endpoint is a participant count used to define a response proportion, not a reported rate model. The registry record does not report a count-model analysis or an assessment of over-dispersion, so this concept should not be read as a feature of the study’s reported analysis.

Multiplicity. When several outcomes, time points, or statistical tests are examined, the chance of at least one apparently notable result can increase. Methods for addressing this include prespecifying a primary question and adjusting tests, but the registry record does not describe any multiplicity strategy. The endpoint listing alone does not establish how multiple outcomes were prioritized or analyzed.

Analysis population and missing observations. The primary outcome lists FAS as its population, but the registry record does not define the term or give the number analyzed. In general, the analysis population determines which participants contribute to an estimate. Missing outcome data can affect that estimate, particularly if the likelihood of missingness is related to response. The registry record does not describe missing-data methods, imputation, sensitivity analyses, or the endpoint denominator.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("QM1114-DP in the GL")
n      <- c(847)
events <- c(769)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  QM1114-DP in the GL  847  769  90.8  88.6  92.7  88.7  92.6  88.7  92.6

11. Multiplicity, Missing Data and Analysis Populations

The primary outcome names FAS as the analysis population, but the registry record does not define FAS or report the number of participants included in that population. Enrollment is recorded as 902; that enrollment figure does not, by itself, establish how many participants contributed to the Week 4 endpoint.

The registry record does not report how missing Week 4 assessments were handled. It does not describe imputation, a missing-data model, sensitivity analyses, or reasons for missingness. In general, a response estimate can be affected when outcome data are unavailable, especially if the probability of missing an assessment is related to the outcome. Without the analysis denominator and missing-data approach, the endpoint’s precision and susceptibility to missingness cannot be assessed from the registry entry.

The record identifies a primary endpoint and lists two outcome measures, but it does not report a statistical analysis plan, a multiplicity strategy, or an inferential analysis. When several outcomes or time points are tested, multiplicity procedures can help control the chance of false-positive findings across tests. Whether such procedures were used in this study is not reported in the registry record. No adjustment or hierarchy should be inferred from the available endpoint descriptions.

The record reports zero analyses. It therefore does not provide enough information to determine which outcomes were formally analyzed, how repeated measurements were handled, or whether planned analyses differed from those posted. These gaps limit interpretation of statistical uncertainty and the relationship between the stated endpoint and any reported findings.

12. 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 1% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: appendicitis (0.1%), covid-19 (0.1%), cholecystitis infective (0.1%), post procedural infection (0.1%), urinary tract infection (0.1%).

The safety entry records 23 participants affected by serious adverse events among 902 at risk. It also records 243 participants affected by other adverse events among 902 at risk, and 1 death. These are participant counts in the QM1114-DP study group, not comparisons against a control group. The registry record does not state whether events were judged related to treatment.

The listed serious adverse event terms are Appendicitis, COVID-19, Cholecystitis infective, Post procedural infection, Urinary Tract Infection, and Urosepsis. Each is listed as 0.1%. These entries describe the terms and percentages posted in the registry; the record does not provide additional context about event timing, duration, outcome, or attribution for those terms.

In general, an adverse event is an occurrence recorded during a study and is not necessarily caused by the intervention. A serious adverse event is a category based on seriousness criteria, not a statement that the event was treatment-related. The posted counts should therefore be read descriptively. With no comparator group, they do not establish a comparative risk, and the registry record does not report a causal assessment of the death or events.

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

The record establishes that QM1114-DP was studied in a phase 3, multicenter, open-label, single-group study enrolling 902 participants for long-term treatment of moderate to severe glabellar and lateral canthal lines. It identifies a Week 4 glabellar-line investigator-rated endpoint and reports safety counts for the treated group. These registry entries describe the study’s scope and the information registered.

The record does not report the observed primary endpoint count or percentage. It therefore does not show how many participants met the Grade/Level 0 or 1 threshold, how precise that estimate was, or how it changed over time. The study summary’s emphasis on long-term safety does not substitute for posted outcome estimates across a long-term follow-up period.

Because there was no randomized comparator group, within-study observations cannot establish what would have happened under a different treatment or without treatment. The open-label design also means masking was absent; the record does not establish whether that influenced investigator assessments. These design features do not invalidate descriptive observations, but they constrain causal interpretation.

The safety counts are not evidence by themselves that QM1114-DP caused the recorded events. The record does not report event attribution or a comparison with another group. Likewise, a count of deaths does not establish cause of death. The appropriate reading is limited to what was recorded: the number of participants affected and the named serious event terms and percentages.

Overall, the registry record conveys the design and selected safety information but does not provide the primary outcome result or an inferential analysis. It cannot support a conclusion about the magnitude, precision, or comparative effect of treatment on the primary endpoint.

14. Why This Trial Matters Statistically

This study illustrates an important distinction between a trial’s stated objective and the results available in its registry entry. The study summary describes long-term safety evaluation, while the listed primary endpoint is a Week 4 investigator-rated glabellar-line response. The endpoint and the safety objective address different questions, and an endpoint label is not itself an observed result.

The single-group, open-label structure also shapes what can be learned statistically. It permits the registry to describe events observed among participants receiving QM1114-DP, but there is no randomized control group for estimating a treatment contrast. This matters when readers encounter event counts or response outcomes: counts within one group do not show how outcomes differ from a relevant alternative.

Outcome reporting is essential for interpretation. The primary endpoint specifies a threshold and assessment time, but the registry record does not give the observed count, percentage, uncertainty interval, or analysis. Without those, readers cannot assess the size or precision of the response estimate. The safety counts add descriptive information, but do not provide a comparative risk estimate or causal attribution.

Finally, the record lists an analysis population but does not define it, explain missing-data handling, or describe multiplicity procedures. Such details affect how estimates are constructed and how multiple findings should be interpreted. The case underscores that registry design details, outcome definitions, analysis methods, and numerical results each contribute distinct evidence; one cannot replace what is missing from another.

15. 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 most direct limitation for interpreting efficacy is that the registry record does not report the primary endpoint result. It names a Week 4 threshold-based outcome but gives no observed participant count, percentage, confidence interval, or test result. The record also reports zero analyses, leaving the statistical treatment of the outcome undocumented.

The study was open-label and single-group, with allocation listed as not applicable. There is no randomized comparator against which to interpret response or safety counts, and no masking to limit possible influence on investigator assessment. These features restrict causal conclusions and comparative interpretation. The record does not establish that assessment bias occurred, only that masking was absent.

The study summary refers to long-term treatment and safety, but the registry entry does not report a full treatment schedule, dose, duration of follow-up, or results at successive time points. The listed primary endpoint is at Week 4, so it cannot by itself describe persistence of response over long-term treatment. The record does not report specific long-term efficacy estimates.

Further limitations include the absence of a definition for FAS, a reported endpoint denominator, and details on missing observations. The statistical analysis plan, sample-size justification, multiplicity strategy, and treatment of repeated measurements are not reported in the registry record. Safety entries do not give event attribution, timing, or contextual clinical details. Together, these omissions limit assessment of precision, bias, and the scope of conclusions that can be drawn from the posted information.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Long-term Treatment of Moderate to Severe Glabellar Lines and Lateral Canthal Lines — NCT04225260.
• Registry record last updated 2023-06-18; status last verified 2020-07.
• Results first posted 2023-06-18.
• 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.

19. Record Summary

NCT04225260 is a completed phase 3, multicenter, open-label, single-group study sponsored by Galderma R&D. It enrolled 902 participants and evaluated QM1114-DP, a BoNT Type A, for moderate to severe glabellar and lateral canthal lines. The recorded start date is 2020-01-27, and the primary completion date is 2021-04-12.

The primary endpoint is the percentage achieving Grade/Level 0 or 1 on the glabellar-line investigator scales at maximum frown at Week 4. The registry record does not report the endpoint result or an inferential analysis. Safety entries report 23 participants with serious adverse events, 243 with other adverse events, and 1 death among 902 at risk. These are descriptive counts without a comparator or reported event attribution.