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 A Study Using Botulinum Toxin Type A as Headache Prophylaxis in Adolescents With Chronic Migraine (NCT01662492), a randomized phase 3 study. The primary outcome is Change From Baseline in the Frequency of Headache Days.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01662492 |
| Phase | Phase 3 |
| Condition | Migraine Disorders |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Triple |
| Enrollment | 125 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Allergan |
| Results posted | Yes |
2. Clinical Question
Population
Adolescents aged 12 to 17 with chronic migraine. The primary outcome population is described as the Intent-to-Treat population, defined as all randomized subjects.
Intervention
Botulinum toxin type A in two dose groups. The intervention descriptions state that the injections were intramuscular and given into specified muscles; details of those muscles are not reported in the registry record.
Comparator
Placebo, described as normal saline, administered by intramuscular injections into specified muscles.
Primary question
How did the frequency of headache days change from baseline to the 12-week assessment in the botulinum toxin type A groups compared with placebo? The numerical results needed to answer that question are not reported in the registry record.
The study was registered as a phase 3 clinical trial of headache prophylaxis in adolescents with chronic migraine. Its stated purpose was to evaluate efficacy and safety for botulinum toxin type A versus placebo. The registry lists 125 participants and identifies three intervention groups: two botulinum toxin type A dose groups and a normal-saline placebo group.
The primary outcome focuses on change in headache-day frequency rather than a single headache episode. A headache day was defined as a calendar day with one or more total hours of headache, recorded by the patient in an electronic diary. The assessment covers the 28-day period ending with Week 12, with baseline serving as the point of comparison.
The clinical question is therefore about the comparative change in a diary-based measure over the specified follow-up period. The registry record does not report the group-level changes, a between-group effect estimate, its uncertainty, or a test of the primary comparison. It is not possible to determine from the registry record whether the observed changes differed between either dose group and placebo, or how precisely any difference was estimated.
3. Trial Design
The registry classifies this as a phase 3, randomized, triple-masked, parallel-group trial. Randomization means assignment to study groups is intended to occur by chance; masking is intended to limit the influence of treatment knowledge on conduct or assessment. The record does not describe which parties were masked, how the random sequence was generated, or how allocation was concealed. Those details are not reported in the registry record.
The parallel-group structure means participants were assigned to a group and followed under that assignment, rather than crossing between treatments. The listed groups are botulinum toxin type A Dose 1, botulinum toxin type A Dose 2, and placebo (normal saline). The intervention descriptions identify intramuscular injections into specified muscles. The specific injection schedules, dose amounts in the intervention descriptions, and muscle sites are not reported in the registry record. The safety groups are labelled Botulinum Toxin Type A 155 U, Botulinum Toxin Type A 74 U, and Placebo; the record does not explicitly map the intervention labels Dose 1 and Dose 2 to those safety labels.
The registry lists enrollment as 125. The study status is completed. Its recorded start is 2012-10, and primary completion is recorded as 2016-08. These are registry dates; they do not by themselves provide information about the timing or conduct of individual assessments.
The primary outcome is change from baseline in frequency of headache days, assessed at baseline and 12 weeks. The endpoint description specifies a diary-based definition and identifies the Intent-to-Treat population as all randomized subjects. The registry lists four additional outcomes concerning severe headache-day frequency, cumulative headache hours on headache days, the proportion with a substantial decrease in headache-day frequency, and prescription of oral rescue migraine prophylactic treatment. Detailed outcome results and analysis methods are not reported in the registry record.
The record does not report the planned allocation ratio, target sample-size justification, detailed statistical analysis plan, or whether any interim analyses were planned or conducted. Enrollment alone does not establish the allocation achieved in each group.
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 | Botulinum Toxin Type A 155 U | Botulinum Toxin Type A 74 U | Placebo (Normal Saline) |
|---|---|---|---|
| STARTED | 45 | 43 | 37 |
| COMPLETED | 42 | 42 | 31 |
| NOT COMPLETED | 3 | 1 | 6 |
Reasons for not completing this period:
| Reason | Botulinum Toxin Type A 155 U | Botulinum Toxin Type A 74 U | Placebo (Normal Saline) |
|---|---|---|---|
| Other miscellaneous reasons. | 1 | 0 | 1 |
| Withdrawal by Subject | 0 | 0 | 1 |
| Protocol Violation | 1 | 0 | 0 |
| Lost to Follow-up | 0 | 0 | 2 |
| Lack of Efficacy | 1 | 1 | 2 |
Analysis population for the primary outcome, as defined in the registry: Intent-to-Treat (ITT) Population: All randomized subjects.
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 | Botulinum Toxin Type A 155 U | Botulinum Toxin Type A 74 U | Placebo (Normal Saline) | Total |
|---|---|---|---|---|---|
| Participants analysed | 45 | 43 | 37 | 125 | |
| Age, Continuous | years | 15.1 (SD 1.4) | 15.0 (SD 1.5) | 15.2 (SD 1.5) | 15.1 (SD 1.5) |
| Sex/Gender, Customized: Male | participants | 8 | 11 | 8 | 27 |
| Sex/Gender, Customized: Female | participants | 37 | 32 | 29 | 98 |
6. Primary Endpoint
The registry lists the primary outcome as Change From Baseline in the Frequency of Headache Days, measured over Baseline, 12 Weeks.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Standard Deviation |
| Unit | Headache days |
| Endpoint classification | Continuous Endpoint |
The primary endpoint is change from baseline in the frequency of headache days, measured in headache days. The assessment compares baseline with Week 12 and uses the 28-day period ending at Week 12. A headache day is defined as a calendar day on which the participant records one or more total hours of headache in an electronic diary. The named analysis population is the Intent-to-Treat population, defined in the registry as all randomized subjects.
This endpoint is used to quantify how often headache occurs over a defined observation period. A diary-based count can represent repeated days of headache, rather than relying only on a participant’s recall at a later visit. Comparing a follow-up period with baseline also expresses change relative to each participant’s starting measurement. These are general reasons such measures can be useful; the registry does not state a separate rationale for selecting this endpoint.
Change in a group average can describe the overall pattern, but interpretation of a treatment comparison also depends on the difference between groups and its uncertainty. The registry record does not report the observed group means, standard deviations, change estimates, confidence intervals, or p-values for this endpoint. It therefore does not establish the size or precision of any comparative change.
The endpoint description identifies the measurement window and population, but does not report how diary entries were handled when missing, how baseline and follow-up values were incorporated into the analysis, or whether any covariates were included. Those details are not reported in the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record identifies a randomized comparison of two botulinum toxin type A dose groups with normal-saline placebo, and it defines a primary endpoint based on change in headache-day frequency. However, the record does not report numerical primary-outcome results. In particular, it does not report group-level changes, a treatment contrast, standard errors or confidence intervals, or a p-value. The comparative effect and its precision are therefore not available from the registry record.
This absence of endpoint results limits what can be inferred from the posted information. The stated trial objective is to evaluate efficacy and safety, but an objective is not a finding. Neither the trial’s completion status nor its randomized, masked design supplies evidence about the direction or size of an outcome effect. Without the reported outcome values, it is not possible to characterize the primary comparison as favoring any group or to assess whether any difference is compatible with a wide or narrow range of effects.
The endpoint is defined as a mean continuous measure: change in frequency of headache days. For a mean outcome, the group mean describes the average observed change, while a standard deviation describes variation among participant measurements. A between-group estimate would directly express the comparison of interest. A confidence interval, if reported, would communicate the statistical uncertainty around that estimate; it would not by itself establish clinical importance. Neither these values nor an interpretation of clinical importance is reported in the registry record.
The record lists four secondary outcomes, but does not report their numerical results or analysis details. The registry also indicates no posted analyses. This means the record does not offer an analysis output from which to evaluate consistency across outcomes, compare dose groups, or examine whether conclusions depend on a particular analysis. Absence of posted analyses should not be interpreted as evidence that a particular effect was absent.
Safety information is reported as counts in the listed groups. Serious adverse events affected 1 of 43 participants in the 155 U group, 2 of 43 in the 74 U group, and 0 of 37 in the placebo group. Other adverse events affected 8 of 43, 14 of 43, and 8 of 37 participants, respectively. These counts describe the posted safety data, but do not replace a full accounting of event types, timing, severity, or causal assessments. Death counts are not reported in the registry record.
The registry lists Cellulitis, Appendicitis, and Migraine among serious adverse event terms, each with 2.3%. It does not provide enough context in that listing to assign those terms to a specific arm. The overall interpretation remains limited: the record describes the trial and some safety counts, but does not provide the primary efficacy results needed to estimate or judge the treatment comparison.
9. Statistical Methods Explained
The design labels provide a framework for understanding the comparison, but do not disclose the full statistical methods. Randomization, masking, parallel assignment, endpoint definition, and the stated analysis population are reported. The procedures used to implement those features, the model used for the primary analysis, and the handling of incomplete data are not reported in the registry record.
What does a mean change represent?
In general, a mean change summarizes the average difference between measurements at baseline and follow-up across participants included in the analysis. The endpoint is continuous, and its unit is headache days. A mean can be useful for describing the overall shift in a group, but it does not show how much participants differed from one another. The primary outcome identifies standard deviation as the dispersion measure, but numerical means and standard deviations are not reported in the registry record.
For a treatment comparison, a difference between group mean changes is usually more directly informative than separate within-group changes. A change within a treatment group can reflect more than the assigned intervention, including changes that may also occur in a comparison group. The registry record does not report the between-group estimate or specify the exact contrast used in the primary analysis, so no such comparison can be reconstructed.
How should uncertainty be read?
In general, a confidence interval gives a range of values compatible with the observed data under the statistical model and its assumptions. Its width reflects precision: a narrower interval indicates less statistical uncertainty than a wider interval. A p-value, in general, describes how unusual data at least as incompatible with a specified null hypothesis would be under that hypothesis and the model. A p-value is not the probability that the null hypothesis is true, and it does not quantify clinical importance. The registry record does not report a confidence interval or p-value for the primary outcome.
Standard deviations and standard errors serve different roles. In general, a standard deviation describes spread among individual observations, while a standard error describes uncertainty in an estimated quantity. A standard deviation is named for the primary endpoint, but its results are absent; the registry does not specify a standard error method. No precision statement can be derived from the recorded design information alone.
What do randomization and masking contribute?
In general, random allocation aims to make treatment groups comparable with respect to measured and unmeasured baseline characteristics, on average. Masking can reduce bias when treatment knowledge might influence participant reports, investigator decisions, or outcome assessment. These design features support interpretation, but they do not guarantee balanced groups or eliminate all bias. The registry labels the trial randomized and triple-masked, but the sequence-generation, concealment, and masking procedures are not reported in the registry record.
The primary measure depends on patient electronic-diary entries. In general, a consistent diary definition can make the outcome more reproducible, while incomplete or inconsistent recording can affect the measured count. The registry does not report compliance, validation procedures, missing-entry rules, or any sensitivity analyses for diary data.
Why do analysis choices matter?
In general, a statistical model defines how outcome measurements are summarized and how comparisons and uncertainty are estimated. Choices can include whether to adjust for baseline values, how to account for repeated or correlated measurements, and which assumptions to make about the distribution of the outcome. The primary result is identified as a mean and standard deviation, but no model or adjustment strategy is stated. Those analysis choices are not reported in the registry record.
Over-dispersion is a general concern when count data vary more than a simple model assumes. If a count model assumes less variability than the data contain, its uncertainty estimates may be too small and confidence intervals too narrow. Other approaches can allow greater variability. This is a general statistical consideration, not a statement about the model used in this trial. The registry record does not report a count model or an over-dispersion assessment; the primary endpoint is described in terms of a mean and standard deviation.
The registry includes a planning illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. Such planning figures illustrate sample sizes under stated assumptions; they are not observed power and do not establish the trial’s own design justification. The registry does not report a sample-size justification for the original design. Planning calculations also cannot substitute for the missing primary outcome estimate, and no numerical treatment result should be inferred from them.
Because the registry reports no posted analyses, readers cannot assess model fit, residual behavior, the handling of multiple comparisons, or the robustness of an estimate to alternative assumptions. These are general components of statistical assessment. Their application in this trial is not reported in the registry record.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists the primary endpoint and four secondary outcomes. Those secondary outcomes address severe headache-day frequency, cumulative headache hours on headache days, the proportion of participants with a substantial decrease in headache-day frequency, and prescription of oral rescue migraine prophylactic treatment. The record does not report a multiplicity procedure, such as an adjustment to account for testing several outcomes or comparisons. It also does not state a prespecified hierarchy for interpreting the outcomes. These plans are not reported in the registry record.
In general, when several hypotheses are tested, the chance of at least one apparently unusual result can increase if each is treated as an isolated test. Multiplicity procedures can help control that issue, while a prespecified hierarchy can clarify which outcomes are confirmatory and which are exploratory. Without a reported plan and outcome analyses, it is not possible to determine how multiplicity was handled or how results across outcomes should be interpreted.
The primary outcome specifies an Intent-to-Treat population consisting of all randomized subjects. The registry does not report the number included in the primary analysis, the number with missing measurements, or how missing diary data or withdrawals were handled. It does not describe imputation, exclusion rules, or sensitivity analyses. These details are not reported in the registry record.
In general, missing-data methods matter because conclusions can depend on why observations are missing and how the analysis treats them. An analysis that excludes incomplete records can differ from one that models or imputes missing values, and assumptions about unobserved outcomes cannot be checked from a population label alone. The Intent-to-Treat definition identifies the intended analysis population, but it does not disclose the missing-data method or establish that every randomized participant contributed a primary endpoint measurement.
The registry lists 0 analyses. Consequently, it does not provide posted analytical results with which to assess population flow, endpoint availability, multiplicity, or missing-data sensitivity.
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 |
|---|---|---|---|
| Botulinum Toxin Type A 155 U | 1 | 43 | 2.3% |
| Botulinum Toxin Type A 74 U | 2 | 43 | 4.7% |
| Placebo (Normal Saline) | 0 | 37 | 0.0% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Botulinum Toxin Type A 155 U | 8 of 43 |
| Botulinum Toxin Type A 74 U | 14 of 43 |
| Placebo (Normal Saline) | 8 of 37 |
Most frequent serious adverse event terms
| Event term | Organ system | Botulinum Toxin Type A 155 U | Botulinum Toxin Type A 74 U | Placebo (Normal Saline) |
|---|---|---|---|---|
| Cellulitis | Infections and infestations | 1 of 43 | 0 of 43 | 0 of 37 |
| Appendicitis | Infections and infestations | 0 of 43 | 1 of 43 | 0 of 37 |
| Migraine | Nervous system disorders | 0 of 43 | 1 of 43 | 0 of 37 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Botulinum Toxin Type A 155 U | Botulinum Toxin Type A 74 U | Placebo (Normal Saline) |
|---|---|---|---|---|
| Neck Pain | Musculoskeletal and connective tissue disorders | 3 of 43 | 5 of 43 | 0 of 37 |
| Upper Respiratory Tract Infection | Infections and infestations | 0 of 43 | 3 of 43 | 4 of 37 |
| Migraine | Nervous system disorders | 1 of 43 | 3 of 43 | 1 of 37 |
| Musculoskeletal Pain | Musculoskeletal and connective tissue disorders | 1 of 43 | 3 of 43 | 0 of 37 |
| Dizziness | Nervous system disorders | 3 of 43 | 0 of 43 | 1 of 37 |
| Bronchitis | Infections and infestations | 1 of 43 | 0 of 43 | 2 of 37 |
| Oropharyngeal Pain | Respiratory, thoracic and mediastinal disorders | 0 of 43 | 0 of 43 | 2 of 37 |
Serious events with the highest arm-level rate: cellulitis (2.3%), appendicitis (2.3%), migraine (2.3%).
The registry reports serious adverse event counts for three safety groups. In the Botulinum Toxin Type A 155 U group, 1 of 43 participants was affected; in the Botulinum Toxin Type A 74 U group, 2 of 43 were affected; and in the placebo group, 0 of 37 were affected. The listed counts for other adverse events are 8 of 43, 14 of 43, and 8 of 37, respectively. These are participant counts, not a complete description of event timing, duration, severity, or attribution.
The registry also lists Cellulitis, Appendicitis, and Migraine as serious adverse event terms, each with 2.3%. The record does not assign those terms to specific groups in the information. Death counts are not reported in the registry record.
In general, serious adverse events are a distinct safety category from other adverse events; counts in the categories should not be assumed to represent identical events or reporting rules. Small group counts can also be imprecise descriptions of underlying event frequencies. These safety counts alone do not establish whether an event was caused by a treatment, and the registry record does not report causal assessments or a comparative statistical analysis of safety.
12. What the Result Does, and Does Not, Mean
The registry record documents a randomized, triple-masked, parallel-group phase 3 trial examining botulinum toxin type A and placebo for headache prophylaxis in adolescents with chronic migraine. It specifies a primary measure of change in headache-day frequency from baseline to Week 12 and gives a diary-based definition of a headache day. It also lists secondary outcomes and reports selected adverse event counts.
What the record does not establish is the primary treatment effect. Group-level endpoint results, a between-group estimate, confidence intervals, and p-values are not reported in the registry record. Without these values, the direction, magnitude, and precision of any difference cannot be assessed. The trial’s stated objective is not evidence of an outcome, and its completed status does not fill the gap in the posted results.
The available safety counts can be described as recorded, but they are not a full comparative safety analysis. The counts do not show the event timing, event-level detail, or causality, and death counts are not reported in the registry record. The listed serious adverse event terms also do not identify their arm assignment in the information available.
In general, statistical evidence and clinical importance are related but distinct. An estimate and its uncertainty help show what range of effects is compatible with data; clinical importance requires interpreting the size and nature of that effect in context. Since the outcome estimates are absent, neither statistical precision nor clinical importance can be evaluated from the registry record.
Accordingly, the defensible interpretation is limited to the design, endpoint definitions, and posted safety counts. No conclusion about the comparative efficacy of the study groups follows from the information reported in the registry record.
13. Why This Trial Matters Statistically
This trial raises statistical questions common to clinical research: how to define a diary-based endpoint, compare changes from baseline, communicate uncertainty, and distinguish a stated objective from a reported result. Its primary endpoint is a continuous summary of headache-day frequency over a defined period, with an explicit diary rule for what constitutes a headache day. Clear outcome definitions are important because they determine what is measured and which observations contribute to the analysis.
The randomized, masked, parallel-group design is also relevant to interpretation. In general, randomization and masking can reduce some sources of bias, but the labels alone do not provide the procedural detail needed to assess how they were implemented. The registry record does not report the allocation methods, masking procedures, or a complete statistical analysis plan.
The difference between an endpoint definition and an endpoint result is particularly important. The record provides a measure, population, and assessment period, but does not report the group-level values or the uncertainty around a treatment contrast. Without those results, readers cannot evaluate how large or precise any observed difference was. The presence of a planning illustration does not resolve this: planning calculations are not trial outcomes or observed power.
The record also illustrates why the handling of multiple outcomes and missing data matters. It lists several secondary measures, but does not report multiplicity methods, missing-data procedures, or posted analyses. Those omissions prevent a reader from assessing the strength and consistency of results across the planned outcomes.
For biostatistical interpretation, the principal lesson is to separate what the registry documents from what it leaves unreported. Design features and safety counts can be described, but they cannot be used to reconstruct missing efficacy estimates or statistical tests.
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 most consequential limitation in the registry record is that numerical primary-outcome results are not reported. There are no reported group means, standard deviations, treatment contrasts, confidence intervals, or p-values for change in headache-day frequency. Thus, the principal comparative question cannot be answered from the posted record.
The registry lists 0 analyses, and the secondary outcome results are not reported. As a result, there is no posted analysis with which to assess whether the primary endpoint findings were consistent with other measures, whether dose groups differed, or whether conclusions depended on a specific analysis. The record does not describe multiplicity control or a hierarchy among outcomes.
Important details of the analysis and data collection are also absent. The record does not report the statistical model, baseline adjustment, missing-diary rules, withdrawals, endpoint completeness, or sensitivity analyses. Although the primary population is defined as all randomized subjects, the number contributing data to the primary analysis is not reported in the registry record.
The safety information is limited to selected participant counts and serious adverse event terms. Event timing, severity detail, treatment attribution, and death counts are not reported. The record does not provide a statistical comparison of these safety counts.
Other trial details that could inform appraisal are not reported in the registry record, including allocation implementation, masking procedures, dose schedule, and the specific muscle sites for injection. The registry lists enrollment as 125, but that figure alone does not describe the number analyzed in each group. These limitations restrict interpretation to the design and outcomes as recorded, rather than a full assessment of trial conduct or treatment effects.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: A Study Using Botulinum Toxin Type A as Headache Prophylaxis in Adolescents With Chronic Migraine — NCT01662492.
- Registry record last updated 2017-09-05; status last verified 2017-07.
- Results first posted 2017-09-05.
- 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, triple-masked, parallel-group trial of botulinum toxin type A versus normal-saline placebo for headache prophylaxis in adolescents with chronic migraine. Enrollment is listed as 125. The recorded study start is 2012-10, and primary completion is 2016-08.
The primary endpoint is change from baseline in headache-day frequency at 12 weeks, measured over the 28-day period ending with Week 12. A headache day is a calendar day with one or more total hours of headache recorded in an electronic diary. The primary population is defined as all randomized subjects.
The record lists four secondary outcomes and reports safety counts for the 155 U, 74 U, and placebo groups. It does not report primary or secondary efficacy estimates, confidence intervals, p-values, missing-data methods, or multiplicity procedures. The registry lists 0 analyses.