Duration of Benefit for OnabotulinumtoxinA in Treatment of Chronic Migraine: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Duration of Benefit for OnabotulinumtoxinA in Treatment of Chronic Migraine (NCT02037425), a na phase 4 study. The primary outcome is Subject Global Impression of Change.

2. Clinical Question

The official title describes an exploratory study of natural history, clinical outcomes, and neuronal endplate changes among subjects reporting short-duration versus long-duration benefit. However, the registry entries available for the primary outcome do not define these groups or report a comparison between them. The record also lists secondary measures covering headache days, disability, social readjustment, global impression, mood, anxiety, sleep quality, and acute medication use. Their numerical results are not reported in the registry record. The clinical question should therefore be read as a description of the study’s intended focus, rather than as evidence of an estimated treatment effect or a comparison between benefit-duration groups.

3. Trial Design

This is a completed, Phase 4, exploratory, single-group study of onabotulinumtoxinA in chronic migraine. Enrollment was 44. The registry record lists allocation as NA and masking as none. Those features mean the study was not organized as a randomized, masked comparison between treatment and control groups. The record does not describe a control intervention or a comparator population, so the study cannot provide a randomized between-group estimate from the design information recorded.

The stated purpose was to obtain a patient-specific understanding of response by collecting and correlating pre- and post-treatment subject-specific history, clinical outcomes, and histological changes. The primary outcome was Subject Global Impression of Change at weeks 12, 24, and 36 post randomization. The outcome description refers to Groups A, B, and C, but their definitions and allocation are not reported in the registry record. The analysis population for this outcome includes subjects completing the treatment period 1 injection cycle and returning at visit 3. How that population relates to all enrolled participants is not reported.

The intervention description states that the first treatment was given at visit 2 on Day 29 (+/-3 days), with 155 U in 31 fixed-site, fixed-dose injections across seven specified head and neck muscle areas. The description says injections would be repeated at day, but the schedule is truncated and not reported in full in the registry record. The start date is 2014-04, primary completion was 2015-09, and the study status is completed.

The record lists secondary outcomes including headache days, MIDAS, SRRS, PGIC, BDI-II, STAI, sleep quality, and acute medication usage. It records 13 outcome measures and 0 analyses. The protocol, statistical analysis plan, sample-size justification, interim analyses, and detailed methods for handling follow-up are not reported in the registry record. As a result, the design can be described, but important details needed to assess how the intended analyses were conducted are unavailable.

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: Subjects included in this outcome measure analysis include those completing treatment period 1 injection cycle and returning at visit 3.

5. Baseline Characteristics

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

Population: 44 subjects screened, 3 subjects failed inclusion/exclusion at screening, 9 subjects did not meet criteria after baseline. 32 subjects randomized to treatment. While 32 subjects randomized and were used for reporting demographics, two subjects didn't complete any outcome measures, therefore only 30 participants were used for endpoint analysis.

6. Primary Endpoint

The registry lists the primary outcome as Subject Global Impression of Change, measured over Weeks 12, 24, and 36 Post Randomization.

The primary endpoint is Subject Global Impression of Change (SGIC), assessed at weeks 12, 24, and 36 post randomization. The registry describes SGIC as a subject-reported measure on a 7 point scale, with 0 meaning Very Much Worse and 7 meaning Very Much Improved. The outcome is presented as a continuous measure, with the mean and standard deviation specified as the summary form. The population is participants who completed treatment period 1 injection cycle and returned at visit 3.

General: A global impression measure asks participants to summarize their perceived change, rather than reporting only a single symptom count. Such measures can capture an overall subjective assessment of change over time. A mean can describe the average score in an analyzed group, while the standard deviation describes how spread out individual scores are around that mean. These summaries answer different questions: the mean concerns the group average, and the standard deviation concerns variability among participants.

The endpoint description does not report the actual means, standard deviations, baseline values, change scores, or uncertainty intervals. It also does not specify how a score was handled if a participant did not complete an assessment. The registry record mentions Groups A, B, and C in its description, but does not define them. Consequently, the endpoint’s measurement scale and planned time points are known, but the observed scores and the interpretation of any group-specific result cannot be assessed from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary endpoint is a continuous measure summarized using a mean and standard deviation. General: the mean is the arithmetic average of observed scores in the analysis population. The standard deviation describes the extent to which scores vary around that average. A mean alone can hide substantial variation among participants, while a standard deviation alone does not locate the group’s average on the scale. Together, they provide a compact description of the score distribution, but they do not show every participant’s experience or establish why scores varied.

The SGIC scale is described as having 7 points, with 0 meaning Very Much Worse and 7 meaning Very Much Improved. A score is therefore interpreted in relation to the scale’s stated anchors. The registry record does not report the observed means or standard deviations at weeks 12, 24, and 36, nor does it report changes between assessments. No recalculated estimate can be described without posted summary statistics. The registry record also does not state whether the primary analysis compared scores across time, summarized each time point separately, or used another model.

General: an uncertainty interval, such as a confidence interval, is used to show how precisely an estimate is determined under a statistical model. A narrow interval indicates more precision than a wide interval, while neither width nor position can be judged without the numerical interval. The record does not report a confidence interval for the primary endpoint. It likewise does not report a p-value or a test statistic for that outcome. A missing p-value is not evidence that a result was or was not statistically significant; it means the registry record does not report the result needed to make that assessment.

The study is described as single-group, with allocation NA and no masking. General: a single-group study can describe the observed outcomes among participants, but without a concurrent control group it does not supply a randomized estimate of the difference between treatment and control. Changes over time can have multiple explanations, so within-group observations should not be treated as a randomized treatment effect. The record does not report an analysis plan that would permit a more specific assessment of how the study intended to address such issues.

The primary outcome population is described as participants who completed treatment period 1 injection cycle and returned at visit 3. This makes the analysis population narrower in description than enrollment alone, but the number meeting those conditions is not reported in the registry record. General: an analysis population defines which participants contribute to a particular estimate. Results can depend on that definition, especially when not all enrolled participants contribute data. The record does not describe whether analyses included all enrolled participants, only those with complete assessments, or other analysis populations for outcomes beyond the specific primary outcome description.

The study record states that sample-size planning illustrations use a two-sided significance level of 0.05, equal allocation between two hypothetical arms, and a normal approximation. It also says the effect to detect is a stated fraction of the observed effect. These are described as planning illustrations computed from the observed effect, not as the trial’s own design. For time-to-event illustrations, the stated quantity is the total number of events; other illustrations are stated as participants per arm. General: such calculations examine the sample size associated with specified assumptions. They are planning aids, not observed power and not evidence that the trial was designed or conducted as a two-arm study. The registry record does not report the numerical illustration values or the trial’s own sample-size justification.

General: over-dispersion occurs when outcome variability is greater than a statistical model assumes. If ignored, standard errors and uncertainty estimates may be too small, making results appear more precise than they are. Whether over-dispersion is relevant depends on the outcome and model. The registry record does not report a model or analysis for the primary endpoint, so no claim can be made that over-dispersion was assessed or that a particular model was appropriate.

The record lists 0 analyses and does not report statistical tests, model specifications, covariate adjustment, handling of repeated measurements, or rules for selecting an analysis. It also does not report whether results were recalculated from posted summaries. No adjusted or unadjusted estimate can therefore be attributed to the registry record. Any interpretation should remain at the level of the endpoint definition and design details that are actually recorded.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists 13 outcome measures, including the primary SGIC outcome and secondary measures related to headache days, disability, social readjustment, physician global impression, depression, anxiety, sleep quality, and acute medication use. It does not report a statistical analysis plan specifying which outcomes were confirmatory, how testing across outcomes was handled, or whether any adjustment for multiple comparisons was planned. Multiplicity methods and their use are therefore not reported in the registry record.

General: when many outcomes or comparisons are examined, the chance of finding an apparently notable result by chance can increase. A prespecified hierarchy or adjustment method can help make the interpretation of multiple tests clearer. Without a stated approach, the registry record does not allow readers to determine how any collection of outcome tests was intended to be interpreted. Since numerical outcome analyses are not reported, there are no reported tests to assess for multiplicity in any case.

The primary outcome population is defined as subjects completing treatment period 1 injection cycle and returning at visit 3. The number of participants in that population is not reported in the registry record. The record does not describe missing-data rates, reasons for missing assessments, imputation, sensitivity analyses, or how participants with incomplete follow-up were handled. It is therefore not possible to judge whether missing observations could have affected an outcome estimate.

The registry record also does not describe all analysis populations, or whether the same participants contributed to each outcome and time point. The stated enrollment of 44 should not be assumed to equal the number analyzed for every measure. The lack of reported analysis details limits assessment of both the representativeness of the analyzed population and the robustness of any result.

11. Safety Results

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

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: dizziness (2.3%), expressive aphasia (2.3%), unsteady gait (2.3%), spontaneous abortion (2.3%).

For the onabotulinumtoxinA group, the registry record reports 44 participants at risk for serious adverse events and 2 affected. It reports 44 at risk for other adverse events and 23 affected. The deaths field is null; a death count is not reported in the registry record.

The listed serious adverse event terms are Dizziness, Expressive Aphasia, Unsteady Gait, and Spontaneous Abortion, each reported as 2.3%. These are registry-listed percentages. The record does not provide corresponding term counts, event timing, duration, or participant-level details. The listed terms should not be treated as a complete description of every event or as evidence that each event was caused by the intervention.

General: an adverse-event count describes what was recorded among participants at risk, not necessarily what was caused by treatment. A serious adverse event is a safety classification, and the affected-participant count is distinct from a count of all event episodes. The registry record does not provide enough information to determine whether participants experienced more than one event, how events were adjudicated, or how the listed terms relate to the serious-event total. These figures are descriptive safety information and do not establish a comparison with an untreated or control group.

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

The registry record documents a completed Phase 4 exploratory, single-group study of onabotulinumtoxinA in chronic migraine. It describes the primary endpoint, the planned assessment times, the analysis population in general terms, and adverse-event counts. It does not report numerical primary-outcome results or statistical analyses. Consequently, the record cannot show the observed average SGIC score, the variability of scores, or the precision of an estimated change.

The result does not establish whether participants’ global impressions changed over time, how large any change may have been, or whether findings differed between groups described as A, B, and C. Those groups are not defined in the registry record. The title’s reference to short-duration and long-duration benefit does not provide a definition or a numerical comparison, and should not be used as a substitute for reported results.

General: a single-group study can provide descriptive information about observations among enrolled participants, but it does not create a randomized comparison with a control group. Without a like-for-like comparator, observed changes cannot be attributed to treatment by the design alone. This does not imply that a change did or did not occur; the primary outcome results are not reported in the registry record.

The adverse-event figures describe participants recorded as affected, and the serious-event terms are accompanied by percentages. They do not establish causality, comparative safety, or the full clinical context of each event. Further detail on event timing, severity beyond serious classification, and outcomes is not reported in the registry record.

In short, the record supports an account of the trial’s purpose and structure, along with limited descriptive safety counts. It does not support a quantitative conclusion about the primary endpoint, a treatment-versus-control effect, or the relative outcomes of benefit-duration groups. No medical decision should be inferred from the absence of posted outcome analyses.

13. Why This Trial Matters Statistically

This study is statistically notable because its stated aim is patient-specific: to collect and correlate subject-specific history, clinical outcomes, and histological changes. Such an aim differs from estimating a single average effect for a randomized treatment comparison. The registry record identifies a global impression outcome and multiple secondary measures, but does not report the analyses needed to assess how individual-level information was combined or interpreted.

The design details matter for interpretation. This is a single-group study, allocation is listed as NA, and masking is none. The record does not describe a like-for-like control comparison. These features define the limits of what an observed change could establish, even if numerical outcome results were available. The primary outcome description also specifies an analysis population based on treatment-cycle completion and return at visit 3, while the size and completeness of that population are not reported.

The record lists 13 outcome measures but 0 analyses. With no posted numerical outcome results, readers cannot assess the estimates, uncertainty, model assumptions, or the handling of multiple outcomes. The absence of a reported analysis plan also leaves open how repeated assessments and the stated groups were intended to be analyzed.

The safety information illustrates a separate issue: recorded adverse-event counts can be useful descriptively, but without a comparator and event-level detail they cannot quantify comparative risk or establish attribution. Taken together, the trial record is informative about the exploratory question and some design features, but its statistical contribution cannot be judged through outcome estimates because those analyses are 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 registry record does not report numerical results for the primary SGIC endpoint, despite specifying its scale and assessment times. There are no reported means, standard deviations, changes, uncertainty intervals, or p-values to evaluate. It also records 0 analyses, limiting the available evidence to study descriptions and safety counts.

The single-group design has no reported randomized comparator. Allocation is listed as NA and masking as none. Therefore, the design information does not support a like-for-like control comparison. The record refers to Groups A, B, and C for the primary outcome, but does not define them or report their results. Although the official title refers to short-duration and long-duration benefit, the registry record does not report how those categories were determined or compare outcomes between them.

The primary analysis population is described as subjects completing treatment period 1 injection cycle and returning at visit 3, but its size is not reported. Missing-data frequency, reasons for missingness, and methods for handling incomplete assessments are also not reported in the registry record. The schedule for repeated injections is truncated after the statement that injections would be repeated at day, so the full regimen timing is unavailable.

The registry record does not report the statistical analysis plan, sample-size justification, interim analyses, multiplicity approach, model specifications, or any sensitivity analyses. It also does not provide detailed event-level safety information. These omissions prevent assessment of analysis choices, precision, robustness, and the context of adverse events beyond the recorded counts and terms.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Duration of Benefit for OnabotulinumtoxinA in Treatment of Chronic Migraine — NCT02037425.
• Registry record last updated 2016-08-11; status last verified 2016-07.
• Results first posted 2016-03-08.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

18. Record Summary

NCT02037425 is a completed Phase 4 exploratory, single-group study of onabotulinumtoxinA for chronic migraine, sponsored by Cady, Roger, M.D. Enrollment was 44. The study started in 2014-04, with primary completion in 2015-09. Allocation is listed as NA and masking as none.

The primary outcome was Subject Global Impression of Change at weeks 12, 24, and 36 post randomization, described on a 7 point scale and summarized by mean and standard deviation. The primary outcome population was subjects completing treatment period 1 injection cycle and returning at visit 3. Numerical outcome results and statistical analyses are not reported in the registry record.

The record lists 13 outcome measures and 0 analyses. It reports 2 participants affected by serious adverse events and 23 affected by other adverse events among 44 at risk in each category. Serious-event terms and percentages are listed, while the deaths count is not reported in the registry record.