"Follow the Sutures". A New Procedure for Injection of Botulinum Toxin for Chronic Migraine: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for "Follow the Sutures". A New Procedure for Injection of Botulinum Toxin for Chronic Migraine (NCT03543254), a na phase 2 study. The primary outcome is Number of Adverse Events.

2. Clinical Question

In statistical terms, the central question addressed by the posted primary outcome is whether participants receiving this procedure experienced recorded adverse events during the specified follow-up. It is not a question about whether the procedure is better than an alternative, because no comparator group is recorded. Nor does the event count establish the frequency of outcomes beyond the participants represented in that count. The study’s open, single-group structure is useful for describing what was recorded among treated participants, but it cannot isolate the effects of the injection procedure from other influences on event reporting or participant experience.

3. Trial Design

The registry record identifies this as a phase 2, open, multicenter, multinational pilot study. Its official title describes a new procedure for injecting botulinum toxin in the head against chronic migraine. The design is listed as single group, with allocation marked NA and masking listed as none. BoNT-A injected is the sole intervention group described. No randomized comparator or control arm is recorded, so the results are descriptive rather than a direct treatment comparison.

The intervention description states that BoNT-A was injected at specific sites in the head at half the usual concentration. The study summary describes the procedure as injections along the sutures. The record does not report the number of injections, detailed site locations, the amount administered, or a fuller account of how the procedure was delivered. Those details should not be inferred from the title or summary.

The registry lists enrollment of 20 and a completed status. The listed start date is 2018-05-01, and the primary completion date is 2021-01-01. These dates describe the registry record; they do not supply additional information about each participant’s follow-up. The primary outcome timeframe is 12 weeks. The primary outcome description says all included participants received botulinum toxin and reports one event among 19 participants. How that denominator relates to the enrollment figure, including any participant flow or missing outcome information, is not reported in the registry record.

The named primary outcome is Number of Adverse Events, measured as participants. The registry lists Injection Time as a secondary outcome. Although the study title and summary mention exploring effect as well as tolerability and safety, the registry does not report a specific migraine efficacy outcome result in the registry record recorded for this study. It also does not report an analysis plan, sample-size justification, or a detailed protocol for handling withdrawals. The study summary presents the pilot as a possible basis for a later randomized, blinded, controlled study, but that proposed future design is not the design evaluated by this 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

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: All included got injection of botulinum toxin. One out of 19 (5.3%) had reduced power of chewing

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: 20 patients with chronic migraine

6. Primary Endpoint

The registry lists the primary outcome as Number of Adverse Events, measured over 12 weeks.

The primary outcome is named Number of Adverse Events, with the unit stated as participants and the event measure defined as a count of participants. Its description says that adverse events other than those clearly related to migraine were to be recorded in participant diaries and reviewed during scheduled visits. The specified timeframe is 12 weeks. The posted outcome description reports that one out of 19 participants had reduced power of chewing.

A participant count is a way to express how many people experienced at least one event meeting the outcome definition. It differs from a count of all event episodes: repeated events in one person do not necessarily increase a participant count. The registry record does not explain whether multiple events in a person were handled in any particular way beyond naming the outcome as a count of participants. Nor does it give a complete event-by-event listing for this endpoint.

Safety and tolerability outcomes are relevant in a pilot study of a procedure because they describe events recorded during treatment and follow-up. However, this endpoint alone does not measure migraine improvement, establish a causal link between the procedure and an event, or compare safety with another approach. The record explicitly excludes events clearly related to migraine from the primary adverse-event definition, while the posted result identifies reduced chewing power. Further details about assessment, severity grading, relatedness judgments, and the timing of that event are not reported in the registry record.

The denominator matters when interpreting an event count: the record reports the outcome using 19 participants, while enrollment is listed as 20. Without participant-flow details, the reason for that difference cannot be established. The endpoint therefore supports a narrow description of the recorded safety outcome, not a complete account of all enrolled participants’ experiences.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The main statistical feature of this study is its single-group design. A single-group study describes outcomes among participants who received the intervention. Without a concurrent comparison group, it cannot estimate a treatment contrast within the trial. For example, an event recorded after treatment may be temporally associated with treatment, but the design alone cannot determine whether the event would have occurred without the procedure or under a different procedure. This is a general limitation of uncontrolled designs, not a claim about the cause of the chewing-power event in this record.

What does a participant count represent?

The primary outcome is expressed as a count of participants with adverse events, rather than a count of event episodes. In general, participant-based event counts focus on whether a person experienced an event meeting the definition during the follow-up period. They do not necessarily show how many times the event occurred, how long it lasted, or how severe it was. The registry describes diary recording and review during scheduled visits, but does not report further event-coding or adjudication procedures. The posted result identifies reduced power of chewing in one out of 19 participants.

The outcome definition excludes events clearly related to migraine. This makes the precise classification rule important: deciding whether an event is migraine-related or a separate adverse event can affect which outcome category receives it. The registry does not report how such judgments were made, whether they were independently reviewed, or whether assessors used a prespecified coding guide. This absence does not show that no procedure existed; it means the procedure is not reported in the registry record.

Why does the denominator matter?

A count is interpreted in relation to the number of participants whose outcomes are represented. The registry lists enrollment of 20, while the primary outcome and safety figures refer to 19 participants. The record does not explain the difference or give participant-flow details. In general, missing outcome information can affect a descriptive estimate if the participants without recorded outcomes differ from those with recorded outcomes. Since the reason for the denominator is not reported, neither the presence nor the impact of missing outcome data can be established from this record. It would be inappropriate to assume that the result applies to every enrolled participant.

For event outcomes, researchers may report a proportion or an interval around a proportion to convey uncertainty. No such interval is reported in the registry entries, and a new value should not be inferred from the count. A confidence interval is a statistical range that reflects uncertainty under a specified method and assumptions; it is not a guarantee that the true value lies within that range. In a small pilot, uncertainty can remain substantial even when an observed count is straightforward to describe.

What can an uncontrolled result say?

The study is open and has no recorded comparator. In general, lack of masking may influence how participants report subjective experiences or how study personnel record and interpret them. This is a methodological consideration, not evidence that reporting was biased in this study. The registry does not report masking procedures, independent outcome assessment, or a comparison that could help distinguish treatment-associated events from background events.

Random allocation, when used in a comparative study, helps make groups comparable on average with respect to measured and unmeasured factors. It is not listed for this study, and there is no second arm. Consequently, adjustment or comparison between trial arms is not available from the recorded design. A statistical model cannot create the missing control group or recover a causal contrast that the design does not contain.

How should the planning assumptions be read?

The record gives assumptions for a planning illustration: 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. It states that time-to-event planning uses a total event count and other planning outputs use participants per arm. These are planning assumptions, not the design features of the completed single-group study. They do not establish that this trial used a two-arm allocation, nor do they describe an observed power calculation. Any sample-size figures generated from such assumptions are planning illustrations, not observed power.

A normal approximation is a general statistical method that can be used to approximate the behavior of an estimator or test under specified conditions. Its suitability depends on the outcome, sample size, and model assumptions. Over-dispersion is a general issue for count data when observed variability exceeds what a chosen model expects; accounting for it can affect standard errors and uncertainty estimates. The registry record does not report a model for the primary outcome, an over-dispersion assessment, or a statistical analysis plan. These concepts therefore explain possible analytic considerations, not methods confirmed to have been used in this trial.

Are there inferential results to interpret?

The registry lists zero analyses. It does not report a p-value, confidence interval, adjusted estimate, or model-based result for the primary outcome in the recorded details. A p-value, in general, assesses how compatible data are with a specified null model under the assumptions of a test; it is not a measure of clinical importance or proof that a hypothesis is true. Without a reported test and its analysis details, no inferential conclusion should be attached to the observed count. The result remains descriptive: one participant was reported to have reduced power of chewing among the 19 used in the outcome statement.

The registry summary says the pilot could open the way for a later randomized, blinded, controlled study. That is a rationale for possible future research, not evidence that a later trial was conducted or that its design was finalized. The record does not report sample-size justification for the current study, interim analyses, or a prespecified statistical plan. Those details should be regarded as not reported in the registry record.

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("BoNT-A Injected")
n      <- c(19)
events <- c(1)
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  BoNT-A Injected  19  1  5.3  0.1  26.0  0.9  24.6  1.2  24.9

11. Multiplicity, Missing Data and Analysis Populations

The registry identifies Number of Adverse Events as the primary outcome and Injection Time as a secondary outcome. The study description also refers broadly to exploring tolerability, safety, and effect, but the recorded details do not specify a complete hierarchy of outcomes or identify additional efficacy endpoints. The registry does not report how multiple outcomes or multiple analyses were handled. A multiplicity procedure, such as an adjustment to account for repeated hypothesis tests, is therefore not reported in the registry record.

Multiplicity matters in general when several outcomes or analyses are tested: the chance of obtaining at least one apparently unusual result can increase as the number of tests increases. That general concern does not establish that any particular result in this study is spurious. The record lists zero analyses and does not provide inferential results, so there is no reported set of tests from which to assess multiplicity or reproduce an adjustment.

Enrollment is listed as 20, whereas the primary outcome statement and safety figures refer to 19 participants. Participant flow, withdrawals, exclusions, and missing outcome handling are not reported in the registry record. It is therefore not possible to determine why the denominators differ or whether missingness could have affected the observed result. No imputation method or sensitivity analysis is reported.

The registry record also does not define analysis populations beyond stating that all included participants got an injection. It does not specify an intention-to-treat, per-protocol, or safety population, or describe rules for assigning participants to such populations. The outcome statement should be read using its stated group and denominator, without assuming a broader population definition. These omissions limit reproducibility and make it difficult to assess whether the recorded result represents all enrolled participants, all treated participants, or another analysis set.

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 5% reporting threshold.

Most frequent non-serious adverse event terms

The safety figures list 19 participants at risk for serious adverse events, zero serious adverse events, 19 participants at risk for other adverse events, one other adverse event, and zero deaths. The primary outcome description identifies the reported event as reduced power of chewing in one out of 19 participants. The record does not list serious adverse-event terms.

These figures distinguish serious events from other adverse events. A zero count for serious events means none were recorded in the stated group and follow-up information; it does not demonstrate that serious events are impossible or that the procedure has no serious risks. Likewise, the single other event is a description of what was recorded, not proof that the procedure caused it. The registry does not report an event-relatedness judgment for the chewing-power outcome, nor does it provide detail on the event’s severity or duration.

The at-risk denominator is 19, while listed enrollment is 20. The reason is not reported in the registry record. The safety counts should therefore be interpreted with their stated denominator, not treated as covering every enrolled participant. The record specifies a 12-week timeframe for the primary outcome, but does not provide additional detail about safety follow-up or event ascertainment beyond diary recording and scheduled-visit review.

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

The result does show that the registry’s primary outcome description recorded reduced power of chewing in one participant among 19. The separate safety figures report no serious adverse events and no deaths among the participants listed as at risk, with one other adverse event. These are descriptive observations from the treated group, not comparative estimates. They provide a record of what was reported within the study’s stated outcome framework and timeframe.

The result does not establish that the injection procedure caused the chewing-power event. It does not show how the observed safety experience compares with another procedure, a different concentration, or no treatment, because no comparator group is recorded. The open design also means the record does not document masked outcome assessment. No analysis or inferential result is reported, so the event count should not be given a p-value, confidence interval, or causal interpretation that the registry does not provide.

The study’s stated interest in exploring treatment effect is not itself an efficacy finding. The registry entries do not include a posted result for migraine improvement, a comparison of migraine outcomes, or a result for Injection Time. It is therefore not possible to use the recorded safety count to judge whether the procedure reduced migraine symptoms or was preferable to another approach.

The difference between the enrollment figure of 20 and the outcome denominator of 19 also limits interpretation. The record does not say why the figures differ, how missing data were handled, or which analysis population was used. Consequently, the observed count should be understood as applying to the stated outcome group rather than automatically to all enrolled participants.

Overall, this record is most useful as a small pilot’s descriptive account of a new injection procedure and the safety events reported for it. It can inform questions for further study, such as how outcomes should be defined and how a comparator could be incorporated. It does not, on its own, provide evidence of comparative benefit, establish safety for a wider population, or settle whether the procedure should be used.

14. Why This Trial Matters Statistically

This trial matters statistically because it illustrates the difference between describing an outcome and estimating a comparative effect. The study records one intervention group and no control group. Its primary safety outcome can describe events recorded among treated participants, but it cannot show whether those events occur more or less often than under another approach. That distinction is essential when a study’s broad rationale includes exploring both safety and effect.

The record also makes the denominator issue visible. Enrollment is listed as 20, while the primary outcome and safety figures use 19. Without participant flow or an explanation of the difference, readers cannot establish how completely outcomes were observed or which analysis population the figures represent. Clear reporting of participant disposition and outcome denominators is important because counts are meaningful only in relation to the group they describe.

A pilot study can be valuable for describing implementation and identifying questions for later research, but the precision and scope of its estimates depend on its size, design, and outcome reporting. Here, no confidence interval or inferential analysis is reported. The single observed event should therefore not be treated as a precise estimate of the rate expected elsewhere, and the absence of recorded serious events should not be mistaken for proof that such events cannot occur.

The record’s planning assumptions also illustrate why design-stage calculations must be kept separate from trial results. The stated planning framework refers to a two-arm comparison, equal allocation, and a normal approximation, whereas the completed study is recorded as a single group. Any sample-size illustration based on those assumptions is a planning exercise, not an observed power result and not evidence that the completed study tested a two-arm contrast.

Finally, the registry’s description of a possible later randomized, blinded, controlled study highlights the difference between a pilot’s descriptive findings and the evidence needed to assess a comparative question. The current record can help define questions and outcomes for future research, but it does not answer those comparative questions itself.

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 design is open and single group, with no comparator recorded. This prevents a direct comparison and limits causal interpretation. Differences between the observed experience and what might have occurred under another treatment or without treatment cannot be estimated from this design. The registry does not report masking of outcome assessors or other procedures to limit subjective influences on recording.

The enrolled count is 20, but the primary outcome and safety figures use 19 participants. The registry record does not explain the difference, provide participant flow, or say how missing information was handled. This makes it difficult to assess completeness of follow-up and the population represented by the reported count.

The primary outcome description gives a participant count and one event description, but does not provide severity, duration, resolution, event-relatedness, or a full event listing. The record does not report detailed procedures for coding or adjudicating adverse events. It also gives no result for the listed secondary outcome, Injection Time, and no posted efficacy result in the recorded details, despite the study’s stated interest in exploring effect.

Statistical reporting is limited: the registry lists zero analyses and does not report a statistical analysis plan, confidence interval, p-value, adjusted estimate, interim analysis, or sample-size justification. It is not possible to assess prespecified analysis choices, multiplicity handling, or the influence of missing data from the record. The planning assumptions listed for a two-arm calculation do not describe the single-group trial design and do not establish observed power.

The registry lists a completed status, but the available outcome information remains narrow. These limitations do not negate the descriptive observations; they define what can responsibly be concluded from them. The event count and absence of recorded serious events should not be generalized as definitive estimates of comparative safety or clinical effect.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: "Follow the Sutures". A New Procedure for Injection of Botulinum Toxin for Chronic Migraine — NCT03543254.
• Registry record last updated 2024-01-30; status last verified 2024-01.
• Results first posted 2024-01-30.
• 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

This completed phase 2 pilot study is registered as an open, multicenter, multinational, single-group study of BoNT-A injections for chronic migraine. The treatment description specifies injections at sites in the head at half the usual concentration, while the study summary describes injections along the sutures. Enrollment is listed as 20.

The primary outcome is the number of participants with adverse events other than events clearly related to migraine, assessed over 12 weeks. The outcome description reports reduced power of chewing in one out of 19 participants. Safety figures list one other adverse event, no serious adverse events, and no deaths among 19 participants at risk. The record does not explain the difference between enrollment and the outcome denominator.

Injection Time is listed as a secondary outcome, but no result for it is included in the recorded details. The registry lists zero analyses and does not report a comparative efficacy result. With no control group, the posted findings are descriptive and do not establish a treatment contrast or causal effect.