Sphenopalatine Ganglion Blocks RCT: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Sphenopalatine Ganglion Blocks RCT (NCT03666663), a randomized phase 4 study. The primary outcome is Number of Participants With a Reduction in Headache Days From Baseline to Month 8 of Treatment.

2. Clinical Question

3. Trial Design

The registry describes a randomized, parallel-group trial comparing sphenopalatine ganglion blocks with three anesthetics against blocks with saline placebo. The listed active groups are lidocaine, bupivacaine, and ropivacaine; the comparator is placebo (saline). The record identifies the study as phase 4 and reports that it is completed. Enrollment was 10 participants.

The study title describes the trial as double blind and placebo controlled, while the registry’s masking classification is quadruple. These descriptions are both retained as recorded; the record does not explain which people were masked or how masking was implemented. Allocation is listed as randomized, but the method used to generate or conceal the allocation sequence is not reported in the registry record.

The posted outcome counts are three participants in the lidocaine group, one in the bupivacaine group, three in the ropivacaine group, and three in the placebo group. These are very small groups, particularly the bupivacaine group, so the observed counts provide limited information about how outcomes might vary beyond these participants. The record does not report a target enrollment or a sample-size justification for the original trial design.

The primary outcome was assessed at month 8. The record does not describe the timing of any earlier assessments, the treatment schedule, or how adherence was handled. It also does not report whether any interim analyses were planned or conducted. These details matter when interpreting how the trial was conducted, but cannot be inferred from the posted design information.

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

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 Number of Participants With a Reduction in Headache Days From Baseline to Month 8 of Treatment, measured over 8 months.

The primary endpoint counts participants who had a reduction in headache days from baseline to month 8 of treatment. It is a binary outcome: each participant is classified as having a reduction or not having a reduction. The record says the assessment was based on patient self-report, a headache diary, and retrospective chart review documentation. It does not define the size of reduction required to count as a reduction, or explain how information from these sources was combined when they differed.

A binary endpoint can make a result straightforward to describe: the posted values indicate how many participants in each arm met the recorded yes/no outcome. It also omits detail. Participants with different amounts of change may be placed in the same category, and the record does not show the underlying number of headache days or each participant’s change from baseline.

The endpoint focuses on change over the stated treatment period, rather than a single measurement at baseline or month 8. This makes the response dependent on how baseline and follow-up headache days were assessed. General statistical consideration: defining the outcome consistently is important because differences in measurement or classification can affect the group counts. The registry record does not provide a detailed endpoint definition beyond the description of reduction in headache days and the sources used to document it.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What kind of outcome is reported?

The primary endpoint is binary because each participant is classified as having a reduction in headache days or not having a reduction. The registry record reports the number of participants in each arm with the positive classification. For this kind of outcome, the basic data are counts of participants in each category, together with the number assessed in each group. Here, the posted arm counts are small, including a group with one participant. Counts are useful for showing exactly what was recorded, but by themselves do not quantify uncertainty in a comparison.

General statistical explanation: a comparative analysis of a binary outcome can estimate how the probability of the recorded outcome differs between groups. The choice of method depends on the design, the estimand, and the amount and structure of the data. With sparse counts, standard large-sample approximations may be unreliable, so analysts may consider methods suited to sparse data. The registry record does not report a method used for the primary outcome, and no comparative analyses are posted.

Why does uncertainty matter?

A confidence interval is a range of values that, under the assumptions of a statistical method, expresses uncertainty around an estimated quantity. A narrow interval indicates greater precision than a wide interval; neither an interval nor a point estimate alone resolves questions about study design or bias. No confidence interval for the primary comparison is reported in the registry record. Because the outcome groups are so small, the counts should not be mistaken for precise population estimates. Without an analysis and its uncertainty measures, readers cannot assess how compatible the data are with a range of possible comparative effects.

A p value, when reported, describes how unusual data at least as discrepant as those observed would be under a specified null model and its assumptions. It is not the probability that a treatment works, nor a measure of the size or clinical importance of an effect. No p value for the primary comparison is posted. The absence of a reported p value is not evidence that a comparison was nonsignificant; it means the registry record does not provide that result.

What does the planning illustration represent?

The registry material includes a sample-size planning illustration based on the observed effect, rather than the trial’s own design. Its stated assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is expressed as a stated fraction of the observed effect. Such calculations describe the number of participants per arm that a hypothetical design would require under those assumptions. They are planning illustrations, not the number of participants actually studied and not observed power.

General statistical explanation: planning calculations depend on the effect chosen for detection, the significance level, allocation, and assumptions about the outcome and analysis. An illustration based on an observed effect is especially dependent on that observed estimate. When data are sparse, the observed effect may be imprecise, so a planning calculation derived from it should not be treated as a stable estimate of the sample needed for a future study. The record does not report the original trial’s sample-size justification, and the illustration cannot establish what assumptions guided the original enrollment.

How should the four groups be considered?

The design includes three active anesthetic groups and a saline placebo group. A set of comparisons among several groups raises questions about which contrasts were planned and how the chance of false-positive findings was controlled. Multiplicity refers generally to the increased opportunity for an apparently notable result when many hypotheses are tested. The registry record does not report a multiplicity adjustment or a prespecified hierarchy of comparisons. Because no primary comparative analysis is posted, there is no reported analysis from which to determine how multiple comparisons were handled.

The trial is described as randomized and parallel group. General statistical explanation: randomization aims to make assigned groups comparable, on average, with respect to factors known and unknown at assignment. In small trials, however, randomization does not guarantee balance in the characteristics of the participants who happen to enter each group. The registry record does not provide baseline characteristics or enough methodological detail to assess balance, allocation concealment, or the analysis strategy.

The outcome description mentions self-report, headache diaries, and retrospective chart review. These sources may capture information in different ways. General statistical explanation: outcome classification can be affected by how missing or conflicting measurements are resolved, so a clear prespecified rule supports reproducibility. The record does not explain such rules, report missing-data handling, or identify the population included in the primary analysis. No model, covariate adjustment, or sensitivity analysis is reported.

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("Lidocaine", "Bupivacaine", "Ropivacaine", "Placebo (Saline)")
n      <- c(3, 1, 3, 3)
events <- c(3, 1, 1, 0)
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  Lidocaine  3  3  100.0  29.2  100.0  43.9  100.0  39.8  99.4
ARM  Bupivacaine  1  1  100.0  2.5  100.0  20.7  100.0  15.8  98.7
ARM  Ropivacaine  3  1  33.3  0.8  90.6  6.1  79.2  6.8  80.6
ARM  Placebo (Saline)  3  0  0.0  0.0  70.8  0.0  56.1  0.6  60.2

11. Multiplicity, Missing Data and Analysis Populations

The study has several active groups and a placebo group, creating the possibility of multiple comparisons. General statistical explanation: evaluating several contrasts can increase the chance of at least one false-positive finding if the comparisons are treated as independent opportunities for significance. A protocol may address this through prespecified primary contrasts, a testing hierarchy, or an adjustment method. The registry record does not report which comparisons were prespecified or whether any multiplicity procedure was planned or used. Since no comparative analyses are posted, the handling of multiplicity cannot be assessed from the results record.

The record also does not describe missing-data methods for the primary endpoint. The outcome counts are presented by arm, but the registry does not state how participants with unavailable or incomplete month 8 information would be handled, whether any outcome was imputed, or whether all randomized participants were included in the analysis. An analysis population, such as all randomized participants or only participants with evaluable outcomes, is not reported in the registry record.

These omissions matter because the way missing outcomes and analysis populations are defined can affect group comparisons. General statistical explanation: analyses restricted to participants with observed outcomes can be biased if missingness is related to the outcome or differs across groups. Imputation methods also rely on assumptions, which should be stated and examined. The record does not provide the information needed to assess these issues, and the posted counts alone cannot establish what analytic choices were made.

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 0% reporting threshold.

The adverse-event record lists zero serious adverse events in each of the four groups. It also lists zero other adverse events in each group, and zero deaths in each group. The groups at risk are recorded as three for lidocaine, one for bupivacaine, three for ropivacaine, and three for placebo. These counts are the safety information posted in the registry record.

These observations should be read in light of the very small number of participants in each arm. A count of zero means that no event of that type was recorded among the participants represented in the corresponding group; it does not establish that the event cannot occur. Sparse safety data are especially limited for judging uncommon events, and the record does not provide detailed descriptions of adverse-event collection, severity grading, relatedness assessment, or follow-up beyond the posted information.

The record lists no serious adverse-event terms. It does not provide additional narrative about safety monitoring or events not classified in the posted categories. These figures describe what was recorded; they do not establish that an intervention is safe or unsafe, and they are not a substitute for a larger body of safety evidence.

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

The registry results describe a small randomized trial with a binary primary outcome: whether a participant had a reduction in headache days from baseline to month 8. The posted counts show positive outcome classifications in the lidocaine, bupivacaine, and ropivacaine groups, and no positive classification in the placebo group. The group sizes are very small, and the record does not include a statistical comparison or estimates of uncertainty. The counts therefore describe the recorded participants, rather than providing a precise estimate of how the groups would compare in a broader population.

The endpoint does not communicate how many headache days participants experienced, how large any reduction was, or whether the change was sustained. The registry record does not state the threshold used to define a reduction. It also does not report baseline characteristics or the details needed to evaluate missing outcomes, the analysis population, or how comparisons across groups were handled.

These results do not establish that any anesthetic is superior to placebo, equivalent to placebo, or ineffective. The absence of a posted comparison is not the same as a finding of no difference. Likewise, the recorded counts are not enough to determine whether any apparent difference is statistically reliable or clinically meaningful. A randomized design is relevant to the intended comparison, but the limited enrollment and missing analytic details constrain what can be inferred from the registry record.

The appropriate reading is descriptive and bounded: the record documents the outcome counts and the trial’s general design, while leaving important questions about precision and analysis unresolved. The results do not give medical guidance and should not be interpreted as a recommendation about treatment.

14. Why This Trial Matters Statistically

This trial is statistically instructive because it places a randomized, multi-arm design alongside a very small enrollment. Randomization is intended to support fair comparisons, but it cannot make a small dataset precise. The outcome counts show why group size matters: the bupivacaine group contains only one participant, while the other groups also contain few participants. Consequently, each recorded classification carries substantial weight in the descriptive group result.

The endpoint also illustrates a tradeoff in binary outcomes. A yes/no classification is easy to communicate, but it compresses the underlying experience into a single category. The record does not state the threshold for counting a reduction and does not provide the number of headache days or the size of each participant’s change. Thus, the posted counts cannot reveal the distribution of change or whether participants classified as having a reduction experienced similar outcomes.

Finally, the record distinguishes descriptive reporting from inferential analysis. A randomized trial may be designed to compare groups, but the registry results do not include a formal comparative analysis, uncertainty intervals, or a p value. Without these, readers should not treat numerical differences in counts as established evidence of a group effect. The planning illustration based on the observed effect is also distinct from the original trial design and should not be confused with observed power. These features make the study a useful example of why design labels and outcome counts need to be considered alongside sample size, precision, and transparent analysis reporting.

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 main trial-specific limitation is the small enrollment of 10 participants distributed across four groups. The posted outcome counts show that the group sizes range from one participant to three participants. This leaves little information for estimating how outcomes vary within an arm or for assessing the stability of comparisons. The registry record does not report a sample-size justification for the original design.

The primary outcome is reported as a yes/no reduction in headache days at month 8, but the record does not specify the threshold for a reduction. It describes self-report, headache diaries, and retrospective chart review, without explaining how these sources were reconciled or how the final classification was determined. The record also does not provide the underlying headache-day measurements or participant-level results.

No comparative statistical analyses are posted. Confidence intervals, p values, the analysis model, adjustment for multiple comparisons, and analysis populations are not reported in the registry record. Missing-data handling is also not described, so the effect of any unavailable or incomplete endpoint information cannot be evaluated.

Further design details are absent, including eligibility criteria, baseline characteristics, allocation-sequence methods, concealment procedures, treatment schedule, and details of masking. Although the title describes double blinding and the registry classification is quadruple masking, the record does not identify who was masked or how masking was maintained. These limitations restrict assessment of both internal validity and how broadly the observations may apply.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Sphenopalatine Ganglion Blocks RCT — NCT03666663.
• Registry record last updated 2021-10-11; status last verified 2021-09.
• Results first posted 2021-10-11.
• 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

The registry record describes a completed phase 4 randomized, parallel-group study of sphenopalatine ganglion blocks for adults with migraine. It compares lidocaine, bupivacaine, and ropivacaine with saline placebo and reports enrollment of 10 participants. The title describes a double-blind placebo-controlled trial; the registry lists quadruple masking.

The primary outcome is the number of participants reporting a reduction in headache days from baseline to month 8, assessed using self-report, headache diaries, and retrospective chart review documentation. The posted counts are three in the lidocaine group, one in the bupivacaine group, one in the ropivacaine group, and zero in the placebo group. No comparative analyses are posted. The adverse-event record lists no serious adverse events, other adverse events, or deaths in any group.

The registry record does not report the original sample-size justification, analysis population, missing-data strategy, or details of multiplicity handling. These omissions, together with the very small groups, limit statistical interpretation.