Ginger Capsules for the Acute Treatment of Migraine Attacks: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Ginger Capsules for the Acute Treatment of Migraine Attacks (NCT02568644), a randomized na study. The primary outcome is Change in Headache Severity..

2. Clinical Question

The registry identifies this as a randomized, double-masked, parallel-group trial. Randomization supports a comparison between assigned groups, while masking is intended to limit influences from knowledge of treatment assignment; details about how either process was carried out are not reported in the registry record. The comparison should be read as an estimate of the difference between the two capsule groups in this trial context, with ketoprofen listed for both arms. The primary result alone does not describe every symptom or outcome mentioned in the study objective. Serum biomarker change is listed as a secondary outcome, but numerical secondary results are not posted in the registry record.

3. Trial Design

The registry record describes a randomized, double-masked, parallel-group trial. The study status is completed, and the listed enrollment is 60. The study start is recorded as 2014-07 and primary completion as 2014-10. The sponsor is Federal University of Minas Gerais. The phase is recorded as NA.

The two listed arms differ in the capsules given: the ginger arm received two capsules of ginger extract containing 5% of gingerols, and the comparison arm received two cellulose placebo capsules. Both arm descriptions list intravenous ketoprofen (100mg). Each arm’s posted primary-outcome result has a group size of 30. The registry descriptions identify people of both genders presenting with a migraine attack at the emergency room of Hospital Vera Cruz in Belo Horizonte, MG, BR. More detailed eligibility criteria are not reported in the registry record.

The primary outcome is titled “Change in Headache Severity.” It is a continuous measure reported as a mean with standard deviation, measured at 2 hours. The stated four-point scale ranges from absence of pain to severe pain, with higher scores meaning a worse outcome. The registry also lists change in serum levels of biomarkers as a secondary outcome. Although the record lists four outcome measures, it does not post secondary numerical results in the information available for interpretation; the record lists one secondary outcome by name.

Procedural details such as the random sequence method, allocation concealment, how masking was maintained, treatment adherence, and handling of protocol deviations are not reported in the registry record. The original sample-size justification and the trial’s prespecified statistical analysis plan are also not reported. These omissions limit how fully readers can assess design execution and whether the posted comparison follows a prespecified analysis.

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 Change in Headache Severity., measured over 2 hours.

The primary endpoint is the change in headache severity at 2 hours, reported as a group mean with a standard deviation. Headache severity was assessed on a four-point scale: 0 denotes absence of pain, 1 mild pain, 2 moderate pain, and 3 severe pain. Higher scores indicate a worse outcome. The unit is described as units on a scale.

A change endpoint is intended to describe how an outcome differs over time, rather than only its value at one observation. In general, measuring change can help represent improvement or worsening from an earlier assessment. However, the registry record does not specify the baseline assessment, the subtraction order used to calculate change, or any other details of the change-score calculation. The posted means therefore should be interpreted as the reported change values, without assuming a particular sign convention beyond the stated scale direction.

In general, a continuous mean summarizes the central value of observations, while the standard deviation describes how spread out observations are around that mean. The primary endpoint gives a common scale-based summary for the two capsule groups at the stated time. It does not, by itself, describe individual responses, the full distribution of scores, or outcomes at other times. The registry record does not report a threshold defining a clinically important difference on this scale, so the numerical contrast cannot be classified from the record alone as clinically important or unimportant.

7. Results Posted in the Registry

• Cellulose: mean 0.97 versus 0.81 on control; difference 0.16 (95% CI 0.13 to 0.19), standardized effect d = 2.81; z-test p = <0.001.

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is continuous and is summarized by a mean and standard deviation for each arm. In general, a mean gives a central summary of the recorded values, while a standard deviation describes their dispersion. The posted means are 0.81 for ginger extract and 0.97 for cellulose; the corresponding standard deviations are 0.04 and 0.07. The registry describes the result as change in headache severity, but does not state how the change score was calculated or how baseline observations were handled.

What does the mean difference represent?

The posted mean difference is 0.16, with the cellulose group as the comparison against ginger extract. The component means also indicate the order of subtraction: the cellulose mean is compared with the ginger mean. A difference in means expresses the contrast in the outcome’s original units, which are units on the four-point scale. In general, this preserves a direct connection to the measure, unlike a standardized effect size. Since the scale states that higher scores mean worse outcomes, the difference describes a higher reported mean change in the cellulose arm. The absent change-score convention means it should not be relabeled as a numerical improvement without qualification.

What do the confidence interval and p-value contribute?

In general, a confidence interval gives a range of values compatible with the observed data and the method used to construct it. It communicates uncertainty around an estimated contrast, rather than only whether a hypothesis test crosses a significance threshold. The registry’s reported interval excludes zero, which is consistent with a nonzero contrast under the interval’s assumptions. The interval endpoints are reported with more than three decimal places and are not reproduced. The unadjusted p-value is <0.001. In general, a p-value measures how unusual data at least as incompatible with a null hypothesis would be if that hypothesis and the test assumptions held. It is not a measure of the probability that a result is due to chance or of clinical importance.

The record does not identify the precise test or model used for the reported comparison, nor does it describe whether assumptions were checked. A general comparison of means can rely on assumptions about independent observations and the behavior of sampling distributions; the suitability of a particular method also depends on design and data features. Because the outcome is bounded by the stated scale, distribution shape and potential floor or ceiling patterns can matter. The registry does not post individual observations or distributional summaries that would allow readers to assess those features.

What is a standardized effect size?

The record lists a standardized effect size of 2.807. Generally, a standardized mean difference expresses the contrast in units of a pooled standard deviation. It allows results on differently scaled measures to be described on a common scale, but depends on the spread used to standardize the contrast. It does not mean that the outcome difference is 2.807 points on the headache scale, nor does it independently establish clinical importance. In this record, the scale-specific mean difference is more directly connected to the endpoint’s units.

The comparison uses an unadjusted p-value. The registry record does not report covariate adjustment, an adjusted estimate, or a prespecified statistical analysis plan. It also does not report whether the analysis followed intention-to-treat, per-protocol, or another analysis population definition. Randomization is listed as the allocation method, but sequence generation and concealment details are not reported. These registry entries are important context for interpreting the estimate; they do not permit a reconstruction of the sponsor’s analysis.

The record lists four outcome measures, but only one secondary outcome by name and no secondary analyses. It does not explain the relationship among the four measures, identify a multiplicity-control procedure, or state whether the primary outcome and its analysis were prespecified in the form posted. As a general matter, testing multiple outcomes or analyses can increase the chance of at least one apparently strong result unless the analysis plan accounts for multiplicity. Whether that concern applies, and how it was handled, is not reported in the registry record.

Over-dispersion is a general concern when observed variability is greater than a statistical model assumes; it can make uncertainty estimates too narrow if not accommodated. The posted primary summary gives standard deviations, but the record does not identify a distributional model or report checks for over-dispersion. That concept is not a claim that over-dispersion occurred in this trial. Likewise, the registry does not report interim analyses, stopping rules, or the trial’s original sample-size assumptions. No unreported design or analysis detail should be inferred from the completed status or the observed result.

10. Confidence Intervals and Precision

The reported mean difference for the primary outcome is 0.16, comparing cellulose with ginger extract. Its registry confidence interval is reported as 0.131 to 0.189. The interval excludes zero, so the reported estimate is not compatible with a zero difference under the method used to calculate that interval. The unadjusted p-value is <0.001. Together, these summaries indicate a statistically precise estimate for the posted comparison under its analysis assumptions, but they do not address every source of uncertainty.

A confidence interval is a range of estimates that, in general, reflects sampling uncertainty under a specified method. It is not a range containing a fixed proportion of individual participants’ outcomes, and it is not the probability that the true effect lies within the particular interval. The registry record does not name the interval method or the statistical model used. Nor does it report diagnostics or individual-level data with which to assess whether the method’s assumptions are appropriate.

The interval’s narrow span should be considered alongside the reported group standard deviations and the trial context. Precision of a statistical estimate is different from certainty that the estimate is unbiased, reproducible, or clinically important. Potential sources of uncertainty include the change-score definition, missing outcome data, analysis population, and possible multiplicity; the relevant details are not reported in the registry record. The registry also does not state a threshold for a clinically important difference on the headache scale. Therefore, the confidence interval helps describe statistical uncertainty around the posted contrast, but does not settle its clinical meaning or its applicability beyond this trial.

11. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The sample-size figures are planning illustrations based on the observed effect, not a report of the trial’s original design assumptions. The listed figures are participants per arm, not total events. The planning assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The target effect is set to the stated fraction of the observed effect. The original trial’s sample-size justification and design assumptions are not reported in the registry record.

For each effect scenario, the 80% power column gives the planned number of participants per arm for a design with an 80% chance of detecting that assumed effect under the stated planning assumptions, if the effect and model assumptions hold. The 90% power column gives the corresponding per-arm planning figure for a 90% chance. These are design concepts: power is the probability of detecting an effect of a specified size under a particular model when that effect is present.

The rows describe planning for 100% of the observed effect, 75% of the observed effect, and 50% of the observed effect. The listed per-arm figures are respectively 2 and 3, 4 and 5, and 8 and 11 for the 80% and 90% targets. Smaller effects need more participants to detect, all else equal, which is why the planning counts increase as the assumed fraction of the observed effect decreases. The very small figures are a consequence of using the large observed standardized contrast as the starting point; they should not be treated as a recommendation or as a validation of the trial’s design.

This is not observed power. It is not a measure of how likely the reported result is to be true, and it does not describe the achieved precision of the trial. The planning assumptions do not include a reported allowance for missing data, multiplicity, or other design features. No curve values beyond the stated planning figures are reported in the registry record.

12. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = 0.160; pooled standard deviation σ = 0.057.
2. n = 2 × (1.96 + 0.842)² × 0.057² / 0.160² = 2.0, rounded up to 2 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
delta <- 0.16                      # observed difference in means
sigma <- 0.0570087712549569                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(2568644)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 2 (80% power), 3 (90% power)
 75% of observed effect: n per arm = 4 (80% power), 5 (90% power)
 50% of observed effect: n per arm = 8 (80% power), 11 (90% power)
power.t.test: 3.3 
Simulated power at n = 2 per arm: 0.360 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

13. Multiplicity, Missing Data and Analysis Populations

The registry record lists four outcome measures and identifies change in serum levels of biomarkers as a secondary outcome, but it posts no secondary analyses. It does not explain how the listed outcome measures relate to one another, which were prespecified as primary or secondary in the original protocol, or whether additional outcomes were assessed. The primary endpoint is identified as change in headache severity, and its 2-hour result is posted.

Multiplicity is the issue that arises when more than one outcome, time point, subgroup, or statistical test is examined. In general, the more tests considered, the greater the chance that at least one may appear statistically unusual by chance. Researchers can address this through prespecified testing hierarchies or statistical adjustments, among other approaches. Whether any such procedures were planned or used is not reported in the registry record. The primary result is described with an unadjusted p-value, so readers should not assume a multiplicity adjustment was applied.

The record does not describe missing primary-outcome data, reasons for missingness, imputation, or sensitivity analyses. It also does not name the analysis population. The posted group sizes are 30 in each arm, but those figures alone do not establish whether every randomized participant contributed a primary-outcome observation or whether the analysis followed an intention-to-treat or another population definition. The handling of withdrawals, protocol deviations, and unavailable measurements is not reported.

In general, missing-data methods can affect estimates when the availability of measurements is related to outcomes or treatment assignment. The extent and direction of any such effect cannot be determined from this record. The original statistical analysis plan, prespecified handling of missing data, and any interim analyses are not reported in the registry record. These omissions make it difficult to assess whether the posted comparison was selected from a broader set of analyses or whether its analysis population matches the randomized population.

14. 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 0% reporting threshold.

Most frequent non-serious adverse event terms

The registry reports serious adverse events for 30 participants at risk in the ginger-extract group and 30 in the cellulose group, with zero serious adverse events in each arm. The posted figures therefore show no serious adverse events recorded in either listed group in this record. Death counts are not reported in the registry record.

For other adverse events, the registry reports 3 affected participants among 30 at risk in each group. The record does not provide the event terms or descriptions in the information posted for this comparison. It also does not explain how adverse events were defined, collected, or judged related to study treatment. The listed figures should therefore be read as registry counts, not as a complete account of all possible harms.

In general, absence of a recorded serious event in a group does not establish that the risk is zero. Safety estimates depend on how events are monitored and reported, the amount of observation, and the size and characteristics of the study population. No exposure duration, event timing, severity details for other events, or comparative statistical analysis is reported. These figures describe the adverse-event entries in the registry, not a basis for treatment advice.

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

The posted primary result is a mean difference of 0.16 in the reported change in headache severity at 2 hours, comparing cellulose with ginger extract. The registry reports group means of 0.97 for cellulose and 0.81 for ginger extract, with standard deviations of 0.07 and 0.04, respectively. The reported confidence interval excludes zero, and the unadjusted p-value is <0.001. These findings describe a statistical contrast in this trial, not an independent conclusion about treatment effectiveness.

The endpoint is a four-point scale on which higher values indicate worse headache severity, but the exact calculation and sign convention for “change” are not reported. That prevents a fully secure interpretation of the direction of change from baseline. The record also does not give a threshold for a clinically important difference, so statistical evidence alone cannot establish whether the size of the contrast matters to patients.

The comparison involved ginger extract or cellulose capsules, with intravenous ketoprofen (100mg) listed in both arms. It therefore addresses ginger as an addition to ketoprofen in the described trial context; it does not isolate ginger as a standalone treatment. The result does not cover other interventions, other migraine outcomes, or other assessment times. Serum biomarker change is listed as a secondary outcome, but numerical results for that outcome are not reported in the registry record.

Precision of the estimated contrast does not resolve limitations in reporting about the statistical plan, analysis population, missing data, outcome measurement, or multiplicity. The registry identifies randomization and double masking, but does not report their implementation details. The reported findings should consequently be understood as the posted primary comparison with its statistical uncertainty and reporting limitations, rather than as a complete assessment of benefits, harms, or applicability beyond the participants described.

16. Why This Trial Matters Statistically

This trial illustrates the importance of distinguishing the outcome’s original scale from a standardized effect. The mean difference of 0.16 is expressed in units on the four-point headache scale, while the posted standardized effect size is 2.807 and uses a pooled standard deviation as its reference. The first remains tied to the endpoint; the second provides a relative summary whose magnitude depends on the observed spread. Neither statistic, on its own, determines clinical importance.

The result also shows why an endpoint’s definition matters. The registry identifies the measure as a change in headache severity and specifies that higher scale values mean worse outcomes, but does not describe how change was calculated. Without that information, even a clearly reported contrast and confidence interval require careful wording about direction. A precise estimate does not compensate for ambiguity in the outcome definition.

Finally, the planning illustration highlights a general statistical issue: calculations based directly on an observed effect can yield very small planning figures when that observed effect is large. The illustration is not evidence of the original design’s adequacy and does not describe observed power. Its assumptions are explicit, while the trial’s own sample-size rationale is not reported. Keeping those two kinds of information separate is essential when interpreting a completed trial.

17. 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.

Several trial-specific reporting gaps constrain interpretation. The registry describes the primary outcome as change in headache severity, but does not state the baseline measurement, change-score calculation, or sign convention. Although the scale is defined and its direction is stated, the absence of these details limits translation of the group contrast into a clear statement about change from baseline.

The record does not provide detailed eligibility criteria, recruitment procedures, adherence information, or how randomization and double masking were implemented. It identifies the emergency room of Hospital Vera Cruz in Belo Horizonte, MG, BR, in both arm descriptions, but does not give information to assess how representative the participants were of other clinical settings. The record does not report the original sample-size justification, statistical analysis plan, analysis population, or the handling of missing measurements.

The record lists four outcome measures, but only one secondary outcome by name and no secondary analyses. Multiplicity procedures and interim analyses are not reported. Although the primary comparison is posted with a confidence interval and unadjusted p-value, the method used to calculate them is not described. Individual-level data and distributional summaries are not available in the registry record, limiting assessment of the bounded scale’s distribution.

Safety reporting is also limited: death counts are not reported, and the registry does not provide event terms for the reported other adverse events or details about event collection. These limitations do not establish that bias or data problems occurred; they identify information not reported in the registry record that would be needed for a fuller assessment.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: Ginger Capsules for the Acute Treatment of Migraine Attacks — NCT02568644.
• Registry record last updated 2020-04-07; status last verified 2020-03.
• Results first posted 2020-04-07.
• 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.

21. Record Summary

The registry record describes a completed, randomized, double-masked, parallel-group trial sponsored by Federal University of Minas Gerais. It lists an enrollment of 60 and compares two capsules of ginger extract containing 5% of gingerols with two cellulose placebo capsules; both arms also received intravenous ketoprofen (100mg), according to the arm descriptions.

The primary outcome is change in headache severity at 2 hours, measured on a four-point scale where higher scores mean worse outcomes. The posted group means are 0.81 for ginger extract and 0.97 for cellulose, and the reported mean difference is 0.16 for cellulose compared with ginger extract. The unadjusted p-value is <0.001. The registry lists change in serum levels of biomarkers as a secondary outcome but posts no secondary analyses.

Serious adverse events are recorded as zero in both arms; other adverse events are recorded for 3 participants in each arm. Death counts are not reported in the registry record. Details about the change-score calculation, analysis population, missing data, multiplicity, and original design assumptions are not reported.