A Study to Assess the Efficacy and Safety of Mebendazole for the Treatment of Helminth Infections in Pediatric Participants: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study to Assess the Efficacy and Safety of Mebendazole for the Treatment of Helminth Infections in Pediatric Participants (NCT02034162), a randomized phase 3 study. The primary outcome is Cure Rate for Ascaris Lumbricoides at the End of Double-blind Treatment Period.

2. Clinical Question

The primary outcome is specific to Ascaris lumbricoides. The record also identifies Trichuris trichiura egg-count reduction and mebendazole plasma pharmacokinetic measures as secondary outcomes. The primary comparison therefore addresses a defined infection, a defined period, and a laboratory-based cure criterion; it does not by itself describe every infection or outcome considered in the study.

3. Trial Design

This was a Phase 3, randomized, double-blind, multicenter, parallel-group, placebo-controlled study. The registry record gives enrollment as 295 and status as completed. The recorded study start is 2014-12, and primary completion is recorded as 2015-09. The study’s stated purpose was to evaluate mebendazole compared with placebo in pediatric participants with helminth infections.

During the double-blind period, the mebendazole group was assigned a single 500-mg chewable tablet at baseline, Day 1; the placebo group received a matching single-dose chewable tablet at the same visit. The mebendazole arm description also specifies an open-label mebendazole dose at Visit 4, Day 21. The primary endpoint was assessed at Visit 3, Day 19, at the end of the double-blind treatment period. The registry record does not describe further details of the open-label period or the treatment received by the placebo group after the double-blind assessment.

The primary outcome population was the intent-to-treat analysis set, defined in the record as randomized participants with a pretreatment stool sample positive for one or more worms of interest. For the Ascaris cure-rate outcome, the registry lists 81 participants analyzed in the placebo group and 86 in the mebendazole group. These endpoint-specific denominators are distinct from the enrollment figure and should be used when reading the primary result.

The record identifies the primary endpoint as the cure rate for Ascaris lumbricoides. Other listed outcomes include egg-count reduction for Ascaris and Trichuris and measures of mebendazole plasma exposure. The registry record does not report the original study’s sample-size justification, detailed allocation procedures, or further operational details of masking.

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.

Before assignment: Of the 792 participants screened, a total of 295 were randomly assigned to study treatments, of which 278 completed the study. 17 participants were withdrawn from study with following reasons: Withdrawal by participant (12), Lost to follow-up (3), Physician decision (1) and Protocol violation (1).

Double-blind

Reasons for not completing this period:

Open-label

Analysis population for the primary outcome, as defined in the registry: The intent-to-treat (ITT) analysis set included all randomized participants with a pretreatment stool sample positive for 1 or more worms of interest. Here 'N' signifies number of participants analysed for this outcome measure.

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 Cure Rate for Ascaris Lumbricoides at the End of Double-blind Treatment Period, measured over At Visit 3 (Day 19) of Double-blind treatment period.

The primary endpoint is the percentage of participants classified as cured of Ascaris lumbricoides at the end of the double-blind treatment period, assessed at Visit 3, Day 19. The registry defines cure as a post-treatment egg count of zero among participants who had a positive egg count at baseline. This definition makes the outcome a binary participant-level measure: each eligible participant either meets the zero-count criterion or does not.

A stool egg-count endpoint provides a direct, prespecified way to classify the measured infection outcome at the assessment visit. Restricting the cure definition to participants with a positive baseline egg count ensures that the endpoint is evaluated in participants who had evidence of the infection at study entry. The result is expressed as a percentage, which allows the observed proportion meeting the criterion to be described separately for each randomized group.

That measure has a specific scope. It concerns Ascaris lumbricoides, the stated baseline-positive analysis population, and the post-treatment assessment at Day 19. It is not a measure of symptom change, long-term recurrence, or cure of every helminth infection. The registry lists a separate Trichuris trichiura egg-count reduction outcome, but that is not the primary endpoint. Nor should the primary endpoint be read as a summary of the later open-label dosing period: it was assessed at Visit 3, before the Visit 4 dose described for the mebendazole arm.

7. Results Posted in the Registry

• Double-blind Mebendazole 500 mg: 83.7% (72/86) versus 11.1% (9/81) on control; risk difference 72.6 percentage points (95% CI 62.2 to 83.0), risk ratio 7.53 (4.04–14.05); unadjusted two-proportion z-test p = <0.001.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Maximum Plasma Concentration (Cmax) of Mebendazole

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Mebendazole: Group 2 (3 to 6 Years): mean 49.90 versus 210.00 on control; difference -160.10 (95% CI -249.98 to -70.22), standardized effect d = -0.93; z-test p = <0.001.
  • Mebendazole: Group 3 (7 to 16 Years): mean 34.20 versus 210.00 on control; difference -175.80 (95% CI -264.80 to -86.80), standardized effect d = -0.99; z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for Mebendazole: Group 2 (3 to 6 Years) than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for Mebendazole: Group 3 (7 to 16 Years) than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Area Under the Plasma Concentration-time Curve From Time 0 to 8 Hours (AUC8h) of Mebendazole

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Mebendazole: Group 3 (7 to 16 Years): mean 182.00 versus 697.00 on control; difference -515.00 (95% CI -677.26 to -352.74), standardized effect d = -1.68; z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for Mebendazole: Group 3 (7 to 16 Years) than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Area Under the Plasma Concentration-Time Curve From Time Zero to Time of the Last Quantifiable Concentration AUC(0-last) of Mebendazole

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Mebendazole: Group 2 (3 to 6 Years): mean 416.00 versus 1,320 on control; difference -904.00 (95% CI -1,277 to -530.93), standardized effect d = -1.30; z-test p = <0.001.
  • Mebendazole: Group 3 (7 to 16 Years): mean 387.00 versus 1,320 on control; difference -933.00 (95% CI -1,305 to -561.18), standardized effect d = -1.31; z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for Mebendazole: Group 2 (3 to 6 Years) than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for Mebendazole: Group 3 (7 to 16 Years) than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

The registry lists secondary outcomes spanning egg-count reduction for Ascaris lumbricoides and Trichuris trichiura and pharmacokinetic measures of mebendazole. The posted pharmacokinetic summaries describe maximum plasma concentration and two area-under-the-curve measures across age groups. Together, these outcomes add information about measured drug exposure and other infection-related endpoints, but they address questions different from the primary Ascaris cure-rate comparison.

Across the posted pharmacokinetic summaries, the reported mean values are lower in the older age groups than in the 1 to <3 Years group for the measures with numerical summaries. The means and standard deviations are descriptive, and the registry record does not report sponsor inferential analyses for these comparisons. The age-group summaries do not establish a randomized treatment contrast: they compare age categories among participants with pharmacokinetic measurements, not mebendazole against placebo for the primary endpoint.

The registry record lists egg-count reduction outcomes for both Ascaris and Trichuris, but numerical results for those outcomes are not reported in the registry record. As a result, the secondary information cannot be used to determine whether the primary cure-rate pattern is accompanied by a particular egg-count reduction pattern across both infections.

Secondary outcomes usually carry less inferential weight when many outcomes or comparisons are examined and no adjustment strategy is reported. Each additional analysis creates more opportunity for a chance finding, while the record does not report whether multiplicity was controlled or which secondary outcomes were designated for confirmatory testing. The secondary results are therefore best treated as supportive or descriptive context, not as independent confirmation of the primary result. Their differing measurement scales, populations, and assessment times also mean they should not be combined into a single overall conclusion.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Egg Count Reduction Rate (Percent) for Ascaris Lumbricoides Infestation at the End of Double-blind Treatment Period
• Egg Count Reduction Rate (Percent) for Trichuris Trichiura Infestation at the End of Double-blind Treatment Period
• Maximum Plasma Concentration (Cmax) of Mebendazole
• Time to Reach Maximum Plasma Concentration (Tmax) of Mebendazole
• Area Under the Plasma Concentration-time Curve From Time 0 to 8 Hours (AUC8h) of Mebendazole
• Area Under the Plasma Concentration-Time Curve From Time Zero to Time of the Last Quantifiable Concentration AUC(0-last) of Mebendazole

9. Statistical Interpretation

10. Statistical Methods Explained

The primary outcome is binary because each analyzed participant either met the cure definition or did not. For a binary outcome, the group percentage describes the observed frequency of the event of interest—in this case, cure according to the recorded zero egg-count criterion. A percentage is readily interpretable, but it does not show the amount of uncertainty on its own. That is why the registry also reports confidence intervals for each group.

How to read the group percentages

The placebo group’s reported cure rate is 11.1%, with a 95% confidence interval from 5.2% to 20.1%. The mebendazole group’s reported cure rate is 83.7%, with a 95% confidence interval from 74.2% to 90.8%. Each percentage is an estimate based on the participants analyzed in that group. The denominators are 81 for placebo and 86 for mebendazole. The record’s enrollment figure of 295 refers to the study overall, not to the number analyzed for this particular endpoint.

These arm-specific intervals answer a different question from an interval for the between-group contrast. An arm-specific interval describes uncertainty around one group’s cure percentage. A contrast interval describes uncertainty around the estimated difference between groups. The recalculated risk-difference interval is reported in the statistical results; its limits are not repeated in prose because the displayed precision exceeds the limit for written numerical values. Its position above zero indicates that the recalculated interval does not include no difference. This interpretation applies to the unadjusted recalculation, not to an unreported sponsor confidence interval.

What the risk difference means

A risk difference compares the event proportions in two groups by subtracting one proportion from the other. It retains the original outcome scale and expresses the contrast as an absolute difference in proportions. For this result, the event is cure, and the comparison is mebendazole versus placebo. An absolute contrast is useful because it conveys how far apart the observed group proportions are, rather than describing only a relative comparison. The posted recalculation is unadjusted, so it is based on the posted summary counts and does not account for additional covariates or strata unless those are built into the reported analysis.

Other common binary-outcome measures include a risk ratio and an odds ratio. A risk ratio compares event probabilities as a ratio; an odds ratio compares event odds. They answer related but different questions and can appear numerically quite different, especially when an outcome is common in one group. They should not be treated as interchangeable with the risk difference. The recalculated comparisons include these measures, but the primary interpretation remains anchored to the reported group percentages and the sponsor’s own analysis.

How to interpret the p-values

A p-value describes how compatible the observed data are with a specified null hypothesis under the assumptions of the statistical test. It is not the probability that the null hypothesis is true, and it does not quantify the size or practical importance of an effect. The unadjusted recalculation reports p < 0.001. The sponsor’s reported analysis also reports p < 0.001. The record identifies the sponsor method as Cochran-Mantel-Haenszel, but the strata and other implementation details are not reported in the registry record.

The Cochran-Mantel-Haenszel method is a general approach for assessing an association across strata. In general, considering strata can account for the way observations are distributed among defined groups, but what strata were used in this study is not reported in the registry record. The posted summary-statistic recalculation is unadjusted and therefore is not a reconstruction of the sponsor’s full method. Its role is to provide a simple comparison based on the posted group summaries.

For binary outcomes, the count of participants with the event and the denominator both matter. A similar percentage based on different amounts of information can have different precision. Here, the posted event counts are 9 of 81 in placebo and 72 of 86 in mebendazole. These counts correspond to the registry’s reported percentages after rounding. No further calculations from those counts are needed to read the posted estimates.

Why dispersion matters for other outcomes

The pharmacokinetic endpoints are continuous measures, reported as means with standard deviations. A mean describes the center of a set of values; a standard deviation describes how spread out individual observations are around that mean. The means alone do not show whether individual measurements are tightly clustered or widely dispersed. In general, greater dispersion makes a group mean less precise when the amount of data is unchanged. These summaries are presented by age group, and the record does not report sponsor inferential analyses for the displayed pharmacokinetic comparisons.

Continuous-outcome recalculations compare group means and use the reported variability to estimate uncertainty. Those recalculations are unadjusted comparisons of posted summaries, not replacements for an analysis model specified by the study investigators. They also do not imply that the age groups were randomized against one another. The reported age categories are descriptive groupings for pharmacokinetic summaries.

The record does not report the primary analysis’s full statistical model, any covariate adjustment, handling of missing data, or details of an interim-analysis plan. Those elements should not be inferred from the method label or the reported p-value. Statistical interpretation is strongest when the endpoint definition, analysis population, estimate, uncertainty, and analysis method are considered together, while keeping unreported design details separate from what the posted results establish.

11. Confidence Intervals and Precision

Precision concerns how much uncertainty surrounds an estimate. A confidence interval gives a range of values compatible with the data and the method used to construct it. A narrower interval generally indicates greater precision than a wider one, though the interval does not remove uncertainty or guarantee that the true value is contained within its limits.

For the primary cure percentage, the placebo estimate is 11.1%, with a 95% confidence interval of 5.2% to 20.1%; the mebendazole estimate is 83.7%, with a 95% confidence interval of 74.2% to 90.8%. These intervals show uncertainty in the group-specific percentages. Their separation is consistent with the observed contrast, but the intervals for each group are not a substitute for the confidence interval for the difference between groups. The unadjusted risk-difference interval is reported separately in the posted results.

The endpoint analysis denominators are 81 for placebo and 86 for mebendazole. The registry defines the analysis population as randomized participants with a pretreatment stool sample positive for one or more worms of interest. Because enrollment and endpoint analysis use different populations or stages of data availability, the enrollment figure alone does not indicate the precision of this endpoint estimate.

Precision should also be distinguished from statistical significance. A small p-value does not communicate the range of plausible effect sizes, and a confidence interval does not by itself establish clinical importance. The sponsor-reported p-value is available, but a confidence interval for that sponsor analysis is not reported in the registry record. The registry record also does not describe how missing endpoint data were handled, which limits evaluation of uncertainty related to incomplete outcome measurement.

12. 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 reconstruction of the study’s original design calculation. For the binary primary endpoint, the figures are participants per arm. The general assumptions listed for these illustrations are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect to detect is set to the stated fraction of the observed effect. The original design assumptions and sample-size justification are not reported in the registry record.

The 80% power column gives the planned number of participants per arm under the stated assumptions for a design with an 80% chance of detecting the specified effect if that effect is the true one and the assumptions hold. The 90% power column expresses the corresponding planning target for a 90% chance. These are design quantities, not descriptions of what happened in the completed study. This is not observed power.

The rows that use a smaller fraction of the observed effect represent planning for a smaller difference between groups. Smaller effects are generally harder to distinguish from random variation, so they require more participants under otherwise unchanged assumptions. Conversely, a calculation based on the full observed effect should not be treated as a reliable expectation for a future study: the observed estimate is itself uncertain and may not recur.

For time-to-event outcomes, the planning convention would be total events; the primary endpoint is binary, so its planning figures are per arm. The same per-arm convention applies to the other non-time-to-event outcomes. The illustrations simplify the design through equal allocation and a normal approximation. They do not incorporate unreported features of the original trial design, and they should be read as conditional planning aids rather than as evidence about the study’s actual operating characteristics.

13. 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, p₀ and p₁ are the control and treatment proportions, and p̄ is their average.

Worked calculation for this trial

1. Control proportion p₀ = 0.111; treatment proportion p₁ = 0.837; average p̄ = 0.474.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.7062 = 1.3841.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.4848 = 0.4080.
4. n = (1.3841 + 0.4080)² / (0.7261)² = 6.1, rounded up to 7 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
p0 <- 0.111111111111111                          # control proportion
p1 <- 0.837209302325581                          # treatment proportion
n_per_arm <- function(power, frac = 1) {
  q1 <- p0 + (p1 - p0) * frac               # smaller effect = fraction of the observed difference
  pbar <- (p0 + q1) / 2
  z_b <- qnorm(power)
  ceiling(round((z_a * sqrt(2 * pbar * (1 - pbar)) + z_b * sqrt(p0 * (1 - p0) + q1 * (1 - q1)))^2 / (q1 - p0)^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 (unrounded n per arm)
cat("power.prop.test:", round(power.prop.test(p1 = p0, p2 = p1, power = 0.80)$n, 1), "\n")

# Simulation: how often does the z-test reject at the 80%-power sample size?
set.seed(2034162)
n    <- n_per_arm(0.80)
reps <- 20000
x0 <- rbinom(reps, n, p0); x1 <- rbinom(reps, n, p1)
ph <- (x0 + x1) / (2 * n)
z  <- ((x1 - x0) / n) / sqrt(ph * (1 - ph) * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(z) > z_a, na.rm = TRUE), reps))

Output from running the code

100% of observed effect: n per arm = 7 (80% power), 8 (90% power)
 75% of observed effect: n per arm = 12 (80% power), 15 (90% power)
 50% of observed effect: n per arm = 24 (80% power), 31 (90% power)
power.prop.test: 6.1 
Simulated power at n = 7 per arm: 0.887 (20000 replicates)

The simulation draws many pairs of event counts at the planned sample size and counts how often the two-proportion z-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.

14. Analyses Reported by the Sponsor

The sponsor’s reported comparison of the two primary-outcome groups uses the Cochran-Mantel-Haenszel method and reports p < 0.001. The registry record does not report a numerical estimate or confidence interval for that analysis, or identify the strata used. The sponsor’s test is therefore the appropriate reference for what the sponsor reported, while the posted recalculation serves as a separate, unadjusted check based on the available summary counts.

The recalculated comparison reports an unadjusted p-value of <0.001 and a risk-difference confidence interval that lies above zero. The group percentages are 11.1% for placebo and 83.7% for mebendazole. These figures describe the observed outcome proportions; they do not recreate the sponsor’s method. The two p-values are similar in their reported threshold, but that agreement does not make the analyses identical or establish that the recalculation includes any stratification or adjustment in the sponsor analysis.

The registry record does not report information that would allow the sponsor analysis to be independently reconstructed in full. The sponsor’s own analysis takes precedence over the simple recalculation for the sponsor-reported inferential result. The recalculation should be interpreted as a transparent, unadjusted comparison of posted summaries, not as a correction to or replacement for the analysis reported by the sponsor.

15. Multiplicity, Missing Data and Analysis Populations

The registry record lists a primary outcome and multiple secondary outcomes, including cure and egg-count reduction measures and pharmacokinetic measures. It records 10 outcome measures and 4 analyses. The record does not report a multiplicity-adjustment procedure, a hierarchy for testing outcomes, or which secondary comparisons, if any, were intended as confirmatory. When several outcomes are tested, the chance of at least one apparently unusual result can increase. Without a stated strategy, secondary p-values or comparisons should not be read as if each were the sole planned test.

The sponsor-reported primary analysis gives a p-value, but details of the strata for the Cochran-Mantel-Haenszel analysis are not reported in the registry record. The registry also does not report the complete statistical analysis plan, any interim analyses, or the rules used to select participants for each analysis. Those details are important for assessing whether the posted analysis follows the intended plan and how the reported inferential result should be interpreted.

The primary analysis population is described as randomized participants with a pretreatment stool sample positive for one or more worms of interest. The registry does not report how missing post-treatment stool samples were handled, whether any participants were excluded after randomization for reasons beyond the stated population definition, or how protocol deviations were addressed. It also does not report sensitivity analyses for missing outcomes. Thus, the endpoint denominator is available, but a complete account of missing-data assumptions and their potential influence is not.

These reporting gaps do not change the posted group percentages or p-values. They do limit independent evaluation of the analysis process, the impact of missing outcome data, and the strength of conclusions drawn across multiple endpoints. The primary result should be kept distinct from exploratory or descriptive secondary findings, particularly where the analysis plan and multiplicity handling are not reported in the registry record.

16. 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 lists serious adverse events for the double-blind placebo group, the double-blind mebendazole group, and an open-label mebendazole group. No serious adverse events are recorded among 140 participants at risk in the placebo group, 144 at risk in the double-blind mebendazole group, and 278 at risk in the open-label mebendazole group. These are group-specific safety denominators; they should not be added together or treated as the primary endpoint population.

Other, non-serious adverse events are recorded for 8 of 140 participants at risk in the placebo group, 9 of 144 in the double-blind mebendazole group, and 7 of 278 in the open-label mebendazole group. The registry record does not provide serious-adverse-event terms in the listed results. Death counts are not reported in the registry record.

These figures are descriptive counts over the registry’s safety reporting period. The double-blind groups and open-label group represent different treatment periods or conditions, so the counts should be read separately rather than as a direct comparison across equivalent randomized groups. The registry summary does not provide enough information to assess event timing, duration, severity details for non-serious events, or causal attribution. Zero recorded serious events in a group is not proof that no serious risk exists.

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

The primary result describes a marked difference in the observed Ascaris lumbricoides cure percentages between the randomized groups at the end of the double-blind period. The registry reports a cure rate of 83.7% in the mebendazole group and 11.1% in the placebo group, using a definition based on a post-treatment egg count of zero among participants positive at baseline. The posted confidence intervals and reported p-values convey uncertainty and statistical evidence for the comparison, but they do not answer every question about the treatment or the study.

The result applies to the endpoint analysis population and the assessment at Visit 3, Day 19. It does not establish a result for participants who did not meet the stated baseline-positive definition, for another parasite, or for a later period. The record identifies Trichuris trichiura egg-count reduction as a secondary outcome, but numerical results for that outcome are not reported in the registry record. The primary finding should therefore not be generalized to that infection on the basis of the Ascaris outcome alone.

A statistically significant comparison is not, by itself, a measure of clinical importance, durability, or individual response. Group percentages do not predict what will happen to a particular participant. The registry record does not report long-term follow-up results for the primary endpoint, nor does it provide a full account of missing outcome data or the sponsor analysis’s confidence interval.

The safety counts are also limited: they describe recorded events in the listed groups and do not provide a complete account of event types, timing, or attribution. The study’s stated aim included safety, but the posted counts should not be taken as proof that an intervention is free of risk. These results are a statistical description of the trial record, not medical advice or a recommendation about treatment.

18. Why This Trial Matters Statistically

This trial illustrates why endpoint definitions and analysis populations matter as much as headline percentages. Cure was defined using a laboratory measure—zero post-treatment egg count—in participants with a positive baseline egg count. That definition makes the outcome concrete and reproducible in principle, while also limiting the result to a particular infection and visit. Reporting the endpoint-specific denominators alongside the percentages helps readers avoid confusing the primary analysis with overall enrollment.

It also demonstrates the value of separating an arm-specific estimate from a between-group comparison. Each group percentage has its own confidence interval, while the risk difference addresses the contrast directly. Reading both kinds of information helps distinguish the observed outcome in each group from the estimated difference between groups. The sponsor’s reported Cochran-Mantel-Haenszel test and the unadjusted recalculation provide related but non-identical inferential views.

The secondary outcomes show another important statistical distinction: pharmacokinetic summaries by age group are not equivalent to randomized treatment comparisons. Different outcomes can inform different parts of the research question, but they should not be merged into one claim. Missing details about multiplicity, missing data, and analysis implementation matter because they affect how confidently readers can interpret results beyond the primary comparison.

Finally, safety results require their own denominators and context. The double-blind and open-label counts describe different groups or periods, and no single number captures the full safety profile. Careful reading of what was measured, in whom, and when is central to drawing appropriately bounded conclusions from a clinical trial registry record.

19. 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.
• Participant counts were reconstructed from posted percentages and arm sizes, so small rounding differences are possible.

The primary endpoint addresses Ascaris lumbricoides at Visit 3, Day 19. The result does not directly answer the corresponding question for Trichuris trichiura. Although the registry lists egg-count reduction outcomes for both infections, numerical results for those outcomes are not reported in the registry record. The primary cure definition also depends on having a positive baseline egg count, so it does not describe all enrolled participants.

The primary analysis denominators are smaller than the enrollment figure, but the registry record does not explain the complete flow from enrollment and randomization to endpoint analysis. It does not report how missing stool samples or missing post-treatment results were handled, whether exclusions occurred after randomization, or what sensitivity analyses were conducted. That makes it difficult to assess the possible influence of missing data on the estimated cure percentages.

The sponsor’s reported method is identified as Cochran-Mantel-Haenszel, but the strata and other implementation details are not reported in the registry record. A simple unadjusted recalculation cannot reproduce an analysis that may use information not contained in the posted summary counts. The registry also does not report a confidence interval for the sponsor analysis or a full statistical analysis plan.

Other limitations include unreported multiplicity procedures and the absence of numerical results for some listed secondary outcomes. The pharmacokinetic summaries are organized by age groups and are descriptive; they should not be treated as randomized comparisons of age categories. Safety reporting is limited to the listed counts, with no serious-event terms and no death counts reported in the registry record. The record does not provide enough detail to assess event timing, attribution, or longer-term safety.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: A Study to Assess the Efficacy and Safety of Mebendazole for the Treatment of Helminth Infections in Pediatric Participants — NCT02034162.
• Registry record last updated 2016-11-04; status last verified 2016-09.
• Results first posted 2016-11-04.
• 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.

23. Record Summary

The registry record describes a completed Phase 3 randomized, double-blind, multicenter, parallel-group, placebo-controlled study in pediatric participants with helminth infections. It reports enrollment of 295 and compares a single 500-mg chewable mebendazole tablet with matching placebo during the double-blind period.

The primary endpoint was Ascaris lumbricoides cure at Visit 3, Day 19, defined as a post-treatment egg count of zero among participants positive at baseline. The reported cure percentages were 11.1% for placebo and 83.7% for mebendazole. The sponsor-reported Cochran-Mantel-Haenszel analysis gives p < 0.001; the unadjusted recalculation also reports p < 0.001.

Secondary outcomes include egg-count reduction and pharmacokinetic measures. Safety counts are listed for double-blind and open-label groups. The registry record does not report the original sample-size justification, detailed handling of missing data, multiplicity procedures, or all analysis details.