A Comparative Study of JNS013 in Participants With Post-Tooth-Extraction Pain: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Comparative Study of JNS013 in Participants With Post-Tooth-Extraction Pain (NCT00737048), a randomized phase 3 study. The primary outcome is Total Pain Relief Based on Numerical Rating Scale (NRS) Score.

2. Clinical Question

3. Trial Design

This was a Phase 3, randomized, double-blind, parallel-group study. The registry lists 328 participants enrolled and marks the study as completed. The treatment question concerned a single oral dose for pain after tooth extraction, specifically extraction of a mandibular impacted wisdom tooth. The registry record gives a study start of 2008-03 and primary completion of 2008-09.

The posted primary analysis included 132 participants in the tramadol-plus-acetaminophen arm, 66 in the tramadol arm, and 130 in the acetaminophen arm. The registry calls this the final analysis set, defined as participants who received study treatment and had efficacy assessment data. These arm counts describe the primary endpoint analysis; they should not be assumed to describe every analysis population or every endpoint unless the registry says so.

Each active treatment was administered as a single dose, with matching placebo dosage forms used in the component-treatment arms. The combination arm description specifies two tablets containing tramadol hydrochloride and acetaminophen, along with two matching placebo capsules. The other arm descriptions also refer to matching placebo forms. Treatment was given after pain reached the threshold described in the registry, although the available arm descriptions are truncated and do not provide a complete account of all administration details.

The primary outcome was total pain relief on a numerical rating scale over 8 hours. Other listed outcomes included summed pain-intensity and pain-relief measures, changes in visual analog scale scores, pain relief over time, and time to onset or recurrence. The registry record does not report the original sample-size justification, detailed randomization procedures, or planned interim analyses.

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: Final analysis set (FAS) population included all the participants who received the study treatment and had efficacy assessment data.

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 Total Pain Relief Based on Numerical Rating Scale (NRS) Score, measured over 8 hours.

The primary endpoint was total pain relief based on numerical rating scale scores over 8 hours. The registry describes a scale from 0 to 32: 0 indicates no treatment response, and 32 indicates the most improved response. A higher score therefore represents greater reported pain relief on this measure. The posted arm results are means with standard deviations.

A cumulative pain-relief score can capture the reported experience across the assessment period rather than relying on a single measurement. In general, repeated assessments can describe how relief accumulates over time, while a mean offers a concise summary for comparing groups. The scale’s interpretation depends on its stated direction: higher scores indicate greater response. It is not a direct measure of every aspect of recovery, nor does a group mean show the range of individual experiences.

The registry identifies the analysis population as the final analysis set, consisting of participants who received study treatment and had efficacy assessment data. The combination arm’s mean was 17.7, compared with 12.4 for tramadol and 13.3 for acetaminophen. The registry also lists standard deviations of 7.91, 8.36, and 8.07, respectively. These summaries describe the observed scores in each analysis group; they do not by themselves establish how the study handled missing assessments or whether all measurements contributed to the endpoint in the same way.

7. Results Posted in the Registry

• Tramadol Hydrochloride and Placebo: mean 12.40 versus 17.70 on control; difference -5.30 (95% CI -7.73 to -2.87), standardized effect d = -0.66; z-test p = <0.001.
• Acetaminophen and Placebo: mean 13.30 versus 17.70 on control; difference -4.40 (95% CI -6.34 to -2.46), standardized effect d = -0.55; 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.

Sum of Pain Intensity Difference (SPID)

• 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:
  • Tramadol Hydrochloride and Placebo: mean 2.90 versus 6.40 on control; difference -3.50 (95% CI -5.09 to -1.91), standardized effect d = -0.62; z-test p = <0.001.
  • Acetaminophen and Placebo: mean 4.10 versus 6.40 on control; difference -2.30 (95% CI -3.72 to -0.88), standardized effect d = -0.39; z-test p = 0.002.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for Tramadol Hydrochloride and Placebo 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 Acetaminophen and Placebo than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Sum of Pain Relief Combined With Pain Intensity Difference (SPRID)

• 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:
  • Tramadol Hydrochloride and Placebo: mean 15.30 versus 24.00 on control; difference -8.70 (95% CI -12.43 to -4.97), standardized effect d = -0.68; z-test p = <0.001.
  • Acetaminophen and Placebo: mean 17.40 versus 24.00 on control; difference -6.60 (95% CI -9.77 to -3.43), standardized effect d = -0.50; z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for Tramadol Hydrochloride and Placebo 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 Acetaminophen and Placebo than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Number of Participants Treated With a Relief Analgesic

• Endpoint type: Binary: the number of participants with the event, compared as proportions.
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Tramadol Hydrochloride and Placebo: 37.9% (25/66) versus 28.0% (37/132) on control; risk difference 9.8 percentage points (95% CI -4.1 to 23.8), risk ratio 1.35 (0.89–2.04); unadjusted two-proportion z-test p = 0.159.
  • Acetaminophen and Placebo: 41.5% (54/130) versus 28.0% (37/132) on control; risk difference 13.5 percentage points (95% CI 2.1 to 24.9), risk ratio 1.48 (1.05–2.08); unadjusted two-proportion z-test p = 0.022.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Tramadol Hydrochloride and Placebo and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval excludes no difference, so the proportion with the event is statistically higher for Acetaminophen and Placebo than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

The listed secondary outcomes cover several related aspects of pain: summed pain-intensity differences, combined pain-relief and intensity measures, repeated pain scores, relief over time, and the timing of onset or recurrence. The posted secondary summaries include mean scores and participant counts for selected outcomes, as well as a count outcome for use of a relief analgesic. Across the available continuous summaries, the combination arm’s group means are generally higher on scales oriented toward relief or improvement. The registry also reports a higher number of participants treated with a relief analgesic in the component-treatment arms than in the combination arm.

This broad pattern is consistent with the direction of the primary endpoint, but the secondary measures are not independent tests of the same question. They measure overlapping concepts, and some are derived from assessments taken during the same post-treatment period. Agreement across related measures can offer context, but it should not be treated as a series of wholly separate replications.

Some unadjusted recalculations for secondary outcomes have p-values below conventional thresholds, while the comparison for relief-analgesic use between tramadol and the combination does not. These unadjusted results do not account for the number of outcomes and pairwise comparisons examined. When many related hypotheses are tested, the chance of at least one apparently notable result can increase. Without a reported multiplicity plan, individual secondary p-values carry less weight than the primary outcome analysis.

The registry lists 12 outcome measures and 11 posted secondary outcomes. The available results do not include every listed secondary endpoint in the registry record used for this analysis. The registry record does not report a comprehensive adjustment procedure or enough detail to establish how all secondary measures were prioritized. Secondary results are therefore best understood as supporting descriptive context, not as a substitute for the primary endpoint or a stand-alone basis for broad conclusions.

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

• Total Pain Relief Based on Numerical Rating Scale (NRS) Score Every 4 Hours up to 8 Hours
• Sum of Pain Intensity Difference (SPID)
• Sum of Pain Relief Combined With Pain Intensity Difference (SPRID)
• Change From Baseline in Visual Analog Scale (VAS) Score at 0.5, 1, 2, 3, 4, 5, 6, 7 and 8 Hours Post-administration of Study Treatment
• Mean Change Over Time for Pain Intensity Difference (PID) at 0.5, 1, 2, 3, 4, 5, 6, 7 and 8 Hours Post-Administration of Study Treatment
• Mean Change Over Time for Pain Relief (PAR) at 0.5, 1, 2, 3, 4, 5, 6, 7 and 8 Hours Post-administration of Study Treatment
• Mean Change Over Time for Pain Relief Combined With Pain Intensity Difference (PRID) at 0.5, 1, 2, 3, 4, 5, 6, 7 and 8 Hours Post-administration of Study Treatment
• Time to Reach the Onset of Drug Efficacy and Time to Recurrence of Pain After the Onset of Drug Efficacy

9. Statistical Interpretation

10. Statistical Methods Explained

The statistical summaries describe continuous outcomes as means and standard deviations. A mean is the arithmetic average of observed scores in a group. A standard deviation describes how spread out individual scores are around that group average. It is not the uncertainty in the mean itself: uncertainty in a mean comparison also depends on the number of participants and the variability of their scores.

What does a mean difference express?

A mean difference expresses the contrast between two group averages in the units of the endpoint. For the primary endpoint, those units are points on the total pain-relief scale. The recalculated comparisons use the combination arm as the reference and subtract its mean from the mean in the other arm. A negative estimate therefore means that the component-treatment group’s average was lower than the combination group’s average under this ordering. The registry’s reported analyses also give negative estimates for both comparisons.

Direction must be read alongside the endpoint definition. Here, the registry says higher total pain-relief scores indicate a greater treatment response. A negative component-arm-minus-combination difference therefore corresponds to lower average scores in the component arm. The sign alone does not tell the reader whether a difference is important; its size, uncertainty, and clinical context also matter.

What does a p-value tell the reader?

A p-value assesses how compatible the observed data are with a specified null hypothesis under the analysis model. A small p-value is evidence against that null under the assumptions of the method. It is not the probability that the null hypothesis is true, and it does not indicate the probability that a result is due to chance. It also does not quantify the size of a difference or establish its practical importance.

The registry’s sponsor analyses report p < 0.001 for each primary comparison using Fisher Least Significant Difference. The unadjusted recalculations report p < 0.001 for each. Both sets of values indicate small p-values under their respective analyses, but the calculations are not identical in method or reporting. The sponsor’s named method should be distinguished from the simple unadjusted recalculations based on posted summary statistics.

Why use an interval as well as a test?

A confidence interval gives a range of estimates compatible with the observed data and the assumptions of the calculation. Its width communicates precision: narrower intervals indicate less uncertainty in the estimated contrast, while wider intervals indicate more. For the recalculated primary comparisons, the intervals are expressed in the scale’s units and accompany the estimated mean differences. An interval is not a guarantee that the true value lies within its limits, and it does not by itself determine whether the difference matters clinically.

The registry’s own primary-analysis entries do not list confidence-interval limits. The intervals discussed for the primary contrasts are therefore recalculated from the posted group summaries and should be interpreted as unadjusted estimates. The registry record does not report whether its Fisher Least Significant Difference analyses used a different covariance structure or other model details.

Why can standard deviations and group sizes matter?

Standard deviations describe participant-to-participant variability. Greater variability makes a group mean less precisely estimated when the number of observations is otherwise similar. Larger analysis groups generally provide more information about the group mean, subject to the assumptions of the analysis. In the primary endpoint, the group sizes are not equal: the tramadol arm has fewer participants than either of the other two arms. This affects the precision of pairwise comparisons and is reflected in their intervals.

These are continuous-outcome comparisons. General statistical methods may use pooled variability when estimating a difference between means, but that approach depends on assumptions about the groups and the analysis. The registry’s own analysis method is identified as Fisher Least Significant Difference; the registry record does not report enough detail to reconstruct every feature of that method. The recalculations are simple, unadjusted comparisons and do not account for covariates, repeated observations, or any unreported analysis choices.

Why does over-dispersion matter in other settings?

As a general statistical point, over-dispersion occurs when the observed variation in data is greater than a model expects. If a model assumes less variation than is present, standard errors can be too small and intervals too narrow, making evidence appear more precise than it is. This issue is especially relevant to count outcomes or other models that impose a variance structure. The registry’s primary endpoint is reported as a continuous mean with a standard deviation; the record does not state that an over-dispersion model was used for it. This general concept should not be mistaken for a reported issue in this trial.

The primary results are group summaries from the final analysis set. The registry record does not report detailed missing-data procedures, assumptions about the distribution of endpoint scores, covariate adjustment, or sensitivity analyses. Those omissions limit how fully an outside reader can reproduce or assess the sponsor’s analysis.

11. Confidence Intervals and Precision

The primary endpoint’s mean differences are reported by the registry without confidence-interval limits. The unadjusted recalculations add intervals based on the posted group means, standard deviations, and analysis counts. For tramadol compared with the combination, the recalculated mean difference is -5.3, with a 95% confidence interval from -7.727 to -2.873. For acetaminophen compared with the combination, it is -4.4, with a 95% confidence interval from -6.335 to -2.465.

Both recalculated intervals lie below zero under the stated comparison ordering. That is consistent with lower mean scores in the component-treatment groups than in the combination group, given that higher scores indicate greater treatment response. The interval limits also show that the estimated contrast is not a single exact value. The range captures sampling uncertainty under the calculation’s assumptions; it does not account for every possible source of uncertainty, such as unreported missing-data decisions or model choices.

The acetaminophen comparison has more participants than the tramadol comparison in its component-treatment arm, and its interval is narrower. The observed standard deviations and group sizes both contribute to the precision of a mean difference. This comparison of interval widths is descriptive, not evidence that one result is more clinically important.

Confidence intervals do not express the probability that a particular treatment effect is true, and they do not establish whether a difference is meaningful to participants. The registry’s own reported primary analyses give p-values but no interval limits. Accordingly, the intervals should be read as recalculated, unadjusted estimates rather than as intervals reported by the sponsor.

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 effects, not the trial’s original design calculation. For the continuous outcomes shown in the planning display, the figures mean participants per arm. The stated assumptions are a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect to detect set to the stated fraction of the observed effect. The trial’s original sample-size assumptions and justification are not reported in the registry record.

The 80% power column gives the number of participants per arm that the illustration estimates would be needed to have an 80% chance of detecting the specified effect under those assumptions. The 90% power column gives the corresponding number for a 90% chance. These are conditional planning calculations, not guarantees: their interpretation depends on the assumptions and on the effect size being targeted. They are not observed power.

Rows that use 100% of the observed effect target the full estimated contrast from the posted results. Rows using 75% or 50% target progressively smaller effects. Smaller effects are harder to distinguish from random variation, so the planning figures rise as the targeted effect becomes smaller. This illustrates why sample-size needs depend not just on a desired power level but also on the difference a study is designed to detect.

These calculations are pairwise illustrations, not evidence that the completed trial had those design targets. They do not incorporate any unreported adjustment for multiple comparisons, loss to follow-up, or other design considerations. They should be used to understand the sensitivity of hypothetical planning to the assumed effect, rather than to infer the power actually achieved by the study.

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, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = -5.300; pooled standard deviation σ = 8.062.
2. n = 2 × (1.96 + 0.842)² × 8.062² / -5.300² = 36.3, rounded up to 37 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 <- -5.3                      # observed difference in means
sigma <- 8.06201888297142                     # 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(737048)
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 = 37 (80% power), 49 (90% power)
 75% of observed effect: n per arm = 65 (80% power), 87 (90% power)
 50% of observed effect: n per arm = 146 (80% power), 195 (90% power)
power.t.test: 37.3 
Simulated power at n = 37 per arm: 0.799 (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.

14. Analyses Reported by the Sponsor

The registry reports the sponsor’s primary comparisons using Fisher Least Significant Difference and mean differences in final values. For tramadol compared with the combination, the reported estimate is -5.3 with p < 0.001. The unadjusted recalculation from the posted means is also -5.3, with p < 0.001. The registry’s reported comparison of acetaminophen with the combination is -4.3 with p < 0.001, while the recalculation from the posted means is -4.4 with p < 0.001.

The sponsor’s analysis and the recalculation are distinct. The recalculations use posted group summary statistics and produce unadjusted estimates; they do not reproduce every possible detail of the sponsor’s analysis. The registry record does not list confidence intervals for the sponsor’s primary comparisons, whereas the recalculated intervals are based on the summary data. The p-value thresholds are also reported at different levels of precision.

The registry’s discrepancy indicator is false. The sponsor’s reported analyses remain the registry’s own analyses, and the recalculations are best read as a transparent, simple comparison of the posted summaries rather than a replacement for them. In particular, a small difference in displayed point estimates should not be interpreted as a separate finding without fuller analytic details.

15. Multiplicity, Missing Data and Analysis Populations

Multiplicity arises when a study examines several outcomes, time points, groups, or comparisons. Each statistical test carries a chance of producing a small p-value even when there is no true effect under its null hypothesis. As the number of tests grows, interpreting each p-value as if it were the only planned test can overstate the strength of the overall evidence. This concern is relevant when a study reports multiple secondary endpoints and pairwise comparisons.

The registry identifies Fisher Least Significant Difference as the method for the sponsor’s primary comparisons. It does not report in the record how multiplicity was handled across the primary comparisons, the secondary outcomes, or repeated assessment times. The registry record does not report a hierarchy of hypotheses, a family-wise error procedure, or another overall strategy for controlling false-positive findings. The unadjusted recalculations likewise do not adjust for multiple testing.

Without this information, the primary comparisons should be distinguished from exploratory or secondary findings. The sponsor’s reported primary p-values are the registry’s own results, but the record does not explain whether or how their interpretation accounts for the pairwise comparisons. Secondary p-values deserve particular caution because several outcomes measure related features of pain during the same period.

The primary analysis set is defined as participants who received study treatment and had efficacy assessment data. That definition tells readers who was included, but not how missing measurements were handled. The registry record does not report the amount or pattern of missing data, any imputation method, rules for incomplete follow-up, or sensitivity analyses assessing missing-data assumptions. Nor does it describe whether every participant in the analysis set contributed every scheduled assessment.

These omissions do not show that a particular analysis decision was inappropriate. They mean that the posted record does not provide enough information to evaluate those decisions fully or reproduce the sponsor’s results. Results from the available analysis population should be interpreted with that limitation in mind.

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 serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: drug hypersensitivity (0.8%).

The registry reports serious adverse events in 0 of 132 participants in the combination arm, 0 of 66 in the tramadol arm, and 1 of 130 in the acetaminophen arm. The listed serious-event term is drug hypersensitivity, reported as 0.8%. The displayed group figures are counts of participants at risk and affected, not estimates of comparative risk adjusted for other factors.

These counts are sparse. A zero count in an arm does not establish that an event is impossible or that the treatment has no safety risk. A single reported event also provides limited precision about how frequently such events might occur in a wider population. The registry record does not report deaths as a numeric result; death information is therefore not reported in the registry record.

The record separately lists other adverse events affecting 82 participants in the combination group, 40 in the tramadol group, and 52 in the acetaminophen group. Those are not serious-event counts and should not be conflated with the serious adverse event figures. The registry information does not provide a full account of event severity, duration, relatedness, or treatment discontinuation. The safety counts are descriptive and do not establish that the groups have equivalent safety profiles.

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

The results describe a comparison of a single oral dose of tramadol plus acetaminophen with the component treatments for acute pain after mandibular impacted wisdom-tooth extraction. On the primary total pain-relief score over 8 hours, the combination group had a higher mean than either component-treatment group. The registry’s reported analyses and the unadjusted recalculations both show negative component-arm-minus-combination contrasts.

This finding is limited to the measured endpoint, population, treatments, and assessment period in the registry. It does not establish what would happen with repeated dosing, longer follow-up, other types of pain, other procedures, or populations not described in the record. It also does not show the experience of every participant: group averages can coexist with a wide range of individual scores.

Statistical evidence and clinical importance are different questions. The small reported p-values describe compatibility with a null hypothesis under the analysis, while the mean differences and their intervals describe the magnitude and uncertainty of the estimated contrasts. The registry record does not supply a threshold for a clinically important difference on this scale, so the clinical importance of the observed differences cannot be determined from these results alone.

The safety results are also limited. The serious adverse event counts are low, and the record does not report deaths as numeric results or provide all details needed to compare the safety profiles fully. Absence of a recorded serious event in an arm is not proof that a risk is absent.

These findings are statistical summaries of a completed trial, not individualized predictions or medical guidance. They should be understood alongside the specific trial setting, the analysis population, the uncertainty in the estimates, and the information not reported in the registry record.

18. Why This Trial Matters Statistically

This trial offers a useful statistical example of how a registry record can support a focused comparison while leaving important analytic details unavailable. It reports a randomized, double-blind, parallel-group design, group sizes, endpoint means, standard deviations, and the sponsor’s primary comparisons. Those details allow readers to interpret the direction of the group averages and to examine uncertainty using recalculations from the posted summaries.

The example also shows why sign conventions matter. The registry’s reported contrasts are negative because they compare a component-treatment arm with the combination arm, while the endpoint is oriented so higher scores indicate greater response. Reading the estimate together with its group order and scale meaning avoids mistaking a negative number for an unfavorable result in every context.

Another statistical lesson is the value and limitation of confidence intervals. The sponsor’s primary entries report p-values but not interval limits. Recalculated intervals make the uncertainty around the posted contrasts more tangible, while remaining distinct from the sponsor’s own analysis. Point estimates alone can make a result appear more exact than it is.

Finally, this record illustrates how multiplicity and incomplete reporting affect interpretation. A broad set of pain-related outcomes can provide useful context, but related endpoints and repeated comparisons should not be read as independent confirmations when the analysis plan is unavailable. Sample-size illustrations can show how planning changes with assumed effects, but they do not reveal the study’s original planning assumptions or its observed power. Careful interpretation depends on keeping each of these distinctions clear.

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.

The primary assessment covers 8 hours after a single dose. The registry record therefore does not establish the pattern of outcomes over longer periods or after repeated treatment. The study concerns pain after mandibular impacted wisdom-tooth extraction, so the results should not be assumed to apply to other pain settings or procedures.

The registry’s primary sponsor analyses do not include confidence-interval limits in the posted entries. The intervals discussed for the mean differences are unadjusted recalculations from summary statistics, not sponsor-reported intervals. The record identifies Fisher Least Significant Difference but does not give enough detail to reproduce every aspect of the sponsor’s analysis.

The analysis population includes participants who received treatment and had efficacy assessment data. The registry record does not report the number or pattern of missing assessments, how incomplete outcomes were handled, or whether sensitivity analyses were conducted. The original sample-size justification, detailed allocation procedures, and planned interim analyses are not reported in the registry record.

The record lists multiple secondary outcomes and repeated assessment times, but does not report a comprehensive multiplicity strategy. The secondary results therefore have less evidential weight when considered one by one. Some secondary results are not available among the posted summaries used in this analysis, so the overall secondary-outcome pattern is necessarily limited to what is reported.

Safety interpretation is constrained by the small serious-event counts and the absence of numeric death results. The registry’s adverse-event summaries do not give all details about severity, duration, causal attribution, or discontinuations. These limitations restrict how precisely comparative safety can be characterized from this record.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: A Comparative Study of JNS013 in Participants With Post-Tooth-Extraction Pain — NCT00737048.
• Registry record last updated 2016-03-31; status last verified 2016-03.
• Results first posted 2013-08-01.
• 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 describes a completed, randomized, double-blind, parallel-group Phase 3 study with 328 participants enrolled. It evaluated a single oral dose of tramadol hydrochloride plus acetaminophen against tramadol and acetaminophen component-treatment arms in participants with pain after mandibular impacted wisdom-tooth extraction.

The primary endpoint was total pain relief on a 0-to-32 numerical rating scale over 8 hours, with higher scores indicating greater treatment response. The combination arm’s mean was 17.7; the tramadol and acetaminophen arm means were 12.4 and 13.3. The sponsor reported both primary comparisons as statistically significant using Fisher Least Significant Difference. Unadjusted recalculations give confidence intervals for the contrasts, but are not a replacement for the sponsor’s analysis.

The registry also lists several pain-related secondary outcomes and reports serious adverse event counts of 0, 0, and 1 across the three arms. Missing-data procedures, multiplicity handling, and the original sample-size justification are not reported in the registry record.