This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Study of Long-Acting Acetaminophen in Postoperative Dental Pain (NCT01960114), a randomized phase 2 study. The primary outcome is Time Weighted Sum of Pain Intensity Difference (PID) Over 10 Hours (SPID 0-10).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01960114 |
| Phase | Phase 2 |
| Condition | Dental Pain |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Quadruple |
| Enrollment | 403 |
| Arms in the primary outcome | 2 |
| Lead sponsor | McNeil Consumer Healthcare Division of McNEIL-PPC, Inc. |
| Results posted | Yes |
2. Clinical Question
Population
Participants with postoperative dental pain following third molar extraction(s) were enrolled at a single center. The primary analysis population was the Intent-to-Treat population, which included all randomized participants. The registry record reports 403 participants enrolled, with 134 assigned to placebo and 269 assigned to ACE ER 1500 mg for the primary outcome.
Intervention
The intervention was a single dose of extended-release acetaminophen, 1500 mg, described in the study summary as two 750 mg tablets. The study evaluated efficacy and safety over 10 to 12 hours and also planned to evaluate pharmacokinetics in a subgroup.
Comparator
The comparator was placebo. The arm description identifies it as a single dose of two tablets of acetaminophen ER 750 mg matching placebo.
Primary question
The primary question was whether the groups differed in the time-weighted sum of pain intensity difference scores from baseline over 10 hours, called SPID 0-10 in the registry record. Pain intensity was rated on a 0-10 numerical rating scale, where 0 meant no pain and 10 meant very severe pain.
The primary outcome is a continuous summary of repeated pain ratings, rather than a single rating at one time. The registry record reports the outcome as a least-squares mean and identifies standard error as its dispersion measure. Its posted primary analysis compares the treatment and placebo groups using an analysis of variance method and reports a least-squares mean difference.
The study also listed secondary outcomes concerning first perceptible pain relief, meaningful pain relief, duration of pain relief, and patient global evaluation. The record describes a pharmacokinetic evaluation in a subgroup, but pharmacokinetic results are not reported in the registry record. The question addressed by the posted primary result is therefore limited to the recorded 10-hour pain summary, not every efficacy, safety, or pharmacokinetic aim named in the study summary.
3. Trial Design
This was a phase 2, randomized, parallel-group, placebo-controlled study at a single center. The registry record describes the study as double-blind in its official title and lists quadruple masking in the design information. It was a single-dose study of extended-release acetaminophen in postoperative dental pain following third molar extraction(s). The study status is completed; the recorded start was 2013-10 and primary completion was 2014-04.
The registry record reports 403 enrolled participants. For the primary outcome, 134 participants were in the placebo group and 269 were in the ACE ER 1500 mg group. The primary analysis population is identified as the Intent-to-Treat population, defined in the record as all subjects who were randomized. The trial record does not report how randomization was generated, whether allocation concealment was used, or the details of the masking procedures.
The intervention was one dose of acetaminophen ER 1500 mg, described as two 750 mg tablets. The placebo arm is described as receiving two matching placebo tablets. The study summary states that efficacy and safety were evaluated over 10 to 12 hours, while the primary outcome timeframe is 10 hours. Pharmacokinetics were to be evaluated in a subgroup, but the subgroup size and pharmacokinetic findings are not reported in the registry record.
The primary endpoint was a time-weighted sum of pain intensity difference scores over 10 hours. Other outcomes listed were time to confirmed first perceptible pain relief, time to meaningful pain relief, duration of pain relief, and patient global evaluation. The registry record lists five outcome measures and five analyses, but does not report a complete analysis plan, the order of testing for all outcomes, or the trial’s original sample-size justification. These omissions limit what can be concluded about the planning and analysis choices beyond the information recorded for the posted outcome.
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
| Stage | Placebo | ACE ER 1500 mg |
|---|---|---|
| STARTED | 134 | 269 |
| COMPLETED | 133 | 268 |
| NOT COMPLETED | 1 | 1 |
Reasons for not completing this period:
| Reason | Placebo | ACE ER 1500 mg |
|---|---|---|
| Adverse Event | 1 | 0 |
| Could not swallow study medication | 0 | 1 |
Analysis population for the primary outcome, as defined in the registry: Analysis was based on the Intent-to-Treat (ITT) population, which included all subjects who were randomized.
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.
| Characteristic | Unit | Placebo | ACE ER 1500 mg | Total |
|---|---|---|---|---|
| Participants analysed | 134 | 269 | 403 | |
| Age, Continuous | years | 19.6 (SD 2.66) | 19.5 (SD 2.82) | 19.6 (SD 2.77) |
| Sex: Female, Male: Female | Participants | 72 | 143 | 215 |
| Sex: Female, Male: Male | Participants | 62 | 126 | 188 |
| Region of Enrollment: USA | participants | 134 | 269 | 403 |
6. Primary Endpoint
The registry lists the primary outcome as Time Weighted Sum of Pain Intensity Difference (PID) Over 10 Hours (SPID 0-10), measured over 10 Hours.
| Element | Registry entry |
|---|---|
| Result type | Least Squares Mean |
| Measure of spread | Standard Error |
| Unit | units on a scale |
| Endpoint classification | Continuous Endpoint |
The primary endpoint, SPID 0-10, summarizes pain intensity difference scores from baseline across the first 10 hours. Pain intensity was assessed repeatedly using a numerical rating scale from 0, no pain, to 10, very severe pain. Instead of relying on a single follow-up rating, the summary combines differences at multiple specified times and weights them according to the time intervals described in the registry record. It is reported in units on a scale.
A time-weighted measure can represent both the size and persistence of changes in ratings during the measured period. In general, this can be useful when an intervention is expected to have an effect that develops or changes over time, because repeated observations contribute to one summary measure. It also gives a way to compare groups across the defined 10-hour period rather than making the primary comparison depend on one selected time point.
The registry record reports the endpoint as a least-squares mean with standard error as the dispersion measure. The sponsor’s posted analysis reports a least-squares mean difference and a confidence interval. The record does not give a threshold for interpreting what size of difference would be clinically important, nor does the endpoint description define a minimum meaningful change in SPID. The result therefore quantifies a between-group contrast on the recorded scale; it does not, by itself, establish the practical importance of that contrast.
7. Results Posted in the Registry
- ACE ER 1500 mg: mean 30.99 versus 5.75 on control; difference 25.24 (95% CI 19.08 to 31.40), standardized effect d = 0.83; z-test p = <0.001.
Mean difference: ACE ER 1500 mg
95% CI: 19.08 to 31.40
Recalculated from the posted summary statistics
8. Statistical Interpretation
For the primary endpoint, the posted group values were 5.745 for placebo and 30.99 for ACE ER 1500 mg. The registry’s reported analysis gives a least-squares mean difference of 25.241, with a 95% confidence interval from 19.669 to 30.813 and p < 0.001. The interval lies above zero, and the reported p-value indicates that the analysis found strong evidence against a zero between-group difference under its statistical model.
The endpoint is a weighted summary of pain intensity difference scores from baseline over 10 hours. The numerical result should be read on that endpoint’s scale, not as a difference in the original 0-10 rating at one particular time. The registry record does not state a threshold for clinical importance, so the size of the estimate cannot be classified as clinically important or unimportant from the posted result alone. Nor does the result describe what happened at every individual assessment time.
The analysis population is described as all randomized participants. The record reports 269 participants in the treatment arm and 134 in the placebo arm for the primary outcome. These counts differ by group, and the registry does not explain the allocation ratio or how the group sizes arose. It also does not describe the handling of missing endpoint observations, if any. This means that the estimate can be reported as the registry’s ITT analysis result, but the details needed to assess the impact of missing data are not available in the registry record.
The listed secondary outcomes address timing and duration of pain relief and patient global evaluation. Their names alone do not indicate their results. Numerical results for these outcomes are not reported in the registry record. Similarly, the study summary describes a pharmacokinetic subgroup, but its results are not reported in the registry record. The primary finding should not be extended to those outcomes without their posted estimates.
The study was a single-center phase 2 trial with one dose and a 10-hour primary endpoint. The registry result concerns the measured period and study population only. It does not establish what results would be observed with other dosing regimens, at other centers, in different populations, or over longer follow-up. The statistical evidence in the posted primary analysis is distinct from those questions of clinical scope and generalizability.
9. Statistical Methods Explained
The primary outcome is continuous: it is a numeric summary of repeated pain-intensity-difference assessments. For continuous outcomes, a group mean or model-based mean describes the average measured value in a group. A difference between group means estimates how far apart the groups are on the outcome scale. This kind of contrast does not describe every participant’s response, and it does not show the full distribution of individual values.
What does a least-squares mean represent?
A least-squares mean is a model-based group mean. It is estimated within the statistical model used for the analysis, rather than being simply identified as the arithmetic average of the recorded values. The registry reports a least-squares mean difference for the comparison and identifies ANOVA as the analysis method. It does not list the model’s full specification, any covariates, or the assumptions and diagnostic checks used. Those details are not reported in the registry record.
The primary outcome description also lists standard error as its dispersion measure. In general, a standard error describes the statistical uncertainty in an estimated mean; it is not the same as the spread of individual participant values. The posted arm values are 5.745 with a standard error of 2.506 for placebo and 30.99 with a standard error of 1.895 for ACE ER 1500 mg. These estimates help describe the uncertainty of the group means, while the reported confidence interval describes uncertainty in the between-group contrast.
What does the ANOVA comparison do?
In general, analysis of variance compares group means by separating variation associated with differences between groups from variation among observations within groups. Here, the registry reports an ANOVA analysis and a least-squares mean difference. The reported p-value is < 0.001. A p-value measures how compatible the observed data are with a specified null hypothesis under the analysis assumptions; it is not the probability that the null hypothesis is true, nor does it measure clinical importance.
The registry’s primary analysis uses the Intent-to-Treat population, defined as all randomized subjects. An ITT approach keeps participants in the groups to which they were randomized, supporting an analysis based on the original randomized comparison. However, the record does not report whether all randomized participants had usable primary outcome data or explain any missing-data procedures. The label ITT does not by itself settle how missing observations were handled.
Why use a time-weighted endpoint?
General statistical rationale: repeated measurements can capture how an outcome evolves, while a time-weighted summary incorporates the timing of those measurements into one continuous endpoint. The registry specifies the assessment times and weighting used to form SPID 0-10. Such a summary can be analyzed as a continuous outcome, allowing a group contrast to be expressed as a mean difference. It also compresses the time profile: a single summary cannot show the exact pattern at every follow-up time. Separate results by time point are not reported in the registry record.
The score is based on pain-intensity-difference values from baseline. The registry describes the numerical rating scale anchors but does not provide an interpretation threshold for the resulting weighted sum. The reported contrast therefore communicates the estimated separation on the defined summary scale, while contextual judgments about importance require information the record does not provide.
What is a confidence interval?
In general, a confidence interval gives a range of values compatible with the data and statistical model at a stated confidence level. It communicates precision as well as direction: a narrower interval indicates a more precise estimate, while a wider interval indicates more uncertainty. The registry reports a 95% confidence interval for the primary least-squares mean difference. The interval does not guarantee that the true value lies within its particular endpoints, and it does not incorporate every possible source of uncertainty, such as uncertainty from design limitations or unreported analysis choices.
Over-dispersion is a general concern when observed variability is greater than expected under a statistical model. If it is not accounted for, standard errors and confidence intervals may be too small and p-values may overstate the evidence. The registry record does not report an over-dispersion assessment or indicate that over-dispersion was observed. It is therefore a general consideration, not a documented feature of this trial’s analysis.
What is and is not documented?
The record names ANOVA for the primary comparison and reports the point estimate, confidence interval, and p-value. It does not report a full statistical analysis plan, original sample-size assumptions, interim analyses, multiplicity adjustment, or detailed missing-data methods. It also does not give model diagnostics or enough detail to independently reproduce the sponsor’s analysis from the registry record alone. These missing details should not be filled in by assuming standard procedures were used.
A separate unadjusted re-calculation based on posted summary statistics is an approximation and is not a replacement for the sponsor’s model-based analysis. In general, re-calculations from summary statistics can differ because they do not reproduce all features of a fitted model. The reported sponsor analysis remains the trial’s posted primary result; the re-calculated estimate is best treated as a statistical cross-check using the available summary information.
10. Confidence Intervals and Precision
The sponsor-reported primary estimate is a least-squares mean difference of 25.241, with a 95% confidence interval from 19.669 to 30.813. This interval represents the range of values compatible with the observed data and the assumptions of the reported analysis at the stated confidence level. It indicates that the estimated contrast is above zero across the interval, while also showing that the exact size is uncertain.
The unadjusted re-calculation from posted summary statistics gives a mean difference of 25.24 and a confidence interval from 19.08 to 31.4. This re-calculation uses an approximate standard deviation inferred from the posted summaries; it is not the sponsor’s model-based ANOVA result. The sponsor’s reported interval is the appropriate result to cite as the registry’s own analysis. The two intervals differ in their endpoints, reflecting that the re-calculation and reported model analysis are not identical procedures.
Confidence intervals are useful because the point estimate alone can suggest more certainty than the data support. The reported interval conveys uncertainty in the difference, but it does not resolve questions about clinical relevance, the pattern of responses over time, or the impact of missing data. The registry does not report a threshold for a clinically important SPID difference, and the interval cannot supply that threshold. It also does not account for uncertainties that are not represented in the analysis, such as unreported choices in the statistical plan.
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.
| Effect to detect | Participants per arm, 80% power | Participants per arm, 90% power |
|---|---|---|
| 100% of the observed effect | 23 | 31 |
| 75% of the observed effect | 41 | 55 |
| 50% of the observed effect | 92 | 123 |
The planning figures are participants per arm for 80% power and participants per arm for 90% power, because the primary outcome is continuous and the sample-size assumptions specify equal allocation between two arms. The figures are planning illustrations based on the observed effect, not the trial’s own original design assumptions. The original design assumptions are not reported in the registry record.
The illustration uses a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. It considers the stated fraction of the observed effect as the effect to detect. Planning for 100% of the observed effect gives 23 participants per arm for 80% power and 31 participants per arm for 90% power. Planning for 75% of the observed effect gives 41 participants per arm for 80% power and 55 participants per arm for 90% power. Planning for 50% of the observed effect gives 92 participants per arm for 80% power and 123 participants per arm for 90% power.
In general, power is the probability that a statistical test will reject its null hypothesis under a specified effect and set of assumptions. The 80% and 90% columns show different planning targets: the 90% target seeks a higher chance of detecting the assumed effect, and it consequently requires more participants in these illustrations. Smaller effects are harder to distinguish from random variation and therefore require more participants. These figures are planning illustrations, not observed power.
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 z1−α/2 = 1.960) and the desired power (z1−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
- Observed difference Δ = 25.241; pooled standard deviation σ = 30.409.
- n = 2 × (1.96 + 0.842)2 × 30.4092 / 25.2412 = 22.8, rounded up to 23 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 <- 25.241 # observed difference in means
sigma <- 30.4086290412226 # 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(1960114)
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 = 23 (80% power), 31 (90% power)
75% of observed effect: n per arm = 41 (80% power), 55 (90% power)
50% of observed effect: n per arm = 92 (80% power), 123 (90% power)
power.t.test: 23.8
Simulated power at n = 23 per arm: 0.786 (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. Analyses Reported by the Sponsor
| Method | Estimate | 95% CI | P-value |
|---|---|---|---|
| ANOVA | Least Squares Mean Difference 25.241 | 19.669 to 30.813 | < 0.001 |
The registry’s own primary analysis is an ANOVA comparison reported as a least-squares mean difference of 25.241, with a 95% confidence interval from 19.669 to 30.813 and p < 0.001. This is the sponsor’s posted analysis of the primary endpoint. The unadjusted re-calculation from the posted group summaries gives a mean difference of 25.24, with a confidence interval from 19.08 to 31.4 and p < 0.001.
The re-calculation is a simple comparison based on summary statistics and uses an approximate standard deviation. It does not reproduce the sponsor’s ANOVA model or any unreported details of that model. The estimates are close in their central value but have different confidence interval endpoints. This is not, by itself, evidence of an error: model-based analysis and an unadjusted summary-statistic calculation can yield different uncertainty estimates.
The sponsor-reported ANOVA result should be understood as the official posted primary analysis. The re-calculation is a complementary check on the numerical summaries, not a substitute for the analysis reported in the registry record. Both reported p-values are < 0.001, but p-values do not convey the clinical importance of the difference.
14. Multiplicity, Missing Data and Analysis Populations
The registry record lists one primary outcome, SPID 0-10 over 10 hours, and four secondary outcomes: time to confirmed first perceptible pain relief, time to meaningful pain relief, duration of pain relief, and patient global evaluation. It also lists five outcome measures and five analyses. Numerical results for the secondary outcomes are not reported in the registry record, so their estimates and uncertainty cannot be assessed from the posted primary result.
Multiplicity arises when several outcomes, time points, or comparisons are tested. In general, conducting many tests can increase the chance of finding at least one statistically significant result by chance. Statistical plans may address this through a testing hierarchy or other adjustment, but the registry record does not report whether multiplicity was addressed or how the five analyses were ordered. It would be inappropriate to assume an adjustment or infer one from the listed p-value.
The primary analysis population is identified as the Intent-to-Treat population and defined as all randomized subjects. The primary outcome group counts are 134 for placebo and 269 for ACE ER 1500 mg. The record does not explain whether all randomized participants contributed observed endpoint data, how missing measurements were handled, whether any imputation was used, or whether sensitivity analyses were conducted. These missing-data procedures are not reported in the registry record.
The record identifies ANOVA and gives the least-squares mean difference, confidence interval, and p-value, but does not include a complete statistical analysis plan or the full model specification. Interim analyses and stopping rules are not reported in the registry record. The original sample-size justification and the trial’s planned power assumptions are also not reported. These omissions do not change the figures that are posted, but they constrain assessment of how the analysis was planned and how robust the conclusion might be to alternative analytical choices.
15. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Placebo | 0 | 134 | 0.0% |
| ACE ER 1500 mg | 0 | 268 | 0.0% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Placebo | 14 of 134 |
| ACE ER 1500 mg | 26 of 268 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Placebo | ACE ER 1500 mg |
|---|---|---|---|
| Nausea | Gastrointestinal disorders | 14 of 134 | 26 of 268 |
The registry reports serious adverse events for 0 of 134 participants in the placebo group and 0 of 268 participants in the ACE ER 1500 mg group. These are counts among the participants at risk in the posted safety data. The record lists no top serious adverse event terms. The deaths field is not reported in the registry record.
A count of zero reported serious adverse events does not establish that the risk is absent. It describes what was recorded in these groups during the period and under the reporting in the registry. The study was a single-dose trial, and the record does not give detailed follow-up duration for serious adverse events beyond the study’s stated assessment windows. The counts should therefore be read within that context rather than treated as a complete picture of safety across longer use or other populations.
The registry also reports other adverse events for 14 of 134 participants in the placebo group and 26 of 268 participants in the treatment group. The record does not provide event terms in the details or further breakdowns by severity, timing, or relationship to treatment. These figures are descriptive counts and do not, by themselves, establish a causal comparison between groups. A broader interpretation of safety would require details beyond the posted counts.
16. What the Result Does, and Does Not, Mean
The registry’s primary result is a statistically clear difference between the groups on the 10-hour time-weighted pain-intensity-difference outcome. The sponsor’s ANOVA reports a least-squares mean difference of 25.241, a 95% confidence interval from 19.669 to 30.813, and p < 0.001. These statistics describe the estimated group contrast and its uncertainty under the reported analysis.
That finding is specific to SPID 0-10, which combines repeated assessments into a weighted summary. It is not a direct comparison of pain ratings at one time point, and it does not reveal the detailed trajectory of ratings across the full assessment period. Individual responses may vary, and the group mean difference does not indicate what any particular participant experienced. Time-specific results are not reported in the registry record.
Statistical significance does not establish clinical importance. The registry does not provide a threshold for a clinically meaningful difference on the SPID scale, so the numerical estimate cannot be judged against such a threshold from this record. The p-value is also not a measure of the probability that the treatment is effective or ineffective. It summarizes evidence relative to a statistical null model under the analysis assumptions.
The result should not be generalized beyond what the study measured. The trial was single-center, phase 2, and evaluated a single dose in postoperative dental pain. The primary timeframe was 10 hours. The posted primary result does not determine outcomes with repeated dosing, longer follow-up, other kinds of pain, or other populations. The study summary mentions a pharmacokinetic subgroup and the registry lists secondary outcomes, but their numerical results are not reported in the registry record.
The safety counts are likewise limited. No serious adverse events were reported in the listed groups, but these counts do not establish absence of risk. The other adverse event counts are descriptive, and the record does not provide enough detail to interpret event types or compare their causes. The statistical result and the safety record should therefore be read as evidence about the measured outcomes in this trial, not as a complete assessment of every potential benefit or harm.
17. Why This Trial Matters Statistically
This trial illustrates how a clinical outcome can be summarized across repeated measurements. Rather than choosing a single rating time, the primary endpoint combines pain-intensity-difference scores from baseline using a stated weighting scheme. This makes the outcome a continuous summary over a defined period and allows a between-group difference to be estimated. The trade-off is that a single summary can conceal the shape of the time course.
It also illustrates the distinction between a raw group summary and a model-based comparison. The registry reports an ANOVA least-squares mean difference, while a separate unadjusted calculation from posted summary statistics produces a similar central estimate but a different confidence interval. Understanding which estimate comes from the sponsor’s analysis, and which is a re-calculation, is important when interpreting registry results.
The record also demonstrates why statistical significance and clinical meaning are separate questions. The primary p-value is < 0.001 and the reported confidence interval is entirely above zero, but the registry does not state a clinically important difference threshold for the endpoint. Without that context, the statistics characterize the evidence and precision of the group contrast but do not settle its practical importance.
Finally, the trial record shows the value of identifying what is not documented. The primary result is reported, but details on the full analysis plan, missing-data handling, multiplicity, and original sample-size justification are not reported in the registry record. Those omissions matter for judging reproducibility and the scope of inference. A careful reading separates the reported primary finding from unanswered questions about secondary outcomes, safety detail, and generalizability.
18. 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 registry describes a single-center phase 2 study with a single dose and a 10-hour primary outcome. Those design features limit how far the result can be generalized to other settings, populations, dosing schedules, or longer periods. The registry record does not provide information about participant characteristics beyond the postoperative dental pain context, so the composition of the study population cannot be described in greater detail.
The primary endpoint compresses repeated measurements into a weighted sum. This is useful for a single comparison over time, but it does not show the pattern of group differences at each assessment. The registry record does not report the component time-specific results or define a threshold for clinical importance on the SPID scale. As a result, neither the time course nor the practical meaning of the point estimate can be fully evaluated from the primary result alone.
Several analytic details are not reported in the registry record: the full ANOVA specification, randomization generation and concealment procedures, missing-data methods, multiplicity handling, interim analyses, and the trial’s original sample-size justification. The record identifies the primary analysis population as ITT, but does not explain how missing endpoint data, if any, were handled. These gaps make it difficult to assess robustness to alternative assumptions or reproduce the analysis independently.
Numerical results for the listed secondary outcomes and the planned pharmacokinetic subgroup are not reported in the registry record. Safety reporting includes serious and other adverse event counts, but detailed event terms and the deaths field are not reported in the registry record. These limits mean that the primary statistical result should not be treated as a complete account of all outcomes the study intended to assess.
19. Related Tutorials
20. Related Statistical Calculators
21. Sources
- ClinicalTrials.gov: Study of Long-Acting Acetaminophen in Postoperative Dental Pain — NCT01960114.
- Registry record last updated 2015-07-10; status last verified 2015-06.
- Results first posted 2015-06-10.
- 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.
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22. Record Summary
NCT01960114 is a completed phase 2, randomized, parallel-group, placebo-controlled study of single-dose extended-release acetaminophen in postoperative dental pain following third molar extraction(s). It was conducted at a single center and lists quadruple masking; the official title describes the study as double-blind. The recorded start was 2013-10 and primary completion was 2014-04.
The primary outcome was SPID 0-10 over 10 hours, based on repeated pain ratings from baseline. The registry reports an ANOVA least-squares mean difference of 25.241, with a 95% confidence interval from 19.669 to 30.813 and p < 0.001. The study summary also describes secondary outcomes, safety evaluation, and pharmacokinetics in a subgroup, but numerical results for the secondary outcomes and pharmacokinetic evaluation are not reported in the registry record.