Intranasal Ketorolac for Postsurgical Pain in Dental Implant Patients: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Intranasal Ketorolac for Postsurgical Pain in Dental Implant Patients (NCT01490931), a na phase 4 study. The primary outcome is Comparison of Pain Intensity Scores at 20 Minutes With the Baseline Pain Intensity Score During the Initial 6-hour Evaluation Period..

2. Clinical Question

The registry describes a study of postoperative pain in dental implant patients, a setting the brief summary says had not been evaluated in analgesic studies at the time of the study description. The intervention was a nasal spray rather than an oral or injected study treatment. Participants were expected to record pain intensity and pain relief after taking the dose, with assessments concentrated early after dosing and continuing through the initial evaluation period.

The primary question is within-participant in structure: it concerns the pain score at a post-dose time point in relation to a baseline score. That is different from a randomized comparison of ketorolac with another treatment or with placebo. Because the design is single-group and open-label, the record does not provide a concurrent group to separate changes associated with dosing from changes that could occur over time or through other influences. The registry record does not report a numerical estimate of the primary comparison, its uncertainty, or a test of statistical significance.

The study also describes a later multi-dose phase and lists secondary questions about pain relief, reaching a pain threshold, and patterns of dosing. Those questions broaden the descriptive scope, but numerical findings for them are not reported in the registry record. The available information therefore defines the clinical question and measurement plan more clearly than it establishes the magnitude or precision of any observed change.

3. Trial Design

The registry classifies NCT01490931 as a completed Phase 4 study with a single-group model. Its title identifies it as an open-label pilot evaluating single-dose and multi-dose intranasal ketorolac in dental implant surgery patients with postoperative pain. Masking is listed as none, and allocation is listed as not applicable. These features mean that the record does not describe randomized assignment or blinded outcome assessment.

The registry lists enrollment as 28. The brief description, however, says the pilot would evaluate treatment in 25 patients, and the adverse-event listing uses 25 as the number at risk. The record does not explain the relationship among those figures, so they should not be treated as interchangeable measures of the population contributing to each analysis. The number included in the primary efficacy analysis is not reported in the registry record.

The planned first phase began when postoperative pain reached at least moderate severity. The brief description specifies one spray in each nostril for a total dose of 31.5 mg. Pain intensity and pain relief were to be recorded frequently during the initial evaluation, including at 20 minutes and later time points through 6 hours. The primary outcome title identifies a comparison of the 20-minute pain intensity score with baseline during this initial evaluation period.

After the initial evaluation, participants were to transition to a multi-dose phase. The description says dosing would follow the package insert, up to 4 times per day for 5 days, with records of dose timing, daily overall efficacy, side effects, and rescue medication use. This describes the plan; the registry record does not report actual adherence, the number of doses taken, or how many participants contributed data at each time point.

The study start is listed as 2011-11 and primary completion as 2012-08. Its status is completed. A protocol-level statistical analysis plan, sample-size justification, and details of interim monitoring are not reported in the registry record.

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: Subjects not experiencing moderate pain (at least 40 mm on the pain intensity VAS and moderate or severe pain on the 4-point categorical scale) within 4 hours of surgery were not dosed with ketorolac. Of the 28 enrolled subjects, 25 (89%) achieved at least moderate pain and were dosed.

Overall Study

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

Population: Pilot Study. No power analysis performed.

6. Primary Endpoint

The registry lists the primary outcome as Comparison of Pain Intensity Scores at 20 Minutes With the Baseline Pain Intensity Score During the Initial 6-hour Evaluation Period., measured over 20 minutes post dose.

The primary endpoint is mean pain intensity at 20 minutes after the dose, compared with the baseline pain intensity score during the initial 6-hour evaluation period. Pain intensity was to be recorded by participants using a standard 100 mm visual analog scale. The registry describes the outcome as a continuous measure and identifies its summary as a mean with standard error.

A visual analog scale represents pain intensity along a bounded line, allowing the measurement to retain gradations rather than reducing responses to a small set of categories. In general, analyzing a continuous score can preserve information about differences among participants and changes in scores over time. The baseline comparison gives context for the post-dose score, although it is not equivalent to a comparison against a separate control group.

The early assessment time is relevant to the study’s stated interest in pain relief after dosing. Repeated assessments were planned during the initial evaluation, while the designated primary measure focuses on the 20-minute score relative to baseline. The registry record does not report the observed mean at either point, the estimated change, the standard error, a confidence interval, or a p-value. It is therefore not possible from the record information to describe the size, direction, or precision of the primary outcome result.

The endpoint title calls this a comparison of scores, but the numerical analysis details are not reported in the registry record. In particular, the record does not specify whether the analysis used paired observations, how incomplete score records were handled, or which participants were included. Such details affect interpretation of a mean comparison and its uncertainty.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The record describes a continuous primary outcome: pain intensity on a 100 mm visual analog scale. A continuous outcome can take a range of values, which allows a summary such as the mean to convey the average score across observations. The mean is useful for describing the center of a distribution, but it does not show how widely individual scores vary or whether the distribution is unusually skewed. The registry identifies the primary summary as a mean with standard error. It does not report the observed mean or standard error, so neither the outcome level nor the precision of that mean can be assessed from the record.

Standard error describes the uncertainty in an estimated mean due to sampling variation under the analysis assumptions. It is not the same as the spread of individual participant scores. A confidence interval uses an estimate and its standard error, together with a specified confidence procedure, to communicate a range of values compatible with the data under that procedure. General explanation: narrower intervals indicate greater precision, while wider intervals indicate less precision. No confidence interval is reported for the primary outcome in the registry record, and no interval can be reconstructed without the relevant numerical results and analysis details.

The primary outcome concerns a score at 20 minutes relative to baseline. In general, measurements from the same participant at different times are related rather than independent. A paired analysis uses that relationship when estimating within-participant change; an analysis that treats the measurements as unrelated would answer a different statistical question and could misstate uncertainty. The record does not specify the analysis model or confirm how participant-level pairing was handled. It also does not report the number with complete measurements at both time points.

The single-group design means the primary comparison is not a randomized treatment-versus-control contrast. A baseline score can provide a reference for change, but it does not account for all changes over time that could have occurred without treatment. In general, randomized concurrent controls help distinguish treatment differences from time trends and other influences shared or unshared across groups. This study’s registry record identifies no such comparator. Therefore, even if a numerical pre-post result were available, it would describe change in the observed group rather than a controlled between-group treatment effect.

The open-label status is another design feature relevant to interpretation. Participants knew the treatment being used, according to the absence of masking. General explanation: when an outcome is self-reported, awareness of treatment may influence expectations or reporting. That possibility does not show that reporting was biased in this study, and the record does not quantify any such influence. A validated diary is mentioned in the study description, but use of a validated measure does not remove the design’s lack of masking or create a control group.

Repeated observations were planned during the initial evaluation, and the registry lists several additional outcomes, including the median onset of first perceptible pain relief, the percentage reaching a visual analog scale score of at least 40 mm within 5 hours after surgery, the most frequent number of dosing days, and the median onset of meaningful pain relief. These measures answer different questions and may require different statistical summaries. A time-to-event outcome, for example, concerns the timing of an event and may be summarized using methods that account for participants who do not experience the event during observation. A threshold outcome classifies whether a stated criterion was reached. A count or dosing-duration outcome describes a different aspect of treatment use. These are general distinctions; the registry record does not report the numerical results or detailed analysis methods for these outcomes.

The registry lists 13 outcome measures and 9 analyses. Multiple outcomes or analyses can create multiple opportunities to observe apparently notable results. General explanation: multiplicity concerns the interpretation of a collection of statistical tests or estimates, rather than the meaning of a single test in isolation. Prespecifying a primary endpoint and analysis can help clarify which result is central; adjustment procedures may be used in some settings to address multiple testing. The record identifies a primary outcome by title, but does not report the complete analysis plan or whether any multiplicity procedure was used. It would therefore be inappropriate to assume either that adjustments were made or that none were made.

The posted sample-size assumptions describe an illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. Those assumptions do not match the registered single-group design as described, and the record does not report the calculated sample-size values or the observed effect needed to interpret such an illustration. Any sample-size illustration is a planning exercise, not observed power and not evidence that the study had a particular probability of detecting an effect. The trial’s own sample-size justification is not reported in the registry record.

There is no numerical primary outcome estimate in the registry record from which to reproduce or check a calculation. No recalculated effect estimate or precision measure is therefore described. The statistical methods information that is available identifies the type of outcome and its intended summary, while important implementation details—including the analysis population, model, missing-data approach, and handling of repeated observations—are not reported in the registry record.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("Ketorolac Nasal Spray 31.5 mg (SPRIX)")
n   <- c(25)
m   <- c(14.3)
sp  <- c(4.1)
sd  <- sp * sqrt(n)      # standard errors converted to SDs
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  Ketorolac Nasal Spray 31.5 mg (SPRIX)  25  14.300  20.500  5.838  22.762

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 13 outcome measures and 9 analyses. The primary endpoint is identified as the mean pain intensity score at 20 minutes compared with baseline during the initial 6-hour evaluation period. The record also lists secondary outcomes concerning the onset of pain relief, reaching a specified pain intensity threshold, and duration of analgesic dosing. These outcomes address distinct aspects of pain and use, so they should not be treated as interchangeable evidence about a single endpoint.

When a study evaluates multiple outcomes or performs multiple analyses, interpretation can be affected by multiplicity. In general, the more statistical questions considered, the more important it is to distinguish prespecified primary analyses from exploratory analyses and to understand whether any adjustment or hierarchical testing strategy was planned. The registry record does not report a complete statistical analysis plan or whether multiplicity was addressed. It is therefore not possible to determine how the 9 analyses relate to the 13 outcomes or whether the reported analysis hierarchy, if any, was prespecified.

Missing-data methods and analysis populations are also not reported in the registry record. The record does not state how participants with an absent baseline or follow-up score were handled, whether all enrolled participants were included in efficacy analyses, or how missing diary entries were treated. General explanation: excluding observations with missing measurements can change the set of participants represented by an estimate, while some statistical methods make assumptions to use incomplete records. The appropriateness of any method depends on the pattern and reasons for missingness, which are not reported.

The listed enrollment is 28, the brief description refers to 25 patients, and the adverse-event listing uses 25 at risk. The record does not explain these figures or identify the primary analysis denominator. This uncertainty makes it especially important not to infer an analysis population from enrollment alone.

12. 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 adverse-event listing reports 0 serious events among 25 participants at risk in the ketorolac nasal spray group. It lists 14 participants with other adverse events among the same number at risk. These are registry counts for the listed group; they do not provide event rates calculated from other denominators, and no such rates are stated.

Serious and other adverse events are separate categories in the listing. The absence of a reported serious event in this group does not establish that the treatment is free of risk, nor does the count of other events establish that the treatment caused them. The record does not provide event-level details for the other adverse events in the registry record. It also does not identify serious event terms in the listing.

Deaths are recorded as null, so death information is not reported in the registry record. The relationship between the 25 participants at risk and the enrollment listing of 28 is not explained. As a result, the safety counts should be interpreted with the stated denominator and not assumed to cover every enrolled participant. The registry record also does not provide a comparison group, which limits the ability to compare these safety counts with an untreated or alternative-treatment group.

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

The study record documents a completed, open-label, single-group pilot of intranasal ketorolac for postoperative pain in dental implant patients. It identifies the intervention, the planned single-dose and multi-dose phases, and a primary measure based on pain intensity at 20 minutes relative to baseline. It also reports adverse-event counts for the listed treatment group. These details describe what the study was set up to examine and the safety counts entered in the registry.

The record does not report the numerical primary efficacy result. Without the observed scores, an estimated change, and a measure of uncertainty, it is not possible to state how large or precise the primary comparison was. Completion status does not substitute for an outcome estimate, and the stated study objective is not a result. The secondary outcome titles likewise do not establish that any particular pain-relief threshold was reached or that a specific dosing pattern occurred.

The design also does not support a controlled causal comparison. Because there was no concurrent comparator and masking was absent, a change from baseline, if reported, would remain a within-group observation. General interpretation: such a change can be consistent with an effect of treatment, but other time-related, contextual, and reporting influences cannot be separated from treatment using a single-group pre-post comparison alone.

The safety listing reports 0 serious events and 14 other adverse events among 25 at risk. Those counts describe the registered group and should not be read as comparative evidence or as a complete assessment of risk. The record does not explain the difference between the enrollment listing and the safety denominator, and death information is not reported.

In statistical terms, the strongest conclusions available are about the registered design, outcome definitions, and recorded safety counts. The record does not support a claim about the magnitude of pain-score change, its statistical significance, or its precision. Nor does it establish whether the findings generalize beyond the study population. Those questions require numerical efficacy results, analysis details, and an appropriate comparative design.

14. Why This Trial Matters Statistically

This trial matters statistically because it illustrates the distinction between registering a clinical question and reporting evidence that answers it. The record describes a specific measurement plan: participant-reported pain intensity on a visual analog scale, with a primary comparison at 20 minutes after dosing relative to baseline. Yet the numerical primary outcome result is not reported in the registry record. A clearly named endpoint cannot by itself show the observed effect or how precisely it was estimated.

The study also demonstrates why design labels affect interpretation. A single-group, open-label pilot can describe outcomes after treatment and may offer useful descriptive information about feasibility or measurement. It does not provide the same counterfactual comparison as a randomized controlled study. General explanation: a control group can help distinguish treatment-associated differences from changes that would have occurred over time, while masking can reduce some influences of treatment awareness on reporting. Neither feature is identified for this trial.

The record includes multiple outcomes and analyses, along with a staged dosing description. This makes transparent reporting of the analysis population, timing, missing-data handling, and prespecified outcome hierarchy important. Those details help readers distinguish the main question from additional analyses and assess whether the reported estimates correspond to the planned measurements. They are not reported in the registry record.

Finally, the listed enrollment and safety denominator are not aligned in the information available, and their relationship is unexplained. Clear denominator reporting is essential for understanding who contributed to each result. In this case, the record offers an informative design outline but leaves key efficacy and analysis details unavailable. That is a statistical limitation of the evidence presented, not a conclusion about the treatment itself.

15. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The most important trial-specific limitation in the registry information is the absence of numerical efficacy results. Although the primary endpoint and several secondary outcomes are described, their observed values, effect estimates, uncertainty measures, and significance tests are not reported in the registry record. The direction and magnitude of any change therefore cannot be assessed.

The single-group, open-label design lacks a concurrent comparator and masking. As a general matter, a baseline comparison cannot distinguish treatment-related change from time trends, other postoperative changes, expectations, or reporting influences. This limitation applies even if a pre-post score difference is available; in this record, the numerical difference is not reported.

The registry lists enrollment as 28, while the brief description says 25 patients and the adverse-event listing identifies 25 at risk. The record does not explain the relationship among those figures or report the number included in the primary analysis. It also does not report adherence, actual dosing, completed diary assessments, or the analysis populations. These omissions limit assessment of participant flow and the denominators underlying outcomes.

The registry lists 13 outcome measures and 9 analyses, but does not report a full statistical analysis plan, multiplicity procedures, interim analyses, or missing-data methods. These details are relevant to understanding which findings were primary, how repeated measurements were analyzed, and how incomplete observations affected the estimates. The record also does not provide event-level descriptions for the 14 participants with other adverse events. Death information is not reported in the registry record.

These limitations concern what can be concluded from the registry information. They do not establish that analyses were not performed or that particular outcomes did not occur; the relevant details are simply not reported in the registry record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Intranasal Ketorolac for Postsurgical Pain in Dental Implant Patients — NCT01490931.
• Registry record last updated 2014-05-09; status last verified 2014-04.
• Results first posted 2014-05-09.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

19. Record Summary

NCT01490931 is a completed Phase 4, single-group, open-label pilot of intranasal ketorolac in patients with postoperative pain after dental implant surgery. The registered primary outcome concerns mean pain intensity at 20 minutes after dosing compared with baseline, using a 100 mm visual analog scale during the initial 6-hour evaluation period. The description also includes a multi-dose phase.

The registry lists enrollment as 28. The brief description refers to 25 patients, and the adverse-event listing reports 25 at risk. The relationship among those figures is not reported. The safety listing records 0 serious events and 14 participants with other adverse events; death information is not reported.

Numerical primary and secondary efficacy results, analysis-population details, missing-data methods, and the complete statistical analysis plan are not reported in the registry record. The design and outcome definitions can be described, but the magnitude and precision of the primary efficacy result cannot be assessed from the available registry information.