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 Cranial Blocks for Postoperative Anesthesia (NCT04749797), a randomized phase 4 study. The primary outcome is Visual Analogue Scale.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT04749797 |
| Phase | Phase 4 |
| Condition | Craniotomy Surgery |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Double |
| Enrollment | 11 |
| Arms in the primary outcome | 3 |
| Lead sponsor | University of Pennsylvania |
| Results posted | Yes |
2. Clinical Question
Population
People undergoing craniotomy surgery. The registry record describes the study as comparing approaches to postoperative pain and opioid use in patients receiving craniotomies. It does not provide further eligibility details or a description of the enrolled participants.
Intervention
A cranial block using bupivacaine or liposomal bupivacaine, alongside standard care as described in the registry summary. The arm descriptions name the nerve branches intended for block; parts of those descriptions are incomplete in the registry record.
Comparator
A saline cranial block. The registry summary frames the comparison as standard care versus standard care plus bupivacaine or liposomal bupivacaine. The saline arm description also states that saline was administered as a cranial block, so the record does not present the comparator simply as no block.
Primary question
How did the reported average Visual Analogue Scale pain scores compare across the three groups during admission? The registry record also describes postoperative opioid usage as part of the study’s topic, but posted primary results concern pain scores. Opioid-use results are not reported in the registry record.
The study, NCT04749797, is titled Cranial Blocks for Postoperative Anesthesia. It was randomized, double masked, and parallel-group, with an enrollment of 11. The posted primary endpoint is a mean pain score for each group, based on multiple scores collected over multiple hours during admission. The reported group means are descriptive summaries; the record does not report a statistical test or an adjusted comparison between groups. The question is therefore about the observed pain-score summaries, not whether one approach has been shown to cause a better outcome.
3. Trial Design
NCT04749797, Cranial Blocks for Postoperative Anesthesia, is recorded as a phase 4, randomized, double-masked, parallel-group study sponsored by the University of Pennsylvania. Its enrollment is listed as 11. The registry record gives a start date of 2020-09-02 and a primary completion date of 2021-07-20, and lists the study status as terminated. The primary endpoint timeframe notes that the study was terminated prior to completion.
The listed arms are Bupivacaine, Saline Group, and Liposomal Bupivacaine. The saline arm description says the surgeon administered injectable saline as a cranial block. The other arm descriptions name bupivacaine or liposomal bupivacaine as the block solution. The registry summary describes the broad comparison as standard care against standard care plus one of those drugs. The available arm descriptions are truncated, so some procedural details are not reported in the registry record.
For the primary pain outcome, the posted arm summaries include 4 participants for Bupivacaine, 2 for Saline Group, and 4 for Liposomal Bupivacaine. These are the counts attached to the posted endpoint summaries; adverse-event counts use separate at-risk denominators. The record does not report details about the randomization sequence, allocation concealment, how masking was maintained, or the roles kept masked.
The registry record does not report a protocol-based sample-size justification, planned interim analyses, or a detailed statistical analysis plan. It lists two outcome measures and one posted secondary outcome entry, whose title is incomplete. The posted results should therefore be read as a small set of descriptive endpoint and safety summaries rather than as a complete account of all planned 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
| Stage | Saline Group | Bupivacaine | Liposomal Bupivacaine |
|---|---|---|---|
| STARTED | 3 | 4 | 4 |
| COMPLETED | 2 | 4 | 4 |
| NOT COMPLETED | 1 | 0 | 0 |
Reasons for not completing this period:
| Reason | Saline Group | Bupivacaine | Liposomal Bupivacaine |
|---|---|---|---|
| Did not meet I/E criteria after surgery | 1 | 0 | 0 |
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 | Saline Group | Bupivacaine | Liposomal Bupivacaine | Total |
|---|---|---|---|---|---|
| Participants analysed | 3 | 4 | 4 | 11 | |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 2 | 2 | 3 | 7 |
| Age, Categorical: >=65 years | Participants | 1 | 2 | 1 | 4 |
| Sex: Female, Male: Female | Participants | 2 | 2 | 2 | 6 |
| Sex: Female, Male: Male | Participants | 1 | 2 | 2 | 5 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 0 | 1 | 0 | 1 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 3 | 3 | 4 | 10 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Asian | Participants | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 1 | 0 | 0 | 1 |
| Race (NIH/OMB): White | Participants | 2 | 4 | 4 | 10 |
| Race (NIH/OMB): More than one race | Participants | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 | 0 |
6. Primary Endpoint
The registry lists the primary outcome as Visual Analogue Scale, measured over 10 months (study terminated prior to completion).
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Full Range |
| Unit | score on a scale |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is the Visual Analogue Scale (VAS), a participant-reported measure of pain severity. The registry describes a horizontal line with endpoints labeled 0 and 10: 0 represents no pain and 10 represents extreme pain. Participants indicate a number that best represents their pain, and that number is recorded. A VAS is used to turn a subjective experience into a numeric measure that can be summarized across participants and compared descriptively between groups.
The registry record says each participant reported several pain scores over multiple hours. It describes the arm-level averages as representing the summation of pain scores reported throughout admission. The reported group means are 4.5 for Bupivacaine, 3.0 for Saline Group, and 4.25 for Liposomal Bupivacaine. The listed full range for each group is 0 to 10.
These summaries do not show each person’s scores, how scores changed over time, or how individual observations varied around the group mean. The record does not report a standard deviation, confidence interval, or inferential comparison for this endpoint. The timeframe is listed as 10 months, with a note that the study was terminated prior to completion. How the multiple scores were combined for each participant before the group mean was calculated is not reported in the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The posted primary outcome consists of three group means: 4.5 in the Bupivacaine group, 3.0 in the Saline Group, and 4.25 in the Liposomal Bupivacaine group. The registry reports a full range of 0 to 10 for each group. These values describe the endpoint summaries as posted; they do not establish whether the groups differ beyond the observed summaries. No test statistic, p-value, confidence interval, or adjusted treatment comparison is reported in the registry record.
Each mean represents multiple pain scores collected over multiple hours during admission, according to the endpoint description. It is not an estimate from a single pain assessment at one specified moment. The record does not state how each participant’s repeated scores were combined before calculating the group mean, so the summaries cannot reveal the time course of pain or whether patterns differed at particular hours.
The endpoint counts are small: 4 participants for Bupivacaine, 2 for Saline Group, and 4 for Liposomal Bupivacaine. With these counts, each participant’s experience may have substantial influence on the group summary. The full-range values alone do not show how observations were distributed within each group. A range spanning the scale endpoints does not indicate how many participants reported values near either endpoint, nor does it quantify typical variation around the mean.
The registry describes the study as terminated before completion. The record does not explain the reason for termination or state whether recruitment, follow-up, or outcome collection ended as planned. It is therefore not possible to determine from the posted outcome summaries how the incomplete study status affected the results. The enrollment of 11 also does not establish that the planned recruitment target was reached; that target and its justification are not reported in the registry record.
The study summary mentions postoperative opioid usage, but the posted primary results are VAS pain-score means. Opioid-use results are not reported in the registry record. A secondary outcome entry is present for length of stay, but its title is incomplete, and no secondary analysis results are provided. The posted information consequently does not permit a broad assessment of all outcomes mentioned in the study description.
In general, a confidence interval describes the uncertainty around an estimate under a specified statistical method. No confidence intervals are posted for these means. In general, a statistical test addresses whether observed differences are compatible with a specified null hypothesis, but no test results are reported. The means can be described as the observed group summaries, while claims about precision, statistical evidence, or causal effects would go beyond the analyses reported.
9. Statistical Methods Explained
The registry record identifies a randomized, double-masked, parallel-group design. Randomization is a method intended to assign participants to groups by chance, while masking is intended to limit the influence of knowledge about assignment on study conduct or assessment. Those general purposes do not establish how well the methods were implemented in this study. Details of the randomization process, allocation concealment, and masking procedures are not reported in the registry record.
What does the mean summarize?
A mean is a measure of the average of a set of numeric observations. For this endpoint, the posted means are 4.5 for Bupivacaine, 3.0 for Saline Group, and 4.25 for Liposomal Bupivacaine. The endpoint description says each participant reported several pain scores over multiple hours, and describes the group averages as representing scores reported throughout admission. The record does not specify whether the participant-level summary was an average, a sum, or another quantity before group means were formed. That detail matters because different ways of reducing repeated observations can give different interpretations to a group mean.
In general, repeated measurements from the same participant are related rather than independent. An analysis that uses all repeated scores must account for that within-participant relationship, or otherwise define a participant-level summary before comparing groups. The registry record does not report which approach was used. The posted endpoint summaries therefore do not provide enough information to reconstruct a repeated-measures analysis.
What does the full range communicate?
The registry lists the full range as 0 to 10 for each group, matching the stated endpoints of the VAS. In general, a range identifies the lowest and highest recorded values, but does not describe how observations are distributed between those extremes. It is not a measure of the uncertainty around the mean. The record does not report another measure of spread, such as a standard deviation or interquartile range, for the primary endpoint.
Because the group counts are 4, 2, and 4, the means summarize few participants. In general, small groups tend to produce less stable estimates, and individual observations can have a strong influence on a mean. The posted record does not include participant-level values, so readers cannot assess how much the summaries depend on any one observation. Nor can the ranges alone establish that pain experiences were similar or different across participants.
What would a treatment comparison require?
A comparison of group means can be expressed as an estimated contrast, accompanied by an uncertainty measure and, when appropriate, a test under a stated statistical model. No such inferential comparison is reported in the registry record. The displayed means should not be treated as proof of a statistically reliable difference. In general, a confidence interval would communicate the precision of an estimated contrast, while a p-value would summarize compatibility with a specified null model. Neither can be inferred from the means and ranges alone without additional assumptions and data.
General statistical methods must also match the design and outcome. For a repeated pain measure, choices include defining a participant-level summary or modeling repeated observations over time. The choice can affect the estimand, meaning the specific quantity the analysis aims to estimate. The record does not report a primary estimand beyond naming the VAS endpoint, nor does it explain how multiple scores were handled analytically.
How should planning illustrations be read?
General sample-size calculations estimate how many participants might be needed under stated assumptions to detect a specified effect with a chosen error rate and power. Any planning illustration based on the observed effect is not an observed-power analysis and does not show that the completed study had adequate power. The stated assumptions for planning illustrations are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is a stated fraction of the observed effect. These are planning assumptions, not a reported description of the original trial’s design. A trial-specific sample-size justification is not reported in the registry record.
In general, over-dispersion means that observed variability is greater than a model assumes. If present, a model that underestimates variability can produce uncertainty estimates that are too small. The posted endpoint does not include enough distributional detail to assess over-dispersion or select a particular model. More broadly, the registry record does not report a complete statistical analysis plan, model specification, covariate adjustment strategy, or sensitivity analyses. Those omissions limit the ability to evaluate how the posted descriptive summaries relate to any planned inferential analysis.
10. Multiplicity, Missing Data and Analysis Populations
The study record lists a primary VAS endpoint and two outcome measures in total. It also lists one secondary outcome entry, titled Length of Stay (ICU and, with the title incomplete. Results for that secondary outcome are not reported in the registry record. The study description mentions postoperative opioid usage, but opioid-use results are not reported in the registry record either.
When several outcomes, time points, or group comparisons are examined, the chance of finding an apparently notable result by chance can increase. In general, multiplicity procedures or a prespecified hierarchy can help define how to interpret multiple tests. A multiplicity strategy, planned outcome hierarchy, or list of planned comparisons is not reported in the registry record. No inferential analyses are posted, so there are no reported p-values for which multiplicity adjustment can be assessed.
The primary endpoint description reports several pain scores from each participant over multiple hours, but does not explain how those repeated observations were combined or analyzed. The number and timing of assessments are not reported in the registry record. A plan for handling missing observations, imputation methods, or sensitivity analyses is also not reported in the registry record.
The record does not describe analysis populations, such as whether results were based on all randomized participants or only participants with recorded outcomes. The primary endpoint summaries have participant counts of 4, 2, and 4 across the three arms, while the adverse-event section gives different at-risk counts for the saline group. The record does not explain the difference between those counts. This limits interpretation of which participants contributed to each set of results and how incomplete follow-up was handled.
11. 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 |
|---|---|---|---|
| Saline Group | 1 | 3 | 33.3% |
| Bupivacaine | 1 | 4 | 25.0% |
| Liposomal Bupivacaine | 0 | 4 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Saline Group | 1 of 3 |
| Bupivacaine | 0 of 4 |
| Liposomal Bupivacaine | 0 of 4 |
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 |
|---|---|
| Saline Group | 0 of 3 |
| Bupivacaine | 0 of 4 |
| Liposomal Bupivacaine | 0 of 4 |
Most frequent serious adverse event terms
| Event term | Organ system | Saline Group | Bupivacaine | Liposomal Bupivacaine |
|---|---|---|---|---|
| Edema, cerebral | Nervous system disorders | 1 of 3 | 0 of 4 | 0 of 4 |
| Transient ischemic attack | Nervous system disorders | 0 of 3 | 1 of 4 | 0 of 4 |
Serious events with the highest arm-level rate: edema, cerebral (33.3%), transient ischemic attack (25.0%).
The registry reports serious adverse events for separate at-risk groups. In the Saline Group, 1 of 3 participants at risk had a serious adverse event; the record also lists 1 death. In the Bupivacaine group, 1 of 4 participants at risk had a serious adverse event, and no deaths are listed. In the Liposomal Bupivacaine group, 0 of 4 participants at risk had a serious adverse event, and no deaths are listed. No other adverse events are listed as affecting participants in these group summaries.
The registry lists cerebral edema at 33.3% and transient ischemic attack at 25.0% among the top serious-event terms. It does not provide enough information in the posted record to determine the event counts behind these percentages, their allocation to particular arms, or their relationship to the listed serious-event totals. A death is listed for the saline group, but its cause and relationship to study treatment are not reported in the registry record.
These figures are descriptive counts from small at-risk groups. They should not be read as precise estimates of comparative safety, and the record does not report a statistical comparison of serious adverse events. Differences in at-risk counts and endpoint counts are not explained. The adverse-event information also does not establish that an event was caused by a block or by a study drug; attribution details are not reported in the registry record.
12. What the Result Does, and Does Not, Mean
The posted results establish that the registry contains group-level VAS means for three arms and lists the endpoint range as 0 to 10 in each. The means are 4.5 for Bupivacaine, 3.0 for Saline Group, and 4.25 for Liposomal Bupivacaine. They summarize the pain scores as described in the registry, collected over multiple hours during admission. The record also reports serious adverse-event counts and one listed death in the saline group.
Those summaries do not establish that any one group had a statistically reliable advantage. No inferential analysis, confidence interval, or adjusted comparison is reported in the registry record. The means do not show how scores changed across time, how individual participants responded, or the uncertainty around each group’s estimate. The small endpoint counts make those missing details especially relevant to interpretation.
The study’s status is terminated, and the primary endpoint timeframe notes termination before completion. The registry record does not explain why the study ended or whether the outcome summaries represent all participants originally intended for analysis. The record also does not report results for opioid usage, although that topic appears in the study description, or provide complete results for the listed secondary outcome.
In general, a randomized design can support causal comparisons when assignment, follow-up, outcome measurement, and analysis are appropriately conducted. The posted record does not provide enough detail to evaluate all of those elements, and its descriptive means alone do not establish a causal effect. The results should be read as limited registry summaries from a small, terminated study, not as a definitive assessment of postoperative pain or opioid use.
13. Why This Trial Matters Statistically
This trial is statistically informative as an example of how registry results can be much less complete than the design label alone might suggest. The record identifies a randomized, double-masked study, but reports descriptive means without an inferential analysis. A study design can define a framework for comparison, yet readers still need information about outcome handling, missing data, analysis populations, and uncertainty to judge the strength of the evidence.
The endpoint uses repeated pain scores collected over multiple hours, while the posted result is one mean per arm. That condensation can make results easy to scan, but it leaves important questions unanswered: how were repeated observations combined, how much did scores vary, and did pain patterns change over time? These are general concerns when repeated measurements are reduced to a single summary. The registry record does not report the details needed to answer them.
The small endpoint group counts and terminated status also make clear why observed summaries should not be confused with a completed, adequately powered comparison. A planning illustration based on an observed effect is a design exercise, not evidence that the trial had adequate power. The registry record does not report the original sample-size rationale, a completed analysis plan, or inferential results.
Finally, the study description raises questions about both pain and opioid usage, but the posted results cover only VAS means and serious adverse events. Incomplete outcome reporting can prevent a reader from assessing the full set of questions that motivated a study. The record’s limitations are therefore not only about precision; they also concern which outcomes and analyses are available for interpretation.
14. 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 outcome summaries are based on 4 participants in the Bupivacaine group, 2 in the Saline Group, and 4 in the Liposomal Bupivacaine group. The registry does not provide participant-level observations or a measure of spread beyond the reported full range. This limits assessment of variability, unusual observations, and the stability of each mean.
The study is marked terminated, and the primary endpoint timeframe states that termination occurred prior to completion. The reason for termination, whether enrollment or follow-up stopped early, and the consequences for outcome collection are not reported in the registry record. The listed enrollment is 11, while the endpoint counts cover fewer participants; the record does not explain this.
The endpoint description refers to repeated pain scores over multiple hours, but the method used to combine those scores is not reported in the registry record. Nor does the record report the timing of individual assessments, missing-data handling, or the analysis population. These omissions limit interpretation of what the group means represent and whether the summaries include all randomized participants.
The record provides no inferential comparison for the primary endpoint. It does not report confidence intervals, p-values, covariate adjustments, or sensitivity analyses. The secondary outcome entry is incomplete, and results for opioid usage are not reported in the registry record. The adverse-event section uses at-risk counts that differ from the endpoint counts, without an explanation, and does not report event attribution or the cause of the listed death. These gaps prevent a complete assessment of efficacy-related outcomes and safety.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Cranial Blocks for Postoperative Anesthesia — NCT04749797.
- Registry record last updated 2023-09-13; status last verified 2023-08.
- Results first posted 2023-09-13.
- 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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18. Record Summary
NCT04749797 is a phase 4, randomized, double-masked, parallel-group study titled Cranial Blocks for Postoperative Anesthesia and sponsored by the University of Pennsylvania. The registry lists enrollment of 11, a start date of 2020-09-02, primary completion on 2021-07-20, and status as terminated.
The three listed arms are Bupivacaine, Saline Group, and Liposomal Bupivacaine. The primary endpoint is a mean VAS pain score based on multiple reports over multiple hours during admission. Posted means are 4.5, 3.0, and 4.25, respectively; each group’s reported full range is 0 to 10. No inferential analyses are posted.
The registry also lists serious adverse-event counts and a death in the saline group. It does not provide complete results for opioid usage or the incomplete secondary outcome entry. The reason for termination, a detailed statistical analysis plan, and information about missing data are not reported in the registry record.