Baclofen as a Perioperative Analgesic Adjuvant: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Baclofen as a Perioperative Analgesic Adjuvant (NCT03720717), a randomized phase 4 study. The primary outcome is Postoperative Opioid Requirements.

2. Clinical Question

The clinical question is about opioid use after surgery, rather than a direct measure of pain intensity. The endpoint describes the amount of opioid used for what the record calls acceptable pain control. It therefore reflects medication consumption under the trial’s perioperative care, not pain relief in isolation. The record does not report additional details about the surgical procedures or other elements of postoperative care.

3. Trial Design

The registry record describes a Phase 4, randomized, double-masked, parallel-group study sponsored by the University of Alabama at Birmingham. It lists 34 participants enrolled. The study began on 2020-10-27, had a primary completion date of 2022-10-28, and is recorded as terminated. The reason for termination is not reported in the registry record.

Participants were stratified by reported preprocedure opioid use into opioid-tolerant and opioid-naive groups. The record defines opioid tolerance as daily opioid use for greater than one month. The opioid-naive definition is minimal preoperative opioid use, with non-daily use and/or use for less than one month. Within these strata, participants received baclofen 10 mg orally or placebo. The pills were given within 30 minutes of operating-room entry.

The posted primary outcome results include four groups. In the opioid-tolerant stratum, the baclofen group had 5 participants and the placebo group had 7. In the opioid-naive stratum, the baclofen group had 12 participants and the placebo group had 10. These are the group sizes reported for the primary outcome. The record does not report the allocation sequence, the method used to conceal allocation, or details of who was masked.

The registry record does not report the reason the study was terminated, whether recruitment stopped as planned, or whether the target enrollment was reached. It also does not report a sample-size justification. These missing design details limit what can be inferred about the intended precision or the circumstances in which the study ended. The reported design features describe how the study was classified, but do not establish that all planned procedures were completed.

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

Analysis population for the primary outcome, as defined in the registry: patients were stratified according to preprocedure opioid use into Opioid Tolerant and Opioid Naive groups based on above stated criteria

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 Postoperative Opioid Requirements, measured over From 0 hours post-operatively to 24 hours post-operatively.

The primary endpoint is postoperative opioid requirement, reported as the total oral morphine equivalent amount used from 0 hours to 24 hours after surgery. The record describes this amount as the opioid requirement for acceptable pain control. It is a continuous measure, and the posted group summaries are means with standard errors.

Opioid consumption is used in this trial as a measure of postoperative analgesic medication use. It gives a common unit for summarizing different opioid amounts as oral morphine equivalents. In general, a continuous endpoint retains information about the magnitude of observed values rather than reducing them to categories. However, consumption alone does not establish how much pain participants experienced, whether pain control was acceptable by a consistent assessment, or how other aspects of recovery differed. Those additional measures are not reported in the registry record.

Results are presented separately for opioid-tolerant and opioid-naive participants. The reported means are 85.5 mg for opioid-tolerant participants assigned baclofen and 96.8 mg for those assigned placebo. Among opioid-naive participants, the means are 69.9 mg for baclofen and 40.4 mg for placebo. These are descriptive group summaries. The registry record does not report confidence intervals or a statistical test for either within-stratum comparison, so the precision of the contrasts is not established by the posted results.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The outcome is continuous: each participant’s opioid requirement is expressed as an oral morphine equivalent amount over the stated postoperative interval. The registry record summarizes each group with a mean and standard error. A mean represents the arithmetic average of the measured values in a group. A standard error describes uncertainty in that estimated average, rather than the range of individual observations. It should not be interpreted as a standard deviation or as an interval containing most participants.

What would an inferential comparison add?

General statistical explanation: a treatment comparison estimates how far apart the outcome distributions, or selected summaries of those distributions, are between groups. An uncertainty interval around that estimate helps show which effect sizes remain compatible with the data under the analysis assumptions. A test may also summarize how compatible the data are with a specified null hypothesis. Neither an interval nor a test is reported for the baclofen-versus-placebo comparisons in this registry record. Means and standard errors by themselves do not supply the full inferential result, particularly when group sizes are small and the individual observations are unavailable.

The record lists zero posted analyses. It also notes that values were missing or not estimable for a two-arm comparison of the continuous endpoint. Accordingly, the available result should be treated as descriptive rather than as a completed test of a treatment hypothesis. The group summaries do not indicate whether an adjusted analysis was planned, which model would have been used, or how the opioid-use strata would have entered that model. Those statistical-plan details are not reported in the registry record.

Why stratification matters

Participants were classified by preprocedure opioid use, and results are listed separately for opioid-tolerant and opioid-naive participants. Stratification can be used to organize randomization or analyses around a characteristic considered relevant to outcomes. General statistical explanation: separate summaries can reveal whether observed patterns look similar across strata, but visual or numerical differences between subgroup summaries do not themselves establish that treatment effects differ. A formal interaction analysis would address whether the treatment contrast varies by stratum. No such analysis is reported in the registry record.

The registry’s arm descriptions mention a plan to initiate pseudo-randomization near the end of the trial to assure balance, but the descriptions are incomplete. The record does not give enough detail to determine how that plan was implemented or whether it affected allocation. The study is classified as randomized, but the exact sequence-generation and allocation procedures are not reported. No assumptions about the randomization method should therefore be made beyond the classification in the record.

Understanding precision and small groups

General statistical explanation: uncertainty tends to be greater when a mean is based on fewer observations, all else being equal. The opioid-tolerant results are based on 5 participants assigned baclofen and 7 assigned placebo; the opioid-naive results are based on 12 and 10. These group sizes are important context for reading the means and standard errors. A small standard error is not by itself evidence of a treatment effect, and a larger standard error does not establish the absence of one. The relevant inferential quantity would be the treatment contrast and its uncertainty, neither of which is posted.

Over-dispersion is a general concern when observed variability is greater than a statistical model assumes. If a model assumes less variability than the data contain, its uncertainty estimates can be too small and its tests can appear more decisive than warranted. The registry record does not report an analysis model or individual observations, so it is not possible to assess whether over-dispersion was relevant or how it was handled. The posted standard errors alone do not settle that question.

What planning calculations can and cannot show

General statistical explanation: sample-size calculations are planning tools that translate an assumed effect, variability, significance level, and allocation scheme into a target number of participants. They are not evidence that an effect was observed, and a calculation based on an observed effect is not observed power. The record describes a planning illustration based on a fraction of the observed effect, with a two-sided significance level of 0.05, equal allocation, and a normal approximation. It also distinguishes participant-per-arm planning for non-time-to-event outcomes from total-event planning for time-to-event outcomes. No numerical planning results are stated in the registry record, and no trial-specific sample-size justification is reported.

These planning assumptions should not be confused with the actual trial design or an inferential result. The posted group sizes are not evidence that the study had adequate precision, and the record does not report a prespecified target effect or variability assumption. Without the sponsor’s analysis, confidence intervals, and relevant planning rationale, the statistical evidence for a treatment difference remains unquantified.

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("Opioid Tolerant - Baclofen", "Opioid Tolerant - Placebo", "Opioid Naive - Baclofen", "Opioid Naive - Placebo")
n   <- c(5, 7, 12, 10)
m   <- c(85.5, 96.8, 69.9, 40.4)
sp  <- c(33.6, 17.1, 10, 11.7)
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  Opioid Tolerant - Baclofen  5  85.500  75.132  -7.789  178.789
CARM  Opioid Tolerant - Placebo  7  96.800  45.242  54.958  138.642
CARM  Opioid Naive - Baclofen  12  69.900  34.641  47.890  91.910
CARM  Opioid Naive - Placebo  10  40.400  36.999  13.933  66.867

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists one primary outcome measure and no posted secondary outcomes. It reports zero posted analyses. A multiplicity plan—how inference would be adjusted when several outcomes, comparisons, time points, or subgroups are examined—is not reported in the registry record. With no inferential analyses posted, there is no reported multiplicity adjustment to assess. The separate results for opioid-tolerant and opioid-naive participants are descriptive; the record does not say whether these strata were prespecified as separate hypotheses or whether a combined treatment effect was planned.

Missing-data methods are not reported in the registry record. The posted primary outcome group sizes total 5 and 7 in the opioid-tolerant arms and 12 and 10 in the opioid-naive arms, but the record does not explain whether these counts include every randomized participant or only those with an observed outcome. It does not report how many participants lacked the outcome, why any measurements might be missing, or how missing observations were handled.

The analysis population is also not reported in the registry record. There is no stated intention-to-treat, per-protocol, or other analysis-set definition, and no account of exclusions after randomization. These details matter because analysis populations and missing-data decisions can affect estimates and their uncertainty. The available group summaries therefore cannot establish which participants contributed to the reported means or whether all randomized participants were included.

12. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

The registry record lists zero serious adverse events and zero deaths in each of the four reported groups. The numbers at risk for serious adverse events were 5 for opioid-tolerant baclofen, 7 for opioid-tolerant placebo, 12 for opioid-naive baclofen, and 10 for opioid-naive placebo. It also lists zero other adverse events in each group, with the same group counts at risk for other adverse events.

These are event counts as reported in the registry. They do not establish that adverse events could not occur or that the treatments have equivalent safety. In general, an observed count of zero in a small group leaves uncertainty about the rate of events that could occur in a broader population. The record does not report event-collection procedures, observation duration for safety, definitions of adverse events, or a comparative safety analysis. No serious adverse-event terms are listed. Interpretation should therefore remain limited to the reported counts and the group sizes, without treating zero observed events as proof of zero risk.

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

The registry record establishes that the study was designed to compare a single oral dose of baclofen 10 mg with placebo and that postoperative opioid requirements were summarized within opioid-use strata. It reports group means and standard errors for the primary endpoint and lists adverse-event counts. These results describe the participants included in the posted summaries.

The record does not establish whether baclofen changed opioid requirements. It does not provide an inferential treatment comparison, confidence intervals, or a statistical test. The numerical pattern differs across the two opioid-use strata, but that pattern cannot establish a treatment-by-stratum interaction. Nor do group means alone describe all individual outcomes or establish the amount of pain participants experienced.

General statistical explanation: an estimate is most informative when accompanied by an account of its uncertainty, the analysis population, and the method used to obtain it. Those elements help distinguish a potentially meaningful pattern from variation that could plausibly arise in a small study. Here, the posted group summaries are too limited to quantify the uncertainty in a baclofen-versus-placebo effect. The reason for termination and the missing-data approach are not reported in the registry record, adding uncertainty about study completion and the basis of the summaries.

The results should be read as descriptive observations from a terminated trial with 34 participants enrolled, not as a definitive estimate of an effect. The record neither demonstrates benefit nor demonstrates no effect. It also does not permit a conclusion that the two opioid-use strata respond differently. Those conclusions would require analyses and supporting information that are not reported in the registry record.

14. Why This Trial Matters Statistically

This trial raises a useful statistical question about how to interpret a continuous postoperative outcome when participants are divided into clinically described strata. The reported means differ in their numerical direction across the opioid-tolerant and opioid-naive groups. That makes it especially important to distinguish an observed pattern from evidence that treatment effects differ by stratum. A formal interaction analysis, with an estimate and uncertainty, would be needed to evaluate that question; none is reported in the registry record.

The study also illustrates why group means should not be read without their standard errors and group sizes. The opioid-tolerant groups contain 5 and 7 participants, while the opioid-naive groups contain 12 and 10. These counts frame the limited precision that may be available, but do not themselves quantify the uncertainty in the treatment contrasts. The posted standard errors concern group means, not the treatment effects.

Finally, registration status and outcome summaries are not substitutes for a reported analysis plan and inferential results. The record classifies the study as randomized and double-masked, but does not give important procedural and statistical details. It is marked terminated, with no reason stated. For clinical researchers and statisticians, the distinction between descriptive reporting and an analyzed comparison is central: the former can show what was observed in the groups, while the latter is needed to assess the strength and precision of evidence about the intervention.

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.

Several limitations specific to the registry record constrain interpretation. The trial is marked terminated, but the reason for termination is not reported in the registry record. It lists 34 participants enrolled, while the outcome summaries are divided into four relatively small groups. The record does not explain whether all enrolled or randomized participants contributed outcome data, or whether any were excluded from the posted summaries.

The primary outcome description refers to opioid requirements for acceptable pain control, but no separate pain-intensity result or definition of acceptable pain control is reported. The endpoint covers the period from 0 hours to 24 hours after surgery; conclusions about other postoperative periods are not supported by this measure. Details of the surgical population and perioperative care beyond the stated dose timing are not reported in the registry record.

The registry record does not report the sample-size justification, a complete statistical analysis plan, the analysis population, missing-data methods, or inferential estimates. It gives no confidence intervals or p-values for the treatment comparisons. The arm descriptions are incomplete, so the details of the planned pseudo-randomization procedure cannot be established. These reporting gaps prevent a full assessment of precision, potential bias, and whether the posted summaries represent the intended analysis.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Baclofen as a Perioperative Analgesic Adjuvant — NCT03720717.
• Registry record last updated 2024-09-05; status last verified 2024-08.
• Results first posted 2024-09-05.
• 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

This Phase 4 study, sponsored by the University of Alabama at Birmingham, is recorded as randomized, double-masked, parallel-group, and terminated. It enrolled 34 participants, with a primary completion date of 2022-10-28. The trial compared oral baclofen 10 mg with placebo and stratified participants by preprocedure opioid use.

The primary outcome was opioid requirement, measured as oral morphine equivalents used from 0 hours to 24 hours after surgery. The registry record reports group means and standard errors for opioid-tolerant and opioid-naive participants, along with group sizes. It lists zero serious adverse events, zero other adverse events, and zero deaths in each group. No analyses are posted, and a two-arm continuous-endpoint comparison is not estimable from the registry results. The reason for termination and key analysis details are not reported in the registry record.