Minimal Effective Dose of Hyperbaric Spinal Bupivacaine for Saddle Block: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Minimal Effective Dose of Hyperbaric Spinal Bupivacaine for Saddle Block (NCT02299167), a na phase 3 study. The primary outcome is Minimal Effective Dose of Hyperbaric Bupivacaine.

2. Clinical Question

3. Trial Design

This was a Phase 3, completed, single-group study sponsored by Imam Abdulrahman Bin Faisal University. The registry lists enrollment as 35 and identifies perianal surgery as the condition. The study start is recorded as 2014-01 and primary completion as 2014-09. Allocation is listed as NA, masking as none, and the study model as single group. These features describe a dose-finding study rather than a randomized treatment comparison.

The intervention is named as Dixon's up-and-down method. The arm description says that each patient's bupivacaine dose depended on the response of the previously tested patient. The primary-outcome description gives the rule: the first patient was tested at 1.5 mg; following a failed block, the next dose increased by 0.5 mg, and following a successful block, the next dose decreased by 0.5 mg. The study was to continue until seven crossover midpoints had been obtained. The registry does not report whether that stopping condition was reached.

The listed primary endpoint is the minimal effective dose of hyperbaric bupivacaine, measured in milligrams and summarized as a mean with a 95% confidence interval. The assessment time is 10 min after dural puncture. Secondary outcomes are sacral level of sensory block, motor block score assessed using the Bromage Scale, and patient and surgeon satisfaction. Their numerical results are not reported in the registry record.

The registry record does not report a separate control arm, a masking procedure, or a randomized allocation process. Detailed eligibility criteria, the intended analysis population, and the statistical analysis plan are not reported in the registry record. The listed enrollment should not be treated as the denominator for every outcome: the safety record separately gives 24 at risk for serious and other adverse events.

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: 35 patients were enrolled However; after they have signed the consent. 7 patients were excluded because they have received analgesics in the morning of surgery. and 4 patients refused the saddle block in the operating room. So actually 24 patients out of 35 participants underwent intervention. That has been already specified in the protocol

Overall Study

Reasons for not completing this period:

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: 11 patients have been excluded from the study. The remaining 24 participants completed the study

6. Primary Endpoint

The registry lists the primary outcome as Minimal Effective Dose of Hyperbaric Bupivacaine, measured over 10 min after dural puncture.

The primary endpoint concerns the dose of hyperbaric spinal bupivacaine associated with a successful, reliable saddle block for perianal surgery. The registry specifies assessment 10 min after dural puncture and describes the result as a mean dose in milligrams with a 95% confidence interval. The question is therefore about identifying a dose level using observed block responses, rather than comparing average outcomes between randomized groups.

The study used an adaptive sequence: each dose depended on the response of the previously tested patient. A failed block prompted an increase of 0.5 mg for the next patient, while a successful block prompted a decrease of 0.5 mg. The planned sequence began at 1.5 mg and was to continue until seven crossover midpoints were obtained. This procedure focuses observations around dose levels where responses change between failure and success. The registry record does not report whether the planned stopping condition was met or how success and failure were operationally defined beyond the wording in the endpoint description.

In general, a confidence interval expresses uncertainty around an estimated quantity under the statistical method used. Its width and location help readers assess how precisely the dose is estimated. Here, however, neither the primary mean nor its 95% confidence interval is reported in the registry record. The endpoint definition explains what the study intended to estimate, but the available record does not give the numerical estimate needed to interpret the primary finding.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a modified Dixon's up-and-down method. In general, an up-and-down design assigns the next participant's dose according to the preceding participant's response. This concentrates dose assignments around the boundary between response categories, which can be useful when the research question concerns a dose associated with a specified response. It differs from a conventional parallel-group design in which participants are randomly assigned among fixed dose groups.

How dose assignment is described

The primary-outcome description says that the first patient received 1.5 mg of bupivacaine. If the block failed, the next patient received an increment of 0.5 mg; if the block succeeded, the next patient received a decrement of 0.5 mg. Thus the sequence moves upward after a failure and downward after a success. The registry says the study would continue until seven crossover midpoints were obtained. It does not report the actual sequence, whether that stopping criterion was met, or the precise operational criteria used to classify a block as successful or failed.

In general, a crossover in this design is a change between adjacent responses of different types as the dose sequence changes. Repeated transitions can provide information about the dose range around which outcomes switch. The design's estimate depends on the observed sequence and the specific analysis method. The registry record does not describe the full estimator or give enough outcome data to reproduce or check an estimate.

What the primary summary would convey

The planned primary summary is a mean minimal effective dose in milligrams and a 95% confidence interval, with assessment 10 min after dural puncture. In general, the mean summarizes the central value under the specified analysis, while the confidence interval communicates uncertainty in that estimate. Interpretation requires both the estimate and its interval, along with a clear account of the analysis population and method. Neither the primary numerical estimate nor its interval is reported in the registry record.

The term minimal effective dose is tied to the study's response definition and dose-finding procedure. It should not be read as a universal dose applicable to every patient or setting. In general, dose estimates from a response-guided study describe the study population and conditions under which responses were observed. The registry does not report detailed eligibility criteria, the definition of a satisfactory or reliable block, or information that would support broader generalization.

Dependence and over-dispersion

In general, successive assignments in an adaptive sequence are linked because the current dose depends on an earlier response. This is a design feature, not necessarily an error, but it means the sequence should be analyzed with methods appropriate to the design rather than treated as ordinary independent dose groups. Over-dispersion is general statistical variation beyond what a model expects; when present, it can make uncertainty appear smaller than it should if the analysis assumes less variability. The registry record does not report an assessment of over-dispersion or identify the model used to estimate the primary outcome.

General explanations of these concepts do not establish which assumptions were used in this study. The statistical analysis plan, estimator details, and checks of model assumptions are not reported in the registry record. The absence of these details prevents readers from independently judging whether the reported analysis, if any, accommodated the adaptive sequence and the uncertainty associated with it.

Planning assumptions are not observed results

The registry record includes general sample-size planning assumptions: a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect defined as a stated fraction of the observed effect. These assumptions describe a planning illustration, not the adaptive single-group procedure described for this trial. No sample-size illustration outputs or observed-effect value are reported in the registry record. Such planning assumptions cannot be interpreted as observed power, and they do not supply the missing primary estimate.

In general, power calculations describe a design's ability to detect an assumed effect under specified assumptions. They are not a measure of how likely a result is true after data have been observed. Here, the planning framework refers to two arms, while the registered study model is single group. The record does not explain this mismatch or report a trial-specific sample-size justification.

Interpretation of the design

The design is intended to locate a dose-response transition through sequential adjustment. It is not designed, as described in the registry, to estimate a comparative treatment effect against a control group. The registry reports one intervention and one group, with doses adapting in response to prior outcomes. Any claims about comparative effectiveness, causal differences between dosing strategies, or the success rate of a fixed dose would require information and analyses not reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists several secondary outcomes in addition to the primary dose endpoint: sacral level of sensory block, motor block score assessed using the Bromage Scale, and patient and surgeon satisfaction. The record does not report numerical results for these outcomes. It also does not report whether additional outcomes were collected or analyzed.

When a study tests or estimates multiple outcomes, multiplicity can arise because there are several opportunities to observe a result that appears notable. In general, a statistical plan may specify which outcome is primary, how secondary outcomes will be interpreted, and whether any adjustment or hierarchy will be used. The registry record identifies a primary endpoint and names secondary outcomes, but multiplicity procedures, prespecified testing hierarchies, and the statistical analysis plan are not reported in the registry record. No conclusion can be drawn about whether or how multiplicity was handled.

The record does not report the number of participants contributing data to the primary endpoint or secondary outcomes, the amount of missing outcome data, reasons for missingness, or methods used to address missing data. It also does not identify a formal analysis population, such as all enrolled participants or those with an evaluable block response. These details matter for interpreting the dose sequence and the resulting estimate because an outcome not observed at a planned assessment may affect which responses inform the analysis.

The registry lists enrollment as 35, but gives 24 at risk in each of the serious and other adverse-event entries. It does not explain the difference between enrollment and those safety denominators. This should not be resolved by assuming a particular exclusion, follow-up pattern, or analysis population. The relevant accounting is not reported in the registry record.

In general, transparent reporting of analysis populations, missingness, and multiplicity helps readers distinguish planned analyses from exploratory ones. Those details are not reported in the registry record, so the robustness of the endpoint analyses cannot be assessed from the available information.

11. 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 adverse-event entry lists 24 participants at risk for serious adverse events, with 0 affected and 0 deaths. It separately lists 24 participants at risk for other adverse events, with 0 affected. The registry does not list any serious adverse-event terms. These figures describe the recorded safety counts; they do not establish that adverse events were impossible or that none occurred outside the recorded information.

In general, a zero count does not by itself show that the underlying risk is zero. The interpretation depends on the size and definition of the safety population, the duration and completeness of observation, and how events were collected and classified. The registry record does not report details of adverse-event surveillance, follow-up duration for safety, or the relationship between the 24 listed at-risk participants and the enrollment of 35.

The study is a single-group dose-finding study, not a comparison of safety between randomized groups. The listed counts therefore cannot establish whether the intervention has a different safety profile from another treatment or dose strategy. No comparative safety estimate is reported in the registry record.

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

The registry record describes the question the investigators intended to answer: the minimal effective dose of hyperbaric spinal bupivacaine for a reliable and satisfactory saddle block in perianal surgery. It also describes a response-guided dosing sequence, beginning at 1.5 mg and changing by 0.5 mg according to the preceding patient's block response. These details clarify the study's objective and design.

The record does not report the primary mean dose or its 95% confidence interval. It therefore does not provide the numerical result needed to judge the estimated dose or its precision. The planned endpoint and method cannot be used to infer an outcome that is not recorded. Results for sacral sensory level, motor block score, and patient and surgeon satisfaction are also not reported in the registry record.

The study has no separate comparator group in its registered design. It cannot, on the basis of the described design, provide a randomized comparison between bupivacaine and another treatment or between two fixed dose regimens. The adaptive sequence is suited to a dose-finding objective, but the details of the observed sequence and its analysis are absent.

In general, an estimate from one study applies most directly to the people, procedures, outcome definitions, and conditions studied. The registry does not report detailed eligibility criteria or a full definition of block success, limiting assessment of how broadly any eventual estimate might apply. The listed enrollment of 35 and the safety denominator of 24 also do not identify the number of participants contributing to the primary analysis.

The safety entry records zero serious adverse events and zero deaths among 24 at risk, and zero other adverse events among 24 at risk. Those counts are not proof of no risk and do not constitute a comparison. Overall, the registry record establishes the design and intended endpoint, but leaves the main numerical result and several details needed for interpretation unreported.

13. Why This Trial Matters Statistically

This study is statistically notable because its research question is a dose-finding question rather than a conventional comparison of treatment groups. The dose assigned to each patient depended on the previous patient's response. That adaptive feature is central to understanding both the data structure and the estimand: the investigators aimed to identify a dose associated with a block response, not to compare two independently assigned arms.

The registry describes the decision rule in a way that makes the intended sequence understandable: start at 1.5 mg, increase by 0.5 mg after failure, and decrease by 0.5 mg after success. It also specifies a stopping condition of seven crossover midpoints. These details help readers see how the study sought information around the change between response types. At the same time, the actual sequence and whether the stopping condition was met are not reported in the registry record.

The case also illustrates why a protocol description alone is not enough to interpret a dose-finding trial. The primary outcome was to be presented as a mean dose and a 95% confidence interval, but neither is reported. Without those values and the estimator details, readers cannot assess the result's magnitude, precision, or reproducibility.

The listed planning assumptions use a two-arm framework, while the registered study is single group and adaptive. This underscores the importance of distinguishing general planning illustrations from a trial's actual design and analysis. The registry does not report how those assumptions relate to the study or provide a trial-specific sample-size justification.

Finally, the difference between listed enrollment and the safety denominator is not explained. Clear reporting of analysis populations, outcome-specific denominators, missing data, and the adaptive sequence would help readers judge what information supports a dose estimate. Those elements are not reported in the registry record.

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 most important limitation of the registry information is that the primary numerical result is absent. Although the endpoint is specified as a mean dose with a 95% confidence interval, neither value is reported in the registry record. Without the estimate, its interval, or the underlying dose-response sequence, the primary result cannot be evaluated or reproduced from the record.

The record also does not report whether the planned seven crossover midpoints were obtained, the sequence of doses and responses, or the precise criteria used to define successful and failed blocks. These omissions make it difficult to assess how closely the observed study followed the described adaptive procedure or how the endpoint was derived.

Detailed participant eligibility criteria, baseline characteristics, and the primary analysis population are not reported in the registry record. Enrollment is listed as 35, while the safety entries identify 24 participants at risk for serious and other adverse events. The reason for the difference is not reported, and the number contributing to the primary endpoint cannot be inferred from either figure.

The registry names secondary outcomes but does not report their results. It also does not report missing-data methods, the statistical analysis plan, the estimator used for the dose endpoint, or any assessment of assumptions. Multiplicity handling and the relation between the two-arm planning assumptions and the single-group design are not reported in the registry record.

Finally, the absence of a separate comparator limits the kinds of conclusions the design can support. The registered objective is dose finding within an adaptive sequence, not a randomized comparison. These limitations concern what can be learned from the registry record; they do not establish what was or was not available in other study documents.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Minimal Effective Dose of Hyperbaric Spinal Bupivacaine for Saddle Block — NCT02299167.
• Registry record last updated 2020-11-24; status last verified 2020-09.
• Results first posted 2020-11-24.
• 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.

18. Record Summary

NCT02299167 is a completed Phase 3, single-group study sponsored by Imam Abdulrahman Bin Faisal University. The registry lists enrollment of 35, a study start of 2014-01, and primary completion of 2014-09. The study concerned hyperbaric spinal bupivacaine for saddle block in perianal surgery.

Dose assignment followed a modified Dixon's up-and-down method, with an initial dose of 1.5 mg and adjustments of 0.5 mg based on the preceding patient's response. The primary endpoint was the mean minimal effective dose, assessed 10 min after dural puncture and intended to be reported with a 95% confidence interval. The primary estimate and interval are not reported in the registry record.

Secondary outcomes included sensory level, motor block score, and patient and surgeon satisfaction; their results are not reported. The safety entry lists 0 serious adverse events and 0 deaths among 24 at risk, and 0 other adverse events among 24 at risk. The record does not explain the safety denominator or report the primary analysis population.