Mu-Opioid Receptor Genetic Polymorphism and Intrathecal Analgesia: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Mu-Opioid Receptor Genetic Polymorphism and Intrathecal Analgesia (NCT00418015), a registered phase not stated study. The primary outcome is Duration of Intrathecal Fentanyl Analgesia.

2. Clinical Question

The registry's rationale is pharmacogenetic: variation in OPRM1 might be associated with differences in response to opioid analgesia. Its brief summary discusses the A118G variant and hypothesizes that receptor variation could relate to opioid requirements, duration of analgesia, and effects such as itching or nausea and vomiting. These are motivating ideas, not substitutes for reported estimates from the study. The summary also includes background figures about intrathecal fentanyl and an ED50 finding, but the record does not provide the primary endpoint values needed to assess the duration comparison described in the outcome definition.

3. Trial Design

This is a completed clinical study with enrollment of 293. The registry lists Northwestern University as sponsor, gives a start date of 2005-10 and a primary completion date of 2007-05, and classifies the study as kind other. The intervention is recorded as a blood draw. The treatment descriptions refer to labor analgesia initiated with fentanyl and cesarean delivery analgesia consisting of spinal fentanyl and morphine. These descriptions identify the clinical settings and drugs of interest, but do not amount to a full account of the study procedures.

The reported groups are organized by clinical setting and OPRM1 category: labor analgesia with c304A or c304A>G, and cesarean delivery with c304A or c304A>G. The registry explicitly notes that allocation is not stated and that these arms are not a like-for-like control comparison. Thus, the listed groups should not be read as randomized treatment arms. The record does not specify whether group membership was determined from genotype testing, how samples were processed, or how the two clinical settings related to each participant.

The primary outcome is duration of intrathecal fentanyl analgesia. Its stated population is laboring parturients given intrathecal fentanyl at 25 micrograms, and its timeframe is time from 0-1440 minutes to the first analgesia request. The endpoint description also refers to a request after cesarean delivery, leaving the scope broader than the population description. The registry record does not clarify this wording or report separate primary estimates by setting.

The record lists two secondary outcomes concerning pruritus: severity following fentanyl and participants with pruritus at 24 hours after morphine. It reports five outcome measures and six analyses, but does not describe the full set of measures or analyses in the registry record for this account. Details of randomization, masking, planned sample-size justification, study protocol, and analysis plan are not reported in the registry record. The enrollment figure alone does not reveal how many participants contributed to each endpoint or analysis.

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 were excluded from the labor analgesia group if they had received an opioid analgesic before initiation of intrathecal analgesia or if they received neuraxial analgesia before 2cm of cervical dilation.

Overall Study

Analysis population for the primary outcome, as defined in the registry: Laboring parturients that received intrathecal fentanyl (25 micrograms) for initiation of labor analgesia were evaluated for this outcome per protocol.

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 Duration of Intrathecal Fentanyl Analgesia, measured over Time (0-1440 minutes) to first analgesia request.

The primary endpoint measures elapsed time from intrathecal drug administration until a participant first requests additional analgesia. It is intended to represent the duration of the initial analgesic episode, rather than a direct measurement of pain intensity at every moment. The registry describes this endpoint as a median with a 95% confidence interval and gives the timeframe as time from 0-1440 minutes to first analgesia request. Its population description specifies laboring parturients who received intrathecal fentanyl at 25 micrograms.

Time to first request is a clinically interpretable endpoint because it captures when a participant seeks further pain relief after the initial intrathecal dose. In general, a time-to-event outcome records the time until a defined event occurs; in this study the event is an analgesia request. Such an endpoint can be summarized by a median, which describes the middle of the observed event-time distribution, and a confidence interval, which conveys uncertainty around an estimate under the analysis assumptions.

The record's wording creates an important scope question: the endpoint description mentions requests during labor or after cesarean delivery, whereas the primary population specifically identifies laboring parturients given fentanyl. The registry does not explain whether the same endpoint was analyzed separately in both settings or how a post-cesarean observation entered the primary analysis. Most importantly, no median, confidence interval, group contrast, or associated significance test for the primary endpoint is reported in the registry record. Its definition can therefore be explained, but the size and precision of any genotype-related difference cannot be assessed from the record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Several statistical ideas help interpret the design and endpoint, even though the registry record does not report the primary numerical estimates or a full analysis plan. The following explanations are general; they describe how such methods are commonly understood and do not assert that any unreported method was used in this study.

What does a time-to-event endpoint represent?

In general, a time-to-event endpoint measures the time from a defined starting point until a specified event. Here, the event is the first request for additional analgesia after intrathecal drug administration. The clock's start and the event definition matter: variations in when administration is recorded or how a request is handled can change the measured time. The registry defines the interval and gives a timeframe of 0-1440 minutes, but does not describe how events outside that interval, participants without an observed request, or interruptions in observation were handled.

Time-to-event outcomes can be summarized with a median: the time by which half of the observed event-time distribution has occurred, under the definition and analysis used. A median is often less sensitive than a mean to very long times, but it does not describe every feature of the distribution. Two groups can have similar medians while differing elsewhere in their event-time patterns. The registry names a median as the primary summary but does not report its values, the method for estimating it, or whether a formal comparison of event-time distributions was performed.

How should a confidence interval be read?

In general, a confidence interval communicates uncertainty around an estimate. It is not a guarantee that the true value lies in that particular interval, nor does an interval alone establish whether a difference matters clinically. Its interpretation depends on the method used, the data, and the assumptions behind the analysis. The primary outcome is described as having a 95% confidence interval, but the interval limits are not reported in the registry record. Therefore, the precision of the primary estimate cannot be judged.

A comparison between groups may be expressed as a difference in medians, a ratio, a test statistic, or another measure, depending on the analysis plan. The registry record does not state which comparison measure was planned or used and does not provide a contrast estimate or a p-value for the primary outcome. No effect size should be reconstructed from the background discussion or from enrollment alone.

Why does group structure matter?

Random assignment, when used, aims to balance prognostic characteristics across assigned treatment groups on average. This registry record does not state that participants were randomized; it specifically notes that allocation is not stated and the arms are not a like-for-like control comparison. The listed groups are defined by clinical setting and OPRM1 category. An observed difference between such groups could reflect the genetic category, other differences among participants, the clinical setting, or a combination of factors. General statistical adjustment can address measured differences under assumptions, but the registry record does not state whether adjustment was used or which variables were considered.

The two settings also involve different analgesic descriptions: labor analgesia uses fentanyl, while the cesarean group is described as receiving spinal fentanyl and morphine. These groups should not be treated as interchangeable. The primary population is specified as laboring parturients receiving fentanyl, even though the endpoint description mentions labor and post-cesarean requests. The record does not explain how this wording relates to the actual analysis. Clear reporting of setting-specific populations and estimates would be needed to interpret any cross-setting comparison.

What does over-dispersion mean in general?

For count outcomes, over-dispersion means that observed variability exceeds what a simple model assumes. If present and ignored, standard errors and uncertainty estimates may be unreliable. This is a general consideration for some statistical models, not a reported feature of this study. The record does not identify a count model, report a dispersion assessment, or give enough analysis detail to say whether over-dispersion was relevant.

What can the planning illustration establish?

The record notes that planning illustrations use an observed effect, a two-sided significance level of 0.05, equal allocation, and a normal approximation, with the effect scaled to a stated fraction of the observed effect. It also distinguishes total event counts for time-to-event illustrations from participants per arm for other illustrations. These are planning assumptions, not evidence that the trial used those assumptions in its original design. The registry record does not report the trial's own sample-size justification, and the numerical planning outputs are not part of the registry entries available for this account. Such illustrations are not observed power and should not be read as proof that the completed study had adequate or inadequate power.

Overall, the endpoint type and the stated planning framework can be described, but the actual inferential method cannot. The registry record does not report whether the primary analysis was unadjusted or adjusted, how censoring was handled, what test was used, whether assumptions were assessed, or how estimates were calculated. These details are necessary to evaluate whether an analysis matches the endpoint and design. General methodological explanations should therefore not be mistaken for a description of unreported study procedures.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists five outcome measures and six analyses. It names two secondary outcomes concerning pruritus: severity following fentanyl and participants with pruritus at 24 hours after morphine. The record does not identify all measures and analysis pairings in the registry record, nor does it describe which analyses were designated primary, secondary, exploratory, or subgroup analyses beyond the stated primary endpoint and the named secondary outcomes.

Multiplicity arises when several outcomes, time points, groups, or statistical tests are examined. In general, conducting multiple tests can increase the chance of at least one apparently noteworthy result if each is judged separately. Study plans may address this by identifying a primary outcome in advance, adjusting inferential thresholds, or treating additional analyses as exploratory. The registry record does not report whether any multiplicity strategy was planned or used. It is therefore not possible to assess how the number of analyses affected interpretation or whether reported significance claims, if any, accounted for multiple testing.

Missing-data handling is also not reported in the registry record. The endpoint is a time to first request, but the record does not state how participants with no recorded request, incomplete follow-up, withdrawal, or other missing observations were handled. It does not report endpoint-specific analysis counts or reasons for missingness. The outcome population is described as per protocol, but the criteria for that population and its size are not given.

The record does not describe an intention-to-treat population, a modified intention-to-treat population, or a safety analysis population. Nor does it explain how participants who contributed to one clinical setting or outcome were counted in other analyses. These omissions limit assessment of selection and attrition. They do not establish that data were missing or analyses were inappropriate; they mean only that the relevant information is not reported in the registry record.

11. 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 0.1% reporting threshold.

The registry lists four safety groups: labor analgesia and cesarean delivery, each divided by OPRM1 c304A or c304A>G. For each listed group, serious events are recorded as 0 and other events are recorded as 0. The numbers at risk are reported separately for each group. These entries describe the counts in the registry record; they should not be expanded into a claim that no adverse effects occurred in the entire study or that either analgesia approach is free of risk.

A zero count means that no event in that category is recorded for that group in the posted figures. It does not by itself establish that the true event risk is zero. The record does not provide event definitions, observation completeness, or detail about how the safety counts were collected. It names pruritus outcomes, but their numerical results are not reported in the registry record for this account. Those named outcomes should not be assumed to be included in, or represented by, the zero adverse-event entries.

Death counts are not reported in the registry record; the absence of a numerical death count must not be read as a reported zero. Likewise, the safety group counts should be interpreted in their listed group context rather than combined or compared as if participants had been randomized to matched treatments. The record does not give a statistical comparison or uncertainty interval for safety outcomes. These figures are therefore descriptive registry entries, not evidence of equivalence between groups or a complete assessment of safety.

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

The registry record establishes that a completed study with enrollment of 293 addressed a pharmacogenetic question involving OPRM1 and intrathecal analgesia in labor and after cesarean delivery. It defines a primary outcome as time to first request for additional analgesia and identifies pruritus as a secondary safety-related outcome. It also gives group labels based on clinical setting and OPRM1 category. These details describe the question and structure of the study, but do not establish the size or direction of the primary result.

The primary median and its 95% confidence interval are not reported in the registry record. No comparison estimate or primary significance test is reported in the registry record. It is therefore not possible to determine how long analgesia lasted in each group, how different the groups were, or how precisely any difference was estimated. The completed status does not fill in those missing results.

The brief summary discusses the hypothesis that genetic variation may be related to opioid response. A biological rationale can motivate a study, but it cannot establish that a genetic category predicts an outcome in the study population. Similarly, background figures about fentanyl duration or ED50 are not the same as group-specific estimates for the defined primary endpoint. The registry's group labels and design note also mean that any observed group association, if reported elsewhere, would not automatically be a causal effect of genotype or treatment.

The safety figures record zero serious and zero other events in each listed group, but the record does not report death counts numerically, and it does not give the numerical pruritus results. Those entries cannot support a claim that adverse effects were absent or that groups had equivalent safety. A zero count is a descriptive observation, not proof of zero underlying risk.

Accordingly, the record supports a cautious account of the study question, outcome definition, enrollment, and reported safety counts. It does not support a conclusion that a treatment works or does not work, that genotype does or does not alter analgesia, or that any association is clinically important. Those judgments would require complete outcome estimates, uncertainty measures, analysis details, and context beyond what is reported in the registry record.

13. Why This Trial Matters Statistically

This study is statistically interesting because it connects a genetic hypothesis with a time-to-event endpoint in two distinct analgesia settings. The primary outcome is not simply a measurement of drug administration or pain score: it is the time until a participant requests additional analgesia. That makes the outcome interpretable as duration of the initial analgesic episode while also making its interpretation dependent on a clearly defined event and follow-up process.

The record also illustrates why biological plausibility and statistical evidence should be kept separate. The brief summary describes a proposed role for OPRM1 variation in opioid response. That rationale motivates examining genotype categories, but estimates and uncertainty are still needed to judge whether the categories are associated with the measured endpoint. The registry record does not report those primary estimates.

Design classification matters as well. The record explicitly says allocation is not stated and that the arms are not like-for-like controls. This is a useful caution against reading group labels as randomized treatment assignments. Labor analgesia and cesarean delivery analgesia have different descriptions, and the primary population is specifically defined as laboring parturients. Making setting and population distinctions explicit is essential when interpreting any comparison.

Finally, this record shows why complete reporting includes more than an outcome name and enrollment. A reader needs group-specific results, precision estimates, analysis populations, missing-data procedures, and multiplicity handling to understand how strong the statistical evidence is. The record gives a primary endpoint definition and lists multiple outcomes and analyses, but does not report key inferential details or the primary numerical results. The statistical importance lies in the question and the need to distinguish hypothesis, design, and evidence—not in an unreported treatment effect.

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 principal limitation for interpreting this study from the registry record is the absence of numerical primary endpoint results. The primary measure is defined as a median with a 95% confidence interval, but neither the median nor interval is reported. No group contrast, test result, or estimate of uncertainty is available. This prevents assessment of the magnitude, direction, or precision of the association under study.

There is also ambiguity in the endpoint scope. The endpoint description refers to the time to a request after intrathecal administration in labor or after cesarean delivery, while the primary population is described specifically as laboring parturients receiving intrathecal fentanyl at 25 micrograms. The record does not clarify whether the cesarean setting contributed to the primary outcome, whether analyses were separate by setting, or how these descriptions fit together.

The group structure does not support a simple randomized comparison: allocation is not stated, and the registry cautions that the arms are not like-for-like controls. The registry entries available do not describe participant assignment, genotype ascertainment, baseline characteristics, confounder adjustment, or the method used to compare groups. The treatment descriptions also differ by clinical setting, which limits direct interpretation across settings.

Important analysis details are not reported in the registry record, including sample-size justification, statistical methods, handling of censoring and missing data, analysis population sizes, and multiplicity procedures. Although the registry lists five outcome measures and six analyses, the available information does not permit evaluation of the complete analysis family. Safety interpretation is similarly limited: the listed event counts are zero, death counts are not reported numerically, and numerical results for the named pruritus outcomes are unavailable. These reporting limitations do not establish that the study methods were inadequate; they restrict what can be concluded from the registry record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Mu-Opioid Receptor Genetic Polymorphism and Intrathecal Analgesia — NCT00418015.
• Registry record last updated 2014-04-14; status last verified 2014-03.
• Results first posted 2011-04-18.
• 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

NCT00418015 is a completed study sponsored by Northwestern University, with enrollment of 293. The registry lists Labor Pain and Post-cesarean Delivery, and describes a blood draw as the intervention. Its scientific focus is the relationship between OPRM1 genetic variation and intrathecal analgesia during labor or after cesarean delivery.

The primary outcome is duration from intrathecal drug administration to first analgesia request, summarized as a median with a 95% confidence interval. The stated primary population is laboring parturients receiving intrathecal fentanyl at 25 micrograms. Secondary outcomes include pruritus severity following fentanyl and participants with pruritus at 24 hours after morphine.

The record notes that allocation is not stated and that the groups are not like-for-like controls. It lists zero serious and other events in each safety group, while death counts are not reported numerically. Primary endpoint estimates, detailed statistical methods, missing-data handling, and multiplicity procedures are not reported in the registry record.