A Dose Ranging Effect of Preoperative Diphenhydramine on Postoperative Quality of Recovery After Ambulatory Surgery: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Dose Ranging Effect of Preoperative Diphenhydramine on Postoperative Quality of Recovery After Ambulatory Surgery (NCT01451762), a randomized na study. The primary outcome is Quality of Recovery 40 at 24 Hours.

2. Clinical Question

The trial addresses whether a preoperative intervention might be associated with differences in recovery as measured by a questionnaire covering recovery after anesthesia and surgery. Its stated motivation includes postoperative pain and other outcomes after ambulatory surgery, but the posted primary outcome is specifically the QoR-40 score at 24 hours. The registry record does not provide results for pain, opioid consumption, nausea, or time to meet discharge criteria.

The posted medians are 164 for placebo, 169 for 25 mg diphenhydramine, and 172 for 50 mg diphenhydramine. These are descriptive summaries, not estimates accompanied by a reported test or confidence interval. They do not establish whether group differences are compatible with chance variation or how precisely any underlying difference has been estimated.

3. Trial Design

This completed study is listed as a randomized, quadruple-masked, parallel-group trial. The registry record describes three arms: placebo with intravenous 0.9 normal saline, 25 mg diphenhydramine intravenously before surgery, and 50 mg diphenhydramine intravenously before surgery. It records an enrollment of 90. The reported outcome group sizes are 27 for placebo, 24 for 25 mg diphenhydramine, and 24 for 50 mg diphenhydramine.

The record lists the study start as 2011-09 and primary completion as 2012-09. Its status is completed. The phase is listed as NA, and Northwestern University is the sponsor. The title describes the work as dose ranging, while the posted results show the three assigned groups rather than a single combined treatment comparison.

Random allocation is a design feature intended, in general, to reduce systematic differences between groups at assignment. Masking is also a design feature, but the registry record does not say which people were masked or how masking was maintained. The parallel-group description indicates that the groups are separate arms; details such as the allocation procedure, concealment, and protocol conduct are not reported in the registry record.

The registry record gives a brief sample-size statement: 23 per group was estimated to achieve 80% power to detect a 10 point difference in aggregated QoR-40 score for the three groups. The accompanying text is truncated, so its further qualifications are not available. A fuller protocol, the rationale for the enrolled number, and any changes to the planned design are not reported in the registry record.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Primary outcome was QOR 40 a sample size of 23 per group was estimated to achieve 80% power to detect a 10 point difference in aggregated QOR040 score for the three groups. A 10 point difference represents a clinically relevant improvement in quality of recovery. TO account for drop outs lost to follow up 90 subjects were randomized.

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 Quality of Recovery 40 at 24 Hours, measured over 24 hours post operatively.

The primary endpoint is the QoR-40 score 24 hours after surgery. The QoR-40 is described in the registry record as a questionnaire designed to evaluate recovery after anesthesia and surgery. Its score ranges from 40, representing very poor recovery, to 200, representing outstanding recovery; higher scores therefore correspond to better recovery on the instrument.

A patient-reported recovery measure can summarize experience across aspects of recovery rather than focusing on a single symptom. The registry record’s rationale says the instrument may be particularly valid for examining interventions that affect different aspects of recovery, though the remainder of that description is not available. The endpoint is reported as a median with an interquartile range for each arm. A median describes the midpoint of the observed scores, while the interquartile range describes the spread of the middle portion of those scores. These summaries describe the groups; they do not themselves quantify uncertainty in a comparison between groups.

The posted results contain one primary outcome measure. They do not include a definition of how questionnaires with incomplete answers were handled, whether the endpoint was measured for every randomized participant, or an adjusted analysis. Those details are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry record identifies a randomized, quadruple-masked, parallel-group design with three arms. It reports allocation as randomized, but does not describe the sequence-generation method, allocation concealment, or the roles of the people included in quadruple masking. Those implementation details are not reported in the registry record. In general, randomization is intended to make group assignment independent of participants’ prognostic characteristics, while masking can reduce the influence of expectations on care, measurement, or reporting. These design intentions do not demonstrate that bias was absent in a particular trial.

What do the summaries represent?

The primary outcome is summarized by a median and interquartile range in each arm. The median is the central value when observations are ordered. The interquartile range spans the middle half of the observed values and gives a descriptive sense of their spread. These summaries are often useful when a distribution is skewed or when an average and standard deviation may not represent a typical observation well. That is a general reason to use them; the registry record does not report why this trial selected these summaries.

The reported values are 164 with an interquartile range of 151 to 189 for placebo, 169 with an interquartile range of 159 to 181 for 25 mg diphenhydramine, and 172 with an interquartile range of 157 to 185 for 50 mg diphenhydramine. They locate and describe the outcome values within each reported group. They are not, by themselves, a test of a difference between groups. A comparison analysis would need to specify an estimand and a method, and would ideally report uncertainty around the estimated effect.

Why does the absence of an analysis matter?

The registry record posts no analyses for the primary outcome. In particular, it does not provide a model, a test statistic, a confidence interval, or a p-value for any arm comparison. The record also indicates that the results were not reduced to one comparison. That fits the three-arm presentation, but it does not tell the reader what comparisons were planned or how they would be analyzed. Any particular method, including a pairwise test, a trend test, or a model adjusting for covariates, would be speculation.

In general, an inferential comparison incorporates both the observed difference and its uncertainty. A confidence interval helps express precision: a narrower interval indicates greater precision under the stated method and assumptions, while a wider interval indicates less. A p-value is not a measure of effect size or clinical importance. Neither kind of statistic appears for the primary endpoint in the posted results, so interpretation should remain with the descriptive summaries.

How should the planning statement be read?

The registry record says that 23 per group was estimated to achieve 80% power to detect a 10 point difference in aggregated QoR-40 score for the three groups. This reports a design-stage target as written in the record. The record does not report the assumptions behind that estimate, such as the variability used, the precise test, or the significance level. It also does not provide a full sample-size justification; the text that follows the statement is truncated. These details are not reported in the registry record.

Power is a planning concept: it describes the chance, under specified assumptions and a particular true effect, of rejecting a stated null hypothesis using a specified analysis. The planning figure is not observed power and does not tell us whether the posted data establish a difference. It cannot replace a result estimate with its uncertainty. The calculated sample-size section elsewhere on the page is a separate planning illustration based on observed effects, not the trial’s own design calculation; any such illustration should be read as hypothetical planning rather than as evidence about the trial outcome.

What is not available about the statistical plan?

The registry record does not report the planned primary analysis, the analysis population, handling of missing questionnaire data, covariate adjustment, or any interim analyses. It also does not report a multiplicity procedure or whether comparisons among all three arms were prespecified. In general, these choices can affect how estimates and uncertainty should be interpreted. Without them, readers cannot determine whether the posted summaries follow a prespecified analysis plan or how the investigators intended to control the interpretation of multiple comparisons.

Over-dispersion is a general concern for some count or event models when observed variability exceeds a model’s expected variability. It is not a reported feature or method in this trial’s primary outcome record, which summarizes QoR-40 scores using medians and interquartile ranges. No count-model analysis is posted. The statistical methods that can be described with confidence are therefore limited to the randomized three-arm design and the descriptive summaries recorded for the primary outcome.

10. Multiplicity, Missing Data and Analysis Populations

The trial has three reported arms, so possible questions could include comparisons of each dose with placebo or comparisons across all three groups. The registry record does not report which comparisons were planned, whether a dose trend was to be tested, or how multiplicity would be handled. It posts no analyses. Consequently, there is no basis for describing a prespecified testing hierarchy, adjustment method, or confirmatory comparison. In general, examining several outcomes or contrasts can increase the chance of at least one apparently notable result; prespecified analysis plans and suitable methods can help readers interpret that risk. The record does not say what approach, if any, was used.

The primary outcome description reports a sample-size statement, but no complete statistical analysis plan. Interim analyses, stopping rules, and the significance threshold are not reported in the registry record. The available record also does not describe an analysis population, such as all randomized participants or a subset defined by treatment received.

The outcome group counts are 27, 24, and 24, while enrollment is listed as 90. The registry record does not explain this difference or report how many participants had missing QoR-40 data, why data might be missing, or how missing values were handled. It does not state whether participants were excluded from the outcome summaries or whether any imputation was used. Therefore the displayed group summaries cannot be assumed to represent a particular analysis population beyond the reported outcome groups. Missing-data handling and the relationship between enrollment and outcome counts are 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 5% reporting threshold.

Most frequent non-serious adverse event terms

The registry record reports serious adverse events for each outcome group: zero affected participants among 27 at risk in placebo, zero among 24 at risk with 25 mg diphenhydramine, and zero among 24 at risk with 50 mg diphenhydramine. These are the posted serious-event counts. They describe what the registry reports for these groups and should not be interpreted as showing that serious events are impossible or that risk is absent.

For other adverse events, the record lists 12 affected participants among 27 at risk in the placebo group, 9 among 24 at risk with 25 mg diphenhydramine, and 3 among 24 at risk with 50 mg diphenhydramine. These figures are counts, not comparative estimates with uncertainty. No statistical comparison of adverse-event groups is posted. The registry record does not provide event terms in the serious-event list, and it does not provide death counts; the death values are not reported in the registry record.

In general, safety counts are best interpreted with the event definitions, observation period, and completeness of follow-up in view. Those details are not reported in the registry record for these figures. The counts alone do not establish that one group is safer than another.

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

The posted results show the distribution summaries for QoR-40 scores at 24 hours in three randomized groups. The median scores are 164 for placebo, 169 for 25 mg diphenhydramine, and 172 for 50 mg diphenhydramine, with the interquartile ranges shown in the posted results. This is a descriptive ordering of the reported medians. It is not a formal estimate of the effect of either dose relative to placebo.

The registry record does not include confidence intervals, p-values, or another inferential comparison. It therefore does not show how precisely the group differences are estimated or whether an analysis supports a difference. The interquartile ranges describe the spread of individual scores, not the uncertainty around an estimated treatment effect. Overlap or separation of these ranges is not a substitute for an analysis designed to compare groups.

The record’s sample-size statement refers to a planned ability to detect a 10 point difference in aggregated QoR-40 score for the three groups. That planning target is not evidence that a difference of that size was observed. It does not provide observed power, and it cannot be used to conclude that a result is meaningful or unimportant. The clinical interpretation of any estimated difference would also require context beyond the summaries posted.

Nor do the QoR-40 results answer every question raised in the trial’s background. The registry record does not post results for postoperative pain, opioid consumption, nausea, or time to meet discharge criteria. The available endpoint is quality of recovery at 24 hours, not a complete assessment of all postoperative outcomes.

The appropriate conclusion is limited: the registry record contains group-level descriptive outcome and adverse-event counts, but not the analyses needed to quantify comparative effects. It neither establishes a benefit nor demonstrates an absence of effect. Additional details about missing data, analysis populations, and prespecified methods are also not reported in the registry record.

13. Why This Trial Matters Statistically

This trial is statistically interesting because it places a patient-reported recovery measure in a randomized, three-arm dose-ranging design. The outcome is not a single symptom score in the record’s description: it is a QoR-40 measure intended to evaluate recovery after anesthesia and surgery. A broad recovery measure can make the choice and interpretation of the endpoint important, particularly when an intervention might affect more than one aspect of recovery.

The design also creates a question about what comparison should carry the main interpretation. The placebo group and two dose groups allow several possible comparisons, but the registry record does not identify a primary contrast or report a multiplicity strategy. Without that information, the reader cannot know whether the emphasis was intended to be on dose against placebo, a pattern across doses, or another contrast. The absence of posted analyses means none of these possibilities can be confirmed from this record.

The results illustrate the difference between describing data and estimating an effect. Medians and interquartile ranges help convey the observed group values and their spread. They do not provide the uncertainty around a comparative effect. A statistical report that includes an effect estimate and interval would help readers judge precision; those results are not reported in the registry record.

Finally, the design-stage statement and the outcome summaries serve different purposes. The stated target of 23 per group and 80% power for a 10 point difference is a planning description. It cannot be treated as evidence that the realized study had adequate precision for every possible effect, or as a substitute for the missing analysis. This record is useful for seeing the planned question and the posted descriptive results, while also showing why a complete statistical interpretation depends on reporting the analysis and its uncertainty.

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 interpretation is that the registry record posts descriptive primary-outcome summaries but no analysis comparing the groups. There are no reported effect estimates, confidence intervals, or p-values. The reader therefore cannot assess the precision of the apparent differences among medians or interpret them against a formal statistical test.

The record does not report the statistical analysis plan in enough detail to identify the intended primary contrast, analysis method, or approach to multiple comparisons. It also does not report an analysis population, missing-data procedures, interim analyses, or a full account of the sample-size assumptions. The sample-size text is incomplete. These omissions limit assessment of whether the reported summaries follow prespecified methods.

The relationship between enrollment of 90 and the outcome group counts of 27, 24, and 24 is not explained. The record does not say whether the group counts reflect missing questionnaires, exclusions, or another reason. It also does not report the characteristics of the outcome groups, adherence to assigned treatment, or details of the randomization and masking procedures. Such information is not reported in the registry record.

Only one outcome measure is posted, and the other outcomes raised in the study background are not reported. The serious adverse-event counts are zero in each group, but the record does not provide event definitions or death counts. Other adverse-event counts are listed without a comparative analysis. These results should be interpreted as limited registry summaries rather than a complete account of efficacy, safety, or trial conduct.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Dose Ranging Effect of Preoperative Diphenhydramine on Postoperative Quality of Recovery After Ambulatory Surgery — NCT01451762.
• Registry record last updated 2014-03-14; status last verified 2014-02.
• Results first posted 2014-03-14.
• 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

This completed, randomized, quadruple-masked, parallel-group trial compared placebo with preoperative intravenous diphenhydramine at 25 mg and 50 mg. The primary outcome was QoR-40 score at 24 hours after surgery, reported as a median and interquartile range for each arm.

The posted medians were 164 for placebo, 169 for 25 mg diphenhydramine, and 172 for 50 mg diphenhydramine. The registry record reports no analyses comparing the groups, so the results are descriptive and do not quantify comparative uncertainty. It also does not report missing-data handling, the analysis population, a multiplicity approach, or a complete statistical plan. Serious adverse-event counts were zero in each group; other adverse-event counts are posted without comparative analyses.