A Randomized Controlled Trial of Oral Acetaminophen for Analgesic Control After Transvaginal Oocyte Retrieval: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Randomized Controlled Trial of Oral Acetaminophen for Analgesic Control After Transvaginal Oocyte Retrieval (NCT02418182), a randomized phase 4 study. The primary outcome is Median of Cumulative Pain Scores Up to 60 Minutes Post Procedure.

2. Clinical Question

The trial focused on pain during and after retrieval. Its primary outcome was the median cumulative pain score from assessments at 15, 30, 45, and 60 minutes after the procedure. The score was measured on a visual analog scale from 0 to 10, with 0 defined as no pain and 10 as the worst pain. The registry also records whether participants used analgesics during the period up to 60 minutes after the procedure and during the first 24 hours after discharge.

The clinical question is therefore specifically about pre-procedure acetaminophen compared with pre-procedure placebo in this procedural setting. It is not a comparison of acetaminophen with every possible pain-control approach, nor does the posted record establish effects in other populations or settings. The registry's description notes an interest in pain control and possible narcotic use, but the posted secondary outcomes concern analgesic use generally; a separate narcotic-use result is not reported in the registry record.

3. Trial Design

This was a completed, randomized, parallel-group Phase 4 trial with quadruple masking. The registry lists 99 enrolled participants and identifies the University of Alabama at Birmingham as the sponsor. The listed start was 2015-01 and primary completion was 2016-07. Participants were assigned to receive acetaminophen or placebo before transvaginal oocyte retrieval. The placebo and active treatment were each described as two tablets taken approximately 1 hour before the procedure.

The registry's primary endpoint record gives an analysis population flow. Of 99 patients enrolled, 72 required re-consent. Of those, 39 re-consented and 33 could not be re-consented; those 33 were excluded, leaving 66 patients. Two were then lost to follow-up and excluded, leaving 64 women in the final primary analysis: 31 in the control group and 33 in the active-treatment group. The record does not report whether the secondary-outcome analyses used precisely the same inclusion rules beyond the group counts displayed for those outcomes.

Randomization and masking are important design features for a treatment comparison. In general, random assignment is intended to reduce systematic differences between groups at the outset, while masking can reduce the influence of treatment knowledge on care, reporting, or assessment. The registry labels the trial quadruple-masked but does not specify in the posted record which roles were masked or how masking was maintained.

The registry does not report the allocation sequence method, concealment procedures, a sample-size justification, or protocol details for handling deviations from assigned treatment. It also does not report a sponsor-led statistical analysis for the outcomes. The posted design information establishes the broad comparison and masking category, but it does not supply enough detail to assess every operational feature of trial conduct.

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: Of 99 patients enrolled, 72 required re-consent. Of these, 39 re-consented and 33 could not be re-consented. Therefore, these 33 were excluded, leaving 66 patients for analysis. Two of these were lost to follow-up and were excluded, leaving 64 women (31 control, 33 active arm) in the final analysis.

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: Of 99 patients enrolled, 72 required re-consent. Of these, 39 re-consented and 33 could not be re-consented. Therefore, these 33 were excluded, leaving 66 patients for analysis. Two of these were lost to follow-up and were excluded, leaving 64 women (31 control, 33 active arm) in the final analysis.

6. Primary Endpoint

The registry lists the primary outcome as Median of Cumulative Pain Scores Up to 60 Minutes Post Procedure, measured over 60 minutes post-procedure.

The primary endpoint was the median of cumulative pain scores recorded during the recovery period through 60 minutes after the procedure. Pain was rated on a visual analog scale from 0 to 10, where 0 meant no pain and 10 meant the worst pain. Ratings were taken at 15, 30, 45, and 60 minutes after retrieval. The registry does not give a further formula for how the cumulative score was formed, so its precise construction beyond the stated cumulative measure is not reported in the registry record.

A pain score measured during recovery addresses the immediate post-procedure period, when a pre-procedure analgesic might plausibly be expected to affect reported discomfort. Reporting the median describes the middle of the observed score distribution rather than its arithmetic average. The interquartile range (IQR) gives the range between the lower and upper quartiles, conveying the spread of the central portion of the observations. These summaries can be useful when scores are skewed or include many tied values, although the registry does not state why the median was selected.

The reported median was 2 in both groups. The control group's IQR was 0 to 3, and the experimental group's IQR was 1 to 4. These group summaries describe observed scores; by themselves, they do not provide an estimate of the between-group difference or its uncertainty. A formal comparative estimate and confidence interval for the primary endpoint are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry presents a randomized, parallel-group comparison and posts group summaries for the primary pain endpoint and counts for two secondary analgesic-use outcomes. Statistical interpretation depends on both the choice of summary measure and whether uncertainty around a comparison is reported. The registry provides different levels of information for the primary and secondary outcomes.

What does the median and IQR describe?

The median is the middle value in an ordered set of observations. It is a measure of location and is less affected by extreme observations than an arithmetic mean. The IQR spans the central half of the observations, from the lower quartile to the upper quartile, and describes part of the outcome's spread. General statistical interpretation: two groups can have the same median while differing in other aspects of their distributions, including spread or the frequency of particular values. For that reason, matching medians do not by themselves show that all aspects of the groups' pain outcomes were alike.

For this trial, the median cumulative score was 2 in both groups. The control IQR was 0 to 3, and the experimental IQR was 1 to 4. The registry does not report a confidence interval for a difference between medians or another formal primary-outcome comparison. Therefore, the group summaries do not quantify the precision of a treatment contrast. The registry also does not describe how the cumulative score was calculated from the pain ratings at 15, 30, 45, and 60 minutes.

What is a risk difference?

For a binary outcome, a risk difference compares the observed proportions with the outcome in the two groups. The reported direction is experimental minus control, so a positive estimate means the observed proportion was higher in the experimental group. General statistical interpretation: a risk difference is an absolute contrast on the probability scale. It is distinct from a relative measure, such as a risk ratio, which expresses one group's outcome frequency relative to the other.

For analgesic use up to 60 minutes, the posted risk difference was 0.191. Its 95% confidence interval extended from -0.049 to 0.430. For analgesic use during the first 24 hours after discharge, the estimate was 0.012, with a 95% confidence interval from -0.180 to 0.203. These are unadjusted re-calculations from the posted summary statistics, and the registry does not list reported analyses for these outcomes.

How should confidence intervals be read?

General statistical interpretation: a confidence interval expresses the uncertainty associated with an estimate under the method used to construct it. A narrower interval indicates greater precision than a wider interval on the same scale. An interval that includes zero for a risk difference includes the value corresponding to no group difference; it also includes a range of positive and negative differences. It does not mean that every value in the interval is equally plausible, and it does not guarantee that the interval contains the true value.

Both posted secondary risk-difference intervals include zero. The interval for the first outcome ranges from -0.049 to 0.430; the interval for the later outcome ranges from -0.180 to 0.203. The breadth of these intervals indicates that the estimates are not highly precise. The registry does not report a confidence interval for the primary median comparison, so the primary endpoint's comparative precision cannot be judged in the same way.

What does an unadjusted p-value contribute?

General statistical interpretation: a p-value describes how unusual data at least as incompatible with a specified null model would be, assuming that model and the test's other assumptions hold. It is not the probability that the null hypothesis is true, and it is not a measure of effect size. It should be considered alongside the estimate, interval, design, and analysis plan.

The unadjusted p-values reported for the secondary risk differences are 0.126 and 0.904. Neither is adjusted for testing multiple outcomes. The registry lists no reported analyses and does not report the sponsor's statistical testing approach for these outcomes. Consequently, these p-values should not be treated as a prespecified confirmatory analysis. The registry also does not report a p-value for the primary endpoint.

What do the planning illustrations mean?

The registry includes sample-size planning illustrations based on the observed secondary effects, not on the trial's original design. The stated assumptions are a two-sided significance level of 0.05, equal allocation, and a normal approximation. The illustrations consider detecting 100%, 75%, or 50% of the observed effect. Such values are hypothetical planning scenarios: they describe participants per arm under those assumptions and effect choices. They are not observed power, do not show that the trial was designed to detect the observed effects, and do not establish what effect is clinically important.

Planning based on an observed effect can be especially uncertain when that estimate comes from a small study, because the estimate itself may be unstable. General statistical interpretation: a planning calculation describes the sample size associated with assumptions; it does not repair uncertainty in the observed result or replace a design-stage justification. A sample-size justification for this trial is not reported in the registry record.

Why can over-dispersion matter?

General statistical explanation: over-dispersion occurs when outcome variability is greater than a statistical model assumes. If a model underestimates variability, it can make uncertainty appear smaller than it is. The posted primary outcome is summarized by a median and IQR, and the secondary outcomes are counts with unadjusted comparisons; the registry does not report a model-based analysis or indicate that over-dispersion was assessed. It is therefore not possible to say from this record whether that issue arose in the investigators' analysis.

10. Multiplicity, Missing Data and Analysis Populations

The registry posts one primary outcome and two secondary outcomes, but it does not report the statistical analysis plan, a multiplicity strategy, or reported analyses for the outcomes. The secondary p-values are explicitly unadjusted re-calculations from the posted group summaries. Their interpretation is therefore limited: if several outcomes or comparisons were considered, unadjusted testing does not account for the increased opportunity for chance findings. The registry does not report how many comparisons were planned beyond the posted outcome measures, whether outcomes were ranked in advance, or whether any adjustment was used by the investigators.

The primary outcome has group medians and IQRs, but no reported between-group estimate, confidence interval, or p-value. This prevents an assessment of the primary contrast's statistical uncertainty from the registry result. The record lists no reported analyses for the secondary outcomes either. A statistical analysis plan, including the intended analysis population and handling of missing observations, is not reported in the registry record.

The analysis population flow is important for understanding who contributed to the primary result. Of 99 patients enrolled, 72 required re-consent; 39 re-consented and 33 could not be re-consented. Those 33 were excluded, leaving 66 patients. Two were lost to follow-up and excluded, leaving 64 women in the final analysis, with 31 control and 33 active-treatment participants. These exclusions mean that the reported primary summaries do not represent every enrolled participant. The registry does not report the outcome values for excluded participants or describe methods such as imputation or sensitivity analyses to assess the consequences of missing data.

It is also not reported whether the analysis followed intention-to-treat principles, whether participants were analyzed according to assigned treatment, or how protocol deviations were handled. The group counts reported for the secondary outcomes match the primary analysis group counts, but detailed population rules for each secondary analysis are not reported. Without these details, the effect of missingness and the extent to which the analyses preserve the randomized comparison cannot be fully evaluated.

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.

Most frequent non-serious adverse event terms

The posted adverse-event figures list no serious adverse events in either group: 0 among 31 control participants and 0 among 33 experimental participants. The record also lists other adverse events for 4 control participants and 9 experimental participants. These counts describe what was recorded in the registry's adverse-event summary; they do not by themselves establish whether the groups differ in safety.

General statistical interpretation: when no serious events are recorded in a group, that observation does not prove that the underlying risk is zero. Rare outcomes are difficult to characterize with limited participant numbers, and estimates of safety depend on how events were defined, monitored, and reported. The registry does not provide serious-event terms, and its list of top serious-event terms is empty. Further detail about the nature, timing, severity, or relatedness of the other events is not reported in the registry record.

The adverse-event counts should be kept separate from the efficacy outcomes. They do not explain the pain-score summaries or analgesic-use counts, and they should not be interpreted as a comprehensive assessment of all possible harms. They are a concise record of the categories and counts posted for the two groups.

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

The posted primary result is a median cumulative pain score of 2 in each group, with IQRs of 0 to 3 for control and 1 to 4 for experimental treatment. This describes the observed recovery-period summaries among participants included in the final primary analysis. It does not establish equivalence between groups: the registry does not report a formal primary comparison or its uncertainty, and matching medians alone cannot show that the outcome distributions were the same.

The secondary results provide counts of participants who used analgesics in two follow-up periods, with unadjusted risk-difference estimates and confidence intervals. Both intervals include zero and allow for differences in either direction. These results are compatible with a range of possible underlying effects, and the unadjusted p-values do not establish whether the intervention caused a difference. The registry lists no reported statistical analyses for the secondary outcomes.

These findings do not establish whether acetaminophen changes pain, reduces the need for narcotics, improves satisfaction, or affects outcomes beyond the measures and time periods recorded. Although the registry's brief summary describes those as motivations for the study, separate results for narcotic use and satisfaction are not reported in the registry record. Nor do the posted results automatically generalize to settings or patient groups outside the study population at the University of Alabama at Birmingham.

General statistical interpretation: an estimate is most informative when paired with a clear outcome definition, analysis population, and measure of uncertainty. Here, the primary measure is described but lacks a posted comparative estimate, while the secondary comparisons are unadjusted and imprecise. A careful reading therefore distinguishes the observed group summaries from conclusions about the underlying treatment effect. The record is informative about what was posted, but it does not support a definitive claim that the intervention either does or does not produce a clinically meaningful benefit.

13. Why This Trial Matters Statistically

This trial illustrates why the choice of outcome summary matters. Pain is measured repeatedly during recovery, but the registry reports a median of cumulative scores rather than a mean difference or a model-based estimate. That summary communicates the middle of each group's observed values, but it does not by itself quantify the difference between groups or the uncertainty around that difference. Readers should not infer a precise treatment contrast from the matching medians alone.

The record also demonstrates the difference between a primary endpoint and secondary outcomes. Pain scores and analgesic use address related but non-identical questions. A result for medication use cannot replace a comparative analysis of reported pain, and it does not directly answer the investigators' stated interest in narcotic use or satisfaction. Outcome choice determines what a trial can answer, so the scope of interpretation should follow the measures actually posted.

Missing analysis information is statistically consequential. The registry records exclusions before the final primary analysis, but does not report a formal missing-data strategy or sensitivity analysis. It also does not provide a reported primary comparison or a multiplicity plan. These omissions limit assessment of precision, robustness, and the status of the secondary findings as confirmatory or exploratory. They do not establish that the trial was conducted improperly; they mean the record does not provide enough information to evaluate those aspects.

Finally, sample-size planning illustrations based on observed effects should not be mistaken for evidence about the trial's original design or its power. They are scenario calculations under stated assumptions. Distinguishing planning assumptions, observed summaries, and formal analyses is essential for avoiding overconfident conclusions from a small set of posted outcomes.

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 registry record leaves several trial-specific questions unresolved. Most importantly, it does not report a formal between-group analysis for the primary pain endpoint. The group medians and IQRs describe the observed data, but there is no posted primary contrast, confidence interval, or p-value to show how precisely the groups can be compared. The method used to construct the cumulative score from the repeated pain ratings is also not described beyond the endpoint's name and assessment times.

The final primary analysis excluded participants who could not be re-consented and participants lost to follow-up. The registry does not report their outcome values, reasons for loss beyond the re-consent information, or sensitivity analyses addressing the exclusions. It also does not state whether the analyses followed intention-to-treat principles or how deviations from assignment were treated. These limitations make it difficult to assess how missing observations may have influenced the results.

The secondary comparisons are unadjusted and the registry lists no reported analyses. No multiplicity procedure or prespecified hierarchy among outcomes is reported. As a result, those comparisons should not be treated as definitive tests. The record also does not post separate results for narcotic use or patient satisfaction, despite identifying these topics in the study rationale.

The registry does not report the allocation sequence method, allocation concealment, details of masking by role, or the original sample-size justification. It is therefore not possible to evaluate these design details from the posted information. The single-site setting at the University of Alabama at Birmingham also defines the context of the reported study; generalization beyond it requires evidence not contained in the registry record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Randomized Controlled Trial of Oral Acetaminophen for Analgesic Control After Transvaginal Oocyte Retrieval — NCT02418182.
• Registry record last updated 2020-02-18; status last verified 2020-02.
• Results first posted 2020-02-18.
• 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

The registry record describes a completed, randomized, quadruple-masked, parallel-group Phase 4 trial sponsored by the University of Alabama at Birmingham. The study compared two acetaminophen 500mg tablets with two non-active placebo tablets, taken approximately 1 hour before transvaginal oocyte retrieval. It lists 99 enrolled participants and a final primary analysis of 64 women, with 31 in control and 33 in the experimental group.

The primary endpoint was the median cumulative pain score through 60 minutes after the procedure. The median was 2 in both groups; the IQRs were 0 to 3 for control and 1 to 4 for experimental treatment. A formal primary comparison is not reported in the registry record. Two secondary outcomes record analgesic use after the procedure; their unadjusted comparisons are imprecise, and the registry lists no reported analyses. The record also posts adverse-event counts, including no serious events in either group. Important details about the analysis plan, multiplicity, and missing-data methods are not reported.