Dextromethorphan as a Novel Non-opioid Adjunctive Agent for Pain Control in Medication Abortion: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Dextromethorphan as a Novel Non-opioid Adjunctive Agent for Pain Control in Medication Abortion (NCT03480009), a randomized phase 3 study. The primary outcome is Worst Pain Measurement Via Numeric Rating Scale (NRS-11).

2. Clinical Question

3. Trial Design

The registry describes a completed, randomized, parallel-group trial with quadruple masking. Its brief summary calls the study double-blinded, while the masking field specifies quadruple masking; the registry record does not explain this difference in wording. The listed enrollment is 156, and the four arm descriptions divide participants by study medication and whether they opted for or declined a narcotic prescription.

The active study medication was dextromethorphan hydrobromide. The placebo was Avicel PH101 microcrystalline cellulose. Participants who opted for narcotics could receive oxycodone or other standard narcotics; participants in the other two arms declined a narcotic. The registry presents dextromethorphan-versus-placebo comparisons separately for these two prescription-choice groups. It does not report enough detail to establish how participants’ decision about a narcotic prescription was incorporated into randomization.

The primary endpoint was worst pain measured by text-message self-report during the first 24 hours after misoprostol administration. Secondary outcomes listed in the record include mean pain scores over 24 hours and satisfaction with pain control on a 4-point Likert scale. The posted results include mean pain-score summaries, but satisfaction results are not reported in the registry record.

The record lists the study as Phase 3 and completed. It gives a start date of 2018-07-28 and a primary completion date of 2019-06-30. The protocol’s sample-size justification, details of any interim analyses, and a full statistical analysis plan 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: Intention to treat population where all participants were analyzed as randomized. Missing worst pain responses were imputed as 10 being the worst pain possible.

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: Due to unequal distribution during study conduct, the protocol was modified to recruit all participants rather than into study arms. Data were analyzed as: intervention stratified by narcotic prescription status.

6. Primary Endpoint

The registry lists the primary outcome as Worst Pain Measurement Via Numeric Rating Scale (NRS-11), measured over Over 24 hours starting from misoprostol administration.

The primary endpoint is the participant’s worst pain score during the 24 hours beginning with misoprostol administration. Participants reported pain through a text-messaging system using the Numeric Rating Scale, from 0 for “no pain” to 10 for “the worst pain possible.” The registry reports the endpoint as a median with an interquartile range for each arm.

Worst pain captures the highest reported intensity during the specified period, rather than the average experience across that period. This can be useful when a study question concerns the most intense pain participants experience. In general, a median describes the midpoint of observed scores, while the interquartile range describes the middle half of their distribution; neither alone describes every participant’s experience.

The registry states that all participants were analyzed as randomized for this endpoint. It also states that missing worst-pain responses were imputed as 10. Because that imputation assigns the scale’s highest score to missing responses, the reported summaries reflect both observed responses and that stated missing-data rule. The number of missing responses and the results under other missing-data assumptions are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary endpoint is summarized with medians and interquartile ranges. This is a distribution-oriented description: the median marks the center of the ordered scores, and the interquartile range gives the range containing the middle half. These summaries are particularly interpretable when the outcome is an ordered rating scale and the distribution may not be well represented by a mean and standard deviation. The registry does not report a dispersion estimate beyond the interquartile range for the primary endpoint.

What the Wilcoxon comparison assesses

The registry reports Wilcoxon (Mann-Whitney) tests for the two primary comparisons. In general, this rank-based method compares the ordering of observations between groups. It does not, without additional assumptions, test only a difference between medians. If the shapes or spreads of the group distributions differ, a rank-test result can reflect more than a shift in the medians. The registry does not report the underlying individual scores or additional distributional diagnostics, so the comparison should be interpreted as a test of the observed distributions rather than as a precise estimate of a median difference.

The reported p-value is evidence about how compatible the observed data are with the test’s null hypothesis, under the method’s assumptions. It is not a measure of the probability that the null hypothesis is true, and it does not give the size or practical importance of an effect. A confidence interval, when reported, describes uncertainty around an effect estimate under a specified procedure. The registry does not post confidence intervals for the primary Wilcoxon comparisons.

How to read the mean-score results

The secondary mean pain-score summaries are reported with standard deviations. In general, a mean describes the arithmetic center of scores, while a standard deviation describes their spread around that mean. These summaries answer a different descriptive question from the primary endpoint’s median worst score: they concern marginal mean pain scores over 24 hours rather than each participant’s worst score.

The posted recalculations compare the arm means using unadjusted differences and confidence intervals calculated from the summary statistics. A confidence interval conveys the range of effect values reasonably compatible with the data and the calculation method; it is not a guarantee that the true value lies in the interval. These recalculations are not adjusted analyses, and they do not supersede the registry’s reported analyses. No discrepancy is flagged in the registry data.

The registry’s reported secondary tests are Wald chi-square tests. In general, a Wald test compares an estimated quantity with its value under a null hypothesis, scaled by its estimated uncertainty. The record does not provide the model specification, the exact tested parameter, or enough detail to reconstruct the sponsor’s Wald analyses. The recalculated mean differences and their p-values therefore need not match those reported tests: they are based on a different calculation from the posted group summaries.

Why variability and sample size matter

In general, a noisy outcome makes it harder to distinguish a small group difference from random variation. The secondary mean-score standard deviations are relatively large in relation to the posted mean differences, which is reflected in the broad recalculated confidence intervals. This is a statement about the posted summaries and their precision, not a conclusion that the treatments are equivalent.

The sample-size illustrations use the observed effect as a planning input, with stated assumptions of a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. They show how a hypothetical future study’s required participants per arm would change when planning for different fractions of the observed effect. They are not the trial’s observed power, and they do not establish that the original study was designed using those assumptions. The registry’s own sample-size justification is not reported in the registry record. Because the illustrations are based on observed effects, they should be treated as planning scenarios rather than proof that a particular future sample size is sufficient.

Missing responses and analysis population

The primary outcome population is described as intention to treat, with participants analyzed as randomized. Missing worst-pain responses were imputed as 10. In general, an imputation rule makes an explicit assumption about unobserved outcomes; the result can depend on whether that assumption is plausible and on how many responses are missing. The registry does not report the number of missing responses, the timing or pattern of missingness, or sensitivity analyses. The record also does not describe the analysis population or missing-data handling for each secondary outcome.

The record lists multiple outcomes and comparisons, but the adjustment strategy for multiple testing is not reported in the registry record. Without that information, unadjusted secondary p-values should be treated as exploratory evidence rather than as definitive, stand-alone findings.

10. Analyses Reported by the Sponsor

The registry reports Wilcoxon (Mann-Whitney) tests for the primary worst-pain comparisons, with p = .20 for participants who opted for a narcotic prescription and p = .20 for those who declined one. It does not report a primary effect estimate or confidence interval for either test. Those reported analyses are therefore the direct registry results for the primary endpoint.

For mean pain scores, the registry reports Wald chi-square tests, with p = .99 for the comparison among participants who opted for a narcotic prescription and p = .56 among those who declined one. The recalculations use the posted means and standard deviations to produce unadjusted mean differences, confidence intervals, and p-values. They are simple comparisons from summary statistics and do not reproduce the registry’s Wald analyses. The numerical outputs differ, as can occur when calculations use different methods or model specifications.

No discrepancy is flagged in the registry record. The recalculations should be read as supplementary, unadjusted descriptions, not as corrections to or replacements for the sponsor’s reported analyses. The model details needed to reproduce the Wald tests are not reported in the registry record.

11. Multiplicity, Missing Data and Analysis Populations

The registry reports one primary endpoint with two separate comparisons: dextromethorphan versus placebo among participants who opted for a narcotic prescription, and the same comparison among participants who declined one. It also lists secondary outcomes, including mean pain scores and satisfaction with pain control. The number of hypotheses in the full analysis plan and whether the two primary comparisons were treated as co-primary are not reported in the registry record.

How the investigators handled multiplicity is not reported in the registry record. In general, testing several endpoints or comparisons can increase the chance of at least one apparently unusual result under a set of null hypotheses. Prespecifying a hierarchy or adjusting inference can help control that issue, but the record does not say whether either approach was used. The secondary p-values should therefore be viewed with that uncertainty in mind, rather than as independently confirmatory results.

The primary analysis population is described as intention to treat, meaning participants were analyzed as randomized. For missing worst-pain responses, the registry says the score was imputed as 10. The number of missing responses, the reasons for missingness, and the sensitivity of results to other missing-data assumptions are not reported in the registry record. In general, the effect of an imputation rule depends on both how many outcomes are missing and whether the rule reasonably represents their unobserved values.

Missing-data methods for the secondary outcomes are not reported in the registry record. The registry also does not report interim analyses, the trial’s sample-size justification, or a complete statistical analysis plan. These omissions limit assessment of whether the posted analyses follow a prespecified plan and how robust the findings are to analytic choices.

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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: uterine hemorrhage (1.6%).

The registry reports serious adverse events in the four arms. One participant in the dextromethorphan arm who opted for a narcotic prescription had a serious adverse event; the placebo arm in that prescription-choice group had none. No serious adverse events are reported in either arm among participants who declined a narcotic prescription. The record lists zero deaths in all four arms. Uterine hemorrhage is the listed serious-event term, reported as 1.6%.

These are descriptive counts from the registry, not a formal comparison of safety between groups. The record does not provide enough information to assess the nature, timing, relatedness, or duration of the serious event. A count of zero in an arm does not establish that the risk is absent, and a single event does not by itself establish a treatment relationship. The groups also differ in size, so the counts should be read in the context of each arm’s reported number at risk.

The registry separately reports other, non-serious adverse events, but those counts should not be combined with the serious-event figures. The available safety summaries do not support conclusions about events that were not reported in the registry record.

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

The posted primary results describe worst-pain score distributions in two separate comparisons, defined by whether participants opted for a narcotic prescription. The reported medians and interquartile ranges summarize those distributions, and the Wilcoxon tests provide the registry’s inferential comparisons. The reported p-values do not establish that the groups are equivalent, and the absence of a small p-value is not proof that there is no difference.

The primary results do not include an estimated between-arm effect with a confidence interval. That means the registry record does not show a direct estimate of the size and precision of the primary contrast. The secondary mean-score results offer additional descriptive information, while their recalculated differences and intervals are unadjusted and should not be mistaken for the sponsor’s reported Wald analyses. Satisfaction results are not reported in the registry record.

The trial’s interpretation also depends on the stated handling of missing primary responses: missing worst-pain values were assigned the highest score on the scale, and participants were analyzed as randomized. The number of missing responses and alternative analyses are not reported, so the sensitivity of the endpoint summaries to missing-data assumptions cannot be determined from the record.

These results do not establish whether the study had adequate power for its intended question, because the protocol’s sample-size justification is not reported in the registry record. The sample-size illustrations based on observed effects are planning scenarios, not evidence of the trial’s observed power. Taken together, the posted results describe the analyzed groups and the analyses reported in the registry; they do not by themselves settle the size, precision, or practical importance of any difference.

14. Why This Trial Matters Statistically

This trial illustrates why the choice of endpoint summary matters. Worst pain is a participant-level maximum over the stated period, while mean pain scores describe average pain across that period. Medians and interquartile ranges communicate the center and spread of the worst-score distributions; means and standard deviations describe a different feature of the secondary outcome. These summaries answer related but distinct questions.

The trial also separates comparisons according to participants’ narcotic-prescription choice. That structure is important when reading the results: the registry reports two dextromethorphan-versus-placebo comparisons rather than one overall contrast. The record does not explain the role of prescription choice in the randomization process, so the distinction should be reported as part of the arm structure rather than interpreted as a randomized comparison of choosing or declining narcotics.

Another statistical lesson is the difference between a reported model-based test and a recalculation from group summaries. The registry’s secondary Wald tests and the unadjusted recalculations do not yield identical p-values. Without the model specification, the recalculations cannot reproduce the reported tests, and they should remain supplementary.

Finally, missing-data assumptions, multiplicity, and sample-size planning affect how much confidence readers can place in an interpretation. The registry specifies an imputation rule for the primary endpoint but does not report the amount of missingness or sensitivity analyses. It also does not report a multiplicity strategy or the trial’s sample-size justification. These gaps do not erase the posted findings, but they set limits on what the findings can establish.

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.

The registry’s primary results provide medians, interquartile ranges, and Wilcoxon p-values, but no effect estimate or confidence interval for either primary comparison. This limits direct assessment of the size and precision of the primary contrasts. The record also does not report the individual outcome distributions, so readers cannot examine features such as skewness or the frequency of scores at the scale limits.

Missing primary responses were imputed as 10, but the number of missing responses, reasons for missingness, and sensitivity analyses are not reported in the registry record. The record does not describe missing-data handling for the secondary outcomes. These details matter because missingness and the assumptions used to address it can influence results.

The study is described as both double-blinded in the brief summary and quadruple-masked in the masking field, with no explanation of the different wording. The record also describes four arms that differ according to whether participants opted for or declined a narcotic prescription, but it does not report how that choice was handled in the randomization process. The resulting comparisons should therefore be read as the specific arm comparisons reported, not as evidence about the effect of choosing a narcotic prescription.

Only mean pain-score results are posted among the listed secondary outcomes; satisfaction results are not reported in the registry record. The statistical analysis plan, sample-size justification, multiplicity approach, and details of any interim analyses are also not reported. The small numbers in the arms that declined a narcotic prescription are relevant context for interpreting those comparisons, but the registry does not provide primary effect intervals to quantify their precision.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Dextromethorphan as a Novel Non-opioid Adjunctive Agent for Pain Control in Medication Abortion — NCT03480009.
• Registry record last updated 2020-08-06; status last verified 2020-07.
• Results first posted 2020-08-06.
• 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

NCT03480009 is a completed randomized, parallel-group Phase 3 trial of dextromethorphan as an adjunct for pain control during medication abortion. The registry lists enrollment of 156 and describes quadruple masking, while its brief summary uses the term double-blinded. Participants received dextromethorphan or placebo and were grouped by whether they opted for or declined a narcotic prescription.

The primary outcome was worst pain during the first 24 hours after misoprostol administration, reported as a median and interquartile range. The registry reports Wilcoxon comparisons separately within each prescription-choice group. Mean pain scores are posted as a secondary outcome; satisfaction results are not reported in the registry record. Missing primary responses were imputed as 10. The registry does not report the sample-size justification, multiplicity strategy, or sensitivity analyses for missing data.