This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Efficacy and Safety of Etonogestrel + 17β-Estradiol Vaginal Ring (MK-8342B) in Women With Primary Dysmenorrhea (With Optional Extension) (MK-8342B-059) (NCT02668783), a randomized phase 3 study. The primary outcome is Percentage of Participants With ≥3 Point Reduction in Peak Pelvic Pain Score and no Increase in Number of Ibuprofen Tablets Taken at Treatment Cycle 2, Compared to Baseline..
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02668783 |
| Phase | Phase 3 |
| Condition | Moderate to Severe Primary Dysmenorrhea |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Double |
| Enrollment | 25 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Organon and Co |
| Results posted | Yes |
2. Clinical Question
Population
Women with moderate to severe primary dysmenorrhea were the intended study population. The primary-outcome population was to include participants whose vaginal ring was inserted and who had at least one day of diary entry within a 4-day cramping window during both a baseline cycle and a treatment cycle. Because the study was terminated, the committee that was to determine the cramping windows was not assembled, and those windows were not determined.
Intervention
The active intervention was an etonogestrel 125 μg plus 17β-estradiol 300 μg vaginal ring. The intended regimen was 21 days of ring use followed by 7 ring-free days in each cycle. Participants were to receive 4 cycles, or 6 cycles if they also participated in the optional extension.
Comparator
The comparator was a placebo vaginal ring, with the same intended cycle schedule: 21 days of use followed by 7 ring-free days. Ibuprofen was part of the pain-relief tracking: participants recorded the tablets taken in the cramping window. The registry also lists ibuprofen as an intervention, but it does not describe it as the randomized comparison.
Primary question
At Treatment Cycle 2, was the proportion of participants with at least a 3-point reduction in peak pelvic pain score and no increase in ibuprofen tablets taken greater in the active-ring group than in the placebo-ring group, relative to baseline? The registry record reports no analyzed comparison answering this question.
3. Trial Design
This was a Phase 3, randomized, double-blind, parallel-group, placebo-controlled trial sponsored by Organon and Co. Its registered title identifies an optional extension. The stated purpose was to assess efficacy at Treatment Cycle 2 and to assess safety and tolerability. The registry reports enrollment of 25 and a terminated status. The study start date is 2016-02-11, and the primary completion date is 2016-09-07.
The two described groups were assigned to the etonogestrel and estradiol ring or the placebo ring. In both groups, each cycle was intended to consist of 21 days of vaginal ring use and 7 ring-free days. The planned course was 4 cycles, with 6 cycles for participants also taking part in the extension. The record does not report how many participants were randomized to each group, how many completed treatment, or why the trial was terminated.
Randomization is intended to balance baseline differences between groups on average, while double masking is intended to limit the influence of treatment knowledge on participant reports and study conduct. Those are general design principles; the registry does not report the randomization procedure or how masking was maintained. The placebo-ring comparison was intended to distinguish changes during treatment from changes that might occur with time, participation, or use of a vaginal ring without the active ingredients.
The primary assessment was tied to a 4-day cramping window at baseline and another at Treatment Cycle 2. The registry says a committee was to determine those windows for each participant, but termination meant the committee was not assembled and the windows were not determined. Consequently, the registry record does not provide a completed primary-outcome comparison, nor does it describe an analysis population that could be used to reconstruct one.
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
| Stage | ENG-E2 125 μg/300 μg | Placebo |
|---|---|---|
| STARTED | 13 | 12 |
| Treated | 13 | 11 |
| COMPLETED | 0 | 0 |
| NOT COMPLETED | 13 | 12 |
Reasons for not completing this period:
| Reason | ENG-E2 125 μg/300 μg | Placebo |
|---|---|---|
| Pregnancy | 0 | 1 |
| Protocol Violation | 2 | 1 |
| Study terminated by sponsor | 9 | 10 |
| Subject moved | 1 | 0 |
| Withdrawal by Subject | 1 | 0 |
Analysis population for the primary outcome, as defined in the registry: Population was to consist of all participants in whom vaginal ring was inserted \& who had ≥1 day of diary entry each within a 4-day cramping window during a baseline cycle \& a treatment cycle. Due to termination, committee to determine cramping windows was not assembled, cramping windows were not determined \& efficacy data could not be analyzed.
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.
| Characteristic | Unit | ENG-E2 125 μg/300 μg | Placebo | Total |
|---|---|---|---|---|
| Participants analysed | 13 | 12 | 25 | |
| Age, Continuous | Years | 27 (SD 7) | 29 (SD 6) | 28 (SD 6) |
| Sex: Female, Male: Female | Participants | 13 | 12 | 25 |
| Sex: Female, Male: Male | Participants | 0 | 0 | 0 |
6. Primary Endpoint
The registry lists the primary outcome as Percentage of Participants With ≥3 Point Reduction in Peak Pelvic Pain Score and no Increase in Number of Ibuprofen Tablets Taken at Treatment Cycle 2, Compared to Baseline., measured over Baseline 4-day cramping window and Treatment Cycle 2 4-day cramping window, as determined by committee for each participant.
| Element | Registry entry |
|---|---|
| Result type | N/A |
| Measure of spread | not applicable |
| Unit | not stated |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint was the percentage of participants who had both a reduction of at least 3 points in peak pelvic pain score and no increase in the number of ibuprofen tablets taken at Treatment Cycle 2, compared with baseline. The pain score came from a daily rating of worst pain or cramps in the past 24 hours on a 0-to-10 scale, where 0 meant no pain or cramps and 10 meant extreme pain or cramps. Peak pelvic pain was defined as the highest daily score in the relevant 4-day cramping window.
Ibuprofen use was the total number of tablets taken during that same window. Baseline values were to be formed using the mean across the cramping windows of the 2 screening-period menstruations: the mean of the 2 peak pain scores and the mean total number of tablets. The combined endpoint therefore required improvement in pain while avoiding increased rescue-tablet use. It was designed to capture two related but distinct aspects of the participant’s experience rather than pain score alone.
A threshold-based endpoint can be easier to interpret as a proportion meeting a defined response criterion than as a change in average score. However, it also depends on the chosen cutoff and on whether both conditions are met. The registry record does not report the proportion in either group, an effect estimate, or an uncertainty interval. It also notes that the outcome was not reduced to one comparison, and that the intended cramping windows were never determined.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record does not report an analyzed primary outcome. It gives no group-specific responder proportions, treatment contrast, confidence interval, or significance test for the primary question. The record therefore does not establish the size or direction of any difference between the active ring and placebo ring on the combined pain-and-ibuprofen endpoint. The absence of a reported estimate should not be read as evidence that the groups were equal or that the endpoint showed no effect.
The study status is terminated, and enrollment is reported as 25. The record says the committee responsible for determining individual cramping windows was not assembled because of termination. Since the primary outcome depended on diary entries within windows designated at baseline and Treatment Cycle 2, the failure to determine those windows is directly relevant to whether the endpoint could be assessed as planned. The registry does not state whether any participants had otherwise usable diary data or whether an alternative assessment was made.
The listed secondary outcomes include change from baseline in peak pelvic pain score, days with no impact on physical, work or school, and social or leisure activities, a low pain score with no ibuprofen use, a combined response involving reduced ibuprofen intake, and change in mean pelvic pain score. The record does not report estimates or analyses for these outcomes either. It reports 8 outcome measures but no analyses. No secondary result can therefore fill the gap in the primary comparison.
Precision cannot be assessed without estimates and their uncertainty. In general, a confidence interval describes a range of values compatible with the data under a specified method; it indicates how uncertain an estimate is, rather than guaranteeing that the true value lies within the interval. No confidence interval is reported in the registry record. The enrollment figure alone cannot show how precise a treatment estimate would have been, especially without the number analyzed, outcome variability or event counts for the primary endpoint.
The record’s planning assumptions describe an illustration based on an observed effect, using a two-sided significance level of 0.05, equal allocation, and a normal approximation, with the target effect expressed as a fraction of the observed effect. Those assumptions are not the trial’s own design justification. Such planning values are not observed power and do not recover the missing treatment comparison. No sample-size justification, planned interim analysis, or detailed statistical analysis plan is reported in the registry record.
9. Statistical Methods Explained
The registry describes the trial as randomized, double-blind, parallel-group, and placebo-controlled. These terms describe the intended structure, not the completeness of the reported analysis. Randomization assigns participants to groups by chance; in general, it helps reduce systematic differences at baseline, although it does not guarantee balance in a small study. Double masking aims to keep participants and relevant study personnel unaware of assigned treatment. A parallel design means the assigned groups are followed as distinct groups rather than having every participant receive each treatment in sequence. The record does not report the specific randomization method, allocation concealment procedure, or masking checks.
What was the planned comparison?
The registered primary question compared the proportion meeting a joint response definition in the active-ring group with the proportion in the placebo-ring group at Treatment Cycle 2. A participant counted as meeting the definition only if peak pelvic pain fell by at least 3 points from baseline and ibuprofen use did not increase. This is a binary, threshold-based outcome for each participant, even though the underlying pain ratings and tablet counts are recorded as numerical values. The registry record contains no group proportions or treatment contrast, so no effect measure can be interpreted.
For a comparison of proportions, a statistical analysis would ordinarily estimate each group’s response and quantify the difference or another contrast, then report uncertainty. The choice of contrast and statistical model matters: different methods can target different summaries and rely on different assumptions. These are general principles. The registry record does not report which contrast, model, test, or confidence-interval method was specified or used. It also does not report a p-value.
How were the measurements defined?
Participants were asked to rate their worst pain or cramps in the preceding 24 hours on a 0-to-10 scale. The peak score for a cramping window was the highest daily score within that window. Tablet use was the total number of ibuprofen tablets taken during the same 4-day period. The baseline values were to be based on the mean values from the 2 menstruations during screening. Treatment Cycle 2 was compared against those baseline values.
These definitions matter because endpoint construction determines what counts as response. A peak score captures the highest reported daily pain in the window rather than an average across days. The combined endpoint also requires consideration of rescue medication use, so a pain-score reduction alone would not satisfy the registered response definition. In general, thresholds make a continuous measure into a yes-or-no classification; participants near a cutoff may be classified differently despite having similar underlying scores. The registry does not report how diary completion, missing days, or values at the threshold were handled in analysis.
What can be concluded about precision and planning?
Precision describes the uncertainty around an estimated effect. In general, confidence intervals communicate that uncertainty, while a significance test addresses compatibility with a specified null hypothesis under an analysis model. Neither an interval nor a test is reported for the primary outcome. Without the estimate and its uncertainty, the magnitude, direction, and precision of the planned treatment comparison cannot be evaluated from the registry record.
The registry’s sample-size assumptions describe planning illustrations based on the observed effect, with a two-sided significance level of 0.05, equal allocation, and a normal approximation. The target effect is framed as a stated fraction of the observed effect. The note distinguishes time-to-event planning, which gives a total number of events using the Schoenfeld approach, from other planning calculations, which give participants per arm. These illustrations are not the study’s own design, and sample-size calculations are not observed power. No trial-specific sample-size justification or numerical planning result is reported in the registry record. The record also gives no observed primary effect from which a reader could assess the underlying basis for such an illustration.
Why does termination affect interpretation?
The registry states that termination prevented the committee from determining each participant’s cramping window. That was not a minor detail: the primary outcome required observations in specifically identified baseline and Treatment Cycle 2 windows. If measurement windows cannot be set, the registry’s intended endpoint cannot be assembled in the described manner. The record does not say whether any alternative endpoint definitions or analyses were used. It reports no analyses, so there is no basis for inferring how incomplete measurement was addressed.
In general, over-dispersion occurs when observed variation in count data exceeds what a chosen model expects; if present and ignored, uncertainty estimates can be too narrow. That concept may be relevant to some analyses of tablet counts, but the registry does not report a count-data model or evidence about over-dispersion. It would therefore be inappropriate to claim that over-dispersion was assessed or that a particular model was used. Statistical methods beyond the design labels and planning assumptions described in the registry record are not reported.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists several secondary outcomes, including changes in peak and mean pelvic pain scores, changes in days without impact on activities, and response definitions that combine pain scores with ibuprofen use. Testing multiple outcomes can raise a multiplicity issue: in general, the more hypotheses examined, the greater the chance of at least one apparently unusual result under a set of null effects. Statistical plans may address this by prioritizing outcomes, adjusting inference, or treating secondary analyses as exploratory. The registry record does not report a multiplicity procedure, an ordered testing strategy, or which outcomes were intended to support confirmatory conclusions.
Missing-data handling is also not reported. The primary endpoint required diary entries in defined cramping windows at baseline and Treatment Cycle 2. The registry states that the committee responsible for setting these windows was not assembled, and the windows were not determined. It does not report the amount or pattern of missing diary data, how participants with incomplete records would be classified, or whether imputation or sensitivity analyses were planned or conducted.
The record describes an intended primary-outcome population consisting of participants with an inserted ring and at least one day of diary entry in each of a baseline and treatment cramping window. Because the windows were not determined, the record does not establish who met this criterion. It does not report an intention-to-treat, per-protocol, or safety analysis population, nor does it report how participants were handled after randomization. These omissions prevent assessment of whether the analysis population preserved the randomized comparison and how missing observations might affect interpretation.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| ENG-E2 125 Microgram/300 Microgram | 0 | 13 | 0.0% |
| Placebo | 0 | 11 | 0.0% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| ENG-E2 125 Microgram/300 Microgram | 1 of 13 |
| Placebo | 2 of 11 |
Most frequent non-serious adverse event terms
| Event term | Organ system | ENG-E2 125 Microgram/300 Microgram | Placebo |
|---|---|---|---|
| Vomiting in pregnancy | Pregnancy, puerperium and perinatal conditions | 0 of 13 | 1 of 11 |
| Mood swings | Psychiatric disorders | 1 of 13 | 0 of 11 |
| Vulvovaginal discomfort | Reproductive system and breast disorders | 0 of 13 | 1 of 11 |
The adverse-event record gives separate figures for serious events and other adverse events in the active-ring and placebo groups. For the ENG-E2 125 Microgram/300 Microgram group, 13 participants were at risk for serious adverse events and 0 were reported as affected; 13 were at risk for other adverse events and 1 was affected. For the placebo group, 11 participants were at risk for serious adverse events and 0 were reported as affected; 11 were at risk for other adverse events and 2 were affected.
These are counts in the registry record, not a complete safety analysis. They do not provide event descriptions for the other adverse events, exposure-adjusted rates, timing, severity details, or information about withdrawals due to adverse events. The record lists no serious adverse-event terms. Death counts are not reported in the registry record; a blank value should not be interpreted as a reported count of zero.
Because the study was terminated and the record does not describe the safety analysis population or duration of follow-up for these figures, the counts should be read narrowly. They describe the recorded affected participants in each listed group, not comparative evidence that one ring has a particular safety profile. The registry record does not report a statistical comparison of these safety counts.
12. What the Result Does, and Does Not, Mean
The posted registry record establishes that a Phase 3 randomized, double-blind, placebo-controlled study was planned to compare an etonogestrel and estradiol vaginal ring with a placebo ring for moderate to severe primary dysmenorrhea. It identifies a clinically interpretable primary question: whether more participants would meet a combined pain-reduction and no-increase-in-ibuprofen criterion at Treatment Cycle 2. It also documents an enrollment of 25 and a terminated status.
It does not establish the answer to that question. No primary outcome estimate, group response, effect size, confidence interval, or inferential result is reported. The missing committee determination of cramping windows further prevents a reader from knowing how the intended endpoint would have been assembled. No conclusion that the active ring was better, worse, or similar to placebo follows from the absence of a reported comparison.
The recorded serious adverse-event counts are limited observations, not proof that serious events could not occur or a complete comparison of safety. The other adverse-event counts are also limited and lack descriptions. Follow-up details, the number analyzed, and a fuller account of adverse events are not reported in the registry record.
In general, a trial result is interpreted by considering the estimate, its precision, the analysis population, outcome definitions, missing data, and how the study was conducted. Here, key pieces are not reported, and the primary measurement process was interrupted by termination. The registered objectives describe what the study aimed to assess; they should not be mistaken for evidence that the intended efficacy or safety analyses were completed.
13. Why This Trial Matters Statistically
This trial illustrates why a registered question and a reported answer are not the same thing. The primary endpoint was defined as a joint response: a threshold reduction in peak pelvic pain together with no increase in ibuprofen use. That definition combines symptom measurement and rescue-medication use, making the clinical question more specific than a comparison of pain scores alone. It also makes measurement procedures essential, because both elements must be evaluated over the relevant cramping window.
The registry record says the committee assigned to determine those windows was not assembled after termination. This connects trial operations directly to statistical interpretability: without the defined observation windows, the intended endpoint cannot be interpreted as a completed participant-level response in the way described. The registry lists 25 enrolled participants but reports no analysis, so the distinction between enrollment, outcome measurement, and analysis remains important.
For biostatistical reading, the record is a reminder to separate three kinds of information: a planned estimand or question, the measurement and analysis procedures, and the resulting estimate with its uncertainty. The record gives detail on the intended question and some measurement rules, but does not report an analyzed comparison or a detailed statistical plan. No single treatment effect can be reconstructed from the registry entries.
It also shows why safety counts need context. Counts of participants affected are useful descriptive information, but they do not by themselves convey exposure duration, event characteristics, or the uncertainty around a group comparison. A reader should distinguish those descriptive observations from evidence about comparative risk.
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 efficacy is that the registry reports no analyses and no primary-outcome results. There is no reported response proportion in either group, no treatment-effect estimate, and no uncertainty interval. The study’s terminated status and the absence of committee-determined cramping windows mean the primary endpoint’s planned measurement framework was not completed as described. The reason for termination is not reported in the registry record.
The enrollment of 25 is reported, but group-level randomized numbers, the number treated, the number with usable diary information, and the number analyzed are not reported. The primary-outcome population was described in terms of ring insertion and diary entry in designated windows, but the record does not establish which participants satisfied those criteria. This limits assessment of attrition, missingness, and whether any analysis would preserve the randomized groups.
The registry record does not report the randomization procedure, allocation concealment, details of masking, a statistical analysis plan, multiplicity handling, missing-data methods, or interim analyses. It also does not provide details about the numerical analysis of secondary outcomes. These are not assumptions that can be filled in from the randomized and double-blind design labels.
The safety information is limited to affected-participant counts and group denominators for serious and other adverse events. Event descriptions and follow-up context are not reported, and death counts are not reported in the registry record. The available information should therefore be treated as a partial registry account rather than a complete efficacy or safety evaluation.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Efficacy and Safety of Etonogestrel + 17β-Estradiol Vaginal Ring (MK-8342B) in Women With Primary Dysmenorrhea (With Optional Extension) (MK-8342B-059) — NCT02668783.
- Registry record last updated 2024-05-28; status last verified 2022-02.
- Results first posted 2017-11-14.
- 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.
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18. Record Summary
The registry describes a Phase 3 randomized, double-blind, parallel-group, placebo-controlled trial of an etonogestrel 125 μg plus 17β-estradiol 300 μg vaginal ring for moderate to severe primary dysmenorrhea. The intended primary endpoint was the percentage of participants with at least a 3-point reduction in peak pelvic pain and no increase in ibuprofen tablets at Treatment Cycle 2 compared with baseline. The intended ring schedule was 21 days of use followed by 7 ring-free days per cycle.
The record reports enrollment of 25 and a terminated status. It states that the committee to determine individual cramping windows was not assembled and that the windows were not determined. No analyses or primary-outcome results are reported. The adverse-event record lists 0 serious events among 13 at risk in the active-ring group and 0 among 11 in the placebo group; other adverse events affected 1 and 2 participants, respectively. The record does not provide a treatment-effect estimate or enough information to determine comparative efficacy.