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 in Women at Risk for Pregnancy (MK-8342B-061) (NCT02524288), a na phase 3 study. The primary outcome is Number of In-Treatment Pregnancies Per 100 Woman-Years of Exposure in Participants 18-35 Years of Age (Pearl Index).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02524288 |
| Phase | Phase 3 |
| Condition | Contraception |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 1941 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Organon and Co |
| Results posted | Yes |
2. Clinical Question
Population
The primary efficacy population was participants 18-35 years of age who inserted at least 1 ENG-E2 ring and had at least 1 at-risk treatment cycle, or had a treatment cycle in which a pregnancy occurred. The trial title describes healthy women 18 years of age and older at risk for pregnancy; the primary endpoint description specifies the age range of 18-35 years.
Intervention
Participants received the ENG-E2 125 μg/300 μg vaginal ring. Each cycle consisted of 21 days of ring use followed by 7 vaginal ring-free days, for up to 13 cycles.
Comparator
There was no separate comparator group. The record describes a single-group trial, with allocation listed as NA and masking listed as none. The results therefore do not provide a randomized comparison with another treatment or a control group.
Primary question
The primary question was how many in-treatment pregnancies occurred per 100 woman-years of exposure among participants 18-35 years of age, as measured by the Pearl Index. The registry record cautions that the efficacy result should be interpreted carefully because the trial ended early and the denominator's at-risk cycles came from uncleaned diary data. The primary endpoint result itself is not reported in the registry record.
3. Trial Design
This was a phase 3, single-arm clinical trial of the ENG-E2 125 μg/300 μg vaginal ring in women at risk for pregnancy. The registry lists an enrollment of 1941. Participants could receive the ring for up to 13 cycles. Each cycle was defined as 21 days of vaginal ring use followed by 7 ring-free days. The stated timeframe for the primary endpoint was up to 1 year (13 28-day cycles).
The trial had no randomized allocation: allocation is listed as NA, masking as none, and the model as single group. All participants received the named intervention; there is no concurrently assigned comparison arm described in the record. This design can describe outcomes observed during use in the enrolled population, but it cannot by itself separate treatment-associated outcomes from changes that might occur over time or from other influences.
The record lists the trial status as terminated and says that efficacy results should be interpreted with caution because product development was discontinued and the trial ended early. The dates listed for the start and primary completion are 2015-08-31 and 2016-09-16. The registry record does not report why the trial was terminated beyond the stated discontinuation of product development, nor does it describe whether early stopping was planned.
The stated aims included assessing contraceptive efficacy and safety and tolerability. The primary efficacy measure was the Pearl Index for participants 18-35 years of age. Enrollment does not establish how many participants contributed to this endpoint: the endpoint population had additional eligibility criteria, and the record does not report the endpoint denominator or the number of pregnancies. The sample-size justification and detailed 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
| Stage | ENG-E2 125 μg/300 μg |
|---|---|
| STARTED | 1941 |
| Treated | 1936 |
| COMPLETED | 0 |
| NOT COMPLETED | 1941 |
Reasons for not completing this period:
| Reason | ENG-E2 125 μg/300 μg |
|---|---|
| Adverse Event | 115 |
| Lost to Follow-up | 216 |
| Non-Compliance With Protocol | 32 |
| Non-Compliance With Study Drug | 14 |
| Pregnancy Wish | 6 |
| Protocol Violation | 6 |
| Screen Failure | 2 |
| Site Discontinued Study Participation | 1 |
| Study Terminated By Sponsor | 1417 |
| Subject Moved | 32 |
| Withdrawal by Subject | 76 |
| Pregnancy | 22 |
Analysis population for the primary outcome, as defined in the registry: All participants assigned to treatment who inserted at least 1 ENG-E2 ring, and who had at least 1 "at risk" treatment cycle, or participants with a treatment cycle (at risk or not) in which a pregnancy had occurred (i.e., treatment cycle containing an estimated conception date for a pregnancy).
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 |
|---|---|---|
| Participants analysed | 1941 | |
| Age, Continuous | Years | 27.6 (SD 6.2) |
| Sex: Female, Male: Female | Participants | 1941 |
| Sex: Female, Male: Male | Participants | 0 |
6. Primary Endpoint
The registry lists the primary outcome as Number of In-Treatment Pregnancies Per 100 Woman-Years of Exposure in Participants 18-35 Years of Age (Pearl Index), measured over Up to 1 year (13 28-day cycles).
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | Pregnancies per 100 woman years |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint was the number of in-treatment pregnancies per 100 woman-years of exposure in participants 18-35 years of age, expressed as the Pearl Index. A rate such as this relates the number of pregnancies to time under observation, rather than presenting pregnancy counts without regard to exposure time. In general, expressing an event rate against person-time can help describe outcomes when participants contribute different amounts of follow-up.
The record defines the numerator as in-treatment pregnancies with a conception date in any in-treatment cycle. The denominator includes all treatment cycles for each participant from the first treatment cycle to the last, whether the last cycle resulted from discontinuation or completion, and regardless of whether a cycle was considered at risk. One woman-year is defined as 13 treatment cycles of 28 days each. The registry specifically cautions that the denominator's count of at-risk cycles was based on uncleaned diary data because of product-development discontinuation and early trial termination.
The endpoint is intended to describe pregnancy incidence during treatment exposure, not a comparison against another group. Its estimate and precision would be needed to judge what the observed data indicate. Neither the Pearl Index value nor a confidence interval is reported in the registry record, so the endpoint's observed magnitude and uncertainty cannot be assessed from this record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The trial record identifies a clinically interpretable efficacy question: the frequency of in-treatment pregnancies relative to exposure time among participants 18-35 years of age. However, it does not report the primary Pearl Index estimate, the pregnancy count, the contributing exposure, or an interval expressing uncertainty. Consequently, the posted record does not establish the observed level or precision of the primary outcome. A numerical conclusion about the endpoint cannot be drawn from the information recorded.
The trial's single-group design also sets a limit on interpretation. Without a concurrent comparison group, the results cannot estimate a randomized difference between the ring and another treatment or no treatment. A single-group rate could describe events observed while participants used the ring, but it would not isolate the effect of the intervention from other factors. No comparative efficacy conclusion is supported by this design.
The registry cautions that the denominator for at-risk cycles relied on uncleaned diary data. The Pearl Index definition includes all cycles from first to last treatment cycle, even when a cycle was not considered at risk, while the endpoint population includes participants with at least one at-risk cycle or a pregnancy-containing cycle. This makes careful interpretation dependent on how cycles and pregnancy timing were recorded and classified. The record does not explain the degree or direction of any resulting measurement error, so its effect on the estimate cannot be quantified.
Early termination following discontinuation of product development is relevant to the amount and completeness of follow-up. The record states a maximum follow-up timeframe, not that every participant completed it. It does not report how many completed the intended treatment period, how much exposure was observed, or whether early termination changed the analysis. Therefore, the maximum planned timeframe should not be read as the actual follow-up for all participants.
The registry lists no analysis records and does not report a confidence interval, hypothesis test, or detailed statistical plan. Absence of these details in the registry is not evidence that no analyses were performed; it means their methods and results are not reported in the registry record. The listed enrollment of 1941 is not a substitute for the endpoint analysis population or its exposure denominator.
Safety information is also descriptive. The record lists participants with serious adverse events and serious-event terms, but does not provide a comparison group or establish that those events were caused by the ring. Taken together, the record describes the intended design and endpoint and includes limited safety counts, while leaving the primary efficacy estimate and its precision unavailable. Interpretation should remain bounded by those reporting and design limitations.
9. Statistical Methods Explained
The statistical methods that can be described from the record are limited. The primary endpoint is a Pearl Index, expressed as pregnancies per 100 woman-years. No primary outcome estimate, confidence interval, hypothesis test, or detailed analysis procedure is reported in the registry record. The concepts below explain how such measures are generally interpreted; they do not supply missing results or establish which unreported procedures were used in this trial.
What does a rate per woman-year represent?
In general, an incidence rate relates the number of events to the amount of time participants were observed and exposed. Participants may contribute different follow-up durations, so person-time can provide a common scale for describing event frequency. A rate does not directly state the probability that an individual participant will experience an event over a fixed period. That probability depends on the duration and pattern of risk and cannot be recovered from a rate alone without additional assumptions.
For this endpoint, the record defines one woman-year as 13 treatment cycles of 28 days. It defines the numerator using in-treatment pregnancies with a conception date in an in-treatment cycle. The denominator includes treatment cycles from each participant's first through last cycle, whether treatment ended through discontinuation or completion, and includes cycles whether or not they were considered at risk. Those operational definitions matter: the value would depend on how pregnancy dates, cycle boundaries, and exposure time were classified. The record warns that the at-risk cycle data came from uncleaned diaries.
What does the Pearl Index tell a reader?
In general, the Pearl Index is an event rate scaled to a stated exposure-time unit. It allows event frequency to be described across a group with differing amounts of time under observation. It is not a randomized treatment contrast, and it should not be read as a direct guarantee about any individual outcome. It also does not make follow-up and event ascertainment irrelevant: the interpretation depends on the numerator being captured and the denominator representing the intended exposure.
The registry names the measure and describes its calculation, but does not report its value or the underlying pregnancy count and exposure. It also does not report a confidence interval. Thus, neither the magnitude of the observed rate nor its statistical precision can be reviewed from the record. No additional estimate should be inferred from enrollment alone.
Why is an interval estimate useful?
In general, a confidence interval communicates uncertainty around an estimated quantity. It reflects how compatible a range of values is with the observed data under the interval's statistical assumptions. A narrow interval indicates greater precision than a wide interval, but an interval does not correct bias in measurement, selection, or study design. In a single-group study, an interval around a rate would describe uncertainty in that rate; it would not create a comparison group or establish a causal effect.
No confidence interval or interval method is reported for the primary endpoint in the registry record. The record also does not state whether the analysis accounted for variation between participants, how pregnancy dates were handled when uncertain, or how incomplete diary data were processed.
What can be said about the planning illustrations?
General sample-size planning uses assumptions about the target statistical power, significance level, allocation, analysis method, and effect to be detected. The planning illustrations associated with this analysis are described as using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. They use fractions of the observed effect as planning targets; for time-to-event calculations, the stated output is a total event count, while other calculations are expressed as participants per arm for 80% or 90% power where applicable.
These are planning illustrations, not the trial's own design or an assessment of observed power. The trial itself was single-arm, whereas the stated planning assumptions describe a hypothetical two-arm allocation. The registry record does not report its sample-size justification, and the primary outcome estimate needed to evaluate the illustrations is not reported in the registry record. A planning calculation cannot replace an observed outcome estimate or its uncertainty.
What is the role of over-dispersion?
In general, count outcomes may vary more across participants than a simple statistical model assumes. This extra variability is called over-dispersion. If ignored when present, uncertainty estimates can be too small and statistical evidence can appear more precise than it is. It is not possible to determine from the posted record whether over-dispersion was assessed or whether a model allowing for it was used. The trial-specific analysis model is not reported in the registry record.
10. Multiplicity, Missing Data and Analysis Populations
The registry record does not report a statistical analysis plan, a prespecified hierarchy of outcomes, or a procedure for controlling multiplicity. It lists 5 outcome measures, but does not give enough information to determine which were tested together, whether any formal hypothesis tests were conducted, or how multiple comparisons were handled. In general, multiplicity arises when several outcomes, subgroups, time points, or hypotheses are examined; without a stated plan, the chance of selectively emphasizing a favorable result is difficult to assess. No claim about such analyses can be made from the record.
The primary endpoint population is defined as participants assigned to treatment who inserted at least 1 ENG-E2 ring and had at least 1 at-risk treatment cycle, or participants with a treatment cycle, at risk or not, containing an estimated conception date for a pregnancy. This definition helps identify who could contribute to the efficacy analysis, but the record does not report how many met it or how much exposure they contributed. It also does not report how the population was applied in the final analysis.
Missing-data handling is not reported in the registry record. The warning about uncleaned diary data identifies a data-quality concern for the at-risk cycle denominator, but does not explain the amount of missing or unusable diary information, how it was resolved, or whether sensitivity analyses were conducted. The record likewise does not specify how participants who discontinued treatment were handled beyond defining the endpoint denominator through the last treatment cycle.
The registry lists 0 analysis records. This means that analysis details and results are not represented in those registry entries; it does not establish that no analyses were performed. The endpoint estimate, uncertainty, analysis population size, and missing-data procedures are not reported in the registry record.
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 μg/300 μg | 12 | 1936 | 0.6% |
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 μg/300 μg | 0 of 1936 |
Most frequent serious adverse event terms
| Event term | Organ system | ENG-E2 125 μg/300 μg |
|---|---|---|
| Vitello-intestinal duct remnant | Congenital, familial and genetic disorders | 1 of 1936 |
| Goitre | Endocrine disorders | 1 of 1936 |
| Rectal haemorrhage | Gastrointestinal disorders | 1 of 1936 |
| Appendicitis | Infections and infestations | 1 of 1936 |
| Diverticulitis | Infections and infestations | 1 of 1936 |
| Pneumonia | Infections and infestations | 1 of 1936 |
| Concussion | Injury, poisoning and procedural complications | 1 of 1936 |
| Abortion spontaneous | Pregnancy, puerperium and perinatal conditions | 1 of 1936 |
| Ruptured ectopic pregnancy | Pregnancy, puerperium and perinatal conditions | 1 of 1936 |
| Alcohol withdrawal syndrome | Psychiatric disorders | 1 of 1936 |
Serious events with the highest arm-level rate: vitello-intestinal duct remnant (0.1%), goitre (0.1%), rectal haemorrhage (0.1%), appendicitis (0.1%), diverticulitis (0.1%).
The safety record lists 1936 participants at risk for serious adverse events and 12 participants affected in the ENG-E2 125 μg/300 μg group. It also lists 1936 participants at risk for other adverse events and 0 affected in that category. These are registry counts and should be read as descriptive reporting, not as a comparison between treatments.
The listed serious adverse event terms are Vitello-intestinal duct remnant, Goitre, Rectal haemorrhage, Appendicitis, Diverticulitis, and Pneumonia. Each term is accompanied by 0.1%. The record does not provide additional event-level context in these entries, such as timing, duration, outcomes, or whether an event was considered related to the intervention. The terms and percentages do not establish causation.
Deaths are not reported in the registry record. The single-group design provides no concurrent control rate against which to compare the serious adverse event counts. The safety figures therefore describe what the registry lists for this treatment group, but cannot determine whether the frequency differs from another treatment or background experience.
12. What the Result Does, and Does Not, Mean
The record establishes that a phase 3, single-group study evaluated an ENG-E2 vaginal ring and selected the Pearl Index as its primary efficacy endpoint for participants 18-35 years of age. It also documents the intervention schedule, the intended maximum exposure period, a caution about diary-based at-risk cycles, and limited serious adverse event reporting. These details help define what the trial sought to measure and the context in which the registry asks readers to interpret it.
The record does not report the primary Pearl Index value, the number of in-treatment pregnancies, the exposure denominator, or a confidence interval. It therefore does not show the observed pregnancy rate or how precisely it was estimated. The listed enrollment cannot be treated as the number of participants who contributed to the endpoint, because the primary efficacy population has additional criteria and the record does not state its size.
Even if a single-group estimate were available, it would describe an observed rate during treatment rather than a randomized contrast. There is no control arm in this study record, so it cannot establish how the outcome would compare with another treatment or with no intervention. The safety counts similarly do not demonstrate that an event was caused by the ring or whether its frequency differed from a comparator.
The trial's termination and use of uncleaned diary data for the at-risk cycle denominator add uncertainty about follow-up and measurement. The record does not quantify those effects. The appropriate conclusion is therefore limited: the registry documents the study question and some design and safety information, but it does not provide enough primary efficacy results to characterize the observed Pearl Index or its precision.
13. Why This Trial Matters Statistically
This study illustrates why an endpoint's definition is as important as its name. A Pearl Index depends on both the event count and the exposure-time denominator. The registry specifies which pregnancies count, how treatment cycles contribute, and how a woman-year is defined. It also states that the at-risk cycle denominator was based on uncleaned diary data. That warning directs attention to data quality and event timing as core parts of interpreting a rate, not merely technical details.
The trial also shows the limits of a single-group design. A rate observed during use may describe experience in the studied population, but without a concurrent comparator it cannot estimate a randomized difference. Statistical precision around a single-group rate, if reported, would not resolve that design limitation. This distinction is essential when reading efficacy claims based on event rates.
Early termination is another important context. The registry reports discontinuation of product development and early trial termination, yet does not provide the endpoint estimate, exposure denominator, or confidence interval. Those omissions prevent readers from judging the realized amount of information or the precision of the efficacy outcome. A maximum timeframe and an enrollment figure do not by themselves reveal how much usable exposure was captured.
Finally, the record makes visible the difference between a study's stated aims and its reported results. It identifies efficacy and safety objectives, but the primary efficacy result is not reported in the registry record. Statistical interpretation must therefore distinguish the question a trial was designed to address from the evidence available to answer it.
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.
A central limitation for interpreting this trial is that the primary efficacy result is not reported in the registry record. The record gives the Pearl Index definition but not its estimate, event count, exposure denominator, or confidence interval. Without these, the observed endpoint and its precision cannot be assessed.
The trial was single-group, with no randomized comparator and no masking. Consequently, the design does not support a direct randomized comparison. Outcomes observed in the treatment group could not be contrasted against a concurrent control group in this study. The record does not describe an external comparison or a method for constructing one.
The registry explicitly warns that the at-risk cycle denominator was based on uncleaned diary data because product development was discontinued and the trial ended early. It does not report the extent of diary data problems or how they affected endpoint classification. Since the endpoint depends on cycle exposure and pregnancy timing, this is a specific limitation for interpreting the efficacy measure.
The status is terminated, but actual exposure and completion are not reported. The stated timeframe of up to 1 year (13 28-day cycles) does not establish that participants completed that period. The record also does not report the number who met the efficacy population definition or how discontinuations and missing data were handled in the analysis.
Detailed analysis methods, multiplicity procedures, and a sample-size justification are not reported in the registry record. Safety data are descriptive, without a comparator or information establishing event causality. These limitations do not determine what an unreported analysis might have found; they define what can be concluded from the registry record itself.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Efficacy and Safety of Etonogestrel + 17β-Estradiol Vaginal Ring in Women at Risk for Pregnancy (MK-8342B-061) — NCT02524288.
- Registry record last updated 2024-05-17; status last verified 2022-02.
- Results first posted 2017-09-25.
- 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
This phase 3 trial evaluated an ENG-E2 125 μg/300 μg vaginal ring in women at risk for pregnancy. It was single-group, unmasked, and listed as terminated. Participants could use the ring for up to 13 cycles, each consisting of 21 days of use followed by 7 ring-free days.
The primary endpoint was the Pearl Index: in-treatment pregnancies per 100 woman-years among participants 18-35 years of age. The registry defines the endpoint and cautions that at-risk cycle data came from uncleaned diaries following product-development discontinuation and early trial termination. The primary endpoint estimate and its precision are not reported in the registry record.
The record lists 12 participants affected by serious adverse events among 1936 at risk, and lists serious event terms with 0.1% for each. It does not report deaths. The single-group design and incomplete efficacy reporting limit comparative interpretation.