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 and Levonorgestrel-Ethinyl Estradiol Combined Oral Contraceptive in Adult Women at Risk for Pregnancy (MK-8342B-062) (NCT02616146), a randomized 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 | NCT02616146 |
| Phase | Phase 3 |
| Condition | Contraception |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 2016 |
| Arms in the primary outcome | 2 |
| Lead sponsor | Organon and Co |
| Results posted | Yes |
2. Clinical Question
Population
The trial enrolled healthy women aged 18 years and older who were at risk for pregnancy. The primary efficacy outcome focused on participants aged 18-35 years. Its analysis population was the restricted Full Analysis Set, defined as women with at least one at-risk treatment cycle without documented backup contraception, or participants with a treatment cycle in which a pregnancy occurred. The registry’s population definition is truncated after that description.
Intervention
The intervention was the ENG-E2 125 μg/300 μg vaginal ring. The planned regimen allowed up to 13 cycles, each with 21 days of ring use followed by 7 ring-free days. Because the trial ended early, the ENG-E2 reporting group received up to 10 cycles.
Comparator
The active comparator was LNG-EE 150 μg/30 μg combined oral contraceptive. The planned regimen allowed up to 13 cycles, with one tablet daily for 21 days followed by a 7-day tablet-free interval. The LNG-EE reporting group received up to 9 cycles before early termination.
Primary question
The primary question was how often in-treatment pregnancies occurred during exposure to each contraceptive regimen, expressed as the Pearl Index: pregnancies per 100 woman-years of exposure. The record reports an arm-specific value for each regimen, but no posted analysis comparing the groups.
This was a Phase 3 randomized, active-comparator trial in a parallel-group design. Its stated purpose included assessing contraceptive efficacy and the safety and tolerability of the vaginal ring. The two regimens differ in how they are administered, while the primary endpoint expresses pregnancy incidence in relation to exposure time. That rate-based measure is useful when participants have different durations of follow-up, but it does not by itself show how many pregnancies occurred or how uncertain the rate estimates are. Those details are not reported in the registry record.
3. Trial Design
This Phase 3 study was randomized, open-label, and parallel-group, with an active comparator. It evaluated the ENG-E2 vaginal ring against an LNG-EE combined oral contraceptive in women at risk for pregnancy. The registry lists enrollment of 2016. The study began on 2015-12-01, had a primary completion date of 2016-10-06, and is recorded as terminated.
Each regimen was planned for up to 13 cycles. The ring regimen used 21 days of vaginal ring followed by 7 ring-free days per cycle. The oral regimen used one tablet daily for 21 days followed by a 7-day tablet-free interval. The registry notes that early termination limited exposure: the ENG-E2 reporting group received only up to 10 cycles, and the LNG-EE reporting group only up to 9 cycles. The reason for termination is not reported in the registry record.
The primary efficacy outcome was specified for participants aged 18-35 years in the restricted Full Analysis Set. The registry describes this population as including women with at least one at-risk cycle without documented backup contraception, as well as participants with a treatment cycle in which a pregnancy occurred; the posted definition ends before its final wording is complete. The record does not report the allocation ratio, details of sequence generation or concealment, or procedures for maintaining the open-label design beyond stating that masking was none.
The record also names breakthrough bleeding or spotting and absence of withdrawal bleeding as secondary outcomes, each assessed by cycle. It lists 5 outcome measures overall, but posts no analyses. The enrollment figure should not be treated as the number contributing to each efficacy or safety result: the arm-specific efficacy and safety populations differ, and the eligibility and analysis sets are described separately in the registry.
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 | LNG-EE 150 μg/30 μg |
|---|---|---|
| STARTED | 1512 | 504 |
| COMPLETED | 0 | 0 |
| NOT COMPLETED | 1512 | 504 |
Reasons for not completing this period:
| Reason | ENG-E2 125 μg/300 μg | LNG-EE 150 μg/30 μg |
|---|---|---|
| Adverse Event | 64 | 24 |
| Lost to Follow-up | 23 | 13 |
| Non-compliance with study protocol | 2 | 0 |
| Non-compliance with study drug | 4 | 2 |
| Pregnancy | 2 | 2 |
| Pregnancy wish | 3 | 0 |
| Protocol Violation | 6 | 3 |
| Study terminated by sponsor | 1372 | 432 |
| Participant moved | 4 | 3 |
| Withdrawal by Subject | 30 | 24 |
| Physician Decision | 2 | 1 |
Analysis population for the primary outcome, as defined in the registry: restricted Full Analysis Set (rFAS) population, defined as the population of women with at least one "at risk" treatment cycle without documented use of hormonal or nonhormonal backup contraception during the cycle, or participants with a treatment cycle (at risk or not) in which a pregnancy has occurred.
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 | LNG-EE 150 μg/30 μg | Total |
|---|---|---|---|---|
| Participants analysed | 1512 | 504 | 2016 | |
| Age, Continuous | Years | 27.5 (SD 6.3) | 27.5 (SD 6.3) | 27.5 (SD 6.3) |
| Sex: Female, Male: Female | Participants | 1512 | 504 | 2016 |
| Sex: Female, Male: Male | Participants | 0 | 0 | 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 is the number of in-treatment pregnancies per 100 woman-years of exposure, called the Pearl Index. A woman-year represents a period of 365.25 days. The measure expresses pregnancy incidence relative to time at risk and exposure, which can be useful when participants do not all contribute the same duration of observation.
The registry defines the endpoint as a measure of contraceptive efficacy, or prevention of in-treatment pregnancy. Its timeframe is up to 1 year, corresponding to 13 28-day cycles in the planned regimen. Because the study ended early, the registry says the reporting groups received fewer cycles: up to 10 for ENG-E2 and up to 9 for LNG-EE.
A rate is not the same as a raw count or a probability that an individual participant will become pregnant. Interpretation depends on the accumulated exposure time and the precise definition of which cycles count as at risk. The registry describes a restricted Full Analysis Set that excludes cycles with documented backup contraception unless a pregnancy occurred in a treatment cycle. The number of pregnancies and the total woman-years underlying each reported index are not reported in the registry record. Nor does the record post confidence intervals for the arm-specific values. Consequently, the endpoint values describe the reported rates, but the precision of those rates cannot be assessed from the posted results alone.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry reports Pearl Index values of 1.54 for ENG-E2 and 2.93 for LNG-EE. These are arm-specific estimates of in-treatment pregnancies per 100 woman-years of exposure. They describe the observed rates as reported, rather than a formal estimate of the contrast between treatments. The record does not post a comparative effect estimate, confidence interval, or hypothesis test, and the analysis count is zero.
Without a confidence interval, readers cannot judge the statistical precision of either rate or the range of values compatible with the observed data under the analysis assumptions. Without a between-group estimate and its uncertainty, the posted values do not establish whether the apparent difference reflects a real treatment contrast, sampling variation, or other features of the trial. A difference between two point estimates alone is not a test of statistical significance. No recalculated comparison is available: the registry identifies the endpoint as a count-type outcome, and values needed to estimate a two-arm comparison are missing or not estimable from the posted summary statistics.
The two efficacy groups also had different numbers of participants listed in the registry, and the safety populations have different sizes again. These groups should not be conflated with the total enrollment. The Pearl Index is exposure-based, so participant counts alone do not reveal the amount of follow-up contributing to each rate. The total woman-years, pregnancy counts, and detailed exposure distributions are not reported in the registry record.
Early termination is important context. The planned duration was up to 13 cycles, while the record says the reporting groups received up to 10 and up to 9 cycles, respectively. The reason for stopping, whether the decision was related to accumulating outcomes, and any planned interim monitoring are not reported in the registry record. Shorter exposure can limit the information available for estimating a pregnancy rate, but the posted information does not quantify its effect on these results.
The registry also reports safety counts, but they do not resolve the uncertainty in the efficacy comparison. Safety and efficacy populations are distinct, and adverse-event counts cannot be substituted for the at-risk exposure data underlying the Pearl Index. Overall, the posted results provide two arm-specific rate values and some safety counts, but not the statistical analysis needed to support a comparative conclusion.
9. Statistical Methods Explained
The primary outcome is a rate, not a simple proportion of participants with an event. A Pearl Index relates in-treatment pregnancies to time at risk and expresses the result per 100 woman-years. As a general statistical principle, using exposure time can accommodate unequal observation periods, but the rate still depends on how at-risk time is defined and measured. The registry supplies the definition of a woman-year and describes a restricted analysis population, but does not post the total exposure time or pregnancy counts used for each rate.
What do the arm-specific values represent?
The values 1.54 and 2.93 are reported separately for the ENG-E2 and LNG-EE groups. They are point estimates: single values calculated from the observed trial data under the registry’s endpoint definition. A point estimate does not show its own precision. A confidence interval would describe uncertainty around an estimate under a statistical model, but no confidence interval is posted for either Pearl Index. The registry also does not report a direct estimate of the difference or ratio between groups, or a p-value for a comparison.
The study was randomized, which is intended to support a fair comparison by assigning participants to treatment groups. However, randomization alone does not provide the result of a statistical comparison, and the registry does not describe the sequence-generation or allocation-concealment procedures. The trial was open-label, with no masking. The record does not report whether lack of masking affected outcome assessment or how any such risk was handled.
Why is exposure time relevant?
Participants may contribute different lengths of time under observation. A rate uses the accumulated at-risk time as its denominator, rather than treating everyone as if they had identical follow-up. In general, this can be useful for time-exposure outcomes. It does not eliminate the need to define at-risk time consistently, establish which pregnancies count, or report the amount of exposure. The registry gives the endpoint definition and says backup contraception affects eligibility for the restricted Full Analysis Set, but the detailed exposure totals and pregnancy counts are not reported in the registry record.
General statistical models for event rates may make assumptions about how events occur and how variable the observed counts are. Over-dispersion is a general concern when event counts vary more than a model expects; if ignored, uncertainty estimates can be too narrow. The record does not identify a model for the primary endpoint, describe a dispersion assessment, or provide enough summaries to assess these issues. No particular model should therefore be inferred from the reported Pearl Index values.
What do the planning illustrations mean?
Planning calculations based on an observed effect are illustrations, not observed power and not evidence that the trial was designed around that effect. The stated assumptions for such illustrations are 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. The registry record does not report that these assumptions were used in the trial’s original design, and it does not report the protocol’s sample-size justification. A planning calculation under stated assumptions cannot replace an analysis of the trial data or establish that the trial was adequately powered.
For a time-to-event endpoint, general sample-size methods may count events rather than participants; for other endpoints, planning quantities may be expressed as participants per arm. Such calculations depend on assumptions about the effect to detect and the analysis framework. The record does not report the original design assumptions, any target event count, or any interim analyses. The listed illustrations should be interpreted only as planning scenarios, not as post hoc proof of power or as a description of the actual trial design.
Why is there no posted comparison?
The registry lists no analyses. It also indicates that the available values are missing or not estimable for a two-arm comparison for this count-type outcome. The arm-specific Pearl Index values can therefore be described, but the posted summary does not support a reconstructed comparative test. Recalculating a comparison would require additional quantities or assumptions that are not reported. No recalculated result is presented, and there is no discrepancy between a sponsor analysis and a recalculation to resolve.
More generally, inferential results depend on the prespecified endpoint, analysis population, handling of incomplete follow-up, and model. Those details can affect both the estimate and its uncertainty. The registry describes part of the restricted Full Analysis Set and reports early termination, but the statistical analysis plan, missing-data procedures, and handling of censoring or incomplete exposure are not reported in the registry record. The estimates should therefore be read as the posted descriptive rates, not as a complete account of a comparative statistical analysis.
10. Multiplicity, Missing Data and Analysis Populations
The registry names two secondary outcomes: the number of participants with breakthrough bleeding or spotting by cycle, and the number with absence of withdrawal bleeding by cycle. It lists 5 outcome measures overall, but reports no analyses. A multiplicity strategy, such as whether and how testing across several outcomes or time points was controlled, is not reported in the registry record. Without posted analyses or a stated strategy, the secondary outcomes cannot be used to infer confirmatory findings.
The primary analysis population is described as the restricted Full Analysis Set. It includes women with at least one at-risk treatment cycle without documented use of backup contraception, or participants with a treatment cycle in which pregnancy occurred. The record’s definition is cut off after that description, so its complete operational details are not available. Whether other analysis populations were specified or used is not reported in the registry record.
The registry does not report how missing outcome data, incomplete cycles, withdrawal, or loss to follow-up were handled. It also does not describe how exposure time was censored or how participants with early discontinuation contributed to the primary analysis. Because treatment ended early, these omissions matter for understanding how much data contributed to the rate estimates and whether incomplete follow-up could affect interpretation.
No statistical analysis plan, interim-analysis procedures, or multiplicity adjustments are reported in the registry record. The absence of these details does not establish that such procedures were absent from the study; it means they cannot be described from the registry information. The posted record therefore supports a limited account of the analysis population and reported endpoint values, but not a complete reconstruction of the analysis process.
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 | 8 | 1504 | 0.5% |
| LNG-EE 150 μg/30 μg | 3 | 492 | 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 | 116 of 1504 |
| LNG-EE 150 μg/30 μg | 40 of 492 |
Most frequent serious adverse event terms
| Event term | Organ system | ENG-E2 125 μg/300 μg | LNG-EE 150 μg/30 μg |
|---|---|---|---|
| Visual acuity reduced | Eye disorders | 0 of 1504 | 1 of 492 |
| Dengue fever | Infections and infestations | 1 of 1504 | 0 of 492 |
| Gastrointestinal infection | Infections and infestations | 1 of 1504 | 0 of 492 |
| Influenza | Infections and infestations | 0 of 1504 | 1 of 492 |
| Urinary tract infection | Infections and infestations | 1 of 1504 | 0 of 492 |
| Foreign body | Injury, poisoning and procedural complications | 1 of 1504 | 0 of 492 |
| Epilepsy | Nervous system disorders | 1 of 1504 | 0 of 492 |
| Syncope | Nervous system disorders | 1 of 1504 | 0 of 492 |
| Device deployment issue | Product Issues | 1 of 1504 | 0 of 492 |
| Cystitis haemorrhagic | Renal and urinary disorders | 1 of 1504 | 0 of 492 |
Most frequent non-serious adverse event terms
| Event term | Organ system | ENG-E2 125 μg/300 μg | LNG-EE 150 μg/30 μg |
|---|---|---|---|
| Headache | Nervous system disorders | 116 of 1504 | 40 of 492 |
Serious events with the highest arm-level rate: visual acuity reduced (0.2%), influenza (0.2%), pulmonary embolism (0.2%), deep vein thrombosis (0.2%), dengue fever (0.1%).
The registry reports serious adverse events affecting 8 participants among 1504 at risk in the ENG-E2 safety group and 3 participants among 492 at risk in the LNG-EE safety group. It also reports other adverse events affecting 116 and 40 participants, respectively, among the same arm-specific at-risk populations. These are participant counts, not a comparative statistical analysis. No confidence intervals or between-group tests are posted for these safety figures.
The safety group sizes differ from the efficacy group sizes, and the registry does not explain the relationship between the populations in detail. The serious-event counts should therefore be read using their stated safety denominators, not the efficacy populations or overall enrollment. The record lists serious-event terms including visual acuity reduced, influenza, pulmonary embolism, deep vein thrombosis, dengue fever, and gastrointestinal infection, with the percentages reported for those terms. It does not provide enough detail in the posted summary to reconstruct their event counts or make arm-specific comparisons for each term.
General statistical context: a serious adverse event is classified by seriousness criteria, which are distinct from how intense a symptom may be. A count of participants with at least one event also does not necessarily equal the total number of event episodes. Deaths are recorded as null for both groups; this means the registry does not report a death count, not that it establishes there were no deaths. These safety data are descriptive and do not by themselves establish a causal difference between regimens.
12. What the Result Does, and Does Not, Mean
The posted results establish that the registry reports Pearl Index values of 1.54 for ENG-E2 and 2.93 for LNG-EE in the primary efficacy outcome. They also establish that the trial was terminated early and that the reporting groups received up to 10 and up to 9 cycles, rather than the planned maximum of 13 cycles. The record includes safety counts for each arm and names several serious adverse-event terms.
Those details do not establish the size or statistical certainty of a treatment contrast. There is no posted comparison estimate, confidence interval, or hypothesis test. The arm-specific rates alone cannot show whether the numerical difference is compatible with sampling variation or whether a comparative effect is estimated precisely. Pregnancy counts and total exposure time are not reported, so the rate calculations cannot be independently reconstructed from the registry summary.
The early termination also limits what can be learned from the record. It does not specify why the trial stopped, whether stopping was planned, or what role any interim evidence played. The registry information therefore cannot support an explanation of the termination or a conclusion about its effect on the reported results beyond noting the shorter exposure described.
Safety counts likewise do not establish that one regimen is safer than the other. The groups have different denominators, no comparative uncertainty is posted, and the registry does not report deaths as a count. Listed event terms and percentages should be treated as descriptive entries in the record, not as proof of a treatment-related risk difference.
In general, a registry result is one part of the evidence base, and its interpretation depends on study conduct, prespecified analyses, and complete outcome reporting. Here, the posted information supports description of the trial design, the two efficacy rates, and the safety counts. It does not support a definitive comparative efficacy or safety conclusion.
13. Why This Trial Matters Statistically
This trial raises several important statistical issues for clinical researchers. Its primary endpoint is an exposure-based rate, so interpreting the result requires both the number of events and the amount of time at risk. The registry posts the Pearl Index values but not the underlying pregnancy counts or woman-years. This illustrates why a rate estimate is more informative when its numerator, denominator, and uncertainty are also available.
The study was randomized and used an active comparator, but the registry does not post a statistical comparison. Randomized allocation is a design feature; it does not substitute for reporting the estimated between-group effect and its precision. Without that information, readers should avoid treating the difference between two arm-specific point estimates as a tested result.
Early termination is another relevant issue. The planned regimen allowed up to 13 cycles, while the record reports fewer cycles for both groups. That affects the context in which exposure and event rates were accumulated. The registry does not state why the trial ended early or how incomplete follow-up was addressed analytically.
The record also highlights the importance of clearly defining analysis populations. Its restricted Full Analysis Set excludes certain cycles with backup contraception, while including participants with pregnancy during a treatment cycle. The definition is incomplete in the record, and handling of missing data and censoring is not reported. Those details are essential to reproducing or critically evaluating a rate analysis.
Finally, descriptive safety counts should not be mistaken for comparative safety evidence. The group denominators differ, and no uncertainty estimates are posted. Taken together, the trial is a useful example of why registry interpretation requires attention to endpoint construction, exposure, analysis population, early termination, and completeness of statistical reporting.
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 is incomplete for evaluating the primary efficacy analysis. It reports Pearl Index values but not the corresponding pregnancy counts, total woman-years, confidence intervals, or a formal treatment comparison. The listed values cannot be independently reconstructed from the posted summary. The record also lists no analyses, so there is no reported inferential result to interpret.
Early termination reduced the treatment exposure described relative to the planned maximum of 13 cycles: the ENG-E2 reporting group received up to 10 cycles and the LNG-EE group up to 9. The reason for termination and its relationship, if any, to trial outcomes are not reported in the registry record. The registry also does not report the original sample-size justification, the statistical analysis plan, interim monitoring, or the handling of incomplete follow-up.
The restricted Full Analysis Set definition is truncated, and the record does not fully explain how at-risk cycles, backup contraception, discontinuation, or missing data were handled. Allocation procedures beyond randomized assignment, and any measures to limit bias in the open-label setting, are not described. These omissions make it difficult to assess how closely the reported analysis followed a prespecified plan.
Safety information is also limited. The record gives participant counts for serious and other adverse events, but no comparative estimates or confidence intervals. Death counts are not reported, and the listed serious-event terms do not include enough detail to reconstruct their frequency by treatment group. These limitations restrict interpretation to the descriptive information posted in the registry; they do not establish that unreported procedures or data were absent from the full study record.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Efficacy and Safety of Etonogestrel + 17β-Estradiol Vaginal Ring and Levonorgestrel-Ethinyl Estradiol Combined Oral Contraceptive in Adult Women at Risk for Pregnancy (MK-8342B-062) — NCT02616146.
- Registry record last updated 2024-05-17; status last verified 2022-02.
- Results first posted 2019-01-18.
- 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.
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18. Record Summary
This Phase 3 randomized, open-label, parallel-group trial compared an ENG-E2 125 μg/300 μg vaginal ring with an LNG-EE 150 μg/30 μg combined oral contraceptive in women at risk for pregnancy. Enrollment was 2016. The registry records the study as terminated, with a primary completion date of 2016-10-06.
The primary outcome was the Pearl Index for participants aged 18-35 years in a restricted Full Analysis Set. Reported values were 1.54 for ENG-E2 and 2.93 for LNG-EE. The trial ended before the planned maximum treatment duration, and the registry posts no analyses or formal between-group comparison. It also reports serious and other adverse-event participant counts for each safety group, without comparative uncertainty estimates. The reason for termination, detailed missing-data methods, and complete analysis plan are not reported in the registry record.