To Assess Continued Safety of and Adherence to the Dapivirine (25 mg) Vaginal Ring-004 in Healthy, HIV-negative Women: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for To Assess Continued Safety of and Adherence to the Dapivirine (25 mg) Vaginal Ring-004 in Healthy, HIV-negative Women (NCT02862171), a na phase 3 study. The primary outcome is The Safety Profile of the 25 mg Dapivirine Vaginal Ring-004, When Inserted at Monthly Intervals. Participants Attended RC at Monthly Visits (up to Max of Three Monthly Visits) Followed by 3-monthly Follow-up Visits..

2. Clinical Question

This question is descriptive rather than a comparative treatment-effect question. It asks what safety events were recorded while participants used the ring during follow-up, not whether the ring caused an event or whether event frequency differed from another group. Since the trial has no recorded control arm, any event count must be interpreted in the context of the enrolled, exposed participants and the follow-up period. The registry describes a primary safety timeframe of at least 12 months and up to 17 months, but it does not report individual participants’ actual observation time or duration of use.

3. Trial Design

This was a phase 3, completed, open-label follow-on study of the Dapivirine Vaginal Ring-004 in healthy, HIV-negative women. The registry lists a single-group model, allocation as not applicable, and no masking. Enrollment was 941. The sponsor was International Partnership for Microbicides, Inc. The study began on 2016-07-12, and primary completion was recorded as 2019-01-11.

Participants used the 25 mg vaginal ring monthly. The protocol description allowed screening for up to 45 days before enrollment and ring use for up to 12 months, with an option for the sponsor to extend the trial period. For the safety endpoint, participants attended monthly visits up to a maximum of three monthly visits, followed by 3-monthly follow-up visits. The safety timeframe is stated as at least 12 months and up to 17 months. These are the recorded study plans and timeframe; the registry record does not report the actual duration of use or follow-up for each participant.

The design supports a description of events observed during ring use and subsequent follow-up. It does not establish a concurrent treatment comparison: no other arm is listed, and there is no randomized allocation. Open-label status means the study was not masked; the registry does not describe further procedures for limiting observer or participant knowledge.

The record identifies safety as the primary focus and lists HIV-1 seroconversion and acquisition with HIV-1 drug resistance-associated mutations as secondary outcomes. It does not provide numerical results for those secondary outcomes. It also lists 4 outcome measures and 0 analyses. The specific statistical analysis plan, the rationale for the planned enrollment, and any interim-analysis procedures are not reported in the registry record. Accordingly, the registered design can be described, but its statistical rationale and the full analysis process cannot be reconstructed from this 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.

Before assignment: Overall, 1,034 participants who had participated in IPM 027 were screened for inclusion in IPM 032 open-label trial. Of these, 941 (941/1,034; 91.0%) participants were enrolled, and 848 (848/941; 90.1%) participants completed the trial. Of the 941 enrolled participants, 150 rolled over directly from IPM 027, without any interruption in DVR use.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The safety population included all participants who were enrolled, and received and inserted at least one DVR.

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: Healthy, HIV-negative women who had participated in IPM 027

6. Primary Endpoint

The registry lists the primary outcome as The Safety Profile of the 25 mg Dapivirine Vaginal Ring-004, When Inserted at Monthly Intervals. Participants Attended RC at Monthly Visits (up to Max of Three Monthly Visits) Followed by 3-monthly Follow-up Visits., measured over at least 12 months and up to 17 months.

The primary outcome is described as the safety profile of the 25 mg Dapivirine Vaginal Ring-004 when inserted at monthly intervals. Its unit is participants, and its parameter is a count of participants. The assessment description includes adverse event reporting, all product-related adverse events, Grade 3 or 4 adverse events, and serious adverse events. The safety population includes participants who were enrolled, received the ring, and inserted at least one ring. The stated timeframe is at least 12 months and up to 17 months.

A participant count is useful for describing how many people in the defined safety population experienced an event during the observed period. It is an accessible summary for a safety-focused study, particularly when the key interest is whether events were observed while the intervention was used. It does not, by itself, describe how often events occurred per unit of time, how long participants were exposed, or whether an event was caused by the ring. Those questions require additional information about event definitions, exposure, attribution, and follow-up.

The registry describes several safety categories within the endpoint rather than a single narrowly specified event. It does not give a full operational definition for each category or report numerical results for every named assessment. The posted adverse-event figures can therefore be read as recorded counts, but the registry record does not support treating those counts as a complete account of every component of the primary endpoint.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a single-group study, and the primary outcome is a count of participants. That combination makes the main available interpretation descriptive: count the participants recorded with an event in the defined safety population. There is no concurrent control arm from which to form a treatment contrast. The design information does not support interpreting the counts as evidence that the intervention increased or decreased event frequency relative to another condition.

What does a participant count represent?

A participant count records people rather than event episodes. If one participant experiences more than one event, a count of affected participants does not communicate the total number of episodes unless that is separately tabulated. Conversely, an event-level total may count multiple episodes in one person. The registry’s primary endpoint specifies participants as the unit, so the primary measure is about how many participants meet the event criteria. The record does not provide event-by-event detail or a full definition of each assessed safety category.

A denominator gives context to a count. The safety population is defined as people who enrolled, received, and inserted at least one ring. The adverse-event figures list 941 at risk for the serious and other adverse-event summaries. Even with a denominator, a simple participant count does not account for differing observation times. In general, a rate uses event information alongside time at risk, whereas a participant count does not. The registry record does not report participant-level time at risk or person-time, so these counts cannot be converted into exposure-adjusted rates from the posted information.

Why does the design affect interpretation?

Randomized comparisons can help separate intervention differences from differences between participant groups, because assignment creates groups intended to be comparable. This trial is not recorded as randomized and has a single group. Its adverse-event summaries therefore describe events observed among participants in the trial, without an internal group showing what would have been observed under another intervention or no ring use. General background rates or external comparisons are not reported in the registry record and should not be assumed.

Open-label means the study was not masked. In general, knowledge of intervention use may affect reporting, assessment, or event attribution, depending on the outcome and study procedures. The registry record does not describe particular safeguards or adjudication procedures for these issues. It is therefore appropriate to identify the study as open-label without claiming that any specific bias occurred.

How should uncertainty be understood?

A confidence interval is a statistical range used to express uncertainty around an estimate under specified assumptions. It does not guarantee that the true value lies in the interval, and it does not correct for limitations such as missing data, biased measurement, or lack of a comparison group. No confidence intervals for the primary safety counts are reported in the registry record. The record also lists 0 analyses, so it does not provide a reported inferential model or a statistical test for those counts.

General uncertainty around a count depends on factors such as the number of observed participants, the event definition, follow-up completeness, and the sampling model. A count alone does not capture all those dimensions. For this trial, the registry gives the safety population definition and an at-risk count, but does not give the amount of follow-up per participant, missing-outcome handling, or detailed analysis methods. These omissions limit how precisely the posted counts can be generalized beyond the observed trial population.

What do planning illustrations mean?

The planning illustrations use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. They are computed from an observed effect, with the effect to detect defined as a stated fraction of that observed effect. For time-to-event outcomes, the illustration concerns the total number of events; for other outcomes, it concerns participants per arm. These assumptions describe hypothetical planning calculations, not the design of this single-group trial. They are not observed power, and they do not show that the trial was designed with those assumptions. The trial’s own sample-size justification is not reported in the registry record.

In general, a sample-size calculation estimates the amount of information a future study may need under chosen assumptions about the effect, variability, significance level, and desired power. Changing those assumptions changes the planning result. An illustration based on a fraction of an observed effect should not be interpreted as a new clinical finding or as proof that a study was adequately powered. No numerical planning results are because the registry record does not report the results of those calculations as trial outcomes.

Finally, outcome analysis requires decisions about who is included, how events are classified, and how incomplete observations are handled. The registry defines the primary safety population, but it does not report all analysis procedures. That distinction matters: a clearly described outcome and population make a descriptive count understandable, while a full statistical interpretation also needs analysis rules, uncertainty estimates, and information about missingness.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists 4 outcome measures, including the primary safety outcome and secondary outcomes for HIV-1 seroconversion and HIV-1 acquisition with HIV-1 drug resistance-associated mutations. The record does not report numerical results for those secondary outcomes. It lists 0 analyses, and no multiplicity strategy is reported in the registry record.

Multiplicity arises when multiple outcomes or statistical tests are assessed. In general, testing many outcomes can increase the chance of at least one apparently unusual result, so an analysis plan may specify which outcomes are primary, how secondary results will be interpreted, and whether any adjustment or hierarchy will be used. The registry identifies a primary safety focus, but does not state how any multiplicity would be addressed. Since no inferential analyses are listed, there are no reported p-values or multiplicity-adjusted results to interpret.

Missing-data handling is not reported in the registry record. The safety population definition identifies participants who enrolled and received and inserted at least one ring, but does not explain how participants with incomplete follow-up, unrecorded events, withdrawal, or other missing observations were handled. The record does not report a missingness analysis or imputation method.

The stated safety population is useful for understanding which participants are intended to contribute to the safety assessment. However, the record does not give a separate analysis population for each outcome or explain whether participants were excluded from any particular analysis. These gaps make it difficult to assess whether all participants contributed equally to follow-up and whether the reported counts reflect complete outcome ascertainment. No assumptions about missing outcomes or unreported analyses should be inferred.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 2% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: stab wound, ankle fracture, fibula fracture, muscle strain, soft tissue injury, thermal burn (0.7%), meningitis tuberculous, pyelonephritis, sepsis, vuval abscess (0.4%), abortion spontaneous (0.2%), hypertension, hypertensive crisis (0.2%), sudden death (0.1%).

The adverse-event summary lists 941 participants at risk for the serious-event category and 20 participants affected. It separately lists 941 at risk for the other-adverse-event category and 616 affected. The record also lists 1 death. These are participant counts in the registry summary; they do not state the total number of event episodes or the time each participant was observed.

The serious-event terms are accompanied by percentages: “Stab wound, ankle fracture, fibula fracture, muscle strain, soft tissue injury, thermal burn” at 0.7%; “Meningitis tuberculous, Pyelonephritis, Sepsis, vuval abscess” at 0.4%; “Abortion spontaneous” and “Hypertension, Hypertensive crisis” each at 0.2%; and “Sudden death” and “Diabetes mellitus” each at 0.1%. The registry record does not state the denominator or method used for those percentages. The grouped terms should not be taken to mean that every listed event occurred in a single participant or that the percentage is a rate over person-time.

The endpoint description includes product-related adverse events, Grade 3 or 4 adverse events, and serious adverse events, but the record does not specify which listed events were judged related to the ring. Thus the event summaries describe recorded safety events, not causal attribution. A single-group record without event-level follow-up or a comparison group cannot show whether these events occurred more or less often than they would have under another condition.

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

The results support a limited, descriptive statement: the registry records adverse-event counts among participants in a single-group follow-on study of the 25 mg dapivirine vaginal ring. The safety summary lists 20 participants affected in the serious-event category and 616 in the other-adverse-event category, each with 941 at risk, and it lists 1 death. Serious-event terms are also reported with percentages. These details describe the posted safety record; they do not establish a comparative effect.

The primary outcome is framed around safety and includes assessments of product-related adverse events, Grade 3 or 4 adverse events, and serious adverse events. The record does not show which events were judged related to the ring, nor does it provide complete numerical results for each component. The posted counts therefore cannot be treated as a count of events caused by the ring. The actual follow-up time for each participant is also not reported, so the summaries do not establish an event rate over a common exposure period.

The single-group, open-label design provides no randomized comparison. Without a concurrent comparison group, the observed counts cannot establish whether event frequency would have differed with another intervention or without ring use. The record also does not report inferential estimates, confidence intervals, or numerical results for the secondary outcomes of HIV-1 seroconversion and acquisition with resistance-associated mutations.

Accordingly, the results do not establish that the ring is safe or unsafe in a broader population, do not establish that it caused or prevented any particular event, and do not quantify a comparative treatment effect. They do document what the registry reports for the enrolled safety population during the stated study timeframe. Broader interpretation would require fuller outcome definitions, event attribution, complete follow-up information, and suitable comparative evidence; those details are not reported in the registry record.

13. Why This Trial Matters Statistically

This trial illustrates a central distinction in clinical biostatistics: a large participant count does not by itself create a comparative answer. The registry reports enrollment of 941 and a safety population based on receiving and inserting at least one ring, but the study is recorded as single-group, with allocation not applicable. The design can describe events observed in participants using the ring, but it cannot internally compare those events with what would have happened under another condition.

It also illustrates why the endpoint’s unit matters. A count of participants with an event is not the same as an event total or an exposure-adjusted rate. Repeated events in one person, differing follow-up durations, and missing observation time can all affect how a safety count should be interpreted. The registry gives a safety timeframe of at least 12 months and up to 17 months, but does not report person-time or individual follow-up. Statistical interpretation must respect that distinction rather than turning participant counts into rates.

The record further shows the value of separating descriptive safety reporting from causal claims. The adverse-event summary includes serious-event counts and selected terms, while the endpoint description includes product-related events. The posted figures do not identify which events were attributed to the product. Event occurrence during a study is not, by itself, evidence of causation.

Finally, the record identifies outcomes beyond safety, including HIV-1 seroconversion and acquisition with resistance-associated mutations, but supplies no numerical results for them. The record lists 0 analyses. This makes transparent reporting of analysis methods, missing-data handling, uncertainty, and outcome-specific results especially important. The study is statistically informative as a case in reading a descriptive safety record carefully: population, endpoint, follow-up, comparison structure, and analysis reporting all shape what can and cannot be concluded.

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 main limitation for interpretation is the single-group design. With no concurrent comparator and no randomized allocation, the observed adverse-event counts cannot establish a difference attributable to the ring. The open-label design is recorded, but specific procedures for event adjudication or reducing reporting and assessment bias are not reported in the registry record.

The safety timeframe is stated as at least 12 months and up to 17 months, while actual participant-level follow-up and exposure time are not reported. The record therefore does not allow time-adjusted event rates to be assessed. Although the safety population is defined and the adverse-event summaries list 941 at risk, details about follow-up completeness and the handling of participants with missing observations are not reported in the registry record.

The primary outcome description covers several safety assessments, but operational definitions and complete numerical results for each component are not posted in the registry record. The adverse-event summaries do not report which events were judged related to the product, and the percentages accompanying serious-event terms have no stated denominator or calculation method. The grouped terms also do not provide event-level detail.

The registry lists HIV-1 seroconversion and HIV-1 acquisition with drug resistance-associated mutations as secondary outcomes but does not report their numerical results. It lists 0 analyses and gives no inferential estimates or uncertainty intervals. The statistical analysis plan, multiplicity approach, missing-data methods, interim-analysis procedures, and sample-size justification are not reported in the registry record. These limitations restrict interpretation to the descriptive safety information that is posted.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: To Assess Continued Safety of and Adherence to the Dapivirine (25 mg) Vaginal Ring-004 in Healthy, HIV-negative Women — NCT02862171.
• Registry record last updated 2022-10-25; status last verified 2022-10.
• Results first posted 2022-10-25.
• 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.

18. Record Summary

NCT02862171 is a completed phase 3, open-label, single-group follow-on trial of the 25 mg Dapivirine Vaginal Ring-004 in healthy, HIV-negative women. Enrollment was 941. The recorded study dates are 2016-07-12 for the start and 2019-01-11 for primary completion. Monthly ring use was planned for up to 12 months, with an option to extend the trial period. The safety timeframe is stated as at least 12 months and up to 17 months.

The primary focus is the ring’s safety profile, assessed through adverse event reporting, including product-related events, Grade 3 or 4 events, and serious events. The posted adverse-event summary lists 20 participants affected in the serious-event category, 616 in the other-adverse-event category, and 1 death, with 941 at risk for each category. The record also lists secondary outcomes for HIV-1 seroconversion and HIV-1 acquisition with resistance-associated mutations, but numerical results for those outcomes are not reported in the registry record. No analyses are listed.