Impact of Menstrual Cycle on Antiretroviral Pharmacokinetics in Healthy Women: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Impact of Menstrual Cycle on Antiretroviral Pharmacokinetics in Healthy Women (NCT00869960), a non-randomized phase 4 study. The primary outcome is Tenofovir Systemic Exposure During the Follicular Phase (Days 6-10 After Menses).

2. Clinical Question

The study addresses a pharmacokinetic question rather than a comparison of clinical outcomes. Its rationale is that antiretroviral drug exposure may differ between women and men, and that changing sex-hormone levels during the menstrual cycle could be relevant to exposure in women. The registry description says the study was conducted in healthy women because HIV itself may affect antiretroviral pharmacokinetics. The clinical question is therefore framed around whether drug exposure changes with menstrual-cycle phase in this healthy-volunteer setting, not whether a treatment changes health outcomes in people with HIV.

Four antiretroviral drugs are named in the regimen, but the registered primary endpoint is specifically tenofovir systemic exposure. The record lists eight outcome measures and no analysis entries. It does not report the numerical results for the primary endpoint, a between-phase effect estimate, a confidence interval, or a p-value. Consequently, the stated research question can be described, but its answer cannot be determined from the registry results summarized in the record.

3. Trial Design

The registry lists this as a Phase 4, completed, non-randomized, single-group study with no masking. Enrollment was 24. The sponsor was the University of Alabama at Birmingham. The record describes healthy volunteers receiving tenofovir, emtricitabine, atazanavir and ritonavir, with dosing and pharmacokinetic assessments in two menstrual-cycle windows. The first assessment was described as occurring 6-10 days after menses; the later assessment was described as occurring on days 20-25 after menses.

This is a repeated-measures structure in the sense that the stated plan describes pharmacokinetic measurements for participants at different cycle phases. It is not a randomized comparison between independent treatment arms. The record does not describe a separate untreated or placebo group, and its skip note cautions that the arms are not a like-for-like control comparison. The relevant scientific contrast is therefore the change in measurements across the specified cycle windows, not a treatment-versus-control effect.

The registry specifies the primary outcome as the mean tenofovir systemic exposure during the follicular phase. It defines the outcome as area under the concentration-time curve, measured from dosing through 24 hours after the dose. The stated population for this outcome is women who completed the study. Although the record lists 24 participants enrolled, it does not report the number who completed the study or the number included in the primary outcome analysis.

The record does not report the protocol details needed to reconstruct the full conduct or analysis. For example, the statistical plan, sample-size justification, interim analyses, handling of incomplete pharmacokinetic profiles, and method for comparing cycle phases are not reported in the registry record. The completion status indicates that the study is listed as completed, but it does not by itself establish that every planned measurement was obtained or analyzed.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The number was determined based upon the those women who completed the study.

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.

6. Primary Endpoint

The registry lists the primary outcome as Tenofovir Systemic Exposure During the Follicular Phase (Days 6-10 After Menses), measured over between time of dosing to 24 hours after dose administered.

The primary endpoint is mean tenofovir systemic exposure during the follicular phase, expressed as area under the concentration-time curve. The registry defines the measurement period as the time of dosing through 24 hours after the dose. Blood sampling for pharmacokinetic assessment is described at time zero and at subsequent post-dose times through 24 hours. The record explains that the follicular phase begins on day 1 of the menstrual cycle and identifies the primary assessment window as days 6-10 after menses.

Area under the concentration-time curve combines concentration measurements over time into a measure of overall drug exposure across the specified interval. As a general statistical concept, this can be useful when a question concerns the amount of drug present over a dosing interval rather than a concentration at just one moment. It is still a pharmacokinetic measure, not a direct measure of clinical benefit or harm.

The endpoint is reported as a mean with standard deviation as the dispersion measure. A mean describes the average exposure in the analyzed group, while a standard deviation describes variability among individual measurements. The registry record does not report the mean, standard deviation, or number analyzed for this endpoint. It also does not report a numerical estimate of the difference between cycle phases, so the direction and precision of any observed phase contrast cannot be assessed from the record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry names a continuous primary measure summarized as a mean with standard deviation. It describes area under the concentration-time curve as the measure of systemic exposure and identifies the interval from dosing through 24 hours after dosing. The record does not specify a statistical test or model for the primary question. The concepts below explain how these methods are generally understood; they should not be taken as a description of analyses that the registry record does not report.

What does a mean summarize?

In general, a mean is the arithmetic average of measurements in an analyzed group. For a pharmacokinetic endpoint, it gives a group-level summary of exposure. It can be useful for communicating a typical level, but it does not show how measurements are distributed or whether a small number of observations strongly influence the average. The registry lists standard deviation as the dispersion measure, but does not post the endpoint mean or standard deviation.

What does standard deviation convey?

As a general concept, standard deviation describes how spread out individual measurements are around their mean. A small spread indicates that measurements tend to lie closer to the mean; a larger spread indicates greater variability. It is not the same as a confidence interval. A confidence interval is an uncertainty range for an estimated quantity, whereas standard deviation describes participant-level variability. The registry record does not report a confidence interval for the primary endpoint or a phase comparison.

Why measure area under the curve?

In general, pharmacokinetic sampling records drug concentration at multiple times after a dose. Area under the concentration-time curve summarizes concentration over the measurement interval, rather than focusing on one sampling time. It is therefore suited to questions about overall exposure during that interval. The record lists blood collection at the time of dosing and at later times up to 24 hours, and describes the primary endpoint as exposure from dosing through 24 hours. It does not report the resulting area-under-the-curve values or the procedure used to derive them.

How does the single-group structure matter?

The record identifies a non-randomized, single-group design without masking. The planned measurements span two cycle windows, so the scientific contrast is naturally described as a comparison of measurements across phases. General methods for repeated measurements can account for the fact that observations from the same participant are related. Treating those measurements as if they came from unrelated people can misrepresent uncertainty. The registry does not say whether the analysis used paired comparisons, a repeated-measures model, or another method, so no particular approach should be attributed to this study.

As a general principle, within-person comparisons can reduce the influence of stable differences between participants because a participant is compared with her own measurement at another time. That benefit depends on complete and comparable measurements and an analysis that recognizes the repeated structure. It does not remove possible time-varying influences or guarantee that cycle phase is the only explanation for a change. The record does not report how these issues were addressed.

What would an estimate and confidence interval add?

In general, an effect estimate would quantify the difference or other contrast between phases. Its confidence interval would communicate the range of values reasonably compatible with the data and analysis assumptions. A narrow interval indicates greater precision than a wide interval, while the interval’s location helps assess the direction and size of the estimated contrast. The registry does not report a phase-comparison estimate or confidence interval, so the precision of any possible difference is unknown.

A p-value, in general, describes how compatible observed data are with a specified statistical null model, subject to the assumptions of the analysis. It does not measure the probability that the null hypothesis is true, and it does not show whether a difference is important. No p-value or named statistical test for the primary question is reported in the registry record. Thus, the statistical significance of a phase contrast cannot be assessed from the posted record.

What can sample-size illustrations say?

General sample-size planning uses assumptions about a target effect, variability, significance level, and desired power. Planning illustrations can show how a hypothetical design might perform under specified assumptions, but they are not observed results and do not establish the power achieved by a completed study. The registry record does not report the study’s own sample-size justification or a statistical plan. It also does not provide a numerical observed effect from which a reader could assess any planning illustration. Such illustrations should not be interpreted as evidence that the study had adequate power or as a substitute for the missing outcome estimate.

The listed enrollment is 24, while the stated primary population consists of participants who completed the study. In general, an analysis needs to state the number of participants and observations actually included. If measurements are incomplete, the handling method can affect both the estimate and its uncertainty. The completion count, analysis count, and missing-data method are not reported. These omissions limit the ability to reproduce or fully evaluate the statistical analysis.

Finally, interpretation depends on the measurement definition, analysis population, repeated-measures structure, and assumptions of the chosen method. The registry record supplies some endpoint and design descriptions, but not the statistical model or numerical findings needed to evaluate those assumptions. The most defensible statistical reading is therefore descriptive: the record lays out a planned pharmacokinetic question and measurement approach, but does not provide the results needed to answer that question.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("Antiretroviral Therapy")
n   <- c(22)
m   <- c(2.4)
sp  <- c(1.1)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  Antiretroviral Therapy  22  2.400  1.100  1.912  2.888

11. Multiplicity, Missing Data and Analysis Populations

The registry lists eight outcome measures and no analysis entries. It does not identify which outcomes were treated as confirmatory beyond naming the primary outcome, nor does it report a multiplicity adjustment or a plan for interpreting multiple statistical tests. When a study examines several outcomes or contrasts, general statistical practice recognizes that repeated testing can increase the chance of observing an apparently notable result by chance. Whether that issue arose in this study cannot be assessed from the registry record because the analysis results and multiplicity strategy are not reported.

The primary endpoint population is described as women who completed the study. Enrollment was 24, but the number who completed the study, the number with usable primary endpoint data, and the number analyzed are not reported. These counts matter because enrollment does not necessarily equal the analysis population. The record also does not describe how missing samples or incomplete pharmacokinetic profiles were handled, whether any participants were excluded from an analysis, or whether all planned measurements were obtained.

As a general concept, missing data can affect both the estimated average and its uncertainty, particularly when the availability of measurements is related to participants’ characteristics or outcomes. Different handling approaches rely on different assumptions. Since the registry record does not report the missing-data approach or analysis population in detail, those assumptions cannot be evaluated.

The record does not report interim analyses, a prespecified statistical analysis plan, or a sample-size justification. Those omissions do not establish that such plans were absent; they mean that the details are not reported in the registry record. As a result, it is not possible to assess how outcomes were prioritized, how repeated measurements were analyzed, or how missingness and multiple outcomes were addressed.

12. Safety Results

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

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

The registry safety entry lists 24 participants at risk in the antiretroviral therapy group. It records zero serious adverse events and zero other adverse events. The deaths field is not reported in the registry record. No serious adverse-event terms are listed.

These are counts recorded for this study group, not a comparison of event rates between randomized groups. The study is single-group and non-randomized, and the registry does not provide a separate control group for safety comparison. The record also does not specify the event definitions, collection procedures, observation duration for safety, or whether every participant contributed the same amount of follow-up. Those details are not reported in the registry record.

In general, a zero count means that no events in that category were recorded in the posted results; it does not prove that an event could not occur or that no unrecorded event took place. The counts should not be interpreted as a complete assessment of safety, or as evidence about risks in people with HIV. The described participants were healthy volunteers, and the record does not provide further safety analyses.

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

The record establishes that a completed, non-randomized, single-group study was designed to examine antiretroviral pharmacokinetics across menstrual-cycle phases in healthy women. The regimen included tenofovir, emtricitabine, atazanavir and ritonavir. The primary outcome was mean tenofovir systemic exposure during the follicular phase, measured as area under the concentration-time curve from dosing through 24 hours. The registry describes sampling across two cycle windows and identifies a within-study phase question.

What the record does not establish is whether exposure changed between those windows. It does not report a primary endpoint mean, standard deviation, phase contrast, confidence interval, or p-value. Without an estimate and its uncertainty, the direction and size of any observed difference cannot be assessed. The stated objective is not itself a result, and the fact that the study is listed as completed does not reveal the outcome.

Even if numerical pharmacokinetic results were available, a change in exposure would be a pharmacokinetic finding rather than a direct clinical outcome. The registry does not report a comparison of health outcomes, and the study population was healthy women rather than people with HIV. The findings described by this record therefore cannot answer whether treatment outcomes differ, or establish how results would apply to people with HIV.

The safety entry records zero serious and zero other adverse events among 24 participants at risk, while deaths are not reported in the registry record. These entries are limited to the recorded categories and do not establish the absence of all possible adverse effects. The study design and record also do not support a randomized treatment-effect interpretation.

In sum, the registry provides useful information about the research question, study structure, primary measurement and recorded event counts. It does not provide the numerical pharmacokinetic results needed to determine whether the stated question was answered in the data. Any conclusion about a phase-related change in tenofovir exposure would go beyond what the registry record reports.

14. Why This Trial Matters Statistically

This study is statistically interesting because it frames pharmacokinetics as a within-person question over changing menstrual-cycle phases. Repeated measurements can be informative when the scientific question concerns how a measurement varies within participants over time. They also require analysis that respects the dependence between observations from the same person. The registry describes measurements in two cycle windows, but does not report the analysis method used to compare them.

The study also illustrates the distinction between a registered question and a reported answer. The record gives a specific primary endpoint, measurement interval and stated population, but does not report the endpoint estimate or a phase contrast. Without those results, readers cannot assess magnitude, direction, or precision. This is a central limitation for statistical interpretation, regardless of how clearly the objective is described.

Another important issue is the analysis population. Enrollment is 24, while the endpoint population is described as women who completed the study. The completion and analysis counts are not reported. For repeated pharmacokinetic measurements, knowing how many participants contributed complete or partial profiles would help readers understand the evidence base and evaluate possible missing-data effects.

Finally, the study’s healthy-volunteer population and single-group design define the scope of any interpretation. The registry rationale connects the question to antiretroviral use in women, but the study as described does not compare healthy volunteers with people with HIV or compare randomized treatment groups. Statistical conclusions must remain tied to the population, design and outcomes actually recorded. Here, those features are described, while the numerical primary results are not.

15. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The most direct limitation of the registry record is that it does not report numerical results for the primary endpoint. The mean and standard deviation for tenofovir exposure during the follicular phase are absent, as are a phase-comparison estimate and its uncertainty. The direction and precision of a cycle-phase difference therefore cannot be evaluated.

The record lists enrollment of 24, but the primary outcome is defined for women who completed the study. It does not report the number who completed, the number analyzed, or the availability of measurements across both cycle windows. The approach to incomplete profiles and other missing data is not reported in the registry record.

The study is non-randomized, single-group and unmasked. There is no separate control group described, so the design does not support a randomized comparison between treatment arms. Repeated measurements across phases may be informative, but the registry does not report how the relationship between measurements from the same participant was handled, or how other changes over time were addressed.

The registry lists eight outcome measures and no analysis entries. A statistical analysis plan, multiplicity strategy, interim analyses, and sample-size justification are not reported. The record’s description of the primary outcome and sampling schedule is not enough to reconstruct the full analysis. The safety entry gives event counts but does not report event definitions, detailed ascertainment procedures, or the deaths value.

Finally, the stated population is healthy women. The registry rationale notes that HIV may change antiretroviral pharmacokinetics, so findings from this population would not automatically establish what occurs in people with HIV. The missing numerical results further prevent evaluation of the stated pharmacokinetic question in the study population itself.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Impact of Menstrual Cycle on Antiretroviral Pharmacokinetics in Healthy Women — NCT00869960.
• Registry record last updated 2013-09-06; status last verified 2013-08.
• Results first posted 2012-04-12.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

19. Record Summary

The registry record describes a completed Phase 4, non-randomized, single-group study sponsored by the University of Alabama at Birmingham. Enrollment was 24, and the study population was healthy women. Participants received tenofovir, emtricitabine, atazanavir and ritonavir, with pharmacokinetic measurements described across two menstrual-cycle windows.

The primary outcome was mean tenofovir systemic exposure during the follicular phase, measured as area under the concentration-time curve from dosing through 24 hours. The primary population was defined as women who completed the study. The record lists eight outcome measures and no analysis entries.

Numerical results for the primary endpoint, the phase comparison, the number completing, and the number analyzed are not reported in the registry record. The safety entry records zero serious adverse events and zero other adverse events among 24 participants at risk; deaths are not reported. The record supports a description of the study question and design, but not a statistical conclusion about changes in exposure across menstrual-cycle phases.