Raising Insulin Sensitivity in Post Menopause: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Raising Insulin Sensitivity in Post Menopause (NCT02274571), a randomized early/phase 1 study. The primary outcome is Effect of CE/BZA (TSEC) on Body Composition.

2. Clinical Question

The study’s stated purpose was to examine whether TSEC affects insulin sensitivity and body fat, with particular interest in fat in the liver. The registered primary outcome, however, is body composition, not insulin sensitivity. Insulin sensitivity and several related metabolic measures appear among the secondary outcomes. They should therefore be distinguished from the primary question when interpreting the study.

The crossover design means participants were assigned to receive both TSEC and placebo in sequence, as described in the study summary. This is a within-participant comparison in concept: each participant can contribute observations under both conditions. The registry record does not report the treatment sequence details, period-specific outcome measurements, or the analysis used to account for the crossover. It also does not report numerical primary-outcome results. Consequently, the registered question can be described, but the direction and size of the body-composition comparison cannot be determined from this record.

3. Trial Design

This was a randomized, double-masked, early phase 1 crossover study sponsored by Pennington Biomedical Research Center. The record lists enrollment as 8 and status as completed. The study start is recorded as 2015-09, and primary completion as 2017-04-11. These registry entries describe the study’s design and status; they do not establish what the numerical results were.

The intervention was TSEC, described as Duavee™ and as a combination of conjugated estrogens and bazedoxifene. The comparator was placebo. The brief summary says participants received one pill first and then switched to the other. Randomization and double masking are listed, but the registry record does not report how treatment sequences were generated, how masking was maintained, or whether there was a washout period. Those design details should not be inferred from the general label “crossover.”

The primary outcome is body composition, measured in kilograms, with mean and standard deviation specified as the summary format and 8 weeks as the timeframe. The record also lists 17 outcome measures overall, including secondary outcomes related to fasting laboratory measures, insulin sensitivity assessed with a hyperinsulinemic-euglycemic clamp, free fatty acids, resting metabolic rate, and substrate oxidation. Some secondary outcome descriptions are repeated in the registry listing.

The registry record lists zero analyses. It does not report a statistical analysis plan, the analysis population, methods for handling period or sequence effects, or a sample-size justification for the trial itself. The record’s completed status and enrollment figure do not fill in these missing methodological details. Nor does the early phase 1 designation by itself explain which analyses were planned or how results were to be interpreted.

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: the 10 ineligible were 5 BMI out of range. 2 \> 5 year post menopause. 1 because of medication. 1 for medical condition and 1 failed to return to clinic.

Overall 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 Effect of CE/BZA (TSEC) on Body Composition, measured over 8 weeks.

The primary endpoint is the effect of conjugated estrogens and bazedoxifene, described as TSEC, on body composition. The registered measure is continuous and expressed in kilograms; the record specifies mean and standard deviation as its summary format and gives 8 weeks as the timeframe. The registry does not specify in the endpoint description which body-composition component or components make up the measure, or how those components were measured.

Body composition is relevant to the study’s stated metabolic rationale because the summary describes an interest in body fat, including fat in the liver, and its possible relation to insulin sensitivity. That rationale does not change the registered primary endpoint: body composition is the primary outcome, while insulin sensitivity and other metabolic measures are listed as secondary outcomes. The registry record does not report numerical results for the primary endpoint, so the mean under either condition, the estimated comparison, and its precision are not available in the record.

For a continuous endpoint, a mean describes the central level of the measured quantity, while a standard deviation describes the spread of individual measurements around that mean. These summaries can help characterize the observations, but by themselves they do not show the uncertainty in a treatment comparison. The record does not report the primary outcome values, a treatment-effect estimate, or an interval quantifying that estimate’s uncertainty.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a crossover design compare?

In general, a crossover trial assigns participants to receive more than one study condition in sequence. The comparison can use each participant’s measurements under the different conditions, rather than relying only on differences between separate groups. This can be useful when participant characteristics are stable over the study, because each participant can serve as their own comparison. The registry describes this study as a randomized crossover and says participants switched between TSEC and placebo.

General statistical interpretation of a crossover requires attention to treatment period and sequence. Outcomes may change over time for reasons unrelated to treatment, and effects from an earlier period may persist into a later one. A washout period, when used, is intended to reduce carryover, but the registry record does not report whether one was used. The record also does not report period-specific values or the method used to account for period, sequence, or carryover effects. Thus, the crossover label is not enough to identify the actual analysis.

What do mean and standard deviation describe?

The primary measure is continuous and specified in kilograms, with mean and standard deviation as the summary format. In general, the mean is a measure of the center of a set of observations. The standard deviation describes how dispersed those observations are around the mean. A standard deviation is not the same as the uncertainty around a treatment contrast: it describes variation among measurements, whereas a confidence interval for a contrast describes uncertainty in an estimated comparison.

The registry record does not report the mean or standard deviation for body composition under either condition, nor does it report an estimated difference between conditions. No summary statistic can be reconstructed from the design description or enrollment figure. Likewise, no confidence interval or p-value for the primary comparison is reported.

What can a confidence interval or p-value tell a reader?

In general, a confidence interval communicates the precision of an estimated effect under the statistical model used. A narrow interval indicates greater precision than a wide interval, while an interval spanning both meaningful increases and decreases may leave the direction uncertain. A p-value is a measure of compatibility between the data and a null model; it does not measure the probability that the null hypothesis is true, and it does not describe the size of an effect. These concepts can guide interpretation when estimates are reported, but the registry record does not report them for the primary outcome.

The analysis approach matters to both quantities. In a crossover study, a model may need to account for repeated observations within participants and the structure of treatment periods. Different approaches can yield different estimates or uncertainty if their assumptions differ. The statistical plan and the model used for this study are not reported in the registry record, so a particular method should not be attributed to the investigators.

How should multiple outcomes be considered?

The record lists 17 outcome measures, including a primary body-composition outcome and secondary metabolic outcomes. In general, examining several outcomes can increase the chance of finding an apparently notable result by chance if each is assessed separately without considering multiplicity. A prespecified hierarchy or adjustment may help address that issue, but the registry record does not report a multiplicity strategy. It also lists zero analyses, so no outcome-specific inferential results or adjustment procedures are available to evaluate.

What do the planning assumptions mean?

The record describes sample-size illustrations based on an observed effect, using a two-sided significance level of 0.05, equal allocation, and a normal approximation. It says the effect to detect is a stated fraction of the observed effect, and distinguishes total events for time-to-event illustrations from participants per arm for other illustrations. These are planning assumptions, not evidence about the trial’s observed treatment effect or its statistical power after completion. A sample-size illustration is not observed power, and it is not the same as the trial’s original design justification. The registry record does not report that justification or a trial-specific statistical plan.

Because numerical primary results and analysis details are not reported, the statistical methods that were actually applied cannot be evaluated from the registry record. General explanations of means, uncertainty, crossover structure, and multiplicity describe considerations relevant to this design; they should not be mistaken for a description of analyses confirmed to have been conducted.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists 17 outcome measures. Body composition is designated as the primary outcome, while the remaining listed outcomes concern fasting laboratory measures, insulin sensitivity, free fatty acids, resting metabolic rate, and substrate oxidation. Several secondary outcome descriptions appear more than once in the listing. The record does not state how outcomes were prioritized beyond identifying the primary outcome, or whether any adjustment for multiple testing was planned or applied.

Multiplicity matters because testing several outcomes can increase the chance of at least one apparently noteworthy result when each test is considered separately. In general, prespecifying a primary outcome, defining a testing hierarchy, or adjusting inference can help make interpretation more transparent. The registry record does not report a multiplicity procedure, so it is not possible to assess how the investigators intended to control or interpret multiple comparisons.

The registry lists zero analyses and does not report numerical results for the primary or secondary outcomes. It also does not report missing-data counts, reasons for missing measurements, imputation methods, or sensitivity analyses. The analysis population is not reported in the registry record; it is therefore unclear which participants or treatment periods would have contributed to each outcome analysis.

These omissions limit evaluation of both the numerical findings and their robustness. In particular, the record does not establish whether all randomized participants completed both periods or whether any measurements were excluded. No assumptions about completeness, imputation, or analysis population should be made from the enrollment and safety listings alone.

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 0% reporting threshold.

Most frequent non-serious adverse event terms

The registry lists serious adverse events for the placebo and TSEC groups. For each group, 8 participants are listed as at risk, and 0 are listed as having a serious adverse event. Deaths are listed as 0 in each group. The record separately lists other adverse events: 7 participants at risk and 7 affected in the placebo group, and 8 at risk and 5 affected in the TSEC group.

These counts describe what is recorded in the safety section; they do not establish that the treatments have the same or different safety profiles. The study is a crossover trial, but the safety listing does not explain how exposure periods, repeated events, or participants who received both conditions were handled. The counts should not be combined across groups or treated as independent observations without that information.

The registry record does not provide event descriptions for the serious-event listing, and no serious-event terms are listed. It also does not report timing, severity details for the other adverse events, or an analysis comparing safety between conditions. A zero count in this record means no serious adverse events are recorded in that group; it does not prove that an event is impossible or establish safety beyond the study and its recorded follow-up.

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

The record establishes that a small early phase 1 randomized, double-masked crossover study was conducted to compare TSEC with placebo, and that body composition was its primary outcome. It also identifies metabolic measures that were of secondary interest. These details make the research question and broad design understandable, but they are not numerical evidence about the primary treatment comparison.

The registry record does not report the primary body-composition results, an estimated contrast, or a measure of uncertainty. It therefore does not show whether body composition was higher, lower, or similar under either condition, nor how precisely any comparison was estimated. The absence of reported results cannot be interpreted as evidence of no effect, equivalence, or benefit. It is simply not possible to establish the result from the record.

Similarly, the study’s stated interest in insulin sensitivity and fat does not demonstrate an effect on those measures. They are listed as secondary outcomes, but their numerical results are not reported in the registry record. The study description explains the motivation for examining them; it cannot substitute for measured comparisons and their uncertainty.

The safety counts are descriptive entries and should be read in context of the crossover design and the limited information about event timing and analysis. They do not support a broad conclusion about comparative safety. More generally, the record does not report the analysis plan, missing-data handling, or analysis population, all of which affect how results would be interpreted if estimates were available.

Accordingly, what can be stated is limited to the registered question, design, outcomes, and recorded safety counts. The treatment effect and its precision are not reported in the registry record. No clinical recommendation follows from these registry entries.

13. Why This Trial Matters Statistically

This study is statistically notable for combining a crossover design with a continuous primary outcome. In general, crossover designs can make within-participant comparisons, which may help separate treatment comparisons from stable differences between participants. At the same time, their interpretation depends on how treatment periods and sequence are handled and whether effects carry over. The registry record identifies the design but does not report those analysis details.

The primary outcome is expressed as a mean in kilograms with a standard deviation. That format distinguishes the average measurement from the spread among measurements, but it does not by itself quantify the uncertainty in a treatment contrast. Because the record does not report outcome values or an estimated comparison, readers cannot judge the size, direction, or precision of the primary result.

The study also lists multiple secondary metabolic outcomes. This makes prespecification and multiplicity important statistical considerations. The registry names the primary outcome but does not report a testing strategy for the wider outcome set, and it lists zero analyses. That limits the ability to assess how secondary findings, if any, were intended to complement the primary question.

The record’s sample-size assumptions are described as planning illustrations rather than as a report of the original trial design justification. Keeping planning calculations distinct from observed results is important: a planning scenario cannot establish what the study found or how precise its estimate was. In this case, the absence of numerical primary findings makes that distinction especially relevant.

The trial therefore illustrates why design labels and outcome listings are not enough for statistical interpretation. Numerical estimates, uncertainty, analysis methods, and missing-data information are needed to understand what the observations show. Those details are not reported in the registry record.

14. Limitations

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

The principal limitation for interpreting this study from the registry record is that numerical results for the primary outcome are not reported. The endpoint is identified as body composition in kilograms over 8 weeks, but the record gives no condition-specific summaries, treatment contrast, confidence interval, or p-value. The primary result’s direction, size, and precision therefore cannot be assessed.

The endpoint description does not identify which body-composition components were measured or give measurement procedures. The registry also does not report baseline characteristics or detailed eligibility criteria, so the population represented by the enrolled participants cannot be characterized beyond the description of women after menopause and the condition of menopause.

Important crossover details are absent from the record, including treatment sequence information, period-specific measurements, and whether a washout period was used. The statistical approach to repeated measurements, period effects, sequence effects, and possible carryover is not reported. The analysis population and handling of missing measurements are also not reported, limiting assessment of whether the available data could represent all randomized participants and periods.

The record lists 17 outcome measures and zero analyses, but does not describe a multiplicity strategy or provide numerical secondary-outcome results. Safety entries are recorded by group, but timing and handling of repeated exposure in the crossover design are not explained. These limitations concern the information available in the registry record; they do not establish that the study itself failed to collect or analyze the relevant information.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Raising Insulin Sensitivity in Post Menopause — NCT02274571.
• Registry record last updated 2025-06-04; status last verified 2025-05.
• Results first posted 2025-06-04.
• 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

The registry describes a completed, randomized, double-masked, early phase 1 crossover study sponsored by Pennington Biomedical Research Center. Enrollment is listed as 8. The study start is recorded as 2015-09, with primary completion on 2017-04-11.

The intervention was TSEC, described as a combination of conjugated estrogens and bazedoxifene; the comparator was placebo. The primary outcome was body composition in kilograms, summarized as a mean and standard deviation, with an 8-week timeframe. Secondary outcomes included insulin sensitivity and other metabolic measures.

The registry lists zero analyses and does not report numerical results for the primary outcome. It also does not report the statistical analysis plan, analysis population, missing-data methods, or multiplicity strategy. Serious adverse events and deaths are listed as 0 in both groups; other adverse-event counts are also recorded by group. These entries do not replace the unreported primary treatment-effect estimate and its uncertainty.