Estrogen Receptor Antagonist in Patients With Pulmonary Arterial Hypertension: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Estrogen Receptor Antagonist in Patients With Pulmonary Arterial Hypertension (NCT02911844), a na phase 2 study. The primary outcome is Change From Baseline of Plasma Estradiol Levels.

2. Clinical Question

In plain terms, the study was designed to examine whether administering fulvestrant to this group could be carried out and tolerated, and to characterize measurements before and after administration. The primary question focuses on plasma estradiol, while the summary also names circulating hematopoietic progenitor cells, hormone levels, NT-proBNP, other plasma biomarkers, echocardiographic measures and distance walked in six minutes. Those aims do not establish that a comparison was made against an untreated or alternative-treatment group. With a single group, a change over time describes participants’ measurements across the study period; on its own, it cannot distinguish the intervention’s effect from other explanations for change. The registry record does not report the primary result, so the direction, size and precision of any estradiol change cannot be assessed from the recorded outcome information.

3. Trial Design

The registry identifies this as a Phase 2 study sponsored by the University of Pennsylvania and lists its status as completed. The recorded start date is 2017-04-10, and the primary completion date is 2018-12-05. Enrollment was 5. The condition of interest was pulmonary arterial hypertension, and the study summary specifies post-menopausal women as the intended population.

The design is listed as single group, with allocation recorded as NA and masking as none. One intervention is listed: fulvestrant. The regimen is described as 500 mg administered intramuscularly as two 5 mL injections on days 0, 14, 28 and 56. These descriptions identify the treatment schedule; they do not establish how many participants received every scheduled dose or whether adherence was complete. Such information is not reported in the registry record.

The study summary describes feasibility and tolerability as aims and lists several kinds of measurements to be evaluated following fulvestrant administration. The primary endpoint is plasma estradiol change from baseline to 9 weeks. No concurrent control group is described, so the study is not a like-for-like comparison of treatment groups. The registry record does not report further details on recruitment, participant flow, the reasons for any discontinuation, or the timing of measurements other than the primary timeframe.

The record counts four outcome measures and lists no analyses. Details of the other outcomes beyond the measures named in the study summary are not reported in the registry record. The protocol, statistical analysis plan, and rationale for the enrollment target are also not reported in the registry record. The completed status indicates the study’s recorded status, but does not itself establish that all intended measurements were collected 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

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 Change From Baseline of Plasma Estradiol Levels, measured over Baseline to 9 weeks.

The primary endpoint is change from baseline in plasma estradiol levels, measured using blood samples. The timeframe is baseline to 9 weeks. The registry describes the measure as a median with an inter-quartile range, which indicates that the intended summary emphasizes the middle of the observed values and the spread of the central half of those values. The actual median and inter-quartile range are not reported in the registry record.

In general, a baseline-to-follow-up change measure focuses on how a participant’s measurement differs across the stated study period. It can be useful for describing whether measurements tended to move over time in the enrolled group. In a single-group study, however, a before-and-after change is not the same as a difference between treatment and control groups. It cannot, by itself, establish what would have happened over the same period without the intervention.

The study summary also refers to examining plasma hormone levels and other biological and clinical measurements. The primary endpoint specifically concerns estradiol, while the summary describes broader measures as additional evaluations. The registry record does not report the endpoint values, the participant-level observations, or the statistical method used to analyze the change. Therefore, the size, direction and precision of the primary endpoint result cannot be interpreted from the recorded outcome information.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry record describes the primary outcome using a median and inter-quartile range, but does not report the analysis methods used to obtain or compare those values. The distinctions below explain the statistical ideas relevant to the recorded design; they are general explanations, not claims about analyses performed in this study.

What does a median with an inter-quartile range describe?

In general, the median is the central value after observations are ordered. The inter-quartile range describes the spread between the lower and upper quartiles, covering the central half of the observations. These summaries can be informative when observations are skewed or when a few values are far from the rest, because the median is less sensitive to extreme observations than the arithmetic mean. They do not, by themselves, show each participant’s trajectory, identify the cause of a change, or quantify uncertainty about an estimated effect. The registry record names this summary format for plasma estradiol but does not report the resulting values.

What does a baseline-to-follow-up change represent?

In general, a change score is calculated by comparing a measurement at follow-up with a measurement at baseline for the same participant. A group summary of those changes describes the observed within-participant pattern. The interpretation depends on which observations were available at each time and how missing measurements were handled. The analysis approach and missing-data handling for this endpoint are not reported in the registry record. Nor does the record report participant-level paired measurements that would allow the change to be independently characterized.

A within-group change is distinct from a treatment contrast. A treatment contrast compares outcomes between groups assigned to different conditions, or otherwise defined as comparison groups. This study is listed as single group, with no comparator group described. Thus, any before-and-after change would not directly estimate a difference between fulvestrant and a control. General statistical adjustment cannot create the missing concurrent comparison group; the registry record does not report an adjusted analysis in any case.

How should precision be assessed?

In general, a confidence interval communicates uncertainty around an estimate under a stated model and its assumptions. A narrow interval indicates more precision than a wide interval, but precision is not the same as clinical importance or protection against bias. A p-value summarizes how surprising data would be under a specified null model, given the analysis assumptions. Neither measure replaces inspection of the outcome estimate itself. The registry record does not report a confidence interval, p-value, or other inferential result for the primary endpoint.

Small enrollment can make estimates highly sensitive to the observations of individual participants. That is a general limitation of sparse data, not a numerical claim about the size of any effect in this study. With enrollment of 5, results would need to be interpreted in the context of the observed values and their uncertainty; those values and uncertainty estimates are not reported in the registry record. A median and inter-quartile range can describe a distribution, but with few observations they do not remove the uncertainty associated with limited data.

What do the planning assumptions mean?

General sample-size planning asks how many participants or events would be needed under specified assumptions to detect an effect at a chosen significance level and power. The planning illustration described in the record assumes a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect defined as a stated fraction of the observed effect. For time-to-event illustrations, it specifies total events using the Schoenfeld approach; other illustrations are expressed as participants per arm. These are planning assumptions, not a report of the actual trial’s design or observed power. The trial itself is listed as single group, not as an equal-allocation two-arm comparison. The registry record does not report a sample-size justification for the trial, and no planning estimate should be interpreted as a result from these 5 participants.

Over-dispersion is a general concern when data vary more than a model assumes. It can make standard errors too small if the model fails to account for the extra variation, leading to overconfident inferences. The record does not identify a count-data model or report an over-dispersion assessment, so this is a general methodological consideration rather than a description of the study’s analysis.

The record lists no analyses. It does not report which statistical tests or models, if any, were used for the outcomes, whether estimates were adjusted for other variables, or whether uncertainty estimates were calculated. Therefore, the methods that generated any outcome analyses cannot be evaluated from the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The registry record counts four outcome measures and identifies change in plasma estradiol as the primary endpoint. The study summary also names additional biological, echocardiographic and functional measurements. Considering several outcomes can raise a multiplicity issue: in general, the more hypotheses examined, the greater the chance that at least one result may appear notable by chance when each is judged separately. Approaches to multiplicity can include prioritizing a primary outcome, adjusting inference, or treating additional outcomes as exploratory. The statistical plan for multiplicity is not reported in the registry record, so it is not possible to determine whether or how it was addressed.

The record lists no analyses and does not report results for the primary or additional outcome measures. It is therefore not possible to tell whether all intended measurements were collected, whether any outcomes were omitted from analysis, or whether the planned order of analyses was followed. The registry record does not report a statistical analysis plan or a protocol description that would resolve these questions.

Missing-data methods and analysis populations are also not reported in the registry record. The enrollment of 5 does not establish how many participants contributed data to each measurement or at each time point. The record does not describe exclusions, withdrawals, incomplete measurements, or imputation. In general, missingness can affect interpretation when the participants with available measurements differ from those without them. Without the numbers and reasons for missing observations, the potential impact cannot be assessed.

The registry record does not state whether analyses used all enrolled participants, only participants who completed treatment, or another defined population. No such population can be inferred from the completed status alone. These omissions limit evaluation of both the analysis choices and the reliability of any outcome estimate.

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 safety figures report 5 participants at risk for serious adverse events and 0 affected, with 0 deaths. The record also reports 5 participants at risk for other adverse events and 5 affected. No serious adverse-event terms are listed. These are participant counts in the registry record; they do not describe the number, duration, severity, or timing of individual events.

In general, “at risk” identifies the group included in a safety count, while “affected” counts participants with at least one event in the specified category. A participant count is not the same as an event count: one participant may experience more than one event. The registry record does not provide event-level details for the reported other adverse events, so their nature and clinical seriousness cannot be assessed from these counts.

The reported absence of serious adverse events and deaths among those counted is a description of this small study’s recorded safety figures. It does not establish that no such events could occur in other settings or with more participants. The registry record does not report further safety follow-up details or a causal assessment attributing events to fulvestrant. The figures should be read as recorded counts, not as proof of safety or as evidence of a treatment effect.

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

The registry record documents a completed Phase 2, single-group study of fulvestrant in post-menopausal women with pulmonary arterial hypertension. It specifies an enrollment of 5, a dosing schedule, and a primary endpoint of plasma estradiol change from baseline to 9 weeks. The record also describes broader aims covering feasibility, tolerability, biological measurements, echocardiographic measures and six-minute walk distance. This is useful for understanding what the study set out to assess.

The record does not report the numerical primary endpoint result or analyses. It therefore does not show the size or direction of estradiol change, or the precision of an estimate. Results for the other measurements named in the summary are not reported in the registry record. The absence of reported outcome values is not evidence that there was no change; it means the recorded information does not allow the change to be determined.

Even if a within-group change had been reported, the single-group design would limit causal interpretation. Without a concurrent comparator, observed changes cannot be separated from changes that might have occurred over time for other reasons. This is a design limitation, not a judgment about the intervention or the participants’ outcomes.

The safety figures record 0 serious adverse events and 0 deaths among 5 participants counted at risk, alongside 5 participants affected by other adverse events. Those counts describe the registry entry; they do not establish the complete nature or cause of the events. The study’s small enrollment also means the recorded experience is limited. Overall, the available record supports a description of the study’s design, intended measurements and posted safety counts, but not a conclusion about efficacy, absence of effect, or the precision of the primary endpoint.

13. Why This Trial Matters Statistically

This study is statistically notable because its design and the questions it aimed to address need to be distinguished from the results available in the registry. It was a single-group study with enrollment of 5, and the primary endpoint was a change over time in plasma estradiol. These details define what kind of evidence an analysis could offer: a description of measurements in the enrolled group, rather than a direct comparison of treatment groups.

That distinction is important in clinical research. A measurement changing after treatment is not, by itself, evidence that treatment caused the change. A concurrent comparator can help estimate how outcomes differ under alternative conditions, while a single-group before-and-after assessment cannot directly observe that contrast. The registry record does not describe a comparator, and the endpoint result itself is not reported.

The outcome summary format also matters. A median and inter-quartile range are descriptive statistics that can show the center and spread of observations, but they are not substitutes for an effect estimate with uncertainty. With few participants, individual observations can have substantial influence on group summaries. The actual summary statistics and any uncertainty estimates are not reported in the registry record, so readers cannot evaluate the observed pattern or its precision.

The record additionally illustrates why planning calculations should be separated from trial findings. Its planning assumptions describe a hypothetical two-arm calculation, whereas the trial design is listed as single group. Such an illustration is not the trial’s own sample-size justification or evidence of observed power. The rationale for the enrollment target is not reported in the registry record. Together, these features make careful distinction between study aims, design, planning assumptions and posted results essential to statistical interpretation.

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 trial-specific limitation is the single-group design. No comparator group is described, so a change over time cannot be interpreted as a direct treatment-versus-control difference. This constrains causal interpretation independently of the statistical method used.

Enrollment was 5. This is a limited basis for characterizing outcome distributions or rare safety events, and estimates from a small group can be sensitive to individual observations. The registry record does not report participant-level results or uncertainty measures that would allow the consequences of the limited enrollment to be quantified.

The primary endpoint is identified, but its result is not reported in the registry record. The record lists no analyses and does not provide values for the additional measures described in the study summary. As a result, the direction and magnitude of the outcomes, the variability between participants, and the precision of estimates cannot be assessed. The record counts four outcome measures, but a complete outcome-by-outcome description is not reported in the registry record.

Other information needed to evaluate the study is also not reported in the registry record: the statistical analysis plan, sample-size rationale, analysis populations, missing-data handling, participant flow, and detail on the other adverse events. The registry’s completed status does not resolve these gaps. These limitations concern what can be assessed from the record and should not be mistaken for evidence that an unreported result was favorable, unfavorable, or absent.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Estrogen Receptor Antagonist in Patients With Pulmonary Arterial Hypertension — NCT02911844.
• Registry record last updated 2019-12-09; status last verified 2019-12.
• Results first posted 2019-12-09.
• 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 identifies NCT02911844 as a completed Phase 2 study sponsored by the University of Pennsylvania. It enrolled 5 participants and is listed as a single-group, unmasked study of fulvestrant in post-menopausal women with pulmonary arterial hypertension. The regimen was 500 mg intramuscularly, as two 5 mL injections on days 0, 14, 28 and 56.

The primary endpoint was change from baseline in plasma estradiol levels over baseline to 9 weeks, summarized by median and inter-quartile range. Its numerical result is not reported in the registry record, and the record lists no analyses. Safety counts include 0 serious adverse events and 0 deaths among 5 participants at risk, with 5 affected by other adverse events. Further details on those events are not reported in the registry record.

The record describes aims that include feasibility, tolerability, biological and echocardiographic measurements, and six-minute walk distance. It does not report outcome results for these additional measures, the statistical analysis plan, missing-data methods, or the sample-size rationale. The design and posted counts can be described, but the primary outcome’s magnitude and precision cannot be evaluated from the recorded results.