Sporadic Angiomyolipomas (AMLs) Growth Kinetics While on Everolimus: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Sporadic Angiomyolipomas (AMLs) Growth Kinetics While on Everolimus (NCT02539459), a na phase 2 study. The primary outcome is Number of Patients With Tumor Volume Reduction Greater Than 25%.

2. Clinical Question

3. Trial Design

This is a phase II, single-group study of everolimus in patients with sporadic angiomyolipomas. The registry lists enrollment of 20 and identifies Fox Chase Cancer Center as the sponsor. Allocation is recorded as not applicable, masking as none, and the study model as single group. These details describe a treatment group without a listed concurrent control; they do not support a randomized treatment comparison.

The treatment description says patients would take 10 mg of oral everolimus each day for 4 months. The primary outcome has a 12-month timeframe and is the number of participants whose tumor volume was reduced by greater than 25%, measured using DCE MRI. The treatment duration and endpoint timeframe are different features of the registry description; further details about the timing of scans or follow-up are not reported in the registry record.

The record lists a start date of 2015-09-23 and a primary completion date of 2018-08-20. Its status is terminated. The reason for termination, whether the study ended as planned, and any consequences for recruitment or follow-up are not reported in the registry record. The enrollment figure alone does not establish how many participants completed treatment or had an endpoint measurement.

Safety and tolerability are listed as a secondary outcome. The record includes adverse-event counts for the treatment group, while the primary tumor-volume result and analysis details are absent. There are no reported statistical analyses in the registry record. It does not describe the intended analysis population, a statistical model, or a sample-size justification for the trial itself.

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

Analysis population for the primary outcome, as defined in the registry: Some participants experienced adverse events and were withdrawn from the study, and therefore tumor volume reduction was not measured in these patients.

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 Number of Patients With Tumor Volume Reduction Greater Than 25%, measured over 12 months.

The primary endpoint is the number of participants with tumor-volume reduction greater than 25%, measured by DCE MRI, within a 12-month timeframe. It is a threshold-based outcome: a participant is counted if the measured reduction crosses the stated cutoff. The endpoint is recorded as a count of participants, not as a mean or median percentage change in tumor volume.

A threshold can make an outcome easier to express as a clinically interpretable event, but it also discards detail about the size of changes on either side of the cutoff. A participant with a reduction just short of the threshold and one with little or no reduction would both fall outside the event count; participants who cross the threshold are counted together even if their reductions differ. This is a general feature of dichotomizing a continuous measurement, not a claim about the individual results in this study.

The registry describes the measure as an assessment of efficacy and tolerability, but the endpoint itself concerns tumor-volume reduction. Safety is separately listed as a secondary outcome. The registry record says that some participants experienced adverse events and were withdrawn, so their tumor-volume reduction was not measured. It does not report how many participants met the reduction threshold, how many had evaluable imaging, or the distribution of tumor-volume changes. Without those results, the endpoint definition can be described, but its observed frequency or precision cannot be assessed.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a single-group phase II study, with no masking and no allocation to different study groups. These design features matter when interpreting any result. A single-group study can describe outcomes among participants who receive the study treatment, but it does not create a concurrent comparison for estimating how those outcomes differ from what would have occurred under another treatment or no treatment. This is a general design limitation, not a judgment about the treatment.

What does the primary measure count?

The primary measure is a binary participant-level event summarized as a count: whether tumor volume was reduced by greater than 25%, according to DCE MRI. Each participant with a measurement can be classified as crossing or not crossing the threshold. A count is useful for communicating how many participants met a predefined criterion, but it does not retain the full information in the underlying volume measurements. The record does not report the count, the denominator with an evaluable measurement, or the statistical method used to summarize the endpoint.

In general, binary outcomes can be summarized with a count and a proportion, and uncertainty can be described with a confidence interval. Those summaries require an observed event count and a defined analysis population. The registry record gives neither an endpoint count nor the number of participants with endpoint measurements, and no confidence interval or statistical test is reported. No estimate should be reconstructed from the enrollment figure because the record specifically says tumor-volume reduction was not measured in some participants.

What does a confidence interval communicate?

As a general statistical concept, a confidence interval expresses uncertainty around an estimate under a chosen model and method. It is not a guarantee that the true value lies within the interval, nor does it replace consideration of the study design. For this study, the registry record does not report an estimate or interval for the primary endpoint. Thus, there is no reported precision measure to interpret, and the reliability of any endpoint frequency cannot be assessed from the record.

Why does the single-group design matter?

A concurrent control group can help distinguish treatment-associated outcomes from changes that might occur for other reasons. Without such a group, the study can describe what happened among those enrolled, but the treatment effect relative to an alternative is not identified by a direct comparison. The registry marks the study as single-group and says there is no allocation to comparison arms. No causal effect estimate or comparative hypothesis test is reported. This distinction remains important even if a within-group outcome were available.

The record also describes a planning illustration using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect expressed as a stated fraction of the observed effect. These are planning assumptions for an illustration, not the trial’s own reported design justification. They do not establish that the actual study used a two-arm design, because the registry describes this trial as single-group. The registry record does not report a trial-specific sample-size justification or an observed treatment-effect estimate from which to assess such planning.

Sample-size illustrations are prospective planning aids. They describe sample sizes under assumptions about an effect, variability or event frequency, and a statistical test. They are not observed power, which is not a useful substitute for the uncertainty in an observed estimate. Since the primary endpoint result is not reported, no observed effect can be checked against an illustration using the registry record alone. A numerical planning output, if displayed with the statistical material, should be read as conditional on its stated assumptions rather than as a result from the participants.

Why can over-dispersion matter?

As a general concept, over-dispersion occurs when variation in data is greater than a model assumes. If a model assumes that observations vary less than they actually do, standard errors may be too small and intervals or tests may convey excessive certainty. This concern can arise in count outcomes when participants or events are more heterogeneous than a simple model allows. The registry does not report a count model, a dispersion estimate, or any analysis for the primary endpoint. There is therefore no basis to say whether over-dispersion was assessed or relevant to the sponsor’s analysis.

For the posted safety information, the record gives affected and at-risk participant counts, but does not describe an inferential model or comparative analysis. Such counts are useful descriptively. They do not on their own show whether an event was caused by treatment or how the observed frequency compares with another group. The record’s list of serious adverse-event terms and percentages should be read as descriptive reporting, with the limitations of the available detail.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Treatment (Everolimus)")
n      <- c(10)
events <- c(5)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Treatment (Everolimus)  10  5  50.0  18.7  81.3  23.7  76.3  23.4  76.6

11. Multiplicity, Missing Data and Analysis Populations

Multiplicity concerns arise when a study assesses several outcomes, groups, time points, or statistical comparisons. If multiple hypotheses are tested, the chance of at least one apparently unusual result can increase unless the analysis plan addresses that issue. The registry lists a primary outcome, safety and tolerability as a secondary outcome, two outcome measures, and zero analyses. It does not report a multiplicity procedure, a hierarchy among analyses, or any adjustments to statistical testing. The implications cannot be determined from the record because inferential results and a detailed analysis plan are not reported.

The endpoint description identifies a specific missing-measurement issue: some participants experienced adverse events and were withdrawn, and tumor-volume reduction was not measured in those participants. The number of such participants is not reported in the registry record. Nor does the record state how missing endpoint measurements were handled, whether any imputation was used, or which analysis population was intended. It would therefore be inappropriate to assume that unmeasured participants were counted as not meeting the endpoint, excluded from a particular analysis, or handled through a specific statistical method.

As a general matter, missing outcomes can affect interpretation when the chance of missingness is related to participant condition, treatment experience, or the outcome itself. Here, the registry connects some withdrawals to adverse events, but does not provide enough detail to assess the extent or statistical handling of missingness. The number enrolled should not be treated as the denominator for an endpoint summary unless the analysis population and measurement status support that choice. No endpoint denominator or analysis population is reported, so the primary result’s completeness and potential sensitivity to missing data cannot be evaluated.

12. 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 serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: chest pain (5.0%), flank pain (5.0%), dysuria (5.0%), pneumonitis (5.0%), heart palpitations (5.0%).

The registry reports safety counts for the everolimus treatment group. For serious adverse events, 20 participants were at risk and 3 were affected. For the other adverse events category, 20 were at risk and 20 were affected. The record reports zero deaths. These are counts, not a comparison with an untreated or alternative-treatment group, and they should not be interpreted as comparative risks.

The serious-event terms listed are chest pain, flank pain, dysuria, pneumonitis, and heart palpitations, each with a reported value of 5.0%. The record does not provide further event-level details, such as timing, duration, severity grading beyond the serious classification, or whether the event was considered related to treatment. It also does not report whether participants could have experienced more than one listed term, so the terms should not be treated as mutually exclusive categories or added together.

The registry says some participants experienced adverse events and were withdrawn, and that tumor-volume reduction was not measured for them. It does not identify which specific events led to withdrawal or give the number withdrawn. The safety counts can therefore describe what was recorded, but cannot explain the missing endpoint measurements or establish a cause for them.

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

The registry record establishes the study’s design, intervention, endpoint definition, and some safety counts. It does not report the primary endpoint result. In particular, the number of participants whose tumor volume was reduced by greater than 25% is not reported in the registry record. Without that count and an endpoint denominator, the frequency of the primary outcome cannot be described, and no estimate of its precision can be interpreted.

The result does not permit a conclusion about how the endpoint in this group compares with outcomes under another treatment or no treatment. The study is single-group, and no comparator is listed. Even if an endpoint count were available, an outcome observed in a single group would not by itself provide a randomized treatment contrast.

The safety information is more specific in that it reports affected and at-risk counts, along with serious-event terms and a death count. Those data describe events recorded in the treatment group. They do not establish that everolimus caused or did not cause an event, and they do not provide a comparison against another group. The registry does not report the further information needed to interpret event timing, attribution, or the relationship between particular events and withdrawal.

The study’s terminated status is also part of the record, but the reason for termination is not reported. It cannot be used alone to infer why enrollment or follow-up ended, whether the study stopped early, or how termination affected the results. The absence of a reported primary result likewise does not demonstrate that no measurements were collected; it means that the registry record does not report that result.

Overall, the record supports a description of the research question and the limits of the posted evidence, not a treatment recommendation. The key statistical distinction is between an endpoint being defined and an endpoint result being reported. Here, the definition is present, but the primary count, uncertainty, and analysis details are not.

14. Why This Trial Matters Statistically

This trial raises several important statistical issues in a compact setting. The endpoint is a thresholded imaging outcome, while the design is single-group and the record notes that some participants did not have the outcome measured after adverse-event withdrawals. Each feature affects what can be learned from the result and how confidently it can be described.

A threshold such as tumor-volume reduction greater than 25% offers an accessible way to define a participant-level event. At the same time, thresholding can hide the amount of change among participants and makes the choice and reporting of the denominator especially important. In this record, the threshold is described but the number meeting it and the number measured are not reported. The distinction between enrollment and endpoint evaluability is therefore central to reading the study statistically.

The single-group design illustrates the difference between describing outcomes and estimating a comparative treatment effect. The registry identifies a treatment group but no like-for-like control group. Accordingly, a result from this design would not provide the same kind of treatment contrast as a randomized comparison. This limitation is separate from whether a measured outcome appears favorable or unfavorable.

The record also illustrates why missing data and safety reporting need to be read together but not conflated. It states that some participants were withdrawn after adverse events and consequently did not have tumor-volume reduction measured. That connection makes the missing endpoint information relevant to interpretation, yet the record lacks the counts and analysis methods needed to assess its impact. The safety counts do not fill in the missing efficacy result.

Finally, a terminated study status and an absent primary endpoint result call for restraint. Neither identifies the reason for the missing result. Statistical interpretation depends not just on the question and outcome definition, but also on complete reporting of who was measured, how missing observations were treated, and what analysis was conducted. Those details are not reported in the registry record.

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 primary limitation for interpreting efficacy is that the registry record does not report the primary endpoint count. The number of participants with evaluable imaging is also not reported, although the outcome description states that some participants were withdrawn after adverse events and had no tumor-volume measurement. Consequently, neither the endpoint frequency nor its precision can be assessed from the record.

The study has no listed comparison group. Its single-group design does not support a randomized, like-for-like comparison with another treatment or no treatment. The record also does not report an analysis plan, an inferential method, confidence intervals, p-values, or the intended analysis population. The statistical handling of missing endpoint values is not reported.

Enrollment was 20, and the study status is terminated. The reason for termination and its effect on recruitment, follow-up, or analysis are not reported in the registry record. The record’s dates and status do not establish whether all planned observations were collected or whether the study ended early relative to an intended schedule.

Safety reporting is limited to the listed affected and at-risk counts, the serious-event terms with their percentages, and zero deaths. Further details on event timing, attribution, duration, and relation to withdrawal are not reported. The record also does not say whether the listed serious-event terms overlap within participants. These gaps limit detailed safety interpretation and prevent linking particular events to the missing tumor-volume measurements.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Sporadic Angiomyolipomas (AMLs) Growth Kinetics While on Everolimus — NCT02539459.
• Registry record last updated 2022-12-15; status last verified 2022-12.
• Results first posted 2021-02-17.
• 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 phase II, single-group study of oral everolimus for sporadic angiomyolipomas, sponsored by Fox Chase Cancer Center. Enrollment was 20. The treatment description specifies 10 mg daily for 4 months. Masking is listed as none, and no comparator group is listed. The study status is terminated; the reason is not reported in the registry record.

The primary outcome is the number of participants with tumor-volume reduction greater than 25% on DCE MRI at the 12-month timeframe. The registry record does not report the endpoint count, an analysis population, or statistical analyses. It notes that some participants withdrew after adverse events and did not have tumor-volume reduction measured.

Safety reporting lists 3 participants affected by serious adverse events among 20 at risk, 20 affected in the other adverse events category among 20 at risk, and zero deaths. Five serious-event terms are listed, each with a reported value of 5.0%. These descriptive counts do not provide a comparative treatment estimate.