RAPAMYCIN FOR KIDNEY ANGIOMYOLIPOMAS: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for RAPAMYCIN FOR KIDNEY ANGIOMYOLIPOMAS (NCT00126672), a na phase 2 study. The primary outcome is Objective Response Rate.

2. Clinical Question

3. Trial Design

This was a Phase II, multicenter, single-group study of rapamycin for kidney angiomyolipomas in people with TSC or LAM. The registry lists enrollment as 36, the study status as completed, and Dana-Farber Cancer Institute as sponsor. The recorded start date is 2005-12-20, and primary completion is listed as 2010-04.

Because there was one treatment group and no masking, the design is not a randomized comparison. The registry records allocation as not applicable. Consequently, results from this study can describe outcomes among participants treated in the study, but cannot directly estimate a treatment contrast against a concurrent control group. Differences from other groups or from an external benchmark would require information and assumptions not reported in the registry record.

Rapamycin was given orally. The arm description specifies a 6 mg loading dose on day 1, followed by 2 mg daily, with adjustment to a target blood level of 3-9 ng/ml for the first 16 weeks. After week 16, the target level was increased to 9-15 ng/ml. The dosing description ends partway through a sentence, so further details about the later regimen are not reported in the registry record.

Radiologic response was assessed on treatment for up to 52 weeks. The primary outcome was objective response rate according to RECIST 1.1. The registry lists two secondary outcomes concerning grade 3 or more treatment-related lymphopenia and change in other TSC lesions. More detailed outcome results, participant flow, eligibility criteria, and the statistical analysis plan are not reported in the registry 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.

Overall Study

Reasons for not completing this period:

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 Objective Response Rate, measured over On treatment, patients were evaluated radiologically for response to therapy up to 52 weeks..

The primary endpoint, objective response rate (ORR), is the percentage of participants who achieved a complete response or partial response on treatment. The study defined response using RECIST 1.1 criteria for target lesions. Complete response requires disappearance of all target lesions. Partial response requires at least a 30% decrease in the sum of the longest diameters of target lesions, relative to the baseline sum; the overall response also depends on the status of non-target lesions and the absence of new lesions.

ORR is a binary-outcome summary: each participant is classified as having met or not met the response definition, and the endpoint expresses the responding proportion in the assessed population. In a single-group study, this can describe how often the defined radiologic response occurred among participants receiving the intervention. It does not, by itself, quantify a difference from an untreated or alternative-treatment group.

The registry specifies radiologic evaluation on treatment up to 52 weeks and lists a 95% confidence interval as the measure of dispersion. However, the numerical ORR and confidence interval are not reported in the registry record. The endpoint definition is available, but its observed value and statistical precision cannot be evaluated from the record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary endpoint is a binary response outcome. For each participant, the response assessment determines whether the complete- or partial-response criteria were met. The objective response rate expresses the proportion classified as responders in the analysis population. It is a compact summary of the frequency of a defined radiologic outcome, but it does not retain all information about the amount or timing of change in lesion measurements.

What does the response definition capture?

RECIST 1.1 provides a standardized way to classify radiologic response. In this study, complete response for target lesions means that all target lesions have disappeared. Partial response requires at least a 30% decrease in the sum of the longest diameters of target lesions compared with the baseline sum. The overall response definition adds requirements concerning non-target lesions and the absence of new lesions. These rules matter because a change in target-lesion measurements alone is not necessarily sufficient to classify an overall response.

The endpoint is assessed on treatment, with radiologic evaluation described as continuing up to 52 weeks. That time frame identifies the period in which the response assessments could occur, but the registry record does not explain the exact assessment schedule, the timing used to determine the primary endpoint, or how an assessment outside the expected schedule would be handled.

How should a confidence interval be read?

A confidence interval describes the statistical uncertainty around an estimate under the assumptions of the method used. For an objective response rate, the interval would give a range of values compatible with the observed data and the selected confidence procedure. A narrower interval generally indicates greater precision; a wider interval indicates less precision. The interval does not resolve design limitations, measurement issues, or the lack of a comparison group.

The registry identifies a 95% confidence interval as the dispersion measure for the primary endpoint, but the numerical interval is not reported in the registry record. The interval method is also not reported in the registry record. As a result, neither the interval's width nor the method's suitability for the observed data can be assessed.

What can a single-group result establish?

In a single-group study, an estimated response rate describes the outcomes observed in that group under the study's assessment rules. It is not a randomized treatment-effect estimate. Without a concurrent comparator, the observed proportion cannot separate the effect of treatment from other influences, such as the course of disease, participant selection, or differences in assessment. General statistical principle: randomization helps balance measured and unmeasured factors between groups, while a single-group design does not create that comparison.

Masking is recorded as none. General statistical principle: knowledge of treatment assignment can influence aspects of care, assessment, or reporting, depending on the endpoint and study procedures. The registry record does not describe safeguards used for radiologic review, so their presence or absence cannot be inferred.

Why can over-dispersion matter?

General statistical principle: over-dispersion occurs when observed variability is greater than a statistical model assumes. If a model assumes less variability than the data contain, uncertainty estimates may be too small and inferential conclusions may be overly confident. For a binary endpoint, the choice of interval or model should reflect the data structure and the number of observed responses. The registry record does not report the response count or the method used to calculate the confidence interval, so over-dispersion or other model-fit considerations cannot be evaluated for this endpoint.

How do planning illustrations differ from trial results?

Planning sample-size illustrations are not observed trial outcomes. The described illustration uses 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. It is explicitly a planning illustration rather than the trial's own design. This study itself is single-group, so the illustration's two-arm assumptions do not describe the design used in the registry. Any participant-per-arm values in such planning scenarios would be hypothetical planning quantities, not the number enrolled in this single-group study and not evidence of observed power. The registry record does not report a sample-size justification for the trial.

More broadly, a confidence interval and a planning calculation answer different questions. A confidence interval describes uncertainty in an estimated result, while a planning calculation explores the sample size that might be needed under specified assumptions. Neither can substitute for the missing primary endpoint estimate. Since the registry record does not report the numerical ORR, its interval, or the analysis details, the statistical evidence for the primary outcome cannot be reconstructed from the record.

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("Ramaycin")
n      <- c(36)
events <- c(16)
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  Ramaycin  36  16  44.4  27.9  61.9  29.5  60.4  29.5  60.5

11. Multiplicity, Missing Data and Analysis Populations

Multiplicity concerns arise when a study examines multiple outcomes, comparisons, or analyses. The registry lists an objective response rate as the primary outcome and two secondary outcomes: participants with grade 3 or more treatment-related lymphopenia, and whether changes were observed in other TSC lesions. It also records three outcome measures. The registry record does not report a multiplicity adjustment, a hierarchy of testing, or how conclusions across outcomes were intended to be controlled. It is therefore not possible to determine whether or how the study addressed the increased chance of false-positive findings when considering multiple statistical tests.

Missing data handling is also not reported in the registry record. The registry entries do not specify how participants without an evaluable radiologic assessment were classified, whether assessments were repeated or adjudicated, or how missing measurements were treated in the primary analysis. These details matter because different handling rules can change the response proportion and its uncertainty.

The analysis population is not reported in the registry record. Although enrollment is listed as 36, the number included in the primary endpoint analysis and any exclusions are not given. The registry also lists zero analyses. No statistical analysis plan, interim analysis plan, or rationale for the sample size is reported in the registry record. Those omissions limit assessment of whether the primary analysis followed a prespecified approach and how the reported endpoint, if any, should be interpreted.

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: neutrophil count decreased (88.9%), mucositis oral (13.9%), platelet count decreased (13.9%), aspartate aminotransferase increased (8.3%), anemia (2.8%).

The registry lists serious adverse-event terms for the rapamycin group, including Neutrophil count decreased at 88.9%, Mucositis oral at 13.9%, Platelet count decreased at 13.9%, Aspartate aminotransferase increased at 8.3%, Anemia at 2.8%, and Febrile neutropenia at 2.8%. These are the percentages as recorded; the registry entries do not give event counts for each term or define the denominator and observation period used for each percentage.

The group-level adverse-event fields list 36 participants at risk and 36 affected for the serious and other adverse-event fields, and deaths are listed as 0. The registry record does not clarify how those group-level fields should be interpreted alongside the percentages for individual terms. They should not be read as event-specific counts.

These entries are descriptive safety information, not a controlled comparison. The study has no concurrent control group, and the record does not provide exposure-adjusted rates, timing, duration, severity details for each listed event, or a complete accounting of participants with any adverse event. The figures therefore do not establish that rapamycin caused or did not cause a particular event, nor do they permit a comparative safety estimate.

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

The registry record establishes that this completed Phase II study examined rapamycin in a single group of people with kidney angiomyolipomas in the context of TSC or LAM. It describes the oral dosing approach, the target blood levels stated for the early and later treatment periods, and a primary radiologic endpoint based on RECIST 1.1. It also records selected serious adverse-event terms and percentages.

The main result needed to judge the primary endpoint is absent: the numerical objective response rate and its 95% confidence interval are not reported in the registry record. Accordingly, the frequency of response and the precision of its estimate cannot be summarized. The presence of a response definition is not itself evidence about how often participants responded.

Even if an ORR were available, a single-group response proportion would describe outcomes in the study group rather than estimate a randomized contrast. It would not by itself show what would have happened to similar participants under a comparator, or establish that observed changes were caused by treatment. The registry does not report a concurrent control arm, and allocation is listed as not applicable.

The safety entries also require restraint. The listed percentages describe recorded serious adverse-event terms, but the registry entries do not establish their event-specific denominators, timing, or relationship to treatment. They do not provide a full safety comparison or a complete account of all adverse events.

The registry record is therefore informative about the study question and design but insufficient for a numerical efficacy interpretation. It does not support a claim that the treatment does or does not work, nor a comparative claim about safety. More complete outcome results and analysis details would be needed to evaluate the observed response, uncertainty, missing assessments, and the context of the adverse-event findings.

14. Why This Trial Matters Statistically

This study raises statistical questions that are common in early-phase clinical research. A single-group design can describe the frequency of a prespecified response in a defined population, but the result has a different interpretation from a randomized comparison. The objective response rate is tied to explicit imaging criteria, which can make the endpoint easier to interpret than an unspecified judgment of improvement, while still leaving uncertainty about how the result compares with another treatment or the natural course of disease.

Precision is central to interpreting a proportion. A point estimate alone would not show how much uncertainty surrounds the observed response rate, which is why the registry's stated use of a 95% confidence interval is relevant. In this case, the estimate and interval are not reported in the registry record. That absence prevents readers from assessing both the observed frequency and how precisely it was estimated.

The study also illustrates why reporting the analysis population and missing-data rules matters. The enrollment figure alone does not establish how many participants contributed evaluable assessments to the primary endpoint. Without the analysis denominator and rules for missing or unevaluable imaging, a response proportion cannot be interpreted fully.

Finally, the record includes safety percentages but no concurrent control group. Descriptive event reporting can identify what was recorded in the treated group, yet it cannot provide a controlled estimate of excess risk. Statistical interpretation depends not only on the endpoint definition and study size, but also on complete reporting of denominators, uncertainty, and analysis methods.

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 important trial-specific limitation in the registry record is the absence of the primary objective response rate and its 95% confidence interval. Without these results, the central efficacy outcome cannot be quantified. The registry also does not report the response count, the primary analysis population, or participant flow, so the denominator used for any response estimate is unknown.

The single-group, unmasked design provides no concurrent control for comparing outcomes. The registry records allocation as not applicable and masking as none. Therefore, even a reported response proportion would be descriptive and would not isolate the treatment effect from other explanations. Details about radiology review, outcome adjudication, and protections against assessment bias are not reported in the registry record.

The record does not report the statistical analysis plan, the method used to calculate the stated confidence interval, sample-size justification, or missing-data rules. It also does not report whether there were interim analyses or how multiple outcomes were handled statistically. These omissions make it difficult to assess prespecification and the robustness of the planned analyses.

The treatment description is incomplete after the statement that the target blood level increased after week 16. Detailed treatment duration, adherence, dose modifications, and exposure are not reported in the registry record. The safety entries include selected serious adverse-event terms, but do not provide event-specific counts, observation periods, or a complete safety summary. These limitations restrict both efficacy and safety interpretation.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: RAPAMYCIN FOR KIDNEY ANGIOMYOLIPOMAS — NCT00126672.
• Registry record last updated 2022-04-25; status last verified 2022-03.
• Results first posted 2022-04-25.
• 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.

19. Record Summary

NCT00126672 is a completed Phase II, multicenter, single-group study sponsored by Dana-Farber Cancer Institute. Enrollment is listed as 36. The study evaluated oral rapamycin for kidney angiomyolipomas in people with TSC or LAM; masking is recorded as none and allocation as not applicable.

The primary endpoint was the objective response rate under RECIST 1.1, assessed radiologically on treatment up to 52 weeks. The registry record does not report the numerical response rate, its 95% confidence interval, or the primary analysis population. It lists two secondary outcomes concerning treatment-related lymphopenia and changes in other TSC lesions.

Selected serious adverse-event terms and percentages are recorded, along with group-level fields and zero deaths. The registry entries do not clarify event-specific denominators or reporting periods. The statistical analysis plan, missing-data approach, and sample-size justification are not reported in the registry record.