A Study of Ramucirumab in Participants With Metastatic Renal Cell Carcinoma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of Ramucirumab in Participants With Metastatic Renal Cell Carcinoma (NCT00515697), a na phase 2 study. The primary outcome is Percentage of Participants With Objective Response (Objective Response Rate).

2. Clinical Question

The study focused on a population with metastatic disease after progression on, or intolerance to, tyrosine kinase inhibitor therapy. Its stated purpose was to determine whether ramucirumab was effective treatment in that setting. Statistically, the primary question is descriptive: among the participants treated, how many had a best overall response meeting the stated response criteria? A single-group design can describe observed outcomes under treatment, but without a concurrent control it cannot isolate the treatment’s effect from other explanations for those outcomes.

3. Trial Design

This completed phase II study enrolled 39 participants and used a single-group, nonrandomized design. The registry lists the condition as metastatic renal cell carcinoma and the intervention as ramucirumab. There was no masking. With no comparator arm, the study does not provide a randomized, like-for-like comparison between ramucirumab and another treatment or a control condition.

Ramucirumab was administered by intravenous infusion at 8 milligrams per kilogram on day 1 of every 14-day cycle. The official study title specifies participants with metastatic renal cell carcinoma whose disease had progressed on, or who were intolerant to, tyrosine kinase inhibitor therapy. The study began in 2007-11, reached primary completion in 2011-05, and is recorded as completed.

The primary endpoint was the percentage of participants with an objective response, defined as a confirmed complete response or partial response under RECIST version 1.0. The timeframe is described as first dose through objective progressive disease or death from any cause, up to 34 months. The registry also lists secondary outcomes covering progression-free survival, disease control at Week 12, objective response at 12 weeks, duration of overall response, ramucirumab concentrations, and drug-related treatment-emergent adverse events.

The registry record does not report a control group, a randomization procedure, or masking. It also does not report a detailed statistical analysis plan, a sample-size justification, or interim-analysis procedures. Those details should not be inferred from the phase or design label. In particular, the absence of a control group limits the kinds of causal conclusions available: observed response or safety outcomes describe the treated participants, rather than a contrast that estimates what would have happened under another treatment.

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: This study comprised 3 study periods: pretreatment, treatment, and (posttreatment) follow-up. 40 participants signed the informed consent.

Overall Study

Analysis population for the primary outcome, as defined in the registry: Intent-to-treat population: participants who received any quantity of ramucirumab.

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.

Population: Intent-to-treat population: participants who received any quantity of ramucirumab.

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Participants With Objective Response (Objective Response Rate), measured over First dose to date of objective progressive disease or death due to any cause (up to 34 months).

The primary endpoint is the percentage of participants whose best overall response during therapy was a confirmed complete response or partial response. A complete response requires disappearance of all target and non-target lesions and normalization of tumor marker levels. A partial response requires at least a 30% decrease in the sum of the longest diameters of target lesions, without new lesions or progression of non-target lesions. These definitions follow RECIST version 1.0 as described in the registry.

An objective response rate reduces a set of tumor assessments to a binary outcome for each participant: response or no response under the stated criteria. The percentage then describes the share of the treated population meeting the response definition. This endpoint is useful for characterizing observed tumor shrinkage, while the criteria make the response classification more explicit than an unstructured judgment.

As a general statistical point, a confidence interval communicates uncertainty around an estimated percentage. A narrower interval indicates greater precision under the method used; a wider interval indicates less precision. The registry lists a 95% confidence interval as the endpoint’s dispersion measure, but the response percentage and interval are not reported in the registry record. Therefore, the endpoint definition is available, but the magnitude and precision of the primary response result cannot be evaluated from that record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is a binary response measure summarized as a percentage. Each participant is classified according to whether the best overall response during therapy is a confirmed complete response or partial response. Participants not meeting either response definition do not count as objective responders under the stated endpoint. The registry describes the percentage as the number of participants with either response divided by the number treated, multiplied by 100. It identifies participants who received any quantity of ramucirumab as the intent-to-treat population.

What does a confidence interval add?

The registry lists a 95% confidence interval for the primary percentage. In general, a confidence interval expresses statistical uncertainty about an estimate, conditional on the data and the method used to calculate it. It is not a guarantee that the true value lies inside a particular interval, and it does not correct for limitations in study design or measurement. The exact interval method is not reported in the registry record. Because the response percentage and interval are not reported there, neither the estimated response level nor its precision can be assessed.

Why does the single-group design matter?

In general, an outcome proportion from one treated group is descriptive. A randomized comparison can help distinguish treatment differences from differences in participant characteristics because assignment creates comparison groups under a planned allocation process. This study is recorded as single-group, with allocation not applicable and no masking. There is therefore no concurrent control outcome against which to estimate a treatment contrast. The observed group’s response, if reported, would not by itself show what would have occurred in the same participants under an alternative intervention.

The lack of masking is also part of the design context. In general, knowledge of treatment assignment can influence some aspects of care, assessment, or reporting, depending on the outcome and safeguards in place. The registry record does not describe assessment masking or further procedures to reduce such influences. It is not appropriate to assume either that bias occurred or that particular protections were used.

How should the response criteria be read?

RECIST version 1.0 supplies operational rules for classifying tumor response. In the registry description, complete response requires disappearance of target and non-target lesions and normalization of tumor marker levels. Partial response requires at least a 30% decrease in the sum of the longest diameters of target lesions, without new lesions or progression of non-target lesions. Operational criteria can support consistent classification, but their use does not disclose how often assessments took place, who reviewed them, or how disagreements were handled. Those details are not reported in the registry record.

The timeframe runs from first dose until objective progressive disease or death from any cause, up to 34 months. This describes the stated observation window for the primary endpoint. It does not provide the actual follow-up distribution, the number of participants followed for particular durations, or the timing of response assessments. Those items are not reported in the registry record.

What can be said about secondary outcomes?

The registry lists progression-free survival, disease control at Week 12, objective response at 12 weeks, median duration of overall response, ramucirumab minimum and maximum concentrations, and a summary listing of participants reporting drug-related treatment-emergent adverse events. These outcomes address different questions and may require different statistical summaries. For example, a time-to-event outcome concerns the time until a defined event, whereas a percentage outcome summarizes whether an event or response occurred in a stated population. General statistical methods differ according to the outcome type and the way observations are censored or missing.

The record identifies eight outcome measures and zero analyses. It does not state the detailed models, estimation procedures, censoring rules, or planned contrasts for the listed outcomes. No particular method should be attributed to the investigators beyond the endpoint description and dispersion measure that are explicitly recorded.

What does over-dispersion mean in general?

For count outcomes, over-dispersion means that observed variability exceeds what a simple model assumes. When present, a model that ignores it can understate uncertainty and make results appear more precise than they are. This is a general concept, not a method reported for this study. The primary endpoint is a participant percentage, and the registry does not report an over-dispersion model or a count-model analysis.

Similarly, sample-size planning calculations are distinct from observed results. A planning illustration can show how sample size might vary under stated assumptions, but it is not an observed power calculation and does not change the uncertainty in the data actually collected. The planning assumptions recorded for the illustrations describe a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with an effect to detect stated as a fraction of the observed effect. These are illustration assumptions, not evidence that the single-group trial itself used a two-arm design. The registry record does not report the trial’s own sample-size justification.

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("Ramucirumab")
n      <- c(39)
events <- c(2)
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  Ramucirumab  39  2  5.1  0.6  17.3  1.4  16.9  1.6  16.9

11. Multiplicity, Missing Data and Analysis Populations

The registry identifies objective response as the primary endpoint and lists eight outcome measures overall. It does not report a multiplicity strategy, such as a hierarchy of tests or an adjustment across multiple outcomes. In general, testing several outcomes can increase the chance of at least one apparently notable result when each is considered independently. Whether that issue affects interpretation depends on the analyses actually performed and the prespecified plan. The relevant plan is not reported in the registry record, so no adjustment method or confirmatory status for secondary outcomes can be assumed.

The record identifies zero analyses. This is not a substitute for a detailed statistical analysis plan and does not explain whether analyses were not conducted, not entered, or not reported in the registry. The primary response percentage and its confidence interval are also not reported there.

The primary population is described as the intent-to-treat population, defined as participants who received any quantity of ramucirumab. The record does not explain how missing or unevaluable response assessments were treated, whether any participants were excluded from endpoint calculations, or how missing follow-up information was handled for secondary outcomes. These choices can affect denominators and estimates. Their effect cannot be assessed without the analysis details and outcome data.

As a general principle, a missing-data approach should be described alongside the population and outcome definition, because different assumptions about unobserved outcomes can lead to different interpretations. No imputation procedure or sensitivity analysis is reported in the registry record. The stated population definition alone does not establish how every missing measurement was handled.

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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: cardio-respiratory arrest (2.6%), myocardial infarction (2.6%), fatigue (2.6%), multi-organ failure (2.6%), urinary tract infection (2.6%).

The safety record lists 39 participants at risk for serious adverse events and 12 affected. It also lists 39 participants at risk and 39 affected for other adverse events. These are participant counts in the treated group, not comparisons between treatment arms. The registry record does not report a death count.

The listed serious event terms are cardio-respiratory arrest, myocardial infarction, fatigue, multi-organ failure, urinary tract infection, and anorexia, each reported at 2.6%. These entries describe the reported terms and percentages; they do not establish that each event was caused by ramucirumab. The record does not provide detailed event narratives, timing, duration, recurrence, or participant-level overlap among terms.

In general, serious adverse events are distinct from all adverse events: seriousness relates to regulatory outcome criteria, while severity describes intensity. A count of participants affected is not the same as a count of event episodes. The registry information does not provide enough detail to reconstruct those distinctions for each listed event. These figures characterize reported safety events in this cohort and should not be read as a comparative safety estimate.

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

The record documents a phase II, single-group study of ramucirumab in participants with metastatic renal cell carcinoma after progression on, or intolerance to, tyrosine kinase inhibitor therapy. It specifies the treatment schedule, the primary objective-response definition, the intended population, and several secondary outcomes. It also records participant counts for serious and other adverse events.

Those details do not supply the primary response result. The objective response percentage and its 95% confidence interval are not reported in the registry record. As a result, the observed response frequency and the precision of its estimate cannot be described. The study’s stated purpose is not itself a result, and an endpoint definition does not establish how participants actually responded.

Even if a response estimate were available, a single-group study would describe the outcome among participants who received treatment. Without a concurrent comparator, it cannot quantify a randomized difference or determine how outcomes would have differed under another treatment. General statistical interpretation also distinguishes an observed association from a causal effect; the design and reporting determine which claims are supported.

The safety counts similarly describe the enrolled treatment group. They are not comparative risks, and the listed terms do not by themselves establish causation. More detailed information on event timing, severity, attribution, and overlap is not reported in the registry record. The death count is also not reported.

Accordingly, the registry record supports a description of the study question and design, but not a numerical conclusion about objective response or a comparison of benefit and risk against another treatment. The missing endpoint results and analysis details leave important aspects of efficacy and precision unresolved.

14. Why This Trial Matters Statistically

This study matters statistically because it illustrates the difference between an endpoint definition and an endpoint result. The registry explains what counted as objective response and identifies a 95% confidence interval as the measure of dispersion. But without the response estimate and interval, readers cannot assess the observed response frequency or the uncertainty around it. A clearly defined outcome is necessary for interpretation, but it cannot replace the outcome data.

The single-group design also makes the estimand—the quantity a study aims to describe or compare—important. Here, the primary question concerns the percentage of treated participants meeting response criteria. That is a descriptive quantity for the enrolled population. It is not a randomized treatment contrast. Naming this distinction prevents a response proportion from being interpreted as proof of what would happen relative to an alternative treatment.

The record also shows why population definitions, missing-data handling, and analysis plans matter. The intent-to-treat population is defined as participants receiving any quantity of ramucirumab, but the registry does not explain how missing or unevaluable assessments were addressed. Without these details, readers cannot fully assess the endpoint denominator or how robust an estimate would be to different assumptions.

Finally, the listed safety counts demonstrate the limits of event summaries without comparative data and participant-level context. Counts identify reported events, but do not alone describe causality or comparative risk. These considerations apply broadly to clinical research: a design, endpoint, estimate, uncertainty measure, and analysis population each contribute different information, and none should be mistaken for another.

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 this record is that the objective response percentage and its 95% confidence interval are not reported in the registry record. The endpoint’s definition and timeframe are available, but they do not reveal the observed result or its precision.

The study is single-group, with no comparator. That design supports description of outcomes among treated participants, but it does not provide a concurrent comparison for estimating a treatment difference. The record also reports no masking. Further details about response assessment procedures, including who assessed scans and whether assessments were reviewed independently, are not reported in the registry record.

The registry defines the primary population as participants who received any quantity of ramucirumab, but does not report the response denominator, the number of evaluable participants, or the handling of missing assessments. It also does not report a detailed statistical analysis plan, a sample-size justification, interim-analysis procedures, or a multiplicity approach. These omissions limit assessment of how the analysis was planned and how secondary results should be interpreted.

Safety information is limited to participant counts and selected serious event terms with percentages. Detailed timing, severity, duration, attribution, recurrence, and overlap are not reported in the registry record, and the death count is not reported. The available safety summaries therefore cannot provide a complete account of event patterns or a comparative safety assessment.

The registry lists secondary outcomes, but their numerical results and detailed analyses are not included in the record information described. Accordingly, conclusions about those outcomes cannot be drawn from the listed endpoint names alone.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study of Ramucirumab in Participants With Metastatic Renal Cell Carcinoma — NCT00515697.
• Registry record last updated 2014-06-18; status last verified 2014-05.
• Results first posted 2014-06-18.
• 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

This completed phase II study enrolled 39 participants with metastatic renal cell carcinoma whose disease progressed on, or who were intolerant to, tyrosine kinase inhibitor therapy. It evaluated ramucirumab in a single group, administered by intravenous infusion at 8 milligrams per kilogram on day 1 of every 14-day cycle. The primary endpoint was objective response under RECIST version 1.0, defined as confirmed complete or partial response.

The registry specifies a 95% confidence interval for the primary endpoint but does not report the response percentage or interval. It lists eight outcome measures and zero analyses. Safety reporting lists 12 participants affected by serious adverse events among 39 at risk, and 39 affected by other adverse events among 39 at risk. A death count is not reported in the registry record. The single-group design provides no concurrent comparator for estimating a treatment contrast.