RAD001 and Erlotinib in Patients With Neuroendocrine Tumors: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for RAD001 and Erlotinib in Patients With Neuroendocrine Tumors (NCT00843531), a na phase 2 study. The primary outcome is Objective Response Rate (ORR).

2. Clinical Question

The study asked whether RAD001 plus erlotinib could be used safely and produce objective responses in patients with well- to moderately-differentiated neuroendocrine tumors. It was a phase II study with a single treatment group, rather than a randomized comparison with a control group. The registry record lists an enrollment of 17.

Safety was also part of the study’s purpose. Listed secondary outcomes include dose-limiting toxicity, duration of objective response, overall survival, median progression-free survival, time to progression, and time to treatment failure. The registry record does not report results for these outcomes. Thus, the stated questions can be described, but the posted record does not provide the efficacy analyses needed to assess the primary question or the listed secondary questions.

3. Trial Design

This was a phase II study with a single-group model and no masking. The registry lists the study as terminated and records enrollment of 17. It gives a start date of 2009-06-25 and a primary completion date of 2013-07-16. The reason for termination is not reported in the registry record.

All participants in the treatment group were assigned the combination of RAD001 and erlotinib. Each 28 day cycle specified RAD001 at 5 mg per day by mouth and erlotinib at 100 mg per day by mouth, both self-administered. The record does not describe a separate control arm, a random allocation process, or masking. Consequently, this design can describe outcomes among those treated in the study, but it does not establish a randomized comparison between the combination and another treatment or control.

The primary outcome was objective response rate, with objective response defined as complete response or partial response under RECIST criteria. Its timeframe was up to 2 years. The primary analysis population was efficacy-evaluable patients, defined by receipt of at least one treatment cycle and at least one post-baseline response assessment, or death while on therapy. This is a population definition, not a reported count of people who met the definition.

Other outcomes listed cover dose-limiting toxicity, duration of objective response, overall survival, median progression-free survival, time to progression, and time to treatment failure. The record lists seven outcome measures but no analyses. It does not give outcome estimates, uncertainty intervals, or the number evaluated for each outcome. These omissions limit interpretation of both efficacy and the secondary outcomes.

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 Objective Response Rate (ORR), measured over Up to 2 years.

The primary endpoint is objective response rate, expressed in the registry as a count of participants. An objective response is a complete response or a partial response assessed using RECIST criteria. The endpoint therefore asks whether patients had a measurable tumor response under the specified assessment framework, rather than measuring a time until an event or a continuous change in tumor size.

Response endpoints are used in clinical studies because they provide a defined way to describe tumor shrinkage or disappearance during treatment. In general, standardized criteria help make response assessments more consistent. A response count alone, however, does not describe how long a response lasts, whether disease progression is delayed, or how outcomes compare with those under another treatment. The registry lists duration of objective response and several time-to-event outcomes separately, but does not report their results.

The primary endpoint was assessed for up to 2 years. The specified efficacy-evaluable population included patients who received at least one cycle and had at least one post-baseline response assessment, as well as those who died while on therapy. The registry record does not report how many participants met this definition, how response assessments were handled when unavailable, or the objective response count. Accordingly, the endpoint’s definition is available, but its observed result cannot be interpreted 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 at the participant level: a participant either meets the definition of objective response or does not. The registry defines response as complete response or partial response under RECIST criteria. It records the outcome as a count of participants, but does not report the observed count or an analysis. Without that count and its analysis population, neither the response proportion nor its precision can be described.

In general, a confidence interval expresses uncertainty around an estimated quantity. For a response proportion, it would indicate how compatible a range of underlying response rates is with the observed data under the method used. A wider interval generally signals less precision, while a narrower one signals greater precision. No confidence interval or method for calculating one is reported in the registry record, so no numerical statement about precision is possible for the primary endpoint.

The efficacy-evaluable definition is important because it specifies which participants were intended for the primary analysis. It includes those who received at least one cycle and had at least one post-baseline response assessment, or who died while on therapy. This definition does not tell readers how many participants qualified, whether any assessments were missing, or how participants outside the definition were handled. In general, analysis-population rules affect the denominator and interpretation of an endpoint. The registry record does not report a participant flow or a count for this population.

The study is described as single-group, with no masking. In general, a single-group design can estimate outcomes observed in the enrolled group, but it has no concurrent control group to separate treatment-associated outcomes from other explanations. A randomized comparison is designed to support a different question: whether outcomes differ between assigned groups, subject to the assumptions and conduct of the trial. There is no such comparison described in this record. The record also does not report an adjustment strategy or other modeling details for the primary endpoint.

The registry lists seven outcome measures and zero analyses. It names the primary endpoint and secondary outcomes, but does not provide test statistics, model estimates, confidence intervals, or p-values. A named endpoint should not be mistaken for a completed statistical result. The statistical analysis plan, including any prespecified tests, handling of repeated assessments, or analysis timing, is not reported in the registry record.

The sample-size assumptions describe planning illustrations rather than the study’s own design. They specify 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. Those assumptions do not turn this single-group study into a two-arm comparison, and the record does not report a protocol-based sample-size justification. The sample-size illustrations are not observed power and do not supply missing efficacy results. Any numerical sample-size interpretation must be kept separate from what happened in this study.

For general context, over-dispersion occurs when variability in data is greater than a statistical model assumes. If present, it can make standard errors too small and confidence intervals too narrow unless the analysis accounts for it. The registry record does not report an over-dispersion assessment, and the binary primary endpoint does not have a reported model from which to assess that issue. It would therefore be inappropriate to assume that a particular adjustment was used or needed.

The record lists several secondary outcomes, including survival and progression measures. In general, time-to-event analyses account for the time until an event and may also account for participants whose event has not been observed by the end of follow-up. Their interpretation depends on definitions of the event, censoring, follow-up, and the analysis method. These details and results are not reported in the registry record. No survival estimate or comparison should be inferred from the outcome names alone.

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("RAD001 Plus Erlotinib")
n      <- c(17)
events <- c(0)
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  RAD001 Plus Erlotinib  17  0  0.0  0.0  19.5  0.0  18.4  0.1  18.5

11. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary outcome and several secondary outcomes, but does not report an analysis for them. A study that evaluates multiple outcomes may face multiplicity: testing or interpreting many hypotheses can increase the chance of findings that appear notable by chance. In general, researchers may specify a hierarchy of outcomes or an adjustment approach to address this issue. The registry record does not report whether any such strategy was planned or used.

Missing-data handling is also not reported. The primary analysis population is defined by treatment receipt and a post-baseline response assessment, with an exception for patients who died while on therapy. This definition does not explain how missing assessments were handled, whether all enrolled patients were assessed, or how missingness affected the analysis denominator. It should not be assumed that participants without a recorded assessment were counted as nonresponders or excluded under a particular rule.

The record gives an enrollment of 17, but does not report the number in the efficacy-evaluable population or the number assessed for each secondary outcome. It lists zero analyses. The statistical analysis plan and any analysis populations beyond the stated efficacy-evaluable definition are not reported in the registry record. As a result, neither multiplicity control nor the effect of missing data can be evaluated from the posted information.

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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: diarrhea (5.9%), edema: limb (5.9%), creatinine (5.9%), pain - back (5.9%), pain - extremity-limb (5.9%).

The registry lists 4 participants affected by serious adverse events among 17 at risk in the RAD001 plus erlotinib group. It also lists 17 affected by other adverse events among 17 at risk, and 6 deaths. These are counts as recorded; they do not by themselves establish that an event or death was caused by treatment. The registry record does not provide timing, event-level narratives, duration, severity beyond the serious-event category, or attribution details for these entries.

The serious adverse-event terms listed are diarrhea, edema: limb, creatinine, pain - back, pain - extremity-limb, and incontinence, urinary. Each term is accompanied by 5.9%. The record does not provide additional context for these term-level entries, such as event counts by term or whether a participant could contribute to more than one term. They should therefore be read as registry-listed safety information, not as a complete account of incidence or causality.

Safety counts are descriptive and depend on how events were collected and classified. The registry record does not report those procedures in detail, nor does it explain the relationship between the listed deaths and adverse events. These figures should be interpreted alongside that missing context rather than as a causal estimate of treatment risk.

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

The record establishes that a phase II, single-group study evaluated RAD001 plus erlotinib in patients with neuroendocrine tumors, and that objective response rate was designated as the primary endpoint. It also gives the response definition, treatment schedule, and selected safety counts. These details describe what the study set out to assess and some of the information registered about safety.

They do not establish whether the combination produced objective responses. The response count and response rate are not reported in the registry record, and there is no reported confidence interval or statistical analysis. The record also does not report results for the listed secondary outcomes. Because the study has no separate comparator group, it cannot support a randomized treatment-versus-control estimate. A favorable or unfavorable interpretation of efficacy cannot be drawn from the endpoint definition, enrollment count, or study status alone.

The safety entries also require restraint. Counts of participants with serious and other adverse events, the listed terms, and deaths describe entries in the record; they do not establish causality. Further information about timing, attribution, event definitions, and follow-up is not reported. These counts should not be read as a complete safety profile.

In general, a clinical trial’s conclusions depend on the observed results, how completely outcomes were measured, and the methods used to analyze them. Here, those results and methods are not reported in sufficient detail to evaluate the primary question. The registry record supports a description of design and outcome definitions, not a conclusion that the treatment does or does not work.

14. Why This Trial Matters Statistically

This study is statistically informative as an example of the distinction between a registered research question and a reported analysis. The registry identifies a primary endpoint, defines the response criteria, specifies an efficacy-evaluable population, and lists secondary outcomes. Yet it reports zero analyses and no primary response result. A clearly named endpoint is useful for understanding the study’s aims, but it cannot substitute for an estimate and its uncertainty.

The single-group design also shapes the question the data could address. A single group can describe outcomes among participants who received the combination. It cannot, without a suitable comparator, isolate how those outcomes would differ under another treatment. This distinction matters when readers encounter response or safety counts: descriptive observations are not comparative effects.

The record further illustrates why analysis populations and missing-data procedures matter. The primary endpoint applies to an efficacy-evaluable population defined by treatment exposure and assessment, but the number meeting that definition is not reported. Without the denominator and outcome data, readers cannot judge the scale or precision of a response estimate. The absence of reported methods also prevents evaluation of multiplicity or the handling of incomplete assessments.

Finally, the safety entries show why event counts need context. The registry lists serious and other adverse events and deaths, but does not provide detailed timing or attribution. These registry entries can be recorded without implying causation. A careful statistical reading separates what the record documents from what its design and missing results cannot establish.

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 consequential limitation of the registry record is that it does not report the primary endpoint result or any analyses. The objective response count, the number in the efficacy-evaluable population, and the precision of any estimate are not reported. The listed secondary outcomes likewise have no results in the record. This prevents assessment of the study’s efficacy findings and limits interpretation to the design and outcome definitions.

The study is single-group and has no separate control group, so it does not provide a randomized comparison. The record does not report a detailed statistical analysis plan, sample-size justification for the trial, methods for missing data, or a multiplicity strategy. The sample-size assumptions described are planning illustrations and should not be interpreted as the study’s own design rationale or as observed power.

The record marks the study as terminated but does not report the reason. It also does not give detail on participant flow, response assessment completeness, follow-up for secondary outcomes, or the analysis populations used for those outcomes. Although the safety entries include counts and serious-event terms, event timing, attribution, and other clinical context are not reported. These omissions leave substantial uncertainty about how fully the registered questions were answered and how the listed safety information should be interpreted.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: RAD001 and Erlotinib in Patients With Neuroendocrine Tumors — NCT00843531.
• Registry record last updated 2020-09-29; status last verified 2020-09.
• Results first posted 2020-09-29.
• 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

NCT00843531 is a phase II, single-group study of RAD001 plus erlotinib in patients with neuroendocrine tumors. The record lists enrollment of 17, no masking, and terminated status. The treatment schedule specified oral RAD001 at 5 mg per day and oral erlotinib at 100 mg per day during each 28 day cycle.

The primary outcome was objective response rate, defined as complete or partial response under RECIST criteria, with assessment up to 2 years. The record lists an efficacy-evaluable population definition but does not report its size or the primary endpoint result. It lists secondary outcomes and safety counts, including serious adverse events and deaths, but does not report outcome analyses or detailed event context. The reason for termination and the statistical analysis plan are not reported in the registry record.