This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Trial of RAD001 in Patients With Operable Non-Small Cell Lung Cancer (NSCLC) (NCT00401778), a non-randomized phase 1 study. The primary outcome is Clinical Response as Assessed Metabolically by Changes in Positron Emission Tomography (PET) Scan Between Baseline and Immediately Prior to Surgery..
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00401778 |
| Phase | Phase 1 |
| Condition | Lung Cancer |
| Allocation | Non-Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 33 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Emory University |
| Results posted | Yes |
2. Clinical Question
Population
Patients with operable lung cancer were eligible. The registry title specifies non-small cell lung cancer, and the brief summary describes a pre-operative study. Enrollment was 33; detailed eligibility criteria and the characteristics of participants enrolled are not reported in the registry record.
Intervention
The intervention was RAD001, given sequentially for 21 days at either 5 mg/day or 10 mg/day. The registry describes assessment of molecular target effects, tumor FDG uptake on PET, and safety. How patients entered the two dose groups is not reported in the registry record.
Comparator
The control group consisted of eligible patients who chose not to receive RAD001. Because allocation was non-randomized, this is not a like-for-like randomized control comparison. Reasons for choosing treatment or control, and other differences between groups, are not reported in the registry record.
Primary question
The primary endpoint asks about clinical response assessed metabolically through changes in PET scans from baseline to immediately before surgery, with a stated timeframe of Day 21. The registry does not report the response definition, group results, or an analysis comparing treatment and control.
3. Trial Design
The registry identifies this as a Phase 1, parallel, non-randomized trial with no masking. Its brief summary describes the study as Phase 1b and pre-operative. The stated enrollment was 33, and the status is completed. The listed intervention was RAD001; the registry describes sequential treatment at 5 mg/day or 10 mg/day for 21 days.
The control group was made up of patients eligible for the study who chose not to receive RAD001. This is an important feature of the design: patients were not randomly assigned to treatment or control. The registry record does not report how the two dose groups were formed or whether treatment choice was related to patient characteristics. Differences between groups therefore cannot automatically be attributed to treatment, because groups may differ for reasons other than treatment.
Baseline PET imaging was performed in a fasted state, followed by a repeat scan 3 to 4 weeks later. The repeat scan occurred no longer than 24 hours before surgical resection. The primary endpoint timeframe is given as Day 21. The record also lists safety and tolerability of pre-operative RAD001 and duration of hospital stay following surgery as secondary outcomes.
Start and primary-completion dates are recorded as 2006-11 and 2013-12, respectively. The sponsor is Emory University. The registry record does not report a detailed protocol, the allocation process beyond its non-randomized designation, or a statistical analysis plan.
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: Eligible patients were enrolled concurrently on the active and control arms. Patient preference for a specific arm was entertained until the control cohort was completely filled after which all patients were competitively enrolled on the active treatment arm of the study.
Overall Study
| Stage | Control | Everolimus 5 mg | Everolimus 10 mg |
|---|---|---|---|
| STARTED | 10 | 12 | 11 |
| COMPLETED | 9 | 11 | 10 |
| NOT COMPLETED | 1 | 1 | 1 |
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.
| Characteristic | Unit | Control | Everolimus 5 mg | Everolimus 10 mg | Total |
|---|---|---|---|---|---|
| Participants analysed | 10 | 12 | 11 | 33 | |
| Age, Continuous | years | 63 (54 to 77) | 58 (44 to 66) | 70 (35 to 75) | 64 (35 to 77) |
| Gender: Female | Participants | 6 | 6 | 7 | 19 |
| Gender: Male | Participants | 4 | 6 | 4 | 14 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Asian | Participants | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 3 | 2 | 4 | 9 |
| Race (NIH/OMB): White | Participants | 7 | 10 | 7 | 24 |
| Race (NIH/OMB): More than one race | Participants | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 | 0 |
| Region of Enrollment: United States | participants | 10 | 12 | 11 | 33 |
6. Primary Endpoint
The registry lists the primary outcome as Clinical Response as Assessed Metabolically by Changes in Positron Emission Tomography (PET) Scan Between Baseline and Immediately Prior to Surgery., measured over Day 21.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | percentage of patients |
| Endpoint classification | Binary Endpoint |
The primary outcome is titled clinical response assessed metabolically from changes in PET scans between baseline and immediately before surgery. The record describes baseline and repeat imaging using 18F-2-fluoro-2-deoxy-D-glucose fluorodeoxyglucose (18FDG)-PET. It identifies the unit as percentage of patients and gives Day 21 as the timeframe.
PET imaging is used to assess metabolic activity in a tumor. In general, a change in FDG uptake can serve as an imaging measure of metabolic response, which is distinct from directly measuring tumor size or long-term clinical outcomes. Here, the planned scans were obtained around the pre-operative treatment period, with the repeat scan close to surgery.
The registry record does not report the rule used to classify a patient as having a clinical response, the amount of FDG uptake considered meaningful, or the observed percentage of responders. It also does not provide a treatment-group comparison or an estimate of uncertainty. Without those details, the endpoint's intended measurement can be described, but its results and precision cannot be interpreted.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record describes a clinical question about metabolic PET changes after pre-operative RAD001, but it does not report the primary endpoint result. No number of patients with a clinical response, response percentage, group estimate, confidence interval, or statistical test is reported in the registry record. The record lists zero analyses. As a result, the posted information does not establish the size or precision of any observed difference in PET response.
The non-randomized design is central to interpretation. The comparator consisted of eligible patients who chose not to receive treatment. A comparison between people who chose treatment and those who chose not to receive it may reflect differences in their health, preferences, or other characteristics, as well as any treatment-related differences. The registry record does not provide enough information to assess or adjust for such differences. The control group should therefore not be read as a randomized counterfactual for the treated group.
The posted adverse-event figures describe affected participants by group. In the control group, 0 of 10 participants at risk were recorded as affected by a serious adverse event, and 0 of 10 were recorded as affected by other events. In the group titled Everolimus 5 & 10 mg, 1 of 23 participants at risk was recorded as affected by a serious adverse event, while 21 of 23 were recorded as affected by other events. These are descriptive figures; the registry does not report a comparative safety analysis or uncertainty intervals for them.
The serious adverse-event term listed as a top term is Symptomatic Progression of Lung Cancer, at 4.3%. This entry should be read as a reported term, not as evidence about cause or treatment effect. Death figures are not reported in the registry record. The listed results do not resolve whether events were related to treatment, how event severity was graded, or whether follow-up captured all relevant events.
Overall, the record supports a description of the study question, design, and some safety counts. It does not supply a primary efficacy result, a statistical comparison, or enough methodological detail to draw a precise conclusion about treatment effects. General statistical interpretation requires estimates and uncertainty, as well as consideration of how the groups were formed.
9. Statistical Methods Explained
The posted record contains endpoint descriptions and adverse-event counts, but it does not report inferential analyses for the primary outcome. The methods below explain how such results are generally interpreted and identify which elements are not reported in the registry record.
What does a percentage endpoint represent?
In general, a percentage of patients with an event describes how many participants in a defined group meet a specified outcome rule, relative to the participants assessed. For a clinical-response endpoint, the response rule must be defined before the percentage can be interpreted. It may specify how a scan measurement is translated into a response classification. The registry record names percentage of patients as the unit, but does not report the classification rule, the observed percentage, or the number assessed for the primary endpoint.
A percentage alone does not show how precise the estimate is. In general, a confidence interval gives a range of values compatible with the observed data under a statistical model. A narrow interval indicates greater precision than a wide interval, although interpretation also depends on whether the model and study design are appropriate. No confidence interval for the primary outcome is reported in the registry record.
Why does allocation matter?
Random allocation is used in general to make treatment groups comparable, on average, with respect to both measured and unmeasured characteristics. This trial is identified as non-randomized. Its control group comprised eligible patients who chose not to receive RAD001, so treatment choice may be associated with other characteristics. This creates a risk of confounding: an apparent difference between groups could reflect factors associated with group membership rather than treatment alone.
Parallel groups are followed as separate groups, but a parallel structure does not itself ensure comparability. In this study, the 5 mg/day and 10 mg/day schedules are described as sequential treatment groups, and a separate control group is described. The registry record does not report the process that assigned or selected patients for the two doses, or an adjusted analysis addressing group differences.
What can be concluded from the safety counts?
Adverse-event counts are descriptive summaries. The record lists 0 of 10 control participants affected by serious events and 1 of 23 participants in the Everolimus 5 & 10 mg group affected by serious events. It lists 0 of 10 and 21 of 23 participants affected by other events, respectively. These counts do not by themselves establish whether an event was caused by treatment. A comparative inference would require a defined analysis and consideration of the groups' non-randomized formation. No such analysis is reported in the registry record.
In general, safety summaries should distinguish the number of participants affected from the total number of events, since one participant may experience more than one event. The registry record presents participants affected and at risk, but does not describe event-level counts, grading criteria, attribution rules, or the completeness of event reporting. The listed death values are not reported in the registry record.
How should sample-size illustrations be understood?
General sample-size planning asks how many participants would be needed to detect a specified effect under stated assumptions. The planning illustration described for this trial uses a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; it considers fractions of the observed effect. These assumptions are planning conventions, not evidence that the trial used those design choices. In particular, equal allocation in an illustration does not change the registry's description of a non-randomized trial with a patient-choice control group.
Sample-size calculations based on an observed effect are planning illustrations, not observed power. Observed power is not a substitute for reporting the estimate and its uncertainty. The registry record does not report the trial's original sample-size justification. No sample-size result can fill the gap left by the missing primary outcome estimate, response definition, or analysis.
What is missing from the analysis record?
The registry record does not report the statistical test or model for the primary outcome, adjustment variables, handling of missing scans, analysis population, or treatment of protocol deviations. It also does not report a prespecified analysis plan or interim analyses. Without these details, it is not possible to determine how the planned endpoint would have been analyzed or whether reported results, if any, followed a prespecified approach. The primary analysis itself is not reported in the registry record.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists five outcome measures in total. It identifies PET-based clinical response as the primary outcome and names safety and tolerability of pre-operative RAD001 and duration of hospital stay following surgery as secondary outcomes. The registry record does not report how the remaining outcome measures are defined, or how the set of outcomes was prioritized beyond the primary designation.
When a study evaluates multiple outcomes, timepoints, or comparisons, the chance of at least one apparently notable result can increase if each is examined separately. General statistical approaches may use a prespecified hierarchy or adjust inference to account for multiple testing. The registry record does not report a multiplicity strategy, so it is not possible to tell whether any planned adjustment was intended.
Missing-data handling is also not reported in the registry record. The PET description specifies baseline and repeat scans, but does not state how participants without a repeat scan, an interpretable scan, or an outcome classification would be handled. The analysis population is not reported, including whether all enrolled participants, only treated participants, or participants with evaluable imaging were intended for the primary analysis.
The registry record lists zero analyses and gives no primary outcome estimate. It also does not report interim analyses, a detailed statistical plan, or methods for protocol deviations. These omissions limit assessment of whether the analysis was complete, prespecified, and consistent across outcomes.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Control | 0 | 10 | 0.0% |
| Everolimus 5 & 10 mg | 1 | 23 | 4.3% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Control | 0 of 10 |
| Everolimus 5 & 10 mg | 21 of 23 |
Most frequent serious adverse event terms
| Event term | Organ system | Control | Everolimus 5 & 10 mg |
|---|---|---|---|
| Symptomatic Progression of Lung Cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 0 of 10 | 1 of 23 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Control | Everolimus 5 & 10 mg |
|---|---|---|---|
| Hyperglycemia | Blood and lymphatic system disorders | 0 of 10 | 21 of 23 |
| Hypertriglyceridemia | Blood and lymphatic system disorders | 0 of 10 | 15 of 23 |
| Fatigue | General disorders | 0 of 10 | 14 of 23 |
| Elevated Cholesterol | Vascular disorders | 0 of 10 | 13 of 23 |
| Hypocalcemia | Blood and lymphatic system disorders | 0 of 10 | 12 of 23 |
| Anemia | Blood and lymphatic system disorders | 0 of 10 | 12 of 23 |
| Hypoalbuminemia | Blood and lymphatic system disorders | 0 of 10 | 12 of 23 |
| Cough | Respiratory, thoracic and mediastinal disorders | 0 of 10 | 10 of 23 |
| Elevated AST | Blood and lymphatic system disorders | 0 of 10 | 10 of 23 |
| Hyponatremia | Blood and lymphatic system disorders | 0 of 10 | 10 of 23 |
Serious events with the highest arm-level rate: symptomatic progression of lung cancer (4.3%).
The registry lists serious and other adverse events by group, with participants at risk and participants affected. In the Control group, 0 of 10 were affected by a serious adverse event and 0 of 10 by other events. In the group labeled Everolimus 5 & 10 mg, 1 of 23 were affected by a serious adverse event and 21 of 23 by other events.
The top serious term is Symptomatic Progression of Lung Cancer, listed at 4.3%. This is a registry-reported event term; the record does not state whether it was judged related to treatment. The death figures are not reported in the registry record, so they should not be interpreted as zero deaths.
These counts are descriptive rather than a controlled estimate of safety differences. The study was non-randomized, and the control group consisted of people who chose not to receive treatment. The registry record does not report event grading, causality assessment, event-level totals, or a statistical comparison. The figures also do not by themselves establish how completely events were captured.
12. What the Result Does, and Does Not, Mean
The record documents a pre-operative study of RAD001 in patients with operable lung cancer. It describes two sequential dose schedules, a control group of eligible patients who chose not to receive treatment, PET imaging before treatment and close to surgery, and safety assessment. Those details show what the study set out to examine, but they are not a report of the primary endpoint result.
The primary question concerns metabolic changes measured with FDG-PET. The registry record does not report a clinical-response definition or the number or percentage of patients classified as responders. It also gives no effect estimate, confidence interval, or statistical test. Consequently, the posted information cannot establish the magnitude or precision of a PET response, or whether results differed between groups.
The safety counts provide a limited descriptive account of affected participants. They do not determine whether events were caused by treatment, and the non-randomized, patient-choice comparison makes direct group interpretation difficult. The listed serious-event term and its reported percentage should be understood as registry entries, not as a causal analysis. Death results and several details needed to interpret safety are not reported in the registry record.
In general, a clinical trial's results need to be considered alongside its design, outcome definitions, analysis methods, and uncertainty. Here, the design and some event counts are available, while the primary result and key analysis details are not reported in the registry record. The information therefore supports a description of the study and its reporting limits, not a conclusion about the size or certainty of a treatment effect.
13. Why This Trial Matters Statistically
This trial illustrates why a clearly stated endpoint is not the same as a reported result. The registry specifies metabolic PET response as the primary outcome, identifies the imaging schedule, and gives a unit and timeframe. Yet without the response rule, observed result, and uncertainty estimate, readers cannot assess the endpoint's magnitude or precision.
It also highlights the interpretive consequences of a non-randomized control group. Patients who chose not to receive RAD001 may differ from those who received it. In general, statistical adjustment can address measured differences under suitable assumptions, but cannot guarantee removal of bias from unmeasured differences. The registry record does not report an adjusted comparison or enough details to evaluate one.
The safety entries show a separate reporting challenge: participant counts are useful descriptions, but do not on their own provide causal attribution or a fair comparative estimate. Event definitions, follow-up, and the analysis approach matter when interpreting such counts.
Finally, planning assumptions should not be mistaken for evidence from the trial. A sample-size illustration based on an observed effect is a planning exercise, not observed power and not a substitute for the effect estimate and its uncertainty. This distinction is especially important when the primary analysis is not reported. The trial is statistically informative as an example of how design and reporting determine what conclusions the record can support.
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.
Several limitations are specific to the information recorded for this trial. Allocation was non-randomized, and control participants were eligible patients who chose not to receive RAD001. The groups may therefore differ in ways that affect PET response or safety. The registry record does not report baseline characteristics, the reasons for treatment choices, or an adjusted analysis to help evaluate this concern.
The primary endpoint is described as clinical response based on PET changes, but the response criteria and observed results are not reported in the registry record. The scan schedule is described, but the record does not state how missing or uninterpretable scans were handled, how many participants had evaluable imaging, or which analysis population was used.
The record lists adverse-event counts but does not report event grading, treatment attribution, event-level totals, or a comparative safety analysis. Death results are not reported in the registry record. The treatment schedule is described, but allocation to dose groups and the handling of changes or interruptions are not reported.
The registry record does not report a detailed statistical analysis plan, multiplicity handling, interim analyses, or the original sample-size justification. These gaps limit assessment of the prespecified analysis and the certainty of any result. The primary outcome analysis is not reported, so the endpoint cannot be interpreted quantitatively from the recorded information.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Trial of RAD001 in Patients With Operable Non-Small Cell Lung Cancer (NSCLC) — NCT00401778.
- Registry record last updated 2016-12-21; status last verified 2016-11.
- Results first posted 2015-07-14.
- 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.
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18. Record Summary
NCT00401778 is a completed, Phase 1, non-randomized, unmasked, parallel study sponsored by Emory University. The registry reports enrollment of 33 and describes pre-operative RAD001 for patients with operable non-small cell lung cancer. Treatment schedules were 5 mg/day or 10 mg/day for 21 days; the control group consisted of eligible patients who chose not to receive treatment.
The primary outcome was clinical response assessed through PET changes from baseline to immediately before surgery, with a stated timeframe of Day 21. Safety and tolerability and duration of hospital stay were listed as secondary outcomes. The registry record does not report the primary outcome result, response criteria, statistical analysis, or missing-data methods. It lists descriptive adverse-event counts, but does not report a comparative safety analysis or death results.