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 Study to Collect and Assess Long-term Safety of Everolimus in Patients Who Are on Everolimus Treatment in a Novartis-sponsored Study and Are Benefiting From the Treatment as Judged by the Investigator. (NCT02017860), a na phase 2 study. The primary outcome is Number of Pariticipants With Adverse Events as a Measure of Safety and Tolerability.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02017860 |
| Phase | Phase 2 |
| Condition | Neoplasms |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 4 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Novartis Pharmaceuticals |
| Results posted | Yes |
2. Clinical Question
Population
Participants had completed an eligible Novartis-sponsored oncology study of everolimus, were judged by the investigator to benefit from continued treatment, were not progressing under the parent protocol, and could not access everolimus outside a clinical study. The roll-over study enrolled four participants. Eligible parent studies were selected by Novartis; investigator-initiated trials were excluded.
Intervention
Participants received everolimus in an open-label, single-group roll-over protocol. The study collected safety information during treatment and for 30 days after treatment ended.
Comparator
There was no comparator group. The registry lists allocation as NA and masking as NONE. This was not a randomized comparison, so the study does not provide a like-for-like control group for interpreting event counts.
Primary question
The primary question was how many participants experienced adverse events as a measure of safety and tolerability while receiving everolimus. The registry defines an adverse event as any sign or symptom occurring during study treatment or the 30 days after treatment. The question concerns events observed in this selected group; it is not a controlled estimate of what would have happened without everolimus.
3. Trial Design
This was a Phase 2, open-label, multicenter, single-group roll-over study sponsored by Novartis Pharmaceuticals. It was designed for patients who had completed a previous Novartis-sponsored everolimus study whose objectives had been reached, and whose investigators judged them to benefit from continued everolimus treatment. Participants also had to be not progressing on their current treatment as defined by the parent protocol and unable to access everolimus outside a clinical study. Novartis determined which parent studies were eligible; investigator-initiated trials were not included.
The registry lists the study as starting on 2014-01-16, with primary completion on 2019-04-25, and status COMPLETED. Enrollment was four. There was no masking and no randomized allocation. The design therefore describes ongoing treatment in a selected group, rather than an experimental comparison between treatment strategies.
The primary outcome was the number of participants with adverse events. Events were collected from first dose until the end of study treatment plus 30 days, with a maximum duration of approximately 5 years. The registry defines the Safety Set as participants who received at least one dose of everolimus and had at least one valid post-baseline safety assessment. A report of no adverse events on the adverse-events electronic case report form counted as a valid safety assessment.
The registry record does not report further operational details such as the number of participating centers, the treatment schedule, or the criteria for stopping treatment. Those details should not be inferred from the open-label, multicenter description.
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
| Stage | Everolimus |
|---|---|
| STARTED | 4 |
| COMPLETED | 2 |
| NOT COMPLETED | 2 |
Reasons for not completing this period:
| Reason | Everolimus |
|---|---|
| Adverse Event | 1 |
| Withdrawal by Subject | 1 |
Analysis population for the primary outcome, as defined in the registry: Safety Set-included all subjects who received at least one dose (partial or complete) of everolimus, and had at least one valid post-baseline safety assessment. The statement that a subject had no AEs (on the AEs eCRF) constituted a valid safety assessment.
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: All 4 subjects were included in both the Full Analysis Set and Safety Set.
| Characteristic | Unit | Everolimus |
|---|---|---|
| Participants analysed | 4 | |
| Age, Categorical: <=18 years | Participants | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 3 |
| Age, Categorical: >=65 years | Participants | 1 |
| Sex: Female, Male: Female | Participants | 2 |
| Sex: Female, Male: Male | Participants | 2 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 |
| Race (NIH/OMB): Asian | Participants | 4 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 |
| Race (NIH/OMB): Black or African American | Participants | 0 |
| Race (NIH/OMB): White | Participants | 0 |
| Race (NIH/OMB): More than one race | Participants | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 |
6. Primary Endpoint
The registry lists the primary outcome as Number of Pariticipants With Adverse Events as a Measure of Safety and Tolerability, measured over Adverse events were collected from first dose of study treatment until end of study treatment plus 30 days post treatment, up to maximum duration of approximately 5 years..
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | Count of Participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint counted participants with adverse events as a measure of safety and tolerability. An adverse event was defined as any sign or symptom occurring during study treatment or in the 30 days after treatment. The outcome was a count of participants, rather than a measure of symptom severity, duration, or change in a laboratory value.
Counting participants with events is a direct way to describe how many people in the defined Safety Set had an event recorded. The registry defines that set as participants who received at least one dose, partial or complete, of everolimus and had at least one valid post-baseline safety assessment. A report of no adverse events was considered a valid assessment. This definition matters because it identifies who contributed to the safety outcome; it does not by itself establish that every participant had the same duration of observation.
In general, a participant count is useful for describing the observed burden of events in a study group. It does not account for different time on treatment or follow-up, and it cannot separate treatment-related events from events due to other causes. The registry record does not report an exposure-adjusted event rate or a causal comparison. The endpoint therefore describes reported events in this study population and follow-up period, not the effect of everolimus relative to an untreated or alternative-treatment group.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry reports four participants in the everolimus group. One participant was affected by serious adverse events, four were affected by other adverse events, and the death count was zero. These are descriptive safety observations from a single group. The serious and other adverse-event categories may include the same participant, so the counts should not be added to form a total number of participants with any event.
The listed serious adverse-event terms were diffuse large B-cell lymphoma and pleural effusion, each reported as 25.0%. These entries describe the terms recorded in the registry. They do not establish that either event was caused by everolimus. The record does not provide further details in the information available for this analysis about event timing, severity grading, attribution, or participant-level overlap among terms.
The central interpretive limitation is the absence of a comparator. Participants entered the roll-over study after completing an eligible parent study and were selected because they were judged to benefit from continued treatment and were not progressing under the parent protocol. Consequently, the observed events describe this selected group during continued treatment; they cannot establish how event occurrence would compare under a different treatment or without treatment. The selection criteria also mean that the participants should not automatically be treated as representative of all people with neoplasms or all people receiving everolimus.
Precision is limited by the enrollment of four participants. With a group this small, a count describes only the observed participants and offers limited information about how frequently events might occur in a broader population. No confidence interval or inferential result is reported in the registry record. No statistical analysis results are reported either, so there is no registry-based estimate of a treatment contrast or formal test to interpret.
The adverse-event collection period extended from first dose through treatment and 30 days afterward, up to a maximum duration of approximately 5 years. That long potential observation window does not mean every participant was followed for the same duration; individual exposure and follow-up durations are not reported in the registry record. The reported counts should therefore be read as descriptive counts, not as time-adjusted rates.
Overall, the posted results document adverse events in a small, selected group receiving continued everolimus. They do not establish a causal safety effect, quantify comparative risk, or support conclusions about treatment benefit. The study’s stated purpose was long-term safety collection, and the registry record does not report a comparative efficacy analysis.
9. Statistical Methods Explained
The primary outcome is a participant count. For each participant in the Safety Set, the relevant descriptive question is whether at least one adverse event was recorded during the defined collection period. In general, counts preserve the actual number of participants observed, whereas a percentage expresses a count relative to a denominator. Neither form, by itself, adjusts for how long participants were observed. The registry record gives the event counts and some event-term percentages but does not report exposure-adjusted rates or a comparative estimate.
Why the study design matters
A single-group study observes outcomes in participants receiving the study treatment without a concurrent control group. In general, a comparator helps distinguish the event experience under one treatment strategy from what might occur under another strategy in a similar population. Without that comparison, the events can be described, but differences attributable to treatment cannot be isolated from disease, prior treatment, other care, or other influences. This is particularly important for adverse events, which can occur during treatment without necessarily being caused by it.
The registry lists allocation as NA, masking as NONE, and the model as SINGLE GROUP. There is no randomized comparison to interpret. The participants were also selected from people who had completed an eligible parent study and were judged by investigators to benefit from continued treatment. In general, selection based on prior treatment experience can make the observed group different from a broader population starting treatment. The record does not report a method for adjusting for those differences.
How to interpret counts and percentages
A count is an absolute description: it states how many participants met the outcome definition. A percentage expresses how common an event was in a specified group, but its interpretation depends on the denominator and on how the event term was counted. The registry lists one participant affected by serious adverse events and four affected by other adverse events. These categories are not necessarily mutually exclusive. They must not be summed as if they represented distinct people. The two serious terms are each listed at 25.0%; those term percentages should be read as registry-reported values, not as evidence of causation or a comparison between treatments.
In general, event counts do not capture duration or recurrence. A participant with one recorded event and a participant with repeated events may each count as one participant with an event if the outcome is defined at participant level. The registry’s primary endpoint is a number of participants, not a total number of episodes. Further details on recurrence are not reported in the registry record.
Uncertainty and statistical inference
A confidence interval is a statistical range intended to convey uncertainty around an estimate under a specified model and assumptions. In general, a narrow interval indicates greater precision than a wide interval, but an interval does not remove limitations such as selection or the lack of a comparator. No confidence interval is reported for the primary outcome in the registry record. No statistical analysis results are reported for this endpoint, so the available figures are descriptive rather than a formal test of a treatment effect.
The small enrollment is important for precision: the registry reports four participants, and each participant’s experience contributes directly to the observed counts. Counts from a small group can change substantially with additional observations. This is a general property of small samples, not a basis for estimating unobserved outcomes. The registry record does not report a sample-size justification or a planned precision target.
Planning calculations versus observed evidence
Planning illustrations are not observed trial results and are not a substitute for the study’s design justification. The planning assumptions described for the illustrations use 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 fraction of the observed effect. For non-time-to-event outcomes, such illustrations describe participants per arm for a stated power; they do not describe the number actually enrolled in this single-group trial. They are not observed power. The registry record does not report that these assumptions governed the trial’s design.
In general, over-dispersion means that observed variability is greater than a statistical model assumes. It can affect the precision of estimates and the reliability of tests if the model does not accommodate that extra variability. The registry record does not report a model-based analysis of event counts or an assessment of over-dispersion. No model should be presumed for the descriptive counts.
Finally, the collection window was defined from first dose through treatment plus 30 days, with a maximum duration of approximately 5 years. In general, variation in observation time can affect how many events are recorded, even when the underlying event rate is similar. The registry record does not report participant-specific follow-up durations or an analysis accounting for time at risk. The posted counts should therefore be interpreted within the recorded collection framework, not as rates per unit of time.
10. Multiplicity, Missing Data and Analysis Populations
The registry identifies one primary outcome: the number of participants with adverse events as a measure of safety and tolerability. No statistical analyses are reported in the registry record. A multiplicity adjustment, hierarchy of tests, or other procedure for handling multiple comparisons is not reported in the registry record. Because no inferential results are presented, there are no reported p-values to interpret as adjusted or unadjusted.
The Safety Set included participants who received at least one dose of everolimus, partial or complete, and had at least one valid post-baseline safety assessment. A report of no adverse events on the adverse-events electronic case report form counted as a valid safety assessment. This definition establishes the stated safety analysis population, but it does not explain how participants without a valid assessment were handled. Missing-data procedures, imputation, and sensitivity analyses are not reported in the registry record.
The record also does not report how missing event details, incomplete follow-up, or differences in time on treatment were addressed. The maximum collection duration was approximately 5 years, but participant-level follow-up durations are not reported. No other analysis populations or rules for deviations from the stated Safety Set are reported in the registry record. The available safety counts should thus be understood in relation to the stated population definition, without assuming unreported procedures.
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 |
|---|---|---|---|
| Everolimus | 1 | 4 | 25.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Everolimus | 0 of 4 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 1% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Everolimus | 4 of 4 |
Most frequent serious adverse event terms
| Event term | Organ system | Everolimus |
|---|---|---|
| Diffuse large B-cell lymphoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 1 of 4 |
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | 1 of 4 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Everolimus |
|---|---|---|
| Pericardial effusion | Cardiac disorders | 2 of 4 |
| Stomatitis | Gastrointestinal disorders | 2 of 4 |
| Oedema peripheral | General disorders | 2 of 4 |
| Rhinitis | Infections and infestations | 2 of 4 |
| Blood creatinine increased | Investigations | 2 of 4 |
| Hyperlipidaemia | Metabolism and nutrition disorders | 2 of 4 |
| Pneumonitis | Respiratory, thoracic and mediastinal disorders | 2 of 4 |
| Alopecia | Skin and subcutaneous tissue disorders | 2 of 4 |
| Nail disorder | Skin and subcutaneous tissue disorders | 2 of 4 |
| Dental caries | Gastrointestinal disorders | 1 of 4 |
Serious events with the highest arm-level rate: diffuse large b-cell lymphoma (25.0%), pleural effusion (25.0%).
The registry reports one participant affected by serious adverse events, four affected by other adverse events, and zero deaths in the everolimus group. These are participant counts. The serious and other event categories may overlap, so they do not represent separate, non-overlapping groups and should not be combined into a new total. The registry also lists diffuse large B-cell lymphoma and pleural effusion as serious adverse-event terms, each at 25.0%.
In general, a serious adverse event is a classification of an event’s seriousness, not a statement that the study treatment caused it. The registry record’s figures do not establish causality. The event-term percentages also do not, on their own, convey event timing, recurrence, severity grading, or attribution. Those details are not reported in the registry record.
Because the group contained four participants and had no control group, these figures describe only the recorded experience in this study group. They should not be treated as comparative risks or as rates adjusted for time on treatment. The record does not report participant-specific observation duration.
12. What the Result Does, and Does Not, Mean
The results show that adverse events were recorded among participants who continued everolimus in this roll-over study. The registry reports one participant affected by serious adverse events, four affected by other adverse events, and zero deaths. It lists diffuse large B-cell lymphoma and pleural effusion as serious adverse-event terms, each reported at 25.0%. These are descriptive safety observations from four enrolled participants.
The study’s purpose was to collect and assess long-term safety among people who had completed a Novartis-sponsored everolimus study and were judged by their investigator to benefit from continued treatment. That purpose and selection context shape what the results can address. The observations concern a selected group who were not progressing according to the parent protocol and could not access everolimus outside a clinical study. They do not automatically apply to people with different treatment histories or clinical circumstances.
The results do not show what would have happened to these participants under a different treatment or without everolimus. There was no comparator group or randomized allocation, and an event occurring during treatment is not, by itself, evidence that treatment caused it. The registry also reports no inferential analysis, confidence interval, or comparative estimate for the primary outcome.
Nor do these safety counts establish whether everolimus was beneficial or not beneficial. The primary endpoint counted participants with adverse events; it was not a comparative efficacy endpoint. The investigator judgment of benefit was part of the roll-over eligibility context, not a randomized test of efficacy in this study.
In general, a larger controlled study with clearly reported follow-up and analysis could address different questions about comparison and precision. That is a general methodological point, not a claim about any study beyond this record. The posted results are best read narrowly: they document recorded adverse-event experience in a small group under the study’s stated collection period.
13. Why This Trial Matters Statistically
Statistically, this study illustrates the distinction between collecting safety observations and estimating a comparative treatment effect. The roll-over design allowed adverse-event information to be collected while selected participants continued everolimus after a parent study. That can describe events in the group under observation, but the absence of a control group limits what can be inferred about differences attributable to treatment.
The endpoint also highlights the importance of defining the analysis population. The Safety Set required at least one dose and at least one valid post-baseline safety assessment, with a reported absence of adverse events counting as a valid assessment. A clear population definition helps readers understand who contributes to the safety count. Missing-data and follow-up procedures, however, are not reported in the registry record, so the definition does not resolve every question about completeness.
Enrollment was four, making the results especially important to interpret as counts rather than stable population estimates. A small group can document what happened to its members, but it offers limited precision for generalizing event frequency. The registry’s event-term percentages do not overcome that limitation or supply a controlled comparison.
Finally, the study makes visible a common interpretive boundary: events observed during treatment are not automatically treatment-caused events. Without randomization or a comparator, the posted results are descriptive. Their statistical value lies in documenting the recorded safety experience in the defined roll-over group, while making clear that causal attribution and comparative conclusions are outside what this design and reporting establish.
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.
The most direct limitation is the enrollment of four participants. The observed counts are consequently specific to a very small group and cannot provide precise estimates for a broader population. No confidence interval or other uncertainty estimate is reported in the registry record.
The study had a single group, with allocation listed as NA and masking as NONE. There was no randomized comparator, so the event counts cannot distinguish events associated with treatment from those that might occur for other reasons. The selected eligibility context further limits generalization: participants had completed an eligible parent study, were judged by investigators to benefit from continued treatment, were not progressing according to the parent protocol, and could not access everolimus outside a clinical study.
Follow-up could extend to approximately 5 years, but participant-specific exposure and observation durations are not reported in the registry record. The counts therefore do not provide time-adjusted event rates. The record also does not report event-level details such as timing, recurrence, severity grading, or attribution. The serious and other adverse-event participant counts may overlap.
The record reports no statistical analysis results, missing-data procedures, multiplicity approach, or sample-size justification. The criteria used to select eligible parent studies were decided by Novartis, but further selection procedures are not reported. These omissions limit evaluation of completeness, precision, and analytic choices. The available data support a descriptive account of recorded events in the study group, not a causal or comparative conclusion.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Study to Collect and Assess Long-term Safety of Everolimus in Patients Who Are on Everolimus Treatment in a Novartis-sponsored Study and Are Benefiting From the Treatment as Judged by the Investigator. — NCT02017860.
- Registry record last updated 2020-04-30; status last verified 2020-04.
- Results first posted 2020-04-30.
- 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
NCT02017860 is a completed Phase 2, open-label, multicenter, single-group roll-over study sponsored by Novartis Pharmaceuticals. It enrolled four participants who had completed an eligible Novartis-sponsored everolimus study and were judged by their investigator to benefit from continued treatment. The study is listed as starting on 2014-01-16, with primary completion on 2019-04-25.
The primary outcome counted participants with adverse events during treatment and for 30 days afterward, up to a maximum duration of approximately 5 years. The registry reports one participant affected by serious adverse events, four affected by other adverse events, and zero deaths. Diffuse large B-cell lymphoma and pleural effusion are each listed at 25.0% among the serious adverse-event terms. No statistical analysis results are reported in the registry record. With no comparator and only four participants, the results describe the recorded safety experience in this selected group rather than a comparative treatment effect.