Everolimus Roll-over Protocol for Patients Who Have Completed a Previous Novartis-sponsored Everolimus Study.: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Everolimus Roll-over Protocol for Patients Who Have Completed a Previous Novartis-sponsored Everolimus Study. (NCT01789281), a na phase 4 study. The primary outcome is Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs).

2. Clinical Question

The study addressed continued access to everolimus for participants who had completed a previous Novartis-sponsored everolimus study and, in the investigator’s judgment, were benefiting from continued treatment. The record describes an open-label, single-group roll-over protocol in participants with neoplasms. Participants were receiving everolimus in a previous Novartis-sponsored study, were not progressing on that study treatment, and could not access everolimus outside a clinical trial. Some participants were also receiving Sandostatin LAR Depot with everolimus.

This framing matters when interpreting the results. The record does not describe a trial designed to estimate the comparative effect of everolimus versus another treatment or no treatment. Its stated purpose was to allow continued access for participants already receiving everolimus and judged to be benefiting. The primary outcome focuses on safety reporting; a secondary outcome was the percentage of patients with clinical benefit, but results for that outcome are not reported in the registry record.

3. Trial Design

This was a completed phase 4, open-label, multi-center, single-group roll-over protocol sponsored by Novartis Pharmaceuticals. Enrollment was 34. The study started on 2013-05-14, and primary completion was recorded as 2020-08-28. The registry lists no masking and identifies the allocation as not applicable. Those design features describe an access and follow-on setting, not a randomized controlled comparison.

Eligibility in the arm description centered on prior participation in a Novartis-sponsored study, current everolimus treatment, lack of progression on the current study treatment, and inability to access everolimus outside a clinical trial. Participants were also judged by the investigator to benefit from continued treatment. The record lists everolimus and Sandostatin LAR Depot as interventions. It identifies one group receiving everolimus and another receiving everolimus plus Sandostatin LAR; these groups should not be treated as randomized arms or as interchangeable controls.

The primary outcome was the percentage of participants with adverse events and serious adverse events, with the measure defined as a count of participants. The safety population comprised all subjects who received at least one dose of everolimus after enrolling in the roll-over study. The outcome description distinguishes safety data captured in the safety database from data captured in the clinical database after a protocol amendment. This affects which collection period informs the posted counts and should be kept in mind when describing the findings.

The registry record does not report the rationale for the enrollment target, a formal sample-size justification, detailed statistical analysis methods, interim analyses, or a statistical plan. The record lists a secondary outcome of percentage of patients with clinical benefit, but does not report its result. No randomized comparison can be inferred from the treatment-group labels, and the posted group counts do not establish comparative treatment effects.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: All subjects who received at least one dose of everolimus after enrolling into the roll-over 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 Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs), measured over SAEs collected in safety database from enrollment to end of treatment (EOT) plus 30 days, up to approximately 7.2 years. AEs/SAEs collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years.

The primary endpoint counts participants with adverse events and serious adverse events. The outcome is framed as a percentage, while its reported measure type is a count of participants. These are related ways of describing safety occurrence, but a count alone does not convey event severity, duration, recurrence, or the time each participant was exposed to treatment. The registry record describes an adverse event as any sign or symptom occurring during study treatment or within 30 days after treatment.

Safety outcomes are used to describe what was observed during treatment and the specified follow-up period. Serious adverse events are important to distinguish from the broader category of adverse events because they are captured and reported under a separate safety definition and process. The record states that serious adverse events were collected in the safety database from enrollment through the end of treatment plus 30 days, for up to approximately 7.2 years. After the protocol amendment released on 18 March 2016, adverse events and serious adverse events were also captured in the clinical database from the amendment date through the end of treatment plus 30 days, for up to approximately 4.5 years. Serious adverse events from the two databases are summarized separately.

The endpoint is therefore a descriptive safety measure, not a measure of treatment benefit or a direct estimate of risk relative to an untreated group. The registry record does not report a time-to-event analysis or an adjusted comparison. Counts should be interpreted in the context of the study’s selected population, its safety-collection periods, and the absence of a randomized comparator.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry record identifies the primary outcome as the percentage of participants with adverse events and serious adverse events, measured as a count of participants. It also lists zero analyses. Accordingly, the available results are counts and descriptive term percentages, not estimates from a reported statistical model. The concepts below explain how such safety summaries are generally read; they do not imply that unreported analyses were performed for this study.

What does a participant count describe?

A count of participants with an event indicates how many people in the defined group had at least one event under the outcome’s rules. It is different from a count of all event episodes: a participant with repeated events may still contribute only once to a participant-level count, depending on the analysis definition. The registry describes the outcome as a count of participants, but does not report whether recurrent events were analyzed separately or how multiple events of the same type were handled. A count also does not show when an event occurred, how long it lasted, or whether it resolved.

When the number of participants at risk is also reported, readers can see the size of the group from which the affected count arose. This context is useful, but it does not by itself account for how long each participant was observed or exposed. In studies where follow-up varies, the same participant count can arise under different exposure durations. The registry reports collection windows extending through end of treatment plus 30 days, with upper durations stated for the safety and clinical databases; participant-level exposure times and a person-time analysis are not reported.

Why separate serious and other adverse events?

Safety reporting commonly distinguishes serious adverse events from the broader set of adverse events because seriousness has specific clinical and regulatory meaning. The study description reports serious adverse events from the safety database beginning at enrollment. It also describes a later clinical-database collection period for adverse events and serious adverse events after the protocol amendment. Since these sources cover different periods and are summarized separately for serious events, a reader should retain the database and collection-window distinction when interpreting counts. The record does not give a reconciliation method for combining the sources into a single continuous analysis.

The listed event terms are not necessarily mutually exclusive. One participant may experience more than one type of event, and the registry information does not state whether the percentages are based on participants, events, or another denominator. Thus, the listed term percentages should not be added together or treated as a distribution of all participants. They are descriptive figures as posted, with their calculation details not reported in the registry record.

What would a confidence interval add?

In general, a confidence interval expresses the uncertainty around an estimated quantity under a specified statistical method. For a participant-level event proportion, an interval can indicate how compatible the observed data are with a range of underlying proportions, subject to the method’s assumptions. It is not a guarantee that the true value lies within a particular interval, and it does not correct design limitations such as selection into a study or the absence of a control group. No confidence interval for the primary safety outcome is reported in the registry record.

With no reported inferential analysis, it is not possible to use the record to assess statistical precision beyond the descriptive counts. The absence of an interval does not mean the underlying event frequency is known exactly. Conversely, a confidence interval, if one were reported, would not turn this single-group access study into a comparative trial.

Why is a control group important for comparison?

A treatment comparison asks how outcomes differ between groups that are comparable in the relevant ways. Random assignment is one approach to balancing measured and unmeasured characteristics in expectation. This study is listed as single group and has allocation marked not applicable. Its two treatment group labels do not indicate random assignment, and the record explicitly cautions that the groups are not a like-for-like control comparison. Therefore, differences in their observed counts should remain descriptive. They cannot isolate the effect of everolimus or of adding Sandostatin LAR Depot.

Comparative statistical methods cannot remove this central design limitation without sufficient information and defensible assumptions. The registry record does not report an adjusted analysis, a comparator population, or details of a model for confounding. No causal conclusion should be attached to the group counts.

What does a planning illustration mean?

In general, sample-size planning uses assumptions about the effect to detect, the allocation between groups, the significance level, and the statistical method. A planning illustration based on an observed effect is not the same as the study’s original design justification, and it is not observed power. The registry record does not report the trial’s own sample-size justification or protocol-based power calculation. The enrollment count should therefore be read as the recorded enrollment, not as evidence that the study was powered for a particular safety or efficacy comparison.

The registry lists the study as completed and reports a primary completion date, but those administrative details do not establish that every planned analysis was conducted or reported. Statistical details not reported in the registry record include interim analyses, missing-data methods, analysis populations beyond the stated safety population, and any inferential model. These absences constrain what can be concluded from the posted results.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists a primary safety outcome and a secondary outcome of percentage of patients with clinical benefit. It does not report results for the secondary outcome, a hierarchy of hypotheses, or a plan for controlling multiplicity. Multiplicity arises when several outcomes or comparisons are tested: without an appropriate strategy, the chance of at least one apparently notable result can increase. This general concern does not imply that multiple statistical tests were performed in this study. The record lists zero analyses.

Missing-data handling is not reported in the registry record. The primary safety population is defined as all subjects who received at least one dose of everolimus after enrolling. The record does not describe how participants with incomplete follow-up, withdrawal, treatment interruption, or missing outcome information were handled. Nor does it report whether any participants lacked safety data. The completed status and enrollment count do not, by themselves, answer those questions.

The registry record does not report an intention-to-treat analysis population, a per-protocol population, or an efficacy analysis population. The stated safety population is the only population definition available for interpreting the primary outcome. The secondary clinical-benefit outcome’s population and analytic handling are not reported. No imputation procedure, sensitivity analysis, or missingness assumption is described. These omissions mean that the reader cannot assess whether missing observations could have altered the safety summaries or whether the secondary outcome was analyzed on a consistent basis.

More broadly, no statistical analysis plan, adjustment for multiple outcomes, or interim-analysis procedure is reported in the registry record. These are reporting gaps, not evidence that a particular procedure was or was not used outside what is recorded. Interpretation should stay with the posted descriptive findings and avoid assuming unreported methods.

11. 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: pneumonia (25.0%), cardiac failure congestive (16.7%), acute kidney injury (16.7%), aplastic anaemia (8.3%), thrombocytopenia (8.3%).

For serious adverse events, the posted count is 6 affected among 22 at risk in the everolimus group, 9 among 12 in the everolimus plus Sandostatin LAR group, and 15 among 34 among all subjects. For the other adverse-event count, the corresponding figures are 3 among 22, 5 among 12, and 8 among 34. These are participant counts as recorded, not event totals or estimates from a comparative model.

The group labels do not represent randomized treatment assignments, so the counts should not be used to claim that one regimen caused more or fewer events than another. The participants came from a roll-over setting and had prior treatment with everolimus; the record does not provide a concurrent control group. The posted death counts are 1, 2, and 3 respectively for the everolimus group, combination group, and all subjects. The registry record does not identify cause of death or establish attribution to treatment.

Collection periods matter. Serious adverse events were captured in the safety database from enrollment through end of treatment plus 30 days, up to approximately 7.2 years. After the amendment released on 18 March 2016, adverse events and serious adverse events were captured in the clinical database through end of treatment plus 30 days, up to approximately 4.5 years. Serious adverse events from the databases are summarized separately. The serious-event term percentages are descriptive, and their denominator is not reported in the registry record. No conclusion about comparative risk or causation follows from these figures alone.

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

The posted findings describe adverse-event counts in a selected group of participants who entered a roll-over study after receiving everolimus in a previous Novartis-sponsored study. The participants were eligible for continued access under criteria that included not progressing on their current study treatment and being judged by the investigator to benefit. The safety population was defined by receipt of at least one dose of everolimus after enrollment. This context is important: the participants were not a random sample of all people with neoplasms, and the study was not designed as a randomized efficacy comparison.

The serious-event counts and other adverse-event counts document events recorded under the registry’s stated collection procedures. They can help describe the safety experience captured in this study. The listed serious-event terms provide additional descriptive information, while the death counts document reported numbers without establishing cause or treatment relationship. The differing data sources and collection periods are relevant to interpretation.

The findings do not establish that everolimus caused any specific event, nor do they show how the counts compare with what would have occurred without treatment. They also do not establish that one listed regimen is safer or more effective than the other. The treatment groups were not randomized control arms, and the registry record reports no inferential analysis. A causal or comparative conclusion would require evidence and design features not reported in the registry record.

The record also does not report a result for the secondary clinical-benefit outcome. Therefore, the primary safety counts should not be taken as evidence of clinical benefit. Nor do they summarize the full balance of benefits and harms, since the registry record does not provide the secondary outcome result or the details of a broader benefit-risk analysis.

In general, descriptive findings from a small, selected, single-group study can be informative about what was recorded among its participants, while remaining limited for broader generalization and causal inference. The registry record does not report confidence intervals, missing-data procedures, or a formal analysis plan that would further characterize uncertainty. The most defensible reading is to retain the reported counts, their collection context, and the distinction between description and comparison.

13. Why This Trial Matters Statistically

This study is statistically notable because its purpose and design shape the questions its results can answer. The protocol offered continued access to everolimus for participants who had already been receiving treatment and were judged to benefit. That setting is different from a trial that assigns participants to competing treatments to estimate a causal difference. The single-group design and allocation marked not applicable mean that the posted treatment-group counts are not evidence from randomized comparisons.

The study also illustrates why safety outcomes require attention to definitions and data collection. The primary outcome concerns participants with adverse events and serious adverse events, but the registry describes safety information coming from separate databases and collection periods. The amendment changed the collection process for adverse events and serious adverse events in the clinical database, while serious adverse events were also captured in the safety database from enrollment. A count cannot be interpreted fully without understanding what was collected, when it was collected, and how the analysis population was defined.

Another statistical lesson is the distinction between counts and comparative effects. The numbers describe recorded experience in the enrolled safety population; they do not by themselves estimate treatment-attributable risk. Group labels can look like trial arms, but the record’s design details show why they cannot be treated as like-for-like controls. Similarly, a listed event-term percentage is not necessarily a participant-level risk when its denominator and counting rules are not reported.

Finally, the record illustrates the value of transparent reporting of analysis methods. No analyses are listed, and details such as the statistical plan, missing-data handling, and sample-size justification are not reported in the registry record. Those gaps limit assessment of uncertainty and the intended scope of inference. Careful interpretation separates what the registry documents from what a design or analysis might have established under different conditions.

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 this study record. First, it is an open-label, single-group roll-over study with allocation marked not applicable. The everolimus and everolimus plus Sandostatin LAR groups are not randomized comparison arms, and the record explicitly cautions against treating them as like-for-like controls. Their counts cannot identify comparative treatment effects.

Second, participants were selected from a population already receiving everolimus in a Novartis-sponsored study and judged by the investigator to benefit from continued treatment. The arm description also specifies that participants were not progressing on current study treatment and could not access everolimus outside a clinical trial. Results from this selected group may not describe patients who do not meet those conditions. The registry record does not report further participant characteristics that would allow assessment of representativeness.

Third, safety collection used distinct databases and periods. Serious adverse events were collected in the safety database from enrollment through end of treatment plus 30 days, up to approximately 7.2 years. Adverse events and serious adverse events were captured in the clinical database from the amendment date of 18 March 2016 through end of treatment plus 30 days, up to approximately 4.5 years. The record does not report a method for reconciling these sources into a single analysis.

Fourth, the registry record lists no analyses and does not report confidence intervals, a detailed analysis plan, missing-data methods, or a sample-size justification. The serious-event term percentages are reported without their denominator or counting basis in the record. The secondary clinical-benefit outcome is listed without a result. These gaps restrict assessment of precision, completeness, and the scope of inference. The safety counts remain descriptive and should not be interpreted as proof of causation or comparative risk.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Everolimus Roll-over Protocol for Patients Who Have Completed a Previous Novartis-sponsored Everolimus Study. — NCT01789281.
• Registry record last updated 2021-06-11; status last verified 2021-05.
• Results first posted 2021-06-11.
• 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.

18. Record Summary

NCT01789281 is a completed phase 4, open-label, multi-center, single-group roll-over study sponsored by Novartis Pharmaceuticals. Enrollment was 34. The study started on 2013-05-14, with primary completion on 2020-08-28. Its purpose was to allow continued access to everolimus for participants who had completed a previous Novartis-sponsored study and were judged by the investigator to benefit.

The primary outcome was the percentage of participants with adverse events and serious adverse events, measured as a count of participants. The safety population included all subjects who received at least one dose of everolimus after enrollment. The record reports serious-event counts of 6 in the everolimus group, 9 in the everolimus plus Sandostatin LAR group, and 15 among all subjects. Counts for the other adverse-event measure were 3, 5, and 8, respectively. These groups are not randomized controls.

A secondary outcome of clinical benefit is listed, but its result is not reported in the registry record. The record lists zero analyses and does not report a formal statistical plan, missing-data methods, or sample-size justification. The posted findings are descriptive safety information, not a comparative treatment-effect analysis.