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 Antiproliferative Effect of Octreotide in Patients With Metastasized Neuroendocrine Tumors of the Midgut (NCT00171873), a randomized phase 3 study. The primary outcome is Time to Tumor Progression Documented by Computed Tomography (CT) or Magnetic Resonance Imaging (MRI).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00171873 |
| Phase | Phase 3 |
| Condition | Neuroendocrine Tumors |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Quadruple |
| Enrollment | 85 |
| Arms in the primary outcome | 2 |
| Lead sponsor | Carmen Schade-Brittinger |
| Results posted | Yes |
2. Clinical Question
Population
Patients with metastasized neuroendocrine tumors of the midgut were eligible for the trial. The primary-outcome description specifies a conservative intent-to-treat population consisting of participants who received study drug, with participants lacking liver involvement at the start of the study excluded from that analysis. The record does not give further eligibility criteria or describe the clinical characteristics of the analyzed groups.
Intervention
The intervention was octreotide LAR, also identified as SMS995. The arm description specifies a 30 mg intramuscular dose every 28 days. The primary question concerned the time until tumor progression was documented by computed tomography or magnetic resonance imaging.
Comparator
The comparator was placebo, described as sodium chloride given intramuscularly every 28 days. The registry describes the trial as placebo-controlled and randomized. It does not provide additional details about how the treatment assignments were generated or concealed.
Primary question
In this trial population, how long was it until tumor progression was documented on imaging? The reported primary measure is the median time to progression, in months, for each arm. The posted medians were 14.3 months for octreotide LAR and 6.0 months for placebo. These are arm-specific summaries; the registry record does not report a hazard ratio or a formal statistical test for the primary comparison.
The clinical question is therefore about the timing of radiologically documented progression, rather than only whether progression occurred. A time-to-event endpoint can retain information about when an event was observed and can account for participants whose event time is not observed during the available follow-up, provided the analysis handles censoring appropriately. The record does not describe the censoring rules or give event counts, so those details cannot be assessed. The trial also listed secondary outcomes involving objective response, biochemical response, symptom control, quality of life, and survival. Their presence indicates that the registry covered outcomes beyond tumor progression, but the record does not provide their numerical results.
3. Trial Design
The registry identifies NCT00171873 as a phase III, randomized, parallel-group trial comparing octreotide LAR with placebo. It is described as quadruple-masked. That label indicates masking at multiple levels, but the registry record does not identify which roles were masked or explain how masking was maintained. The planned comparison was prospective and placebo-controlled, according to the brief description.
Enrollment was 85. The octreotide arm description specifies octreotide LAR 30 mg intramuscularly every 28 days; the placebo arm description specifies sodium chloride intramuscularly every 28 days. The registry reports trial start as 2001-09 and primary completion as 2008-06, and the overall status is completed. The primary outcome description says its median was evaluated at the time of a planned interim analysis and included data observed until June 2008. The record does not state when that interim analysis was planned beyond this description or provide details of interim monitoring.
The primary endpoint was median time to tumor progression documented by CT or MRI, with a stated timeframe of up to 7 years. Its population is described as a conservative intent-to-treat population of participants who received study drug, with 3 participants in the octreotide group and 1 participant in the placebo group without liver involvement at study start excluded from this analysis. The outcome-arm counts are 39 for octreotide LAR and 42 for placebo. The registry does not explain the distinction between its general enrollment figure and the endpoint-analysis population beyond the stated exclusions.
Five secondary outcomes are listed: objective response rates assessed at 3-month intervals, biochemical response at 3-month intervals, symptom control at 3-month intervals, quality of life assessed at three-month intervals relative to study start, and survival. The record lists 6 outcome measures overall, but does not provide numerical results for these secondary outcomes in the information. It also does not describe the randomization procedure, allocation concealment, treatment adherence, or the 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.
Overall Study
| Stage | Octreotide LAR (SMS995) | Placebo |
|---|---|---|
| STARTED | 42 | 43 |
| COMPLETED | 33 | 40 |
| NOT COMPLETED | 9 | 3 |
Reasons for not completing this period:
| Reason | Octreotide LAR (SMS995) | Placebo |
|---|---|---|
| Withdrawal by Subject | 4 | 2 |
| Adverse Event | 5 | 0 |
| Switched to Octreotide | 0 | 1 |
Analysis population for the primary outcome, as defined in the registry: Conservative Intent to Treat (ITT) population consisting of all participants who received study drug. 3 participants in the Octreotide group and 1 participant in the placebo group without liver involvement at the beginning of the study were excluded from this analysis.
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 | Octreotide LAR (SMS995) | Placebo | Total |
|---|---|---|---|---|
| Participants analysed | 42 | 43 | 85 | |
| Age, Continuous | years | 63.5 (38 to 79) | 61 (39 to 82) | 62 (38 to 82) |
| Sex: Female, Male: Female | Participants | 22 | 20 | 42 |
| Sex: Female, Male: Male | Participants | 20 | 23 | 43 |
6. Primary Endpoint
The registry lists the primary outcome as Time to Tumor Progression Documented by Computed Tomography (CT) or Magnetic Resonance Imaging (MRI), measured over Up to 7 years.
| Element | Registry entry |
|---|---|
| Result type | Median |
| Measure of spread | 95% Confidence Interval |
| Unit | Months |
| Endpoint classification | Time-to-Event Analysis |
The primary endpoint is time to tumor progression documented by computed tomography or magnetic resonance imaging. It measures the elapsed time until progression is recorded on imaging, rather than a change in tumor size at one fixed visit. The registry reports the endpoint in months and uses the median as its summary measure. The stated timeframe is up to 7 years, and the primary description refers to the planned interim analysis incorporating data observed until June 2008.
In general, a median time-to-event value is the time by which half of the analyzed population has experienced the event, under the analysis definition. It provides a way to describe the central timing of progression without requiring an average event time. For participants whose progression is not observed during follow-up, time-to-event methods can use their observed follow-up up to the point at which their status is no longer known; this is commonly called censoring. The registry record does not report how censoring was defined or handled in this trial, so the endpoint estimate cannot be independently assessed on that basis.
The posted median was 14.3 months for octreotide LAR, with a 95% confidence interval from 11.0 to 28.8 months. For placebo, the median was 6.0 months, with a 95% confidence interval from 3.7 to 9.4 months. A confidence interval conveys uncertainty about an estimate under the analysis and its assumptions; it is not a range containing every participant's progression time. The registry does not report an estimated hazard ratio, a test statistic, or a p-value for the primary comparison.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The posted primary endpoint estimates are medians of 14.3 months for octreotide LAR and 6.0 months for placebo. The accompanying 95% confidence intervals are 11.0 to 28.8 months and 3.7 to 9.4 months, respectively. These values describe the time-to-progression results in the endpoint population specified by the registry. They do not, by themselves, establish the magnitude or statistical significance of a between-arm effect.
Each median is an arm-level summary. A comparison of medians is not the same quantity as a comparison of the full event-time distributions. In general, two groups can have the same median while differing at other parts of their survival curves, or have different medians while the uncertainty in the comparison remains substantial. A formal treatment comparison would require an appropriate estimated contrast and its uncertainty, or a reported statistical test. The registry record does not report a hazard ratio, a p-value, or another formal inferential result for this primary endpoint. The confidence intervals around each arm's median should not be treated as a substitute for a confidence interval around the treatment contrast.
The numerical interval for the octreotide median extends from 11.0 to 28.8 months; the interval for placebo extends from 3.7 to 9.4 months. These intervals express uncertainty in the separate median estimates. In general, interval overlap or non-overlap is not itself a complete test of the between-group effect, particularly when the interval estimates concern separate parameters rather than the contrast of interest. The registry does not provide the method used to construct these intervals, the number of progression events, or the shape of the event-time distributions.
The endpoint population requires careful attention. It is defined as participants who received study drug, with 3 participants in the octreotide group and 1 participant in the placebo group without liver involvement at baseline excluded. The record calls this a conservative intent-to-treat population, but does not provide a broader account of how randomized participants were handled, or explain the rationale for excluding those participants. The arm counts reported for the primary outcome are 39 and 42. They should be read in conjunction with the stated population definition, not assumed to represent every person enrolled or randomized.
The primary outcome description refers to a planned interim analysis using data observed until June 2008. This tells readers the time boundary named for the reported analysis, but not whether the analysis was adjusted for interim monitoring, how the timing was selected, or whether earlier analyses were conducted. Those details are not reported in the registry record. Accordingly, the posted data support a descriptive reading of the medians and confidence intervals, while a more complete inferential interpretation is limited by the absence of a reported primary treatment-effect estimate and analysis details.
9. Statistical Methods Explained
What does a median time-to-event measure describe?
The primary outcome is a time-to-event measure: the time from the relevant study starting point until progression is documented by CT or MRI. The registry reports the median time in each arm. In general, the median identifies the point in the event-time distribution by which half of the analyzed group has experienced the event, subject to the study's event and analysis definitions. It is a useful summary when the distribution of event times may be skewed or when some participants have not experienced the event by the end of their observed follow-up.
A median does not describe every participant's course, nor does it communicate the entire distribution of event times. It also does not indicate the probability of progression at every point in time. For that, an event-time curve or other time-specific summaries would be relevant, but the registry record does not provide those results in the information. The reported medians are 14.3 months for octreotide LAR and 6.0 months for placebo. The corresponding 95% confidence intervals are 11.0 to 28.8 months and 3.7 to 9.4 months.
What does a confidence interval add?
In general, a confidence interval expresses the precision of an estimate under the statistical method and assumptions used to construct it. A wider interval indicates less precision than a narrower interval on the same scale. These intervals apply to the separate arm-specific medians; they are not ranges of individual participant outcomes and are not automatically intervals for the difference between treatments. The registry names 95% confidence intervals but does not state how they were calculated. It does not report an interval for a between-arm contrast.
A comparison of two separate confidence intervals is not equivalent to a direct test of whether the treatments differ. A direct comparison would quantify uncertainty in an explicitly defined contrast. For time-to-event outcomes, a hazard ratio is one possible contrast, but it describes relative event rates over time under assumptions about how that relationship behaves. The registry record does not report a hazard ratio for this endpoint. It also does not report a p-value or another formal test of the primary comparison.
Why do time-to-event analyses consider censoring?
In general, a participant may leave observation or reach the end of the available follow-up before progression is documented. Their exact event time is then unknown, although their event-free observation up to a known time can still contribute information. Time-to-event methods account for this partial information through censoring. Valid interpretation depends on defining the event, the start of follow-up, and the censoring rules, as well as on assumptions about why follow-up ends. The registry names imaging-documented tumor progression and a timeframe of up to 7 years, but does not give event counts, censoring rules, or the handling of incomplete follow-up.
In general, censoring is not the same as observing no progression. It means that the event time is not known beyond a participant's last relevant observation. If censoring differs between groups or is related to progression in ways not accounted for by the analysis, estimates may be difficult to interpret. That is a general methodological consideration, not a claim that such a problem occurred in this trial. The registry record does not provide the information needed to evaluate it.
What does randomization contribute?
Random allocation is intended, in general, to create groups that are comparable on average at the time of assignment, including for factors that may not have been measured. It does not guarantee that the groups are identical in a particular trial. The record identifies this study as randomized and parallel-group, but does not describe its sequence-generation method, allocation concealment, or stratification factors. The registry also labels the study quadruple-masked without specifying which roles were masked. Those omissions limit assessment of how the design was implemented; they do not show that implementation was inadequate.
Masking can reduce the influence of treatment knowledge on care, outcome assessment, or reporting, depending on who is masked and how the masking is maintained. For an imaging-defined endpoint, consistency of assessment and protection against knowledge of assignment can matter. However, the record does not state who reviewed CT or MRI images, whether progression was centrally reviewed, or whether assessors were masked. These are general issues to consider when evaluating imaging endpoints, not documented features of this trial.
What can be inferred from the posted summaries?
The registry provides arm-specific medians and confidence intervals, but not a reported treatment-effect estimate or test. A descriptive contrast between arm summaries can be informative, but it should not be recast as a formal conclusion about statistical significance. The result also applies to the population used for the endpoint analysis: participants who received study drug, excluding 3 participants in the octreotide group and 1 participant in the placebo group without liver involvement at baseline. Interpretation should retain that population definition.
The outcome description calls the analysis a planned interim analysis and says it includes data through June 2008. In general, repeated examination of accumulating trial data can affect false-positive error if statistical decisions are made without an appropriate plan. Interim boundaries or other adjustments may be used to address that issue. The registry record does not report whether such methods were used, how the interim timing was set, or what decisions were linked to the analysis. Therefore, no claim about interim-analysis adjustment can be made from the record.
The registry lists secondary outcomes, but the statistical methods for those outcomes and any approach to multiple comparisons are not reported. In general, testing multiple outcomes can increase the chance of at least one apparently unusual result when each is assessed separately. Prespecified outcome hierarchies, adjusted tests, or a clearly exploratory interpretation can address different questions, but none should be attributed to this trial without documentation. The posted primary summaries remain interpretable as descriptive estimates, with important uncertainty about the analysis details left unresolved.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists secondary outcomes for objective response, biochemical response, symptom control, quality of life, and survival. It reports 6 outcome measures overall, while the record names 5 secondary outcomes. Numerical results for these secondary outcomes are not reported in the registry record in the information. No statistical plan for prioritizing outcomes, controlling multiplicity, or distinguishing confirmatory from exploratory analyses is reported.
In general, multiplicity arises when several outcomes or comparisons are examined. If each is tested separately without adjustment, the chance of at least one result appearing unusual can increase. A prespecified hierarchy, an adjustment procedure, or an explicit exploratory interpretation may be appropriate depending on the study question. The registry record does not identify which, if any, approach was used. It also does not report outcome-specific p-values or treatment-effect estimates for the listed secondary outcomes, so their evidential strength cannot be assessed from these entries.
Missing-data handling is not described in detail. The primary population is called conservative intent-to-treat and includes participants who received study drug, but excludes 3 octreotide participants and 1 placebo participant without liver involvement at study start. The record does not explain why this subgroup was excluded, how participants without evaluable imaging were handled, or what happened when follow-up ended before progression. These omissions matter because time-to-event estimates depend on how incomplete observation and censoring are addressed.
The primary description refers to a planned interim analysis incorporating data observed until June 2008. The record does not report interim monitoring procedures, stopping boundaries, or any adjustment to the inferential analysis. It also does not report whether missing-data sensitivity analyses were conducted. These analysis details are not reported in the registry record and should not be inferred from the stated population label or endpoint summaries.
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 |
|---|---|---|---|
| Octreotide LAR (SMS995) | 11 | 42 | 26.2% |
| Placebo | 10 | 43 | 23.3% |
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 |
|---|---|
| Octreotide LAR (SMS995) | 19 of 42 |
| Placebo | 11 of 43 |
Most frequent serious adverse event terms
| Event term | Organ system | Octreotide LAR (SMS995) | Placebo |
|---|---|---|---|
| General Disorder | General disorders | 11 of 42 | 10 of 43 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Octreotide LAR (SMS995) | Placebo |
|---|---|---|---|
| Gastrointestinal disorders | Gastrointestinal disorders | 6 of 42 | 8 of 43 |
| General Health | General disorders | 8 of 42 | 2 of 43 |
| Hematopoietic system | Blood and lymphatic system disorders | 5 of 42 | 1 of 43 |
Serious events with the highest arm-level rate: general disorder (26.2%).
The safety entries report serious adverse events for 11 of 42 participants at risk in the octreotide LAR group and 10 of 43 participants at risk in the placebo group. Other adverse events are listed for 19 of 42 participants at risk in the octreotide group and 11 of 43 at risk in the placebo group. These are counts of affected participants as represented in the registry entries; they are not, by themselves, a complete account of the number, timing, duration, or severity of individual events.
The record identifies “General Disorder” as the top serious-event term, with 26.2% reported. It does not give the event-term coding details, explain the denominator for that percentage, or attribute that percentage to a particular treatment arm in the information. Death counts are not reported in the registry record.
In general, safety counts should be interpreted in light of the definitions used, observation time, completeness of reporting, and whether participants could experience more than one event. The registry entries do not specify these details, nor do they provide a causal assessment of whether an event was related to study treatment. The counts are descriptive and should not be treated as proof that one arm was safer or less safe.
12. What the Result Does, and Does Not, Mean
The primary result describes median time to imaging-documented tumor progression in the registry's stated analysis population. The median was 14.3 months for octreotide LAR and 6.0 months for placebo. Their 95% confidence intervals were 11.0 to 28.8 months and 3.7 to 9.4 months, respectively. These are the posted arm-specific estimates; they do not fully describe the event-time distributions or, on their own, quantify a formal between-arm effect.
The registry record does not report a hazard ratio, a p-value, or a confidence interval for a treatment contrast. It also does not provide event counts or enough methodological detail to reconstruct the primary comparison. Consequently, the medians should be read as descriptive results with the reported uncertainty around each arm's estimate, not as a complete inferential analysis. Non-overlap of separate intervals, if considered, would not replace a direct test or interval for the contrast.
The result is specific to the endpoint definition and population recorded. Progression had to be documented by CT or MRI, and the analysis excluded 3 participants in the octreotide group and 1 participant in the placebo group who lacked liver involvement at study start. The record does not explain the rationale for this exclusion or provide a sensitivity analysis using another population definition. The stated timeframe was up to 7 years, while the reported analysis description refers to data observed through June 2008.
The registry also lists secondary outcomes and safety counts, but the numerical secondary efficacy results are not reported in the registry record. The safety entries show affected-participant counts for serious and other adverse events, but do not provide sufficient detail to establish causation or make a comprehensive comparative safety assessment. No medical conclusion about an individual patient follows from these aggregate summaries.
In general, interpreting a randomized trial requires the design, population, endpoint, analysis method, uncertainty, and completeness of outcome reporting to be considered together. Here, randomization and masking are recorded, but implementation details and the primary comparative estimate are absent. The posted medians are therefore useful as arm-level summaries, while the registry record leaves important questions about the comparative analysis and missing follow-up unresolved.
13. Why This Trial Matters Statistically
This trial illustrates why a reported median is not the same thing as a complete treatment-effect analysis. The registry provides a median time to progression for each arm and a confidence interval around each median. Those summaries describe the central timing and its uncertainty, but do not directly estimate the between-arm contrast. For time-to-event outcomes, the full event-time pattern and the handling of censoring can matter as well as the median.
The record also demonstrates the importance of keeping analysis populations explicit. Although enrollment was 85, the primary outcome is described for participants who received study drug, with 3 participants in the octreotide group and 1 participant in the placebo group without liver involvement at baseline excluded. The listed primary-outcome arm counts are 39 and 42. Those details define the scope of the reported estimates and caution against treating them as summaries of a different population.
Randomization and quadruple masking are important design labels, but they do not replace documentation of implementation. The registry does not specify the randomization process, which roles were masked, how imaging outcomes were assessed, or how missing observations and censoring were handled. These details help readers judge whether the comparison and outcome measurement support the intended interpretation.
Finally, the record names a planned interim analysis and multiple secondary outcomes, but does not report interim-analysis procedures or a multiplicity strategy. These are not merely technical details: they help establish how uncertainty and repeated analyses were managed. The trial is statistically instructive because it shows the value of distinguishing registered design features and descriptive estimates from methods and comparative results that are not reported.
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 trial-specific limitations of interpretation arise from the registry record. The reported primary endpoint uses a defined population of participants who received study drug, excluding 3 participants in the octreotide group and 1 in the placebo group without liver involvement at the beginning of the study. The record calls this a conservative intent-to-treat population but does not explain the exclusion rationale or provide results under an alternative population definition. The endpoint counts are 39 for octreotide LAR and 42 for placebo, and the registry does not clarify how these counts relate to all randomized participants.
The primary result is reported as arm-specific median times and 95% confidence intervals. The registry does not report a hazard ratio, p-value, event count, or confidence interval for the between-arm contrast. It also does not state the method used to estimate the medians or their intervals. This limits assessment of the comparative effect and the precision of the contrast, even though the separate arm summaries are available.
The outcome depends on progression being documented by CT or MRI, but the record does not describe image review procedures, assessor masking, confirmation requirements, or the handling of scans that could not be evaluated. It labels the study quadruple-masked without identifying the masked roles. Details about follow-up completeness, censoring, treatment adherence, and missing-data sensitivity analyses are also not reported in the registry record.
The primary description refers to a planned interim analysis using data through June 2008, but no interim monitoring or adjustment procedures are described. Statistical methods for the secondary outcomes and any multiplicity approach are likewise not reported. These are limits on what can be concluded from the registry entry; they do not establish that the trial lacked procedures that were not recorded.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Antiproliferative Effect of Octreotide in Patients With Metastasized Neuroendocrine Tumors of the Midgut — NCT00171873.
- Registry record last updated 2020-03-26; status last verified 2020-03.
- Results first posted 2011-03-28.
- 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
NCT00171873 is a completed phase III randomized, parallel-group, placebo-controlled trial of octreotide LAR in patients with metastasized midgut neuroendocrine tumors. The registry labels the study quadruple-masked. Octreotide LAR was given as 30 mg intramuscularly every 28 days; placebo was sodium chloride intramuscularly every 28 days. Enrollment was 85. The trial start is recorded as 2001-09 and primary completion as 2008-06.
The primary endpoint was median time to tumor progression documented by CT or MRI, with a stated timeframe of up to 7 years. The posted medians were 14.3 months for octreotide LAR and 6.0 months for placebo, with 95% confidence intervals of 11.0 to 28.8 months and 3.7 to 9.4 months. The primary analysis population excluded participants without liver involvement at study start, as described in the registry. A hazard ratio and formal primary comparison are not reported in the registry record.
Five secondary outcomes are listed, alongside descriptive adverse-event counts. Numerical secondary efficacy results and several details of statistical methods, missing-data handling, masking roles, and interim analysis procedures are not reported.