Study of Lanreotide Autogel in Non-functioning Entero-pancreatic Endocrine Tumours: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study of Lanreotide Autogel in Non-functioning Entero-pancreatic Endocrine Tumours (NCT00353496), a randomized phase 3 study. The primary outcome is Progression-Free Survival (PFS).

2. Clinical Question

The clinical question concerns the timing of progression or death, rather than tumour response alone or survival alone. The primary endpoint therefore combines two events: documented disease progression and death. A participant’s time to the first of those events contributes to the endpoint. The registry describes tumour assessments through the last scheduled assessment at 96 weeks, with radiological scans scheduled every 12 weeks during the first year and every 24 weeks during the second year.

The record states that the trial was intended to compare lanreotide Autogel with placebo in patients with endocrine tumours in the pancreas or intestines. It does not report further eligibility criteria in the registry record for this analysis. In particular, details such as tumour grade, prior treatment, functional status beyond the non-functioning description, and disease burden are not reported in the registry record. Those details would help readers assess how closely the study population matches a particular clinical setting.

3. Trial Design

This was a Phase III, randomised, double-blind, parallel-group, placebo-controlled, multicentre study sponsored by Ipsen. The official title describes a stratified comparative design and specifies deep subcutaneous lanreotide Autogel 120mg every 28 days. The registry record lists an enrollment of 264 and a completed study. It gives the study start as 2006-06 and primary completion as 2013-04.

Random allocation is intended to make treatment groups comparable at the start of a trial, on average, while masking can reduce the influence of treatment knowledge on care, assessment and reporting. A placebo comparator helps distinguish changes associated with the study treatment from changes that may occur over time or with study participation. These are general design principles; the registry record does not describe how randomisation was generated, how allocation was concealed, or which people remained masked.

The record reports 101 participants in the lanreotide arm and 103 in the placebo arm for the primary outcome, and describes an intent-to-treat population comprising 204 randomised subjects. These figures are not the same as the enrollment figure. The reasons for the difference between enrollment and the primary analysis population, including whether it reflects screening, eligibility, randomisation or endpoint availability, are not reported in the registry record. The record also does not provide a full participant flow account.

The primary outcome was progression-free survival, expressed as a median in weeks with a 95% confidence interval. Its stated timeframe ran from randomisation through the last tumour assessment, scheduled at 96 weeks. Tumour imaging was scheduled at different intervals over the first and second years. The record describes central assessment of progression using RECIST v1.0, but does not report operational details such as adjudication procedures or how deaths without prior documented progression were handled beyond their inclusion in the endpoint definition.

Several secondary outcomes were registered, covering disease status, pharmacokinetics, quality of life, chromogranin A and overall survival. Numerical results are posted for selected secondary outcomes, but not for every outcome named in the record. The original trial’s sample-size rationale and statistical analysis plan are not reported in the registry record.

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: Analysis based on the intent-to-treat (ITT) population which comprised 204 randomised subjects.

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: Analysis based on intent-to-treat (ITT) population comprised of 204 subjects.

6. Primary Endpoint

The registry lists the primary outcome as Progression-Free Survival (PFS), measured over From randomisation up to the last tumour assessment (scheduled at 96 weeks). Radiological scans were performed every 12 weeks during the first year and every 24 weeks during the second year.

Progression-free survival (PFS) measures the time from randomisation until the first recorded disease progression or death. In this trial, progression was centrally assessed using Response Evaluation Criteria in Solid Tumours (RECIST) v1.0. The endpoint therefore captures whether a participant remains alive without documented progression over follow-up, and when the first qualifying event occurs.

Time-to-event outcomes are useful when the timing of an event matters and participants may have different follow-up times. Some participants may experience an event during observation, while others may remain event-free at their last assessment. A time-to-event analysis can use information about both the occurrence and timing of events, rather than treating every participant as though follow-up ended at the same moment. This is a general explanation of the endpoint type; the registry record does not provide full details of censoring rules or event adjudication.

The registry reports the endpoint as median PFS in weeks, accompanied by a 95% confidence interval. A median is the time by which half of the relevant estimated event-time distribution has occurred; it is a summary of the time-to-event pattern, not a statement that each participant experienced an event at that time. In the posted primary results, the placebo median is 72.0 weeks, with a 95% confidence interval from 48.6 to 96.0 weeks. A median and its interval describe the placebo group’s result, but they do not by themselves quantify the comparison between groups.

The principal comparative estimate is the sponsor-reported hazard ratio. It uses the event-time information to compare the event hazard between the randomised groups over the analysis period. The hazard ratio complements the median summary, but it is not the same quantity as a difference between medians.

7. Results Posted in the Registry

• Lanreotide (Autogel Formulation) vs Placebo: hazard ratio 0.47 (95% CI 0.30–0.73), reported p < 0.001 (as reported in the registry).

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Change in the Global Health Status Quality of Life Assessment

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard errors.
• Result:
  • Lanreotide (Autogel Formulation): mean -5.20 versus -4.90 on control; difference -0.30 (95% CI -10.56 to 9.96), standardized effect d = -0.01; z-test p = 0.954.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Lanreotide (Autogel Formulation) and the control. The interval gives the range of effects that remain compatible with the data.

Percentage of Patients With a Greater Than or Equal to 50% Decrease in Plasma Chromogranin A (CgA) Levels

• Endpoint type: Binary: the percentage of participants with the event (counts rebuilt from the posted percentages and group sizes).
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Lanreotide (Autogel Formulation): 42.2% (27/64) versus 4.7% (3/64) on control; risk difference 37.5 percentage points (95% CI 24.3 to 50.7), risk ratio 9.00 (2.87–28.18); unadjusted two-proportion z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the proportion with the event is statistically higher for Lanreotide (Autogel Formulation) than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Percentage of Patients Still Alive Based on Available Overall Survival Data

• Endpoint type: Binary: the percentage of participants with the event (counts rebuilt from the posted percentages and group sizes).
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Lanreotide (Autogel Formulation): 84.2% (85/101) versus 76.7% (79/103) on control; risk difference 7.5 percentage points (95% CI -3.4 to 18.3), risk ratio 1.10 (0.96–1.26); unadjusted two-proportion z-test p = 0.180.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Lanreotide (Autogel Formulation) and the control. The interval gives the range of effects that remain compatible with the data.

The secondary outcomes cover several distinct domains: quality of life, a biochemical marker and available overall-survival status, alongside other registered outcomes for which numerical findings are not posted in the record. The pattern is not uniform across these domains. The quality-of-life estimate is near zero and imprecise; the chromogranin A result shows a group contrast; and the overall-survival estimate is uncertain and compatible with no difference. These findings address different questions from the primary PFS analysis and should not be combined into a single claim.

The secondary findings can add context to the primary result, but they do not independently confirm it. Quality of life captures a patient-reported dimension, chromogranin A is a plasma marker, and overall survival concerns whether participants were alive based on available follow-up. Each has its own measurement, follow-up and missing-data considerations. The primary endpoint instead concerns time to progression or death under the stated tumour-assessment process.

Unadjusted secondary results carry less confirmatory weight when multiple outcomes are examined. If several tests are performed, the chance of at least one apparently notable result can increase. The registry record does not report whether the family of secondary comparisons was controlled for multiplicity, so the posted unadjusted p-values should be understood as exploratory evidence rather than definitive tests across all endpoints.

Not all named secondary outcomes have numerical results reported. The registry lists percentage alive without disease progression, pharmacokinetic profile, quality-of-life change, chromogranin A response and overall survival among secondary outcomes. Quantitative findings for the unreported secondary outcomes are not reported in the registry record. Their absence limits any attempt to describe the full secondary-outcome pattern and should not be interpreted as evidence of no effect.

The differing analysis denominators across secondary endpoints also matter. The available data for one outcome may not represent the same participants or follow-up as another. The registry record does not fully explain those denominator differences or describe missing-data handling. Therefore, comparisons across secondary outcomes should remain qualitative and cautious.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Percentage of Patients Alive & Without Disease Progression
• Pharmacokinetic Profile of Lanreotide
• Change in the Global Health Status Quality of Life Assessment
• Percentage of Patients With a Greater Than or Equal to 50% Decrease in Plasma Chromogranin A (CgA) Levels
• Percentage of Patients Still Alive Based on Available Overall Survival Data

9. Statistical Interpretation

10. Statistical Methods Explained

The primary outcome is a time-to-event measure. Each participant contributes time from randomisation until disease progression or death, if an event is documented; participants without a recorded event contribute follow-up through their last available assessment under the analysis rules. The registry record defines the event and assessment schedule but does not report all rules for censoring or handling incomplete follow-up. Those rules matter because time-to-event estimates depend on how information from participants who leave observation or reach the end of follow-up is used.

What does the hazard ratio describe?

A hazard is the instantaneous event rate among participants who have not yet experienced the event, considered over follow-up. The hazard ratio compares that rate between groups. The reported hazard ratio of 0.47 compares lanreotide with placebo. A value below 1 indicates a lower estimated hazard in the first group under the stated comparison. It does not mean that the median time is 0.47 times as long, and it is not a risk ratio calculated at one fixed follow-up time.

A hazard ratio is often interpreted as a single relative summary over the observation period. That interpretation is most straightforward when the relative hazards are reasonably stable over time. The registry record does not report a proportional-hazards assessment, a time-varying effect analysis or other diagnostics, so whether that condition was examined is not reported in the registry record. The hazard ratio remains the sponsor-reported comparative measure available for the primary endpoint.

Why use a Log Rank test?

The Log Rank method is a standard way to compare time-to-event distributions between groups. In general, it uses the event and follow-up information over time rather than reducing the comparison to a single follow-up snapshot. Its test result is reported with a p-value, while the hazard ratio and confidence interval describe the estimated relative effect and its uncertainty. The registry record names the Log Rank method for the sponsor’s primary analysis, but does not report additional model details, stratification variables used in the analysis, or whether adjusted analyses were performed.

The p-value of <0.001 is evidence against the null comparison under the test’s assumptions. It is not an estimate of the probability that the observed result arose by chance in an unrestricted sense. Nor does it communicate how much the endpoint changed. For that, the effect estimate and its interval are needed. Statistical significance and clinical importance are distinct considerations; the registry record does not define a threshold for a clinically important PFS difference.

How do median and hazard ratio summaries differ?

The median PFS is a time-point summary of the event-time distribution. The placebo median is reported as 72.0 weeks, with a 95% confidence interval from 48.6 to 96.0 weeks. The record does not report a lanreotide median. The hazard ratio instead compares event hazards across follow-up. These summaries answer related but different questions. A difference between medians cannot be inferred from a hazard ratio, and the hazard ratio cannot be converted into an absolute extension of PFS using the information posted.

A confidence interval around a median or hazard ratio describes uncertainty in that estimate, conditional on the analysis and its assumptions. A wider interval indicates less precision than a narrower one on the relevant scale. The interval does not show all possible biases, and it does not account automatically for design limitations, missing information, or selective reporting.

What do the secondary-outcome calculations represent?

For the posted continuous quality-of-life outcome, the group summaries are least-squares means with standard errors. The comparison is reported as a mean difference, with an interval and an unadjusted p-value calculated from posted summary information. Such a recalculation is not the same as a full individual-participant analysis. The registry does not report the full fitted model, covariates, or details of how the standard errors were obtained, so the recalculated comparison should be read as an approximate, unadjusted summary.

For the binary secondary outcomes, a percentage describes the proportion meeting the stated outcome among the participants in the analysis denominator. A risk difference compares the proportions by subtraction; the reported intervals express uncertainty in that difference. The registry’s posted comparisons also include unadjusted p-values. These simple comparisons do not establish that baseline differences, missing outcomes, or other analysis choices have been accounted for. They also do not provide a time-to-event estimate.

The overall-survival outcome is posted as the percentage still alive based on available data through death or last visit, up to 321 weeks. This is a binary summary over the stated available-data follow-up, not a full survival curve or a hazard ratio. The record does not report a sponsor analysis for this outcome in the registry record for this analysis.

Why can over-dispersion matter?

Over-dispersion is a general issue for count data when variability exceeds what a simple probability model expects. It can make standard errors too small if the extra variation is ignored, making intervals too narrow and tests too optimistic. The primary outcome in this trial is time-to-event rather than a count outcome, and the registry record does not report an over-dispersion analysis. This concept is included as general statistical context, not as a claim that over-dispersion affected the trial’s primary analysis.

For all outcomes, the posted numbers need to be interpreted in light of the stated populations and analysis methods. The primary endpoint analysis is described as intent-to-treat. The registry record does not report a full analysis plan, missing-data methods, sensitivity analyses or detailed model diagnostics. Where those details are absent, the statistical interpretation should remain limited to the reported estimates and their stated uncertainty.

11. Confidence Intervals and Precision

The primary hazard ratio is 0.47, with a 95% confidence interval from 0.30 to 0.73. The interval excludes 1, the value representing equal hazards in the comparison, and its endpoints indicate uncertainty about the magnitude of the relative association. It does not mean that the true hazard ratio has a 95% probability of lying in this particular interval. In general, a 95% confidence interval is produced by a procedure that would cover the fixed target value in 95% of repeated studies under its assumptions.

The reported interval is not infinitely precise: it spans values meaningfully different in magnitude. The estimate is more informative when read together with the interval than when read as a point estimate alone. The p-value of <0.001 conveys evidence against the no-difference hypothesis, but does not replace the interval as a description of effect-size uncertainty.

For the placebo median PFS, the estimate is 72.0 weeks and the 95% confidence interval is 48.6 to 96.0 weeks. This interval is broad in relation to the point estimate, indicating uncertainty in the median estimate. No corresponding lanreotide median or interval is reported in the registry record, so the precision of a group difference in medians cannot be assessed from the posted primary summaries.

Secondary intervals also vary in what they allow. The quality-of-life mean-difference interval includes values in either direction. The chromogranin A risk-difference interval is entirely above zero. The overall-survival risk-difference interval crosses zero. These intervals are unadjusted and should be interpreted alongside the number of secondary comparisons, the analysis populations and the limitations of the posted summaries. Confidence intervals quantify sampling uncertainty under a method; they do not incorporate every source of uncertainty or correct for unreported design and analysis choices.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The planning figures are illustrations based on the observed effect, not the trial’s original design calculation. The stated assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect targeted is a stated fraction of the observed effect. The time-to-event planning figures are total event counts, while the other planning figures are participants per arm.

The 80% power column describes the number of events or participants that the planning calculation would require for an 80% chance of detecting the specified effect under those assumptions, if that effect and the model assumptions were correct. The 90% power column uses a higher target chance of detecting the same effect and therefore requires more information. These figures are planning illustrations, not observed power.

Rows that plan for a smaller fraction of the observed effect require more information. A smaller difference is harder to distinguish from random variation, so a study generally needs more events or participants to detect it at the same significance level and target power. This relationship is a general statistical principle and is reflected in the listed planning scenarios.

For the primary time-to-event outcome, the planning quantities are total events, not participants per arm. For quality of life, chromogranin A and overall survival, the quantities are participants per arm. The listed calculations are not the original sample-size justification: the trial’s own design assumptions and planning rationale are not reported in the registry record. The observed enrollment and analysis populations should not be confused with the illustrative requirements generated from the observed effects.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

d is the total number of events needed (Schoenfeld's formula) with 1:1 allocation and proportional hazards.

Worked calculation for this trial

1. Hazard ratio HR = 0.470, so ln(HR) = -0.7550.
2. d = 4 × (1.96 + 0.842)² / [ln(0.470)]² = 55.1, rounded up to 56 events in total for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
hr <- 0.47                              # observed hazard ratio
events_needed <- function(power, frac = 1) ceiling(round(4 * (z_a + qnorm(power))^2 / log(hr^frac)^2, 6))   # Schoenfeld, 1:1 allocation
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: events = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(events_needed(0.80, f), big.mark = ","), format(events_needed(0.90, f), big.mark = ",")))

# Simulation: given d total events under proportional hazards, events in the treatment arm are Binomial(d, hr / (1 + hr)).
# The score (log-rank type) statistic is (D1 - d / 2) / sqrt(d / 4).
set.seed(353496)
d    <- events_needed(0.80)
reps <- 20000
D1 <- rbinom(reps, d, hr / (1 + hr))
z  <- (D1 - d / 2) / sqrt(d / 4)
cat(sprintf("Simulated power with %s events: %.3f (%d replicates)\n", format(d, big.mark = ","), mean(abs(z) > z_a), reps))

Output from running the code

100% of observed effect: events = 56 (80% power), 74 (90% power)
 75% of observed effect: events = 98 (80% power), 132 (90% power)
 50% of observed effect: events = 221 (80% power), 295 (90% power)
Simulated power with 56 events: 0.772 (20000 replicates)

The simulation uses the fact that, with d events in total and proportional hazards, the number of events in the treatment arm is binomial. It is an approximation that conditions on the total number of events, and it should land close to the target power.

14. Analyses Reported by the Sponsor

The primary comparison is the sponsor-reported Log Rank analysis: hazard ratio 0.47, 95% confidence interval 0.30 to 0.73, and p <0.001. The primary outcome is treated as a time-to-event result, and the reported hazard ratio is the comparative estimate used for interpretation. The registry entries do not include an independent recalculation of that primary hazard ratio from group-level summaries.

No discrepancy is flagged between the posted primary result and the analysis representation used for this account. The sponsor’s reported analysis therefore remains the relevant source for the primary hazard ratio. The registry record does not provide enough detail to reconstruct the model or test independently, including event-level data and full analysis specifications.

Some secondary comparisons are recalculations from posted group summaries. They are unadjusted and, for the continuous quality-of-life result, approximate because the calculations rely on summary statistics. No sponsor-reported analyses are listed for those secondary comparisons in the registry record for this analysis. They should not be treated as equivalent to a complete sponsor analysis or as a substitute for the primary time-to-event result. The distinction is especially important because the secondary endpoints use different outcome scales, populations and analysis approaches.

15. Multiplicity, Missing Data and Analysis Populations

Multiplicity arises when an analysis considers multiple outcomes, comparisons or repeated tests. Even if each individual test uses a conventional significance threshold, examining many results can increase the chance of at least one apparently strong finding under a collection of null effects. A prespecified testing hierarchy or other adjustment can help control that risk. The registry record does not report a multiplicity strategy for the secondary outcomes, so the posted secondary p-values are best read as unadjusted.

The primary endpoint is identified as PFS, and the record reports a sponsor analysis for that endpoint. However, a complete statistical analysis plan is not reported in the registry record. It is therefore not possible to establish from the available record which analyses were prespecified, whether additional analyses were undertaken, or how all secondary hypotheses were treated.

The primary analysis population is described as the intent-to-treat population comprising 204 randomised subjects. The arm-level primary-outcome figures are 101 for lanreotide and 103 for placebo. The overall enrollment is reported as 264. The record does not explain the relationship between enrollment and the intent-to-treat analysis population or give a participant flow accounting for those figures.

For a time-to-event analysis, missing assessments and loss to follow-up can affect when participants are censored and how much follow-up information contributes. The registry states the endpoint timeframe and tumour-assessment schedule, but censoring rules, missing-data methods and sensitivity analyses are not reported in the registry record. The handling of missed scans, withdrawal, or incomplete endpoint information is therefore uncertain.

Secondary outcomes use differing analysis denominators. The quality-of-life analysis includes 95 participants in the lanreotide arm and 98 in the placebo arm; the chromogranin A analysis includes 64 in each arm; and the overall-survival result uses 101 and 103. These are outcome-specific analysis populations. The record does not explain all reasons for the different denominators or report whether missing outcomes were imputed.

Without these details, readers cannot fully assess whether the available-data analyses could be affected by missingness or whether the conclusions are robust to alternative assumptions. This is a limitation of what the registry record reports, not evidence that a particular analysis choice was inappropriate.

16. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

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: vomiting (4.0%), anaemia (3.0%), urinary tract infection (3.0%), confusional state (2.9%), abdominal pain upper (2.0%).

The registry reports serious adverse events affecting 25 of 101 participants at risk in the lanreotide group and 32 of 103 at risk in the placebo group. It also reports other adverse events affecting 88 of 101 and 92 of 103, respectively. These are counts of affected participants as recorded in the adverse-event data; they are not estimates of comparative risk adjusted for follow-up or other factors.

The listed serious-event terms include vomiting at 4.0%, anaemia at 3.0%, urinary tract infection at 3.0%, confusional state at 2.9%, upper abdominal pain at 2.0% and hepatic failure at 2.0%. The record does not give the event-specific group breakdowns in the registry record for this analysis, so these terms should not be attributed to one arm or used to compare arms.

Serious adverse events and other adverse events are different reporting categories. Their counts do not by themselves establish causality, severity distribution beyond the category, or comparative safety. The registry record does not report deaths in the adverse-event summary, and further details such as event duration, relatedness and exposure-adjusted rates are not reported in the registry record.

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

The primary statistical result is a sponsor-reported hazard ratio below 1 for progression or death in the lanreotide group relative to placebo, with a confidence interval that excludes 1 and a p-value of <0.001. This describes the reported time-to-event comparison under the analysis used. It does not establish the exact amount of time by which progression-free survival differed, because a lanreotide median PFS is not reported in the registry record.

The result does not mean that every participant experienced the same outcome, or that the hazard ratio applies identically at every point in follow-up. It is a group-level summary. The available record does not report diagnostics for the assumptions behind the hazard-ratio analysis or detailed sensitivity analyses, so interpretation should remain tied to the reported method.

Secondary outcomes provide additional, but incomplete, evidence. Their differing patterns do not negate or prove the primary result, because they measure other constructs and are subject to separate uncertainty. The absence of reported quantitative results for some named outcomes does not show that those outcomes had no effect.

The trial record alone does not establish how well the findings generalize to every person with an entero-pancreatic endocrine tumour. Eligibility details beyond the broad population description, and information about tumour characteristics and prior care, are not reported in the registry record. The study was conducted as a controlled trial, but readers need population and implementation details to judge relevance to other settings.

Statistical evidence is not the same as a treatment recommendation. A p-value is not a measure of clinical importance, and the hazard ratio does not provide an absolute benefit in weeks or an individual prediction. Clinical interpretation would require the full trial report, the balance of benefits and harms, patient priorities, and relevant clinical context; those considerations are beyond what the posted registry results establish.

18. Why This Trial Matters Statistically

This trial illustrates why time-to-event outcomes need more than a single percentage or median. PFS depends both on whether progression or death occurred and on when it occurred. The registry gives a median for placebo and a comparative hazard ratio, which summarize different features of the event-time data. Reading the two measures as though they were interchangeable would misstate what the analysis estimates.

It also demonstrates the value of distinguishing a primary endpoint from secondary outcomes. The primary result is a reported time-to-event comparison, while the secondary findings involve a patient-reported measure, a biological marker and available overall-survival status. Each type of outcome has a different interpretation and a different pattern of uncertainty. A statistically notable secondary result does not automatically carry the same evidential status as the prespecified primary comparison.

The record also highlights the importance of analysis populations and reporting completeness. The enrollment figure differs from the stated primary intent-to-treat population, and secondary outcomes use different denominators. The record does not fully account for these differences or describe missing-data methods. Clear participant flow and analysis-plan reporting are essential for readers to assess how well estimates represent the randomized groups.

Finally, planning calculations based on observed effects must not be confused with the original design rationale or with power measured after the trial. The displayed planning assumptions are illustrative, and the original sample-size assumptions are not reported in the registry record. Keeping those distinctions clear helps prevent retrospective planning numbers from being treated as evidence about the trial’s design quality.

19. 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 registry record provides limited information for evaluating the primary analysis beyond the reported hazard ratio, confidence interval, p-value and Log Rank method. It does not report the detailed statistical analysis plan, the proportional-hazards assessment, censoring rules, sensitivity analyses or event counts. These omissions make it difficult to evaluate the robustness of the primary estimate independently.

The placebo median PFS is available, but the lanreotide median and its interval are not reported in the registry record. This prevents a direct reading of the group medians and rules out describing a median difference from the posted primary summaries. The hazard ratio remains the available comparative summary, but it does not translate directly into weeks of PFS.

The registry states enrollment of 264 and an intent-to-treat population of 204, with primary arm counts of 101 and 103. A participant flow explanation for the difference is not reported in the registry record. Secondary outcomes also have varying denominators, and the record does not fully explain those differences or report missing-data procedures. These gaps limit assessment of selection and missingness concerns.

Numerical secondary results are incomplete relative to the outcomes listed. The record does not report quantitative findings for every named secondary outcome, and no multiplicity strategy is reported. The available secondary comparisons are therefore less comprehensive and less secure as confirmatory evidence than a fully specified, multiplicity-controlled analysis would be.

Finally, the registry record offers limited population detail beyond the broad description of non-functioning entero-pancreatic endocrine tumours. It does not report enough information about tumour characteristics, prior treatment or other eligibility features to assess generalizability in depth. The serious adverse-event summary also lacks event-specific group breakdowns and details on relatedness, duration or exposure-adjusted rates.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: Study of Lanreotide Autogel in Non-functioning Entero-pancreatic Endocrine Tumours — NCT00353496.
• Registry record last updated 2025-03-05; status last verified 2025-02.
• Results first posted 2015-02-18.
• 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.

23. Record Summary

NCT00353496 is a completed Phase III randomized, double-blind, parallel-group, placebo-controlled study sponsored by Ipsen. It compared lanreotide Autogel with placebo in patients with non-functioning entero-pancreatic endocrine tumours. The primary endpoint was progression-free survival, defined as time from randomisation to documented disease progression or death, with progression centrally assessed using RECIST v1.0.

The sponsor-reported primary analysis used the Log Rank method and reported a hazard ratio of 0.47, with a 95% confidence interval from 0.30 to 0.73 and p <0.001. The placebo median PFS was 72.0 weeks, with a 95% confidence interval from 48.6 to 96.0 weeks; a lanreotide median is not reported in the registry record.

Selected secondary results and adverse-event summaries are posted, but analysis populations vary and several methodological details are not reported. The original sample-size rationale, multiplicity approach and missing-data methods are not reported in the registry record.