A Study Evaluating Lanreotide as Maintenance Therapy in Patients With Non-Resectable Duodeno-Pancreatic Neuroendocrine Tumors (REMINET): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study Evaluating Lanreotide as Maintenance Therapy in Patients With Non-Resectable Duodeno-Pancreatic Neuroendocrine Tumors (REMINET) (NCT02288377), a randomized phase 2, phase 3 study. The primary outcome is Proportion of Patients Alive and Progression-free at 6 Months.

2. Clinical Question

3. Trial Design

REMINET is recorded as a European, prospective, multicentre, randomized study with Phase II and Phase III designations. Its official title describes a randomized, double-blind, placebo-controlled study, while the registry masking field says triple masking. The allocation model is parallel, meaning participants were assigned to one of the treatment arms rather than crossing between them. The registry record does not identify which roles were masked.

The comparison was lanreotide versus placebo in patients with metastatic or locally advanced, non-resectable duodeno-pancreatic neuroendocrine tumours after first-line treatment. The lanreotide arm is described as receiving 120 mg every 28 days until disease progression; the placebo arm is described as receiving placebo on the same schedule until progression. The record lists the primary endpoint as a Phase II endpoint, the proportion alive and progression-free at 6 months after randomization. Investigator imaging assessment was to follow RECIST 1.1 criteria.

The registry lists enrollment of 53 and a study status of terminated. Its recorded start is 2015-01 and its primary completion is 2020-01. The primary outcome entries list 24 participants for placebo and 26 for lanreotide; those endpoint denominators should not be treated as an explanation of the enrollment figure. The registry record does not report why the study was terminated, the planned or achieved recruitment trajectory, or details of any protocol changes.

Progression-Free Survival and Overall Survival are listed as secondary outcomes, but secondary outcome results are not reported in the registry record. Although the study title includes Phase II/III, the record does not describe a separate design or endpoint framework for the Phase III component. The original design rationale, target enrollment, and the trial’s own sample-size assumptions 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.

Before assignment: The study was terminated prematurely because of slow recruitment.

Overall Study

Analysis population for the primary outcome, as defined in the registry: 2 patients without tumor evaluation at cycle 4 nor cycle 7 were not evaluable for the primary criterion

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: Baseline population is the Intent-to-treat population, all the patients randomized.

6. Primary Endpoint

The registry lists the primary outcome as Proportion of Patients Alive and Progression-free at 6 Months, measured over 6 months.

The primary endpoint is the proportion of patients alive and progression-free at 6 months after randomization. It combines two conditions at the specified follow-up point: the patient is alive and there is no progression recorded under the endpoint assessment. The registry describes progression status as based on imaging performed by the investigator in line with RECIST 1.1 criteria.

A binary endpoint of this kind records whether each patient meets the defined status or does not. The group result can then be expressed as the number meeting the endpoint relative to the number assessed. The registry posts 13 of 24 for placebo and 19 of 26 for lanreotide. It also notes that 2 patients without tumor evaluation at cycle 4 nor cycle 7 were not evaluable for the primary criterion. The record does not report the detailed rule used to classify patients with missing or unevaluable imaging beyond that note.

A fixed-time endpoint can summarize whether patients are alive without progression at a clinically specified assessment point, rather than reporting only the timing of an event. That makes the result relatively direct to interpret as a status at 6 months. It also means the result depends on assessment availability and the endpoint’s handling of incomplete evaluations. The registry record does not report the imaging schedule beyond the references to cycle 4 and cycle 7, nor does it give additional detail about adjudication or handling of assessments outside the stated criterion.

7. Results Posted in the Registry

• Lanreotide: 73.1% (19/26) versus 54.2% (13/24) on control; risk difference 18.9 percentage points (95% CI -7.3 to 45.1), risk ratio 1.35 (0.87–2.09); unadjusted two-proportion z-test p = 0.164.

8. Statistical Interpretation

9. Statistical Methods Explained

The registry posts a binary primary outcome: whether patients were alive and progression-free at 6 months. For a binary outcome, each assessed participant contributes to a category according to whether the endpoint was met. The posted counts are 13 of 24 for placebo and 19 of 26 for lanreotide. The associated comparison is reported as a risk difference, with a confidence interval and an unadjusted p-value. The registry record does not provide a detailed statistical analysis plan or name the method used to calculate the interval and p-value.

What does a risk difference describe?

In general, a risk difference compares the proportion with an event or endpoint in one group against the corresponding proportion in another group. For this study’s primary endpoint, the event is being alive and progression-free at 6 months. A positive risk difference in the lanreotide comparison indicates a higher observed endpoint proportion in that arm than in placebo. Unlike a relative measure, a risk difference uses the absolute separation between group proportions. Its interpretation remains dependent on how the endpoint and analysis population were defined.

The registry reports a positive estimated risk difference and a confidence interval that crosses zero. Zero represents no difference between the group proportions on the risk-difference scale. An interval extending on both sides of zero reflects uncertainty that includes both directions of difference. The point estimate alone should not be read as a precise estimate of what would occur in a wider population.

What does the p-value add?

The posted unadjusted p-value is 0.164. In general, a p-value describes how unusual the data would be under a specified statistical model in which there is no group difference, assuming that model and its conditions are appropriate. It does not give the probability that the null model is true, the probability that the observed result arose by chance, or the probability of a clinically meaningful effect. An unadjusted value also does not indicate whether any multiplicity correction or covariate adjustment was applied; the registry record does not report those details.

The p-value and confidence interval answer related but different questions. The p-value summarizes evidence against a no-difference model under the test, whereas the confidence interval describes a range of effect values compatible with the data under its method. Neither replaces the observed arm counts. In this record, the interval’s inclusion of no difference and its extension in both directions make the uncertainty especially important when reading the positive point estimate.

Why does the endpoint assessment matter?

The endpoint depends on both survival status and progression status at a fixed follow-up point. Progression was assessed using investigator imaging in line with RECIST 1.1 criteria. In general, consistent assessment criteria help make endpoint classification more reproducible, but interpretation also depends on when imaging occurred, how incomplete assessments were handled, and whether assessments were reviewed consistently. The record does not report further details on those procedures. It specifically notes that 2 patients without tumor evaluation at cycle 4 nor cycle 7 were not evaluable for the primary criterion.

For a binary outcome, missing assessment information matters because a participant without an evaluable scan may not be classifiable as meeting or not meeting the endpoint. Different analysis rules for such cases can affect the group estimates. The registry record does not report imputation, censoring, or other missing-data methods for this primary endpoint. It also does not report whether the analysis used an intention-to-treat population or another analysis population.

What can randomization and masking contribute?

In general, random allocation helps reduce systematic differences between treatment groups at the point of assignment, including differences in prognostic factors that may not be fully measured. It does not guarantee that all characteristics are balanced, particularly in a limited study, and it cannot correct problems arising after randomization, such as incomplete outcome assessment. The registry records randomized allocation and a parallel model. It describes the study as double-blind in the brief summary and reports triple masking in its design field, but it does not identify the masked roles or provide further operational details.

Masking can generally reduce the influence of knowledge of treatment assignment on behavior, care, or outcome assessment. Because the endpoint includes investigator-assessed imaging, masking may be relevant to how the assessment was conducted. The record does not explain the masking procedures or state whether imaging assessments underwent independent review. These design details therefore provide context, not proof that bias was absent.

The registry presents an unadjusted comparison and no posted analysis records. Statistical methods beyond the listed result, missing-data rules, analysis populations, multiplicity procedures, and model diagnostics are not reported in the registry record. General statistical concepts can clarify the result, but they cannot fill those gaps in the documented analysis.

10. Confidence Intervals and Precision

Precision concerns how narrowly the data locate the underlying effect. The registry reports a confidence interval for the risk difference, and that interval includes values on both sides of no difference. Its span indicates that the posted result does not pin down the size or direction of the difference with precision. The positive point estimate should therefore be interpreted together with the interval rather than as a settled estimate.

In general, a confidence interval is a range produced by a statistical method that reflects uncertainty in an estimate. It is not a range containing a fixed proportion of individual patient outcomes, nor is it a guarantee that the true effect lies within the particular interval. Its interpretation depends on the analysis method and assumptions. Those details are not reported in the registry record.

The arm counts are modest, and the registry lists 24 participants for placebo and 26 for lanreotide in the primary outcome entries. With limited observations, a binary outcome can yield wide uncertainty because each participant’s endpoint classification contributes to the group proportion. The confidence interval’s inclusion of no difference is consistent with uncertainty that remains despite a higher observed endpoint proportion in the lanreotide arm.

Precision is distinct from whether an effect is important to patients or clinically meaningful. The registry record does not report a threshold for a clinically important difference. It also does not report a prespecified precision target or the original sample-size justification. The posted confidence interval and counts can describe statistical uncertainty, but they cannot determine clinical importance without additional context.

11. 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 sample-size display gives planning illustrations based on fractions of the observed effect. Its figures are participants per arm, not total participants across arms and not total events. The listed rows plan for 100% of the observed effect, 75% of the observed effect, and 50% of the observed effect. Each row gives a figure for 80% power and another for 90% power.

In plain language, 80% power means that, under the stated planning assumptions and if the selected effect were the true effect, the design would have an 80% chance of detecting a difference by the chosen statistical criterion. The 90% power column describes the corresponding planning target with a 90% chance. These are prospective planning concepts, not probabilities that the posted study result is correct. The illustrations use a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect to detect is the stated fraction of the observed effect.

For the row planning for 100% of the observed effect, the illustrations give 101 participants per arm for 80% power and 134 participants per arm for 90% power. Planning for 75% of the observed effect gives 185 participants per arm for 80% power and 246 participants per arm for 90% power. Planning for 50% of the observed effect gives 424 participants per arm for 80% power and 567 participants per arm for 90% power. Smaller effects require more participants to detect under the same assumptions.

These figures are planning illustrations, not observed power and not the trial’s original design targets. The original design assumptions are not reported in the registry record. The calculations use the observed effect as their reference, so they are sensitive to uncertainty in that estimate. They should not be interpreted as evidence that the trial was designed or conducted using these sample sizes.

12. 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

n is the number of participants in each arm, p₀ and p₁ are the control and treatment proportions, and p̄ is their average.

Worked calculation for this trial

1. Control proportion p₀ = 0.542; treatment proportion p₁ = 0.731; average p̄ = 0.636.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.6804 = 1.3335.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.6671 = 0.5614.
4. n = (1.3335 + 0.5614)² / (0.1891)² = 100.4, rounded up to 101 participants per arm 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
p0 <- 0.541666666666667                          # control proportion
p1 <- 0.730769230769231                          # treatment proportion
n_per_arm <- function(power, frac = 1) {
  q1 <- p0 + (p1 - p0) * frac               # smaller effect = fraction of the observed difference
  pbar <- (p0 + q1) / 2
  z_b <- qnorm(power)
  ceiling(round((z_a * sqrt(2 * pbar * (1 - pbar)) + z_b * sqrt(p0 * (1 - p0) + q1 * (1 - q1)))^2 / (q1 - p0)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (unrounded n per arm)
cat("power.prop.test:", round(power.prop.test(p1 = p0, p2 = p1, power = 0.80)$n, 1), "\n")

# Simulation: how often does the z-test reject at the 80%-power sample size?
set.seed(2288377)
n    <- n_per_arm(0.80)
reps <- 20000
x0 <- rbinom(reps, n, p0); x1 <- rbinom(reps, n, p1)
ph <- (x0 + x1) / (2 * n)
z  <- ((x1 - x0) / n) / sqrt(ph * (1 - ph) * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(z) > z_a, na.rm = TRUE), reps))

Output from running the code

100% of observed effect: n per arm = 101 (80% power), 134 (90% power)
 75% of observed effect: n per arm = 185 (80% power), 246 (90% power)
 50% of observed effect: n per arm = 424 (80% power), 567 (90% power)
power.prop.test: 100.4 
Simulated power at n = 101 per arm: 0.806 (20000 replicates)

The simulation draws many pairs of event counts at the planned sample size and counts how often the two-proportion z-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

13. Multiplicity, Missing Data and Analysis Populations

The registry lists Progression-Free Survival and Overall Survival as secondary outcomes, in addition to the primary 6-month endpoint. It reports three outcome measures but posts no secondary outcome results. The registry also lists zero analysis records. The primary comparison is nevertheless presented with an unadjusted p-value. The registry record does not explain the relationship between the posted summary and the analysis-record count.

When a study assesses multiple outcomes or conducts multiple statistical comparisons, the chance of at least one apparently notable result can increase. In general, multiplicity methods may control that risk by changing the testing procedure or the interpretation of results. The record does not report whether multiplicity was considered, whether outcomes were prioritized beyond the primary designation, or whether any adjustment was planned or performed. The posted p-value should therefore be read as unadjusted, without assuming that it accounts for other outcomes or analyses.

The primary outcome description says that 2 patients without tumor evaluation at cycle 4 nor cycle 7 were not evaluable for the primary criterion. The registry record does not report the complete handling of those cases, the number of other missing assessments, or whether any imputation or sensitivity analyses were performed. It also does not explain whether the primary analysis included all randomized participants, only evaluable participants, or another population. The endpoint arm denominators are listed as 24 for placebo and 26 for lanreotide, but the record does not provide a full participant flow account linking these entries to enrollment.

Other analysis details are also not reported in the registry record, including covariate adjustment, subgroup analyses, interim analyses, stopping criteria, and the method used to calculate the confidence interval. These gaps limit evaluation of the robustness of the primary comparison and the handling of incomplete information. They should be treated as unknowns rather than assumptions about how the study was conducted.

14. 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 4% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: hypokalaemia (4.0%), constipation (4.0%), small intestinal obstruction (4.0%), peritoneal haemorrhage (3.7%), gastrointestinal haemorrhage (3.7%).

The registry reports serious adverse events among 3 of 25 participants at risk in the placebo group and 5 of 27 at risk in the lanreotide group. Other adverse events are reported for 6 of 25 at risk in the placebo group and 9 of 27 at risk in the lanreotide group. These are group-specific counts and denominators; they should be read as posted, without combining categories or interpreting the differences as causal.

Deaths are listed as 7 for placebo and 2 for lanreotide. The registry record does not report the causes of death, timing, or whether deaths were considered related to treatment. It also does not provide enough information to interpret the deaths as a treatment comparison or to reconcile them with the endpoint population.

The listed serious-event terms include hypokalaemia, constipation, and small intestinal obstruction at 4.0% each, and peritoneal haemorrhage, gastrointestinal haemorrhage, and abdominal pain upper at 3.7% each. The record does not identify these terms by treatment arm in this list. Adverse-event counts and terms are descriptive safety information; they do not establish whether a treatment caused an event or provide a complete benefit-harm assessment.

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

The registry results show a higher posted proportion alive and progression-free at 6 months in the lanreotide arm than in the placebo arm: 19 of 26 compared with 13 of 24. The unadjusted p-value is 0.164, and the confidence interval for the risk difference crosses no difference. Together, these results indicate an observed difference in the posted data accompanied by substantial uncertainty about the underlying effect.

The result does not establish that lanreotide caused the higher observed proportion, nor does it prove that there is no difference between the treatments. A p-value is not the probability that a treatment works, and a confidence interval that includes no difference does not demonstrate equivalence. The registry does not report an equivalence or non-inferiority framework. The confidence interval’s range across both sides of no difference means that potentially different effect sizes and directions remain compatible with the posted estimate.

The primary endpoint is a status at 6 months based on investigator imaging under RECIST 1.1 criteria. It does not by itself describe the full timing of progression or survival beyond that assessment point. Although Progression-Free Survival and Overall Survival are listed as secondary outcomes, results for them are not reported in the registry record. The safety entries likewise cannot establish a complete balance of benefit and harm, especially because event attribution, timing, and the causes of deaths are not reported.

The record identifies a terminated study, but the reason for termination is not reported in the registry record. Nor does it report the complete analysis population, missing-data handling, or multiplicity procedures. These limits matter when deciding how broadly to interpret the posted comparison. The results are best understood as a registry-reported primary endpoint comparison with a positive point estimate and imprecise evidence, not as a definitive clinical conclusion or treatment recommendation.

16. Why This Trial Matters Statistically

This trial raises several important statistical issues in a compact setting: a binary endpoint assessed at a fixed time, a randomized comparison, missing imaging assessments, and limited posted outcome information. The endpoint is understandable as a status at 6 months, but it compresses a potentially complex disease course into whether each participant was alive and progression-free at that point. That makes the definition and completeness of assessment central to interpretation.

The posted arm counts show how a point estimate can favor one group while uncertainty remains substantial. The confidence interval crosses no difference, and the unadjusted p-value is 0.164. This distinction between the observed direction and the precision of the estimate is a core statistical lesson. Neither the point estimate nor the p-value alone describes the full evidential picture.

The record also highlights the importance of analysis transparency. It notes that 2 patients without tumor evaluation at cycle 4 nor cycle 7 were not evaluable for the primary criterion, but does not report the missing-data rules or analysis population. It lists secondary outcomes without results and does not report multiplicity procedures. Without these details, readers cannot fully assess how the reported comparison relates to all randomized participants or how other outcomes were handled.

Finally, sample-size planning based on an observed effect can be especially uncertain when that effect comes from limited data. The posted planning illustrations make the relationship clear: targeting smaller effects requires more participants under the stated assumptions. They are not evidence of the trial’s original plan or of its observed power. Distinguishing planning illustrations from trial results, and distinguishing documented methods from unreported ones, is essential for a careful reading of clinical evidence.

17. 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 gives a limited account of the primary outcome analysis. It identifies the endpoint, the imaging basis, the arm counts, a risk-difference comparison, and an unadjusted p-value, but does not report the complete statistical analysis plan or the method used to construct the confidence interval. The analysis population and handling of missing outcome information are also not reported in the registry record.

The endpoint assessment depended on investigator imaging under RECIST 1.1 criteria. The record does not describe the imaging schedule beyond references to cycle 4 and cycle 7, state whether scans were independently reviewed, or explain how assessment timing was managed. It notes that 2 patients without tumor evaluation at cycle 4 nor cycle 7 were not evaluable for the primary criterion, but does not give a full account of other potentially incomplete assessments or their treatment in analysis.

The registry lists enrollment of 53, while the primary outcome entries list arm denominators of 24 and 26. The record does not include a participant flow explanation linking those figures or specify whether the primary results include all randomized participants. It also records that the study was terminated, without reporting the reason or its implications. No inference about the cause of termination is warranted.

Secondary outcomes are named, but results are not reported in the registry record. Safety reporting includes group counts, deaths, and a list of serious-event terms, but does not report event timing, causes of death, or attribution to treatment. The record also does not report multiplicity methods, interim analyses, protocol amendments, or the original sample-size rationale. These omissions constrain interpretation and should remain explicit uncertainties rather than being filled by assumption.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: A Study Evaluating Lanreotide as Maintenance Therapy in Patients With Non-Resectable Duodeno-Pancreatic Neuroendocrine Tumors (REMINET) — NCT02288377.
• Registry record last updated 2023-01-18; status last verified 2022-12.
• Results first posted 2021-10-04.
• 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.

21. Record Summary

REMINET is registered as a European, prospective, multicentre, randomized, parallel Phase II/III study of lanreotide versus placebo for patients with metastatic or locally advanced, non-resectable duodeno-pancreatic neuroendocrine tumours after first-line treatment. Lanreotide was described as 120 mg every 28 days until progression; placebo was scheduled on the same interval. The study is recorded as terminated, with enrollment of 53.

The primary endpoint was the proportion alive and progression-free at 6 months after randomization, based on investigator imaging in line with RECIST 1.1. Posted counts are 13 of 24 for placebo and 19 of 26 for lanreotide. The unadjusted p-value is 0.164, and the risk-difference confidence interval includes no difference. The registry notes 2 participants were not evaluable for the primary criterion because they lacked tumor evaluation at cycle 4 nor cycle 7.

Progression-Free Survival and Overall Survival are listed as secondary outcomes, but their results are not reported in the registry record. The reason for termination, full analysis population, missing-data methods, and original sample-size assumptions are also not reported in the registry record.