Effect of Pasireotide Long Acting Release (LAR) on Gonadotroph Adenomas: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Effect of Pasireotide Long Acting Release (LAR) on Gonadotroph Adenomas (NCT00929669), a na phase 2 study. The primary outcome is Number of Participants With Change in Size of the Adenoma by ≥3 mm in at Least Two Dimensions as Determined by MRI.

2. Clinical Question

This is a focused pilot question about a particular tumor measurement and a hormone concentration in patients with a specified adenoma type. It is not a question about comparative effectiveness, because the study has no concurrent control group. The intended MRI assessment was based on change from baseline, with pituitary MRI planned at baseline, Month 6 and Month 12. The registry’s primary outcome defines a response using a threshold across dimensions rather than simply asking whether any measured dimension changed.

The distinction between the study’s intent and its posted results is important. The brief summary describes the aim of reducing serum FSH to normal and reducing adenoma size, but an aim is not evidence that either change occurred. The registry record does not report the number of participants meeting the MRI threshold, individual measurements, or the secondary FSH outcome. Interpretation must therefore focus on the question and design, not on an unreported treatment effect.

3. Trial Design

This was a Phase 2 pilot study of pasireotide LAR for gonadotroph adenomas, sponsored by the University of Pennsylvania. The registry identifies a single-group model, allocation as NA, and no masking. The intervention description specifies pasireotide LAR at 80 mg IM once monthly. With no control group, the study was not designed as a randomized comparison between treatment and control arms.

The registry enrollment is 2. The brief summary describes an intended study of three patients, while the enrollment field lists 2; the registry record does not explain the discrepancy. The study status is TERMINATED. Its start is recorded as 2009-06 and primary completion as 2011-11. The reason for termination and the circumstances of participant follow-up are not reported in the registry record.

The primary outcome was the number of participants whose adenoma decreased by at least 3 mm in at least two dimensions, as determined by MRI, over 12 months. MRI was planned at baseline, Month 6 and Month 12. The three dimensions named in the endpoint description are cephalocaudal, transverse, and posterior-anterior. A secondary outcome was the number of participants with a change in serum FSH concentration.

A single-group pilot design can describe what was observed among participants receiving the intervention, but it does not by itself isolate treatment effects from other explanations for change over time. This matters especially for imaging outcomes, which may vary because of measurement or assessment processes, and for laboratory outcomes, which may change for reasons not captured by a concurrent control. The record does not report details of MRI reading procedures, assessor training, or whether readings were independently reviewed.

Although an endpoint timeframe and assessment schedule are stated, the record does not provide participant-level measurements, outcome counts, or analysis results. It also does not report a protocol-level statistical analysis plan, sample-size justification, or the reason for ending the study. Those absences limit assessment of how closely the recorded study conduct matched its intended design.

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:

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Change in Size of the Adenoma by ≥3 mm in at Least Two Dimensions as Determined by MRI, measured over 12 months.

The primary endpoint counts participants who met a defined MRI response threshold: a decrease in adenoma size of at least 3 mm in at least two of the three specified dimensions. The assessment timeframe is 12 months. The endpoint description says pituitary MRI was to be performed at baseline, Month 6 and Month 12, allowing the size at follow-up to be considered relative to the baseline scan.

This threshold-based outcome is used to make the imaging question explicit. It distinguishes a qualifying decrease across multiple dimensions from a smaller change or a change limited to one dimension. Defining the threshold in advance can also help make the outcome more reproducible than an informal judgment that a tumor “got smaller.” However, the registry record does not report how dimensions were measured, how images were read, or whether readers were blinded to assessment time.

The endpoint is a participant count, not a continuous estimate of average size change. It therefore does not, by itself, describe the magnitude of change among participants who meet the threshold, or the distribution of changes among those who do not. The record does not report the actual number meeting the endpoint or the MRI measurements used to determine it. Consequently, the threshold and assessment plan can be described, but the observed primary outcome cannot be interpreted from the registry record.

The registry also lists change in serum FSH concentration as a secondary outcome. The brief summary mentions a goal of reducing FSH to normal, but the secondary-outcome wording refers to change in concentration. The record does not report the secondary outcome results or define a threshold for a clinically meaningful FSH change.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical methods help connect a clinical question to a measurable outcome, an analysis, and an interpretation. In this study, the primary outcome is a count of participants meeting a binary MRI criterion: the decrease either meets the defined threshold or it does not. This is different from an outcome that retains each participant’s exact size change. A binary endpoint can be easy to communicate, but it discards information about how far a participant’s change falls above or below the threshold.

What does a participant count tell us?

A count reports how many participants satisfy the endpoint definition. To interpret such a count, readers generally also need its denominator: the number of participants whose outcome could be assessed. The registry lists enrollment as 2, but does not report the number with an evaluable MRI outcome or the primary endpoint count. Enrollment and outcome availability are not automatically interchangeable, particularly when follow-up or outcome status is not documented.

When a binary endpoint is observed in a larger study, an estimated response proportion can describe the frequency of the outcome in the analyzed group. Uncertainty around that estimate is often expressed with a confidence interval. A confidence interval is a range calculated by a statistical procedure that reflects sampling uncertainty under the procedure’s assumptions; it does not guarantee that the true value lies in the interval. With very limited observations, estimates are typically imprecise, and a single participant’s status can have a large effect on the summary. No response proportion or confidence interval is reported for this primary endpoint.

Why does the single-group design matter?

In a single-group study, the observed outcome describes participants who received the intervention. A before-and-after change can be clinically interesting, but it does not establish what caused the change. Without a concurrent comparison group, differences over time may reflect natural variation, measurement variability, other care, or factors not recorded in the study. Random allocation, when used, can help create comparable groups by distributing known and unknown influences; this study’s allocation is listed as NA and its model is single-group. No comparative treatment effect can be estimated from a control group that is not part of the design.

The record also lists masking as NONE. Masking is a method for reducing the possibility that knowledge of treatment or assessment timing influences care, measurement, or interpretation. Its relevance depends on the outcome and study procedures. MRI measurements are more objective than some subjective outcomes, but image acquisition, boundary definition, and reading can still involve judgment. The registry record does not report whether image readers were masked to time point or whether measurement reliability was assessed.

How should the planning illustration be read?

The record describes a sample-size planning illustration using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It describes the target effect as a stated fraction of the observed effect. The record also identifies the illustration as planning, rather than as the trial’s own design. These assumptions do not convert the single-group pilot into a two-arm comparison, and they should not be interpreted as an analysis conducted on trial participants.

A sample-size calculation asks how many participants a future study might need under specified assumptions to have a chosen probability of detecting an effect of a specified size at a chosen significance level. Such calculations are planning tools, not evidence that an effect occurred. “Observed power” calculated after a study using its observed effect is not a useful substitute for an estimate and its uncertainty; a planning illustration should instead be understood as conditional on the assumptions used. The registry record does not report the actual effect estimate needed to evaluate the illustration’s basis, nor does it state that the assumptions were used to design this pilot. Any sample-size figures should therefore be treated as planning illustrations, not as observed power or as a description of the trial’s analysis.

The assumption of equal allocation between two arms is particularly distinct from this study’s single-group design. It belongs to the stated planning calculation, not to the trial’s allocation. The normal approximation is a mathematical method for approximating a sampling distribution. Its suitability depends on the setting and data; the record does not report a trial-specific assessment of that assumption. The record also notes that planning for time-to-event outcomes uses total events, while other planning results are expressed as participants per arm. The primary endpoint is a participant count, not a time-to-event outcome.

What can be concluded from statistical significance?

A significance test, when planned and reported, evaluates how compatible the observed data are with a specified null model under stated assumptions. A p-value does not measure the probability that a treatment works, the size or importance of an effect, or the probability that the null hypothesis is true. A confidence interval complements a test by showing a range of effect values compatible with the data and analysis. Neither a p-value nor an interval is reported for the primary endpoint in the registry record. The record lists 0 analyses, so no statistical analysis result is available to interpret.

Statistical conclusions also depend on the analysis population and missing outcome handling. An analysis population specifies which participants contribute to a particular estimate, such as all enrolled participants or only those with an observed follow-up assessment. Missing-data methods specify how absent measurements are handled and what assumptions are made about why they are absent. Neither an analysis population nor a missing-data approach is reported in the registry record. Because the endpoint requires a follow-up MRI comparison, the availability and handling of those measurements would be important to interpretation.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Pasireotide LAR")
n      <- c(1)
events <- c(0)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Pasireotide LAR  1  0  0.0  0.0  97.5  0.0  79.3  1.3  84.2

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 2 outcome measures: the primary MRI endpoint and a secondary outcome concerning change in serum FSH concentration. It does not report a multiplicity strategy, such as a hierarchy of hypotheses or an adjustment for testing more than one outcome. When several outcomes are examined, the chance of obtaining at least one apparently unusual result can increase if each is tested independently. A prespecified approach helps clarify which findings are confirmatory and how multiple tests are interpreted. Since no outcome analysis results are reported, there are no posted tests to evaluate for multiplicity.

The registry record lists 0 analyses. It does not report an analysis population, an intention-to-treat or per-protocol approach, or the number of participants with outcome data. It also does not report how missing MRI scans, incomplete follow-up, or unavailable FSH measurements were handled. These details matter because an endpoint count requires a clear definition of who was assessed and how participants without an observed outcome contribute to the analysis.

Missingness can affect interpretation when the participants with available measurements differ systematically from those without them. Statistical methods for missing data rely on assumptions about the process that caused observations to be absent. Those assumptions cannot be assessed without information about follow-up and the reasons for missing measurements. The registry record does not report these details, so the amount or potential impact of missing outcome data cannot be determined.

The study’s TERMINATED status does not itself establish that data were missing or that the analysis was stopped for a particular reason. The reason for termination and any analysis decisions connected to it are not reported in the registry record. The brief summary’s intended cohort and the enrollment entry also differ, without an explanation. These gaps limit reconstruction of the study’s analysis history and do not support assumptions about how many participants completed follow-up.

12. 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 0% reporting threshold.

Most frequent non-serious adverse event terms

The registry records 0 participants affected in the serious adverse-event category, with 2 at risk. In the other adverse-event category, it records 2 affected, with 2 at risk. These are the posted counts, and the categories should not be combined or treated as measures of benefit. The registry provides no serious-event terms in its list of top serious terms. The death count is not reported in the registry record.

Safety counts are most informative when the event definitions, observation period, severity grading, and participant-level exposure are clear. The record does not give event descriptions for the other adverse-event category, the timing or duration of observation, or details that would allow assessment of event severity beyond the category labels. It also does not report whether an affected participant experienced one event or more than one event. The counts therefore describe the registry entries, not the full clinical context of each event.

The recorded enrollment is 2, so the safety observations are limited. A count of 0 in a small group does not establish that a risk is absent, while a count of 2 in the other category cannot be interpreted without knowing what events were included and how they were collected. No comparison group is available to contextualize these entries. These figures should be read as descriptive registry data, not as a definitive assessment of the intervention’s safety.

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

The record establishes that investigators registered a Phase 2 pilot study of pasireotide LAR in gonadotroph adenomas, with an MRI-based primary endpoint and a secondary FSH outcome. It gives the intended monthly dose, the planned assessment timeframe, and the threshold used to define a qualifying MRI decrease. It also records enrollment as 2 and status as TERMINATED. These details describe the study question and design, but they do not answer whether the endpoint was met.

The primary MRI result and secondary FSH result are not reported in the registry record. No treatment effect, response frequency, change in hormone concentration, confidence interval, or statistical test result can be derived from the endpoint definitions alone. The brief summary states the study’s goal; it does not report that the goal was achieved. The discrepancy between the intended three patients described in the summary and enrollment of 2 is not explained, and the reason for termination is not reported.

Even if outcome changes had been posted, the single-group design would support description of outcomes in the treated participants, not a controlled estimate of what pasireotide LAR caused. Without a comparator, changes could not be separated from time-related change, measurement variability, or other influences. The absence of masking may be relevant to assessment, but the registry does not describe image-reading procedures sufficiently to evaluate that issue.

The safety entries record 0 affected in the serious adverse-event category and 2 affected in the other adverse-event category, each with 2 at risk. The absence of serious events in this registry entry is not evidence that serious risks are impossible, and the other adverse-event count lacks the event descriptions needed for clinical interpretation. Deaths are not reported in the registry record.

Overall, the registry supplies a narrowly defined pilot question and limited descriptive safety counts, but no outcome analysis that can quantify efficacy or its precision. The findings should not be interpreted as demonstrating benefit or lack of benefit. The missing results, the small recorded enrollment, lack of a control group, and absent analysis details leave the central clinical question unresolved by this record.

14. Why This Trial Matters Statistically

This trial matters statistically because it illustrates the difference between a well-specified outcome and an available result. The MRI endpoint is defined by a threshold, dimensions, assessment method, and timeframe. Those features make the intended measurement understandable. Yet without the observed endpoint count or underlying measurements, the definition cannot be converted into an estimate of what happened in participants.

The pilot scale is also important. The registry enrollment is 2, and the brief summary describes an intention to treat three patients. Such limited enrollment makes each observation consequential and restricts precision. The record does not provide an interval estimate or any statistical analysis, so readers cannot judge the range of effects compatible with the data. The enrollment discrepancy adds uncertainty about the relationship between the study’s intended scope and the recorded enrollment.

The single-group design emphasizes the distinction between change and treatment effect. Measurements before and after intervention may describe a time course, but a control group is needed to help distinguish intervention-associated change from other changes over time. The stated sample-size planning assumptions describe equal allocation between two arms, while the registered trial is single-group. Keeping planning assumptions separate from the actual design prevents readers from treating hypothetical calculations as trial findings.

The record also shows why transparent reporting of analysis populations, missing data, outcome estimates, and safety-event details matters. Without those elements, the clinical question can be understood, but the evidence supporting an answer cannot be evaluated. These are central statistical issues in pilot studies, especially when the endpoint is a participant count and the study status is terminated.

15. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

Several limitations specific to this study constrain interpretation. First, the registry enrollment is 2, whereas the brief summary describes an intention to treat three patients. The record does not reconcile the two figures or state how many participants completed the planned MRI assessments. The reason for the TERMINATED status is not reported in the registry record.

Second, the primary endpoint result is not reported. The record gives a threshold for MRI change but no count meeting that threshold, individual measurements, or estimate of uncertainty. The secondary FSH outcome is named but has no posted result. The registry also lists 0 analyses, leaving no reported statistical test or analysis estimate to assess.

Third, the study is single-group, with allocation listed as NA and masking listed as NONE. There is no concurrent control for interpreting changes over time. The record does not report MRI reading procedures, assessor masking, measurement reliability, or the handling of repeated measurements. These omissions prevent assessment of potential variation in image measurement or interpretation.

Fourth, analysis populations and missing-data methods are not reported. The record does not state how participants without follow-up MRI or FSH values would be handled, or whether outcome availability differed across assessments. The safety entries are also sparse: event terms for the other adverse-event category are not reported, and deaths are not reported in the registry record.

Finally, the registry does not report a protocol-level statistical analysis plan, multiplicity approach, sample-size justification for the pilot, or detailed reasons for termination. These gaps mean that neither the conduct of the analysis nor the completeness of outcome reporting can be fully evaluated from the registry record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Effect of Pasireotide Long Acting Release (LAR) on Gonadotroph Adenomas — NCT00929669.
• Registry record last updated 2017-11-28; status last verified 2017-10.
• Results first posted 2017-11-28.
• 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.

19. Record Summary

NCT00929669 is a Phase 2 pilot study titled “Effect of Pasireotide Long Acting Release (LAR) on Gonadotroph Adenomas.” The sponsor is the University of Pennsylvania. The registry describes a single-group, unmasked study with allocation listed as NA and pasireotide LAR at 80 mg IM once monthly. Enrollment is 2; the brief summary describes an intention to treat three patients. The study status is TERMINATED, with start recorded as 2009-06 and primary completion as 2011-11.

The primary outcome is the number of participants with an adenoma decrease of at least 3 mm in at least two dimensions on MRI at 12 months. Change in serum FSH concentration is listed as a secondary outcome. Neither outcome result is reported in the registry record, and the record lists 0 analyses. Safety entries include 0 affected in the serious adverse-event category among 2 at risk and 2 affected in the other category among 2 at risk. The reason for termination, analysis populations, missing-data handling, and detailed event terms are not reported in the registry record.