PET Imaging of Phosphodiesterase-4 (PDE4) in Brain and Peripheral Organs of McCune-Albright Syndrome: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for PET Imaging of Phosphodiesterase-4 (PDE4) in Brain and Peripheral Organs of McCune-Albright Syndrome (NCT02743377), a non-randomized phase 1, phase 2 study. The primary outcome is Standard UptakeValue (SUV) Area Under the Curve (AUC) (30-120min) - Bladder.

2. Clinical Question

3. Trial Design

This completed Phase 1/Phase 2 study, NCT02743377, was sponsored by the National Institute of Mental Health (NIMH). The registry describes a non-randomized, unmasked, parallel design. Enrollment was 16. The study began on 2018-04-04, and primary completion was recorded as 2019-10-23.

The study concerns McCune-Albright Syndrome, a disorder described in the registry as affecting bones, skin, and some hormone-producing tissues. Its stated aim was to learn about PDE4 in people with MAS and compare PDE4-related measurements with those in people without MAS. The primary outcome description identifies the comparison as participants with MAS versus healthy controls.

The registry describes outpatient participation involving 1 to 4 visits to the NIH Clinical Center, with some visits possibly occurring on the same day. Procedures described for MAS participants include screening, blood and urine tests, magnetic resonance imaging, whole body PET, and brain PET. PET imaging used 11C-(R)-rolipram; the brain scan description also includes an arterial tube. These are features of the recorded study procedures, not evidence that every participant completed every procedure.

The listed interventions include brain PET imaging with 11C Rolipram, whole body PET at baseline with 11C Rolipram, and whole body PET with roflumilast blockade. The arm descriptions identify MAS participants and healthy controls who received whole body and/or brain PET scans. The registry does not describe a randomized assignment between these groups. It also does not report the detailed allocation of every imaging procedure to each participant.

The endpoint population is participants who completed a whole body scan with 11-C Rolipram. The registry record does not state how that population relates numerically to total enrollment or provide endpoint-specific group counts. A study status of completed indicates the record's completion status; it does not itself establish that every planned outcome has a posted result.

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: 16 subjects were enrolled but one subject did not start the study.

Overall Study

Analysis population for the primary outcome, as defined in the registry: Subjects who completed whole body scan with 11-C Rolipram

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 Standard UptakeValue (SUV) Area Under the Curve (AUC) (30-120min) - Bladder, measured over 120 minutes.

The primary endpoint is Standard Uptake Value (SUV) area under the curve (AUC) for the bladder from 30-120min, with units of SUV x min. Its stated purpose is to measure PDE4-related levels in the periphery using 11C-rolipram and compare participants with MAS with healthy controls. The registry specifies a mean as the outcome measure and standard deviation as its dispersion measure. It gives the timeframe as 120 minutes.

AUC combines measurements across a stated interval into a measure of accumulated signal over time. In general, this can summarize a changing imaging signal rather than representing a single measurement at one time. SUV is an imaging measure of tracer uptake; the endpoint is therefore a PET-derived proxy for the biological quantity of interest, not a direct count of PDE4 molecules. The registry describes the endpoint as a way to assess PDE4 levels, but does not provide further validation details or a clinical threshold for interpreting the measurement.

The bladder outcome is the registered primary measure even though the study's broad objective refers to PDE4 in the periphery. The registry record does not report the observed group means, standard deviations, difference, confidence interval, or p-value for this endpoint. As a result, its numerical size, precision, and direction cannot be assessed from the posted results.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary measure is continuous: it is a mean SUV AUC, with standard deviation identified as the dispersion measure. Continuous outcomes can take a range of values rather than belonging to categories. A group mean describes the central level of such measurements, while a standard deviation describes how spread out individual measurements are around that mean. These summaries are useful, but neither substitutes for an estimate of the between-group contrast and its uncertainty.

What does an AUC measure?

In general, an area under the curve combines measurements across a time interval. For this endpoint, the interval is recorded as 30-120min, and the outcome is expressed in SUV x min. The resulting value reflects signal accumulated across the interval, rather than a single SUV value at one time. Its interpretation depends on the imaging protocol, the measurement process, and the biological meaning of tracer uptake. The registry record identifies the intended interpretation as PDE4 levels measured using 11C-rolipram, but does not report further measurement-validation information.

What would a group comparison need to show?

A comparison of means would ordinarily be read alongside the group estimates and an estimate of the difference between them. A confidence interval is, in general, a range of values compatible with the data under a specified statistical procedure. It communicates uncertainty around an estimate; a narrower interval indicates greater precision than a wider interval. A p-value addresses compatibility of the data with a specified null model, but does not give the size or clinical importance of a difference. The registry record does not report a confidence interval or p-value for the primary outcome, so neither precision nor statistical evidence for a difference can be assessed.

The record identifies a mean and standard deviation but does not state the statistical test, model, covariates, or method for calculating uncertainty. These details matter because different methods can answer different questions and rely on different assumptions. For example, a model may adjust for measured participant characteristics, whereas a simple unadjusted comparison does not. The analysis plan is not reported in the registry record, so it is not possible to determine which approach was intended or used.

Why does the design matter?

In general, random assignment helps balance measured and unmeasured characteristics between treatment groups on average. This study is recorded as non-randomized, and the registry explicitly says the arms are not a like-for-like control comparison. That makes the comparison observational. If measured outcomes differ, group composition or other factors could contribute to the difference. Whether any adjustment was used to address confounding is not reported in the registry record.

The study is also recorded as unmasked. In general, masking can reduce the chance that knowledge of group or procedure influences assessments or related decisions. PET measurements are instrument-based, but the record does not describe safeguards for image acquisition, processing, or outcome assessment. It would be inappropriate to assume that masking was used for those tasks when the registry records masking as none.

What can the sample-size illustration tell readers?

The registry's planning assumptions describe an illustration computed from an observed effect, not the trial's own design. The stated assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation; the effect to detect is a stated fraction of the observed effect. Such values, when presented, are planning illustrations. They are not observed power and do not show that the study was designed with those assumptions. The registry record does not report the observed effect or the numerical planning results in the registry record used for this explanation.

In general, a planning calculation estimates the sample size that might be needed under specified assumptions to detect a target effect with a chosen level of statistical power. It depends on the assumed effect, variability, significance level, allocation, and analysis method. Changing those assumptions can change the planning estimate. A calculation based on an observed effect is especially dependent on that estimate and should not be mistaken for a prospectively specified design rationale. The sample-size justification for this trial is not reported in the registry record.

How should multiplicity be considered?

The record lists 13 outcome measures, alongside a named primary outcome. When a study evaluates multiple outcomes or comparisons, the chance of at least one apparently unusual result can increase if each is tested separately without a strategy for multiplicity. In general, statistical plans may identify a primary comparison, control an overall error rate, or treat other outcomes as exploratory. The registry record does not report whether any multiplicity adjustment or hierarchy was specified. It also lists zero analyses, so it does not provide a set of reported tests from which that approach could be inferred.

These general statistical concepts explain what information would help readers assess the endpoint. They do not fill the gaps in the record. In particular, a defined outcome and a completed study status do not provide the group estimates, analysis method, or uncertainty measures needed to evaluate the primary comparison.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("Healthy Control", "Subjects With McCune-Albright Syndrome (MAS)")
n   <- c(5, 4)
m   <- c(575.1, 650.8)
sp  <- c(402.2, 344.7)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  Healthy Control  5  575.100  402.200  75.703  1074.497
CARM  Subjects With McCune-Albright Syndrome (MAS)  4  650.800  344.700  102.305  1199.295

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 13 outcome measures and identifies a primary outcome, but it does not report a multiplicity strategy. In general, multiplicity arises when several outcomes, time points, or comparisons are examined. Testing many hypotheses without an appropriate plan can make chance findings more likely. A prespecified hierarchy or adjustment can help clarify which comparisons are confirmatory and how statistical evidence should be interpreted. Whether such a plan was used is not reported in the registry record.

The record lists zero analyses and gives no primary outcome estimate, p-value, confidence interval, or analysis model. It does not report whether the primary comparison was adjusted for participant characteristics or whether any secondary analyses were exploratory. A detailed statistical analysis plan is not reported in the registry record. The registry record therefore does not support conclusions about how the listed outcomes were analyzed or how any statistical error rates were handled.

Missing-data methods are also not reported in the registry record. The primary outcome population is defined as participants who completed a whole body scan with 11-C Rolipram, but endpoint-specific counts, exclusions, and reasons for missing measurements are not given. No method for handling incomplete imaging data is stated. In general, missing-data procedures matter because an analysis restricted to participants with recorded measurements can differ from an analysis that accounts for missing outcomes, particularly if missingness relates to participant characteristics or measurements.

The record does not describe a broader analysis population, such as an intention-to-treat population, and does not report how participants were included across the intervention descriptions. The primary endpoint's completion-based population is the only stated analysis-population description relevant to that measure. It is not possible to determine how closely it matches enrollment from the registry record.

12. 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 0% reporting threshold.

Most frequent non-serious adverse event terms

The registry lists serious adverse events for the healthy control group and the MAS group. For healthy controls, 0 serious adverse events were reported among 9 at risk; for participants with MAS, 0 were reported among 6 at risk. Deaths were 0 in both groups. The listed other adverse events were 3 among 9 healthy controls and 0 among 6 participants with MAS.

These are descriptive counts, not estimates of a causal effect or a complete safety comparison. The groups were non-randomized and the registry cautions that they are not a like-for-like control comparison. The at-risk groups are small, and the registry record does not provide event descriptions for the other adverse events. The list of top serious adverse event terms is empty.

Zero recorded serious events in these groups means none are listed for the reported at-risk participants; it does not establish that a procedure or intervention has no risk. Likewise, the other-event counts cannot be compared as if group assignment were randomized. The registry does not report event timing, severity details beyond the serious/other categories, attribution, or statistical analysis of safety outcomes.

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

This record is useful for identifying the study's intended biological question and the imaging outcome selected to address it. It describes a comparison of PDE4-related PET measurements in people with MAS and healthy controls, with bladder SUV AUC from 30-120min designated as the primary outcome. It also records whole body and brain imaging procedures involving 11C-(R)-rolipram, as well as whole body PET with roflumilast blockade.

The record does not report the numerical primary outcome or a group comparison. It therefore cannot establish the direction, size, or precision of any difference in the measured signal. Absence of a posted estimate should not be read as evidence that the groups were the same. Nor can the study's stated objective be treated as a result: an objective describes the question researchers sought to answer, not what the data showed.

Even if numerical group results were available, the non-randomized design would require care in interpreting differences. The record explicitly warns that the arms are not a like-for-like control comparison. In general, group differences can reflect characteristics other than the condition being studied, and the registry does not report an adjustment strategy to address that possibility. The PET outcome is also an imaging measure used as a proxy for PDE4-related levels, not a direct clinical outcome.

The listed adverse-event counts are separate from the primary imaging question. They report no serious adverse events or deaths in either group and some other adverse events among healthy controls. Those counts do not establish a comparative safety profile, particularly in the absence of event details and with non-randomized groups.

Accordingly, the defensible conclusion is limited: the registry describes a completed imaging study and its planned primary measure, but the numerical primary results and analysis are not reported in the registry record. The record does not establish whether PDE4-related measurements differed between groups, and it does not support a treatment recommendation.

14. Why This Trial Matters Statistically

The study illustrates how a registry can define a biological imaging question in measurable terms. Rather than relying only on a broad description of PDE4, the primary outcome specifies bladder SUV AUC, a time interval, units, a summary measure, and a target comparison. Clear outcome definitions matter because they help distinguish the primary question from the many other measurements that may be collected in an imaging study.

It also illustrates why design details are essential to statistical interpretation. The study is non-randomized and unmasked, and the registry warns that the groups are not a like-for-like control comparison. Those details limit causal interpretation of any group contrast. In general, a difference in measurements between groups is not automatically a difference caused by the condition; participant characteristics and study procedures may also contribute.

The record lists 13 outcome measures but zero analyses, and it does not report numerical results for the primary outcome. That gap is statistically important. A clearly defined endpoint is not enough to judge the evidence: readers also need group estimates, an estimate of contrast, uncertainty, analysis methods, and information about which participants contributed data. Without these, the result's magnitude and precision remain unknown.

The study's stated imaging objective may be scientifically informative, but the registry record alone cannot show whether the observed data supported the proposed comparison. This distinction between a research question and a reported result is central to sound evidence interpretation. It prevents a study's aims, completion status, or outcome definitions from being mistaken for findings.

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.

The most direct limitation for interpreting this trial is that the registry record does not report numerical primary outcome results. It provides the endpoint definition but not group means, standard deviations, group-specific endpoint counts, a contrast, or uncertainty estimates. The primary comparison therefore cannot be evaluated quantitatively from the record.

The design is non-randomized and unmasked. The registry itself warns that the arms are not a like-for-like control comparison. This limits how confidently a group difference, if reported elsewhere, could be attributed to MAS rather than differences between participants or procedures. The registry does not report an adjustment strategy that could help address those differences.

The primary outcome applies to participants who completed a whole body scan with 11-C Rolipram, while total enrollment is recorded as 16. The endpoint-specific number of participants and reasons for any unavailable measurements are not reported in the registry record. This prevents assessment of outcome completeness and the relationship between enrollment and the endpoint population.

The outcome is an imaging measure described as an indicator of PDE4 levels, rather than a clinical outcome. The registry does not report additional validation information, measurement reliability, or a threshold for interpreting the AUC. The record lists 13 outcome measures, but does not report a multiplicity plan or analysis methods. It also does not report a detailed statistical analysis plan, sample-size justification, or missing-data approach.

Finally, safety details are limited to serious and other adverse-event counts, with no event descriptions for the other adverse events. The record lists no serious adverse event terms. These limitations are specific to the information reported for this study and restrict conclusions about both the primary imaging question and safety.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: PET Imaging of Phosphodiesterase-4 (PDE4) in Brain and Peripheral Organs of McCune-Albright Syndrome — NCT02743377.
• Registry record last updated 2020-10-19; status last verified 2020-05-19.
• Results first posted 2020-10-19.
• 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

NCT02743377 is a completed Phase 1/Phase 2, non-randomized, unmasked, parallel PET imaging study sponsored by the National Institute of Mental Health (NIMH). Enrollment was 16. The study's objective was to compare PDE4-related measurements in people with McCune-Albright Syndrome and healthy controls using 11C-rolipram imaging.

The primary outcome is bladder SUV AUC from 30-120min, expressed as SUV x min, with a mean and standard deviation specified. Its population is participants who completed a whole body scan with 11-C Rolipram. The registry lists 13 outcome measures and zero analyses, but does not report numerical primary results, group estimates, or a statistical comparison.

The adverse-event record lists no serious adverse events or deaths in either group, and lists other adverse events for healthy controls only. The registry cautions that the non-randomized arms are not a like-for-like control comparison. Endpoint-specific sample sizes, missing-data methods, multiplicity handling, and the statistical analysis plan are not reported in the registry record.