PET Imaging of the Dopaminergic and Serotonergic Systems in Treated HIV Positive Subjects: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for PET Imaging of the Dopaminergic and Serotonergic Systems in Treated HIV Positive Subjects (NCT03581305), a non-randomized phase 1 study. The primary outcome is Influx Constant (Ki) for 18F-FDOPA PET..

2. Clinical Question

3. Trial Design

This was a phase 1, parallel, non-randomized study with no masking. The registry record lists enrollment of 46 and a completed status. The listed study dates are 2018-11-20 for the start and 2022-04-06 for primary completion. The sponsor was the National Institutes of Health Clinical Center (CC).

The study concerned PET imaging of dopaminergic and serotonergic systems in treated HIV-positive participants, with HIV-negative participants also described in the arm information. The brief summary says eligible HIV-positive adults had received antiretroviral treatment for at least 1 year; healthy adults were also eligible. All participants had to be enrolled in protocol 13-N-0149. The record does not report how participants were assigned to imaging groups or provide a detailed recruitment flow.

The dopaminergic arm description lists HIV-positive participants with or without co-morbidities and two HIV-negative groups, distinguished by co-morbidities. The serotonergic arm description lists HIV-positive and HIV-negative participants, with or without co-morbidities. The record gives group counts in those descriptions, but does not clarify whether these are planned, eligible, enrolled, or analyzed counts. They should not be read as the number of participants contributing to the primary endpoint without further information.

The brief summary describes one or two PET scans, with a tracer delivered through an intravenous catheter. Participants receiving the dopamine scan were asked to fast for 4-6 hours and take a pill one hour before scanning. Each scan was described as lasting about 1.5 hours. These procedural details do not establish how many participants completed each scan or whether all scans yielded usable data. Those counts 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: Among HIV positive subjects: 1 subject didn't show up to either scan 2 subjects couldn't finish FDOPA and didn't come back for DASB 2 subjects did FDOPA but didn't come back for DASB Among HIV negative subjects 1 subject did DASB but didn't come back for FDOPA

Dopaminergic Study

Reasons for not completing this period:

Serotonergic Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: All participants who completed FDOPA PET scan with usable Data

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: All participants in the dopaminergic and serotonergic arms, irrespective of study completion, based on HIV status

6. Primary Endpoint

The registry lists the primary outcome as Influx Constant (Ki) for 18F-FDOPA PET., measured over 90 minutes of scanning.

The primary endpoint is the influx constant, Ki, for 18F-FDOPA PET, measured in min-1. It is a continuous measure reported in the registry as a mean with standard deviation. The registered population is participants who completed an FDOPA PET scan with usable data. The timeframe is 90 minutes of scanning.

The endpoint description says dynamic PET scans were performed after FDOPA injection. After image reconstruction, time-activity curves were extracted and analyzed using Patlak linear graphical analysis with a reference region. Ki is described as reflecting the rate of FDOPA uptake in specific brain regions. In general, a continuous imaging measure can retain differences in magnitude across participants rather than reducing each observation to a category. A mean describes the central level of the measure in a group, while a standard deviation describes variation among measured values.

The endpoint is used to characterize FDOPA uptake as part of the study’s objective to examine dopamine in the brain in relation to HIV. The registry record does not identify a specific brain region for the registered primary endpoint, report group-level Ki values, or give an estimated HIV-group contrast. It also does not report a confidence interval or a test result for this endpoint. Therefore, the endpoint definition explains what was intended to be measured, but the record does not provide the numerical results needed to judge the observed pattern or its precision.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registered primary measure is continuous: Ki for 18F-FDOPA PET, expressed in min-1 and summarized as a mean with standard deviation. In general, a mean gives a group’s average value, while a standard deviation describes the spread of individual measurements around that average. The standard deviation is not the same as the uncertainty in a group mean or in a difference between groups. A confidence interval is generally used to express uncertainty around an estimated quantity, but no confidence interval for Ki is reported in the registry record.

What does the PET endpoint represent?

The endpoint description links Ki to the rate of FDOPA uptake in specific brain regions. The stated procedure uses dynamic PET scans over 90 minutes after FDOPA injection. Image analysis is described as extracting time-activity curves after scan reconstruction, then applying Patlak linear graphical analysis with a reference region. In general, a kinetic imaging measure uses changes in tracer signal over time to characterize tracer uptake. The registry description names the analysis approach, but does not provide its detailed implementation, software, quality-control criteria, or region-specific results.

The endpoint population includes participants who completed FDOPA PET with usable data. This definition makes scan usability relevant to inclusion in the primary analysis. The record does not state how usability was judged, how many scans were excluded, or whether data were missing for reasons related to participant characteristics or scan results. These details matter because an analysis of usable scans may describe a subset of those enrolled.

How should the group comparison be understood?

The study is non-randomized, and the arm descriptions distinguish groups by HIV status and, in the dopaminergic arm, co-morbidity status. In general, random allocation helps balance measured and unmeasured factors on average, while non-randomized comparisons do not have that design protection. Differences in Ki between groups could reflect HIV status, other group differences, or a combination. The record does not report a statistical model, covariate adjustment, matching method, or other approach to address such differences.

The parallel design indicates that distinct groups are described rather than a within-person crossover comparison. The record does not explain whether any participant contributed to more than one imaging arm or how repeated measurements, if any, were handled. That information is not reported in the registry record. The absence of masking is part of the registered design; it does not by itself reveal whether image processing or outcome assessment was blinded.

What can the analysis record establish?

The record lists five outcome measures and zero analyses. It provides the primary endpoint’s measure, summary form, timeframe, and analysis description, but no outcome values or statistical comparisons. The three listed secondary outcomes concern correlations of 18F-FDOPA with co-morbidities, 18F-FDOPA and 11C-DASB with HIV, and 11C-DASB with neuropsychiatric evaluation. No correlation coefficients, model details, uncertainty intervals, or significance tests are reported in the registry record.

In general, an estimate describes the magnitude and direction of an association or contrast, while a confidence interval describes the range of values compatible with the data under the model’s assumptions. A p-value addresses compatibility with a specified null hypothesis under a statistical model; it does not measure the size or importance of an effect. None of these inferential quantities for the registered endpoint is available in the record, so none should be inferred from the study objective or endpoint description.

How should planning calculations be read?

The study information describes sample-size values as planning illustrations based on an observed effect, using a two-sided significance level of 0.05, equal allocation, and a normal approximation. In general, a planning calculation asks how many participants might be needed to detect a chosen effect under stated assumptions. It is not an estimate of the study’s achieved power, and it does not establish that a study had enough information to answer its question. The calculation note explicitly characterizes these values as planning illustrations, not observed power.

The registry record does not report the numerical planning values, the precise effect fractions used, or the observed effect estimate underlying the illustrations. The actual allocation is also described as non-randomized, so the equal-allocation assumption used for the illustration should not be mistaken for a statement about realized groups. The planning assumptions do not provide a substitute for reporting group sizes and endpoint results.

Dispersion also matters when interpreting a continuous endpoint. In general, a standard deviation summarizes variation, and greater variability can make a group mean or between-group contrast less precise when other features are held constant. If continuous measurements have a distribution with unusually influential values, the mean and standard deviation may not fully describe the data. The registry specifies mean and standard deviation, but does not report distributions, diagnostics, alternative summaries, or a rationale for the chosen summary.

Finally, detailed statistical methods are not reported. The record does not specify a planned hypothesis test, a model for group comparisons, handling of covariates, missing-data procedures, or a multiplicity strategy. These omissions limit reproducibility and make it impossible to determine from the registry record whether the reported endpoint description corresponds to a prespecified final analysis.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists five outcome measures, including the primary FDOPA PET Ki endpoint and three named secondary outcomes concerning correlations with co-morbidities, HIV, and neuropsychiatric evaluation. It reports zero analyses. The record does not describe a multiplicity adjustment, a hierarchy of secondary hypotheses, or a strategy for controlling false-positive findings across outcomes. Those methods are not reported in the registry record.

In general, testing multiple hypotheses can increase the chance of observing at least one apparently notable result by chance. A prespecified hierarchy or adjustment can clarify how multiple results should be interpreted. Because no analysis results or multiplicity plan are reported, there is no basis for judging how any secondary finding would relate to the primary endpoint.

The primary endpoint population is defined as participants who completed FDOPA PET with usable data. The number of participants meeting that definition is not reported. The record does not give participant flow, reasons for missing scans or unusable data, the amount of missing outcome information, or a method for handling missing values. It is therefore not possible to assess whether the endpoint analysis included all eligible participants or whether missingness could have influenced the results.

The record does not identify an intention-to-treat or per-protocol analysis population, and it does not report other analysis-population rules beyond the usable FDOPA scan description. The group counts in the arm descriptions are not explicitly identified as analyzed sample sizes. These details, along with the statistical analysis plan and any prespecified handling of incomplete data, are not reported in the registry record.

11. 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.

The registry record lists separate adverse-event groups for HIV-positive and HIV-negative subjects. Each group has 23 participants at risk for serious adverse events and 23 at risk for other adverse events. The recorded counts are zero for serious adverse events, zero for other adverse events, and zero deaths in each group. No top serious-event terms are listed.

These figures describe the adverse-event entries in the registry record. They do not establish that no events occurred outside the record’s reporting scope, and they do not provide event details, timing, severity categories beyond the serious/other distinction, or participant-level follow-up information. The record does not explain the relationship between these adverse-event denominators and the overall enrollment or the scan-specific analysis populations.

In general, a zero count in a recorded group is not the same as proof that an event is impossible. Interpretation depends on how events were collected, the period of observation, and who was included in the group. Those details are not reported in the registry record. The figures should therefore be read narrowly as the registered counts, rather than as a complete characterization of risk or as evidence about imaging outcomes.

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

The registry record describes an investigation of PET measures related to dopamine and serotonin in HIV-positive and HIV-negative participants. Its primary outcome is FDOPA PET Ki, a continuous measure intended to reflect FDOPA uptake in specific brain regions. The record also identifies secondary correlation questions involving co-morbidities, HIV, and neuropsychiatric evaluation.

What the record does not establish is the direction or magnitude of any observed difference or association. The primary endpoint’s group summaries and inferential results are not reported in the registry record. There are no reported estimates or confidence intervals from which to judge precision, and no reported p-values from which to describe statistical evidence under a particular test. The zero analysis count reinforces that no statistical findings are available in the record.

The design also limits causal interpretation. This was a non-randomized study without masking, and the groups were described in relation to HIV status and co-morbidities. In general, an observed group contrast in such a design may reflect differences between groups other than the characteristic being studied. The record does not report an adjustment plan that would help evaluate those differences. Thus, even if results were available, the design would need to be considered when interpreting an association as distinct from a causal effect.

The registry entry is useful for identifying the intended question, scan procedures, primary measure, and broad participant groups. It is not a report of the numerical answer to that question. The absence of results should not be read as evidence of no difference, as evidence of a difference, or as proof that the study failed to measure the endpoint. It means the endpoint results are not reported in the registry record.

Similarly, the adverse-event counts are limited to the registered figures and do not determine the interpretation of the imaging endpoint. Planning illustrations, where discussed, are not observed power or clinical findings. The clearest reading is that the record documents a completed imaging study and its intended measurements, while leaving the outcome estimates and their uncertainty unavailable.

13. Why This Trial Matters Statistically

This study illustrates the distinction between registering a scientific question and reporting the statistical evidence that addresses it. The registry identifies an imaging endpoint with a defined unit, summary measure, timeframe, and analytic description. Those details help readers understand what the investigators intended to measure. Without outcome values, however, they cannot show the size or precision of the observed pattern.

The design also makes the comparison structure important. HIV-positive and HIV-negative participants were not randomly assigned, and the arm descriptions include co-morbidity groupings. Such distinctions affect how a statistical contrast should be interpreted. In general, a numerical difference between groups is descriptive unless the design and analysis support a stronger interpretation; potential group differences and adjustment methods need to be made transparent.

Endpoint-specific denominators are another central issue. The primary outcome applies to participants with completed FDOPA scans and usable data, while the registry gives an overall enrollment count and arm descriptions without identifying final analysis counts. Reporting the number with usable measurements and explaining exclusions would let readers assess the scope of the endpoint analysis and the potential effect of missing data.

The record also names several outcome questions but reports no analyses. This highlights why statistical reporting should include estimates, uncertainty, analytic populations, and the approach to multiple outcomes, not only outcome titles and methods. A planning illustration cannot replace those elements or indicate achieved power.

For biostatisticians and clinical researchers, the entry is a reminder that a well-described measurement process and a completed study status are not equivalent to a reported statistical result. Transparent reporting connects design, analysis population, estimates, and limitations so that readers can distinguish what was measured from what the data support.

14. Limitations

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

The main limitation for interpreting this trial from the registry record is the absence of reported outcome estimates. The primary Ki mean and standard deviation, group contrasts, confidence intervals, and inferential tests are not reported. The secondary correlation results are also unavailable. As a result, the statistical findings cannot be assessed quantitatively.

The analysis population is not fully characterized. The primary endpoint includes participants with completed FDOPA PET scans and usable data, but the number meeting that definition is not reported. The registry gives an overall enrollment of 46 and arm descriptions with group counts, without clarifying whether those counts refer to planned, eligible, enrolled, or analyzed participants. Participant flow and reasons for missing or unusable scans are not reported.

Non-randomized allocation and lack of masking should also inform interpretation. The record does not report a statistical adjustment strategy or explain how co-morbidities and other potential group differences were handled. The named imaging and correlation objectives do not establish how comparisons were modeled. Detailed statistical methods, including multiplicity and missing-data procedures, are not reported in the registry record.

The endpoint description specifies an imaging analysis approach but does not report implementation details such as quality-control criteria or the specific regional results. The relationship between the adverse-event denominators and the overall enrollment is not explained. These gaps limit independent assessment of measurement, analysis, and reporting completeness.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: PET Imaging of the Dopaminergic and Serotonergic Systems in Treated HIV Positive Subjects — NCT03581305.
• Registry record last updated 2023-03-21; status last verified 2022-04-07.
• Results first posted 2023-03-21.
• 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.

18. Record Summary

This completed phase 1 study, NCT03581305, examined PET imaging of dopaminergic and serotonergic systems in treated HIV-positive participants and HIV-negative participants. It was parallel, non-randomized, and unmasked, with enrollment listed as 46. The primary endpoint was the FDOPA PET influx constant, Ki, summarized as a mean with standard deviation in min-1 over 90 minutes of scanning.

The registry describes FDOPA and DASB imaging procedures and lists secondary correlation questions. It reports no analyses and does not report the primary or secondary outcome estimates. The adverse-event record lists zero serious events, zero other events, and zero deaths in each of the two listed groups, with 23 participants at risk in each group for each event category. Statistical methods for missing data, multiplicity, and group adjustment are not reported in the registry record.