This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Influence of Medication on Functional Connectivity (NCT03612713), a randomized early/phase 1 study. The primary outcome is Change in Functional Connectivity Following Oxycodone Administration.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT03612713 |
| Phase | EARLY/Phase 1 |
| Condition | Prescription Drug Abuse (Not Dependent) |
| Allocation | Randomized |
| Design model | Crossover |
| Masking | Triple |
| Enrollment | 20 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Yale University |
| Results posted | Yes |
2. Clinical Question
The study asks whether functional connectivity within the ventral attention network changes after a single low dose of oxycodone, compared with placebo, in healthy individuals. Functional connectivity is defined in the registry record as a statistical relationship between two brain regions, measured using functional magnetic resonance imaging.
Population
Healthy individuals enrolled in a study with a listed enrollment of 20. The registry’s condition entry is Prescription Drug Abuse (Not Dependent); the brief summary describes the participants as healthy individuals. Further eligibility criteria are not reported in the registry record.
Intervention
A single dose of 15mg immediate release oxycodone, given one hour before an fMRI scan in the oxycodone-first sequence.
Comparator
A single dose of placebo, given one hour before an fMRI scan in the placebo-first sequence. The study is listed as a crossover, but details of the sequence and any interval between study conditions are not reported in the registry record.
Primary question
How does functional connectivity, expressed as a transformed z-score, change between placebo and oxycodone fMRI scans? The listed outcome timeframe is change from the initial fMRI scan to a follow-up MRI scan, up to 4 weeks.
The registry describes a score of 0 as indicating no change and higher scores as indicating increased connectivity. It does not report the observed score, an estimated comparison between conditions, or an uncertainty interval. Consequently, the clinical question can be described from the registered design and outcome definition, but the posted results do not establish the size or precision of any observed difference.
3. Trial Design
Influence of Medication on Functional Connectivity is listed as an early phase 1 study with randomized allocation, triple masking, and a crossover model. Yale University is the sponsor. The registry lists enrollment of 20 and a completed status. The recorded start date is 2018-10-30, and the primary completion date is 2022-06-02.
The two named intervention sequences are Oxycodone Medication First and Placebo First. In the oxycodone-first sequence, participants were to receive a single dose of 15mg immediate release oxycodone one hour before an fMRI scan. In the placebo-first sequence, participants were to receive a single dose of placebo one hour before an fMRI scan. The registry labels both interventions as drugs.
A crossover design means that the study is organized around participants receiving more than one study condition, rather than comparing only separate groups who each receive one condition. That general feature can make within-participant comparisons relevant, but the registry does not provide enough detail to describe the actual sequence structure, the interval between conditions, or how repeated observations were analyzed. Those details are not reported in the registry record.
The primary outcome timeframe is described as change in functional connectivity from an initial fMRI scan to a follow-up MRI scan, up to 4 weeks. The record lists one outcome measure and zero analyses. It does not give numerical primary outcome results, an analysis population, or a statistical analysis plan. The completed status therefore describes the trial’s recorded status, not the availability of a numerical estimate for the primary question.
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
| Stage | Oxycodone Medication First | Placebo First |
|---|---|---|
| STARTED | 10 | 10 |
| COMPLETED | 7 | 8 |
| NOT COMPLETED | 3 | 2 |
Analysis population for the primary outcome, as defined in the registry: Positive and Negative connectivity within the ventral attention network
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.
| Characteristic | Unit | Oxycodone Medication First | Placebo First | Total |
|---|---|---|---|---|
| Participants analysed | 10 | 10 | 20 | |
| Age, Continuous | years | 24.20 (SD 2.82) | 24.40 (SD 2.95) | 24.30 (SD 2.81) |
| Sex: Female, Male: Female | Participants | 5 | 4 | 9 |
| Sex: Female, Male: Male | Participants | 5 | 6 | 11 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 1 | 1 | 2 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 9 | 9 | 18 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Asian | Participants | 5 | 3 | 8 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 1 | 0 | 1 |
| Race (NIH/OMB): White | Participants | 3 | 6 | 9 |
| Race (NIH/OMB): More than one race | Participants | 1 | 1 | 2 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 |
| Region of Enrollment: United States | participants | 10 | 10 | 20 |
6. Primary Endpoint
The registry lists the primary outcome as Change in Functional Connectivity Following Oxycodone Administration, measured over Change in functional connectivity from initial fMRI scan to follow-up MRI scan, up to 4 weeks..
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Standard Deviation |
| Unit | z-score |
| Endpoint classification | Continuous Endpoint |
The primary endpoint is titled Change in Functional Connectivity Following Oxycodone Administration. It concerns positive and negative connectivity within the ventral attention network, measured using functional magnetic resonance imaging. Functional connectivity refers to a statistical relationship between two brain regions; it is not a direct measure of a single region’s activity. The outcome is expressed as a transformed z-score, with the registry defining 0 as no change and higher scores as increased connectivity.
The registered timeframe describes change from an initial fMRI scan to a follow-up MRI scan, up to 4 weeks, and the description says connectivity between placebo and oxycodone fMRI scans will be assessed. The endpoint is relevant to the study’s stated objective because it operationalizes the brain-imaging measure the study intends to compare across medication conditions. The registry record does not explain how the transformation was performed, how positive and negative connectivity categories were combined or kept distinct, or which scan or contrast posted the reported mean.
The endpoint is continuous, with the registry identifying the summary parameter as a mean and dispersion as a standard deviation. However, it does not report a mean, a standard deviation, a treatment contrast, or a confidence interval. Thus, the outcome’s definition and direction can be explained, but its observed magnitude and precision cannot be evaluated from the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The posted registry information describes the study question and the intended functional-connectivity outcome, but it does not include numerical results for that endpoint. No observed mean, standard deviation, comparison estimate, confidence interval, or p-value is reported in the registry record. Without those quantities, the size and direction of the estimated contrast between oxycodone and placebo cannot be assessed, nor can its statistical precision.
The outcome description gives a limited interpretive reference: a transformed z-score of 0 indicates no change, and higher scores indicate increased connectivity. That definition does not substitute for an observed estimate. In particular, it does not show whether the observed score was near zero, higher than zero, or lower than zero. The registry’s primary outcome is framed as a comparison between placebo and oxycodone fMRI scans, but the order and exact calculation of that comparison are not reported in the registry record.
The record lists one outcome measure and zero analyses. This does not provide a basis for reconstructing an analysis or inferring whether a particular comparison was statistically significant. A registry outcome description indicates what was intended to be assessed; it is not itself evidence that the outcome changed. The completed status likewise does not supply an estimate or establish what the study found.
The study lists enrollment of 20, but enrollment alone does not quantify uncertainty around an outcome estimate. Precision depends on the observed values and the analysis used, neither of which is reported. In a crossover study, the relationship between measurements from the same participant can be important to the uncertainty of a condition comparison. The record does not report the participant-level observations or the method used to account for such dependence, so a reader cannot determine how that feature affected the estimate.
The registry includes safety counts for serious and other adverse events, but these are separate from the functional-connectivity outcome. They should not be used to infer an imaging effect. The listed safety counts describe events recorded for the oxycodone and placebo groups; they do not fill the gap in the primary efficacy outcome results.
A sample-size planning illustration, where presented, is not an observed outcome and is not observed power. Its stated assumptions refer to an effect based on the observed effect, but the numerical effect estimate itself is not reported in the registry record. The planning information therefore cannot replace a reported estimate with uncertainty. Overall, the registry supports describing the design and endpoint, while the primary outcome’s result and its precision remain unavailable in the record.
9. Statistical Methods Explained
The registered primary measure is continuous. For a continuous outcome, a mean describes the central value of a set of measurements, while a standard deviation describes how spread out those measurements are around the mean. These are descriptive summaries; on their own, they do not show how precisely a treatment contrast has been estimated. The registry names the mean and standard deviation as the summary parameter and dispersion, but reports neither numerical value for the primary outcome.
What does a crossover comparison involve?
In general, a crossover design compares conditions within participants, so each participant can contribute observations under more than one condition. This can be useful because stable differences between participants may be less influential in a within-participant contrast than in a comparison between unrelated groups. The actual analysis still needs to account for the design and the dependence between measurements from the same participant. The registry identifies this study as a crossover, but it does not describe the exact sequence, the interval between conditions, the number of observations per participant, or the model used. It is therefore not possible to say how the investigators handled those features.
For a continuous crossover outcome, a general approach might estimate a within-participant difference between conditions and report that estimate with an interval expressing uncertainty. This is a general statistical explanation, not a description of the analysis performed in this study. The registry record does not report a contrast estimate, a confidence interval, or an analysis model. It also does not report whether the analysis used participant-level differences or another method.
How should a confidence interval be understood?
In general, a confidence interval gives a range of values compatible with the data and the statistical method used, at a stated confidence level. Its width communicates precision: a narrower interval indicates greater precision than a wider interval under the same method. An interval also helps distinguish an estimate’s direction and plausible magnitude from a simple statement about statistical significance. No confidence interval or confidence level for the primary outcome is reported in the registry record, so the precision of the functional-connectivity comparison cannot be judged.
A p-value, when reported, summarizes how unusual the data would be under a specified null hypothesis and statistical model. It is not the probability that the null hypothesis is true, nor does it describe the size of an effect. No p-value or analysis result is reported for the primary outcome. The registry’s count of zero analyses is consistent with the absence of a posted analysis result in the record, but does not reveal which analyses may or may not have been carried out outside the registry.
What does the transformed score represent?
The endpoint description defines a transformed z-score and gives a direction for interpretation: 0 indicates no change, and higher scores indicate increased connectivity. A transformation can put measurements on a scale useful for statistical analysis, but interpreting that scale requires knowing exactly how the underlying measurements were transformed and what contrast the score represents. The transformation procedure and detailed calculation are not reported in the registry record. The record also identifies positive and negative connectivity within the ventral attention network, but does not explain how those categories contribute to the reported summary.
The outcome’s timeframe refers to change from an initial scan to a follow-up MRI scan, up to 4 weeks, while the description also refers to a comparison between placebo and oxycodone fMRI scans. These phrases identify the intended measurement context, but they do not specify the exact timing of each scan or the formula for the condition contrast. Those operational details are not reported in the registry record.
What can planning calculations tell a reader?
In general, sample-size calculations use assumptions about a target effect, variability, allocation, and a chosen statistical procedure to illustrate how many participants might be needed for a specified power under those assumptions. The registry’s planning description identifies a two-sided significance level of 0.05, equal allocation, a normal approximation, and an effect expressed as a fraction of the observed effect. These are planning assumptions, not findings about the study’s achieved power. Such calculations are not observed power and do not establish the probability that a result is true.
The registry does not provide numerical primary outcome results or a numerical observed effect in the record. Accordingly, a reader cannot use the planning assumptions alone to infer the actual effect, its precision, or whether the study met a planned target. The planning illustration should be interpreted as a design-oriented calculation, distinct from the evidence contained in an observed estimate and its uncertainty interval.
More broadly, a statistical analysis plan would clarify the outcome definition, handling of the crossover structure, analysis population, missing-data approach, and any adjustment for multiple comparisons. Those details are not reported in the registry record. General statistical principles can explain why they matter, but cannot establish which methods were used in this trial.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists one outcome measure, but the primary outcome description identifies positive and negative connectivity within the ventral attention network. The record also flags that the primary outcome has several categories or time points and was not reduced to one comparison. No numerical analysis is reported for those categories or time points. The registry does not state whether investigators treated them as separate tests, selected one comparison in advance, or adjusted for multiple testing. The multiplicity approach is not reported in the registry record.
Multiplicity matters when several outcomes, categories, time points, or contrasts are examined. In general, conducting multiple tests can increase the chance of finding at least one apparently unusual result by chance. Methods such as prespecifying a primary contrast or adjusting inference can address different multiplicity concerns, but the record does not identify a method used in this study. It is not possible to infer the analysis strategy from the outcome title alone.
The registry does not report missing-data counts for the primary outcome, the number of participants included in an outcome analysis, or the method used to handle missing scans or measurements. It also does not define an intention-to-treat, per-protocol, or other analysis population. These matters are not reported in the registry record, so the completeness and composition of the analyzed data cannot be assessed.
Because the record lists zero analyses and gives no numerical endpoint results, it is not possible to evaluate whether missingness or multiplicity affected the reported estimate. These are reporting gaps, not evidence that a particular problem occurred.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Oxycodone Medication | 0 | 20 | 0.0% |
| Placebo | 0 | 20 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Oxycodone Medication | 0 of 20 |
| Placebo | 0 of 20 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Oxycodone Medication | 2 of 20 |
| Placebo | 2 of 20 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Oxycodone Medication | Placebo |
|---|---|---|---|
| Nausea and vomiting | General disorders | 2 of 20 | 2 of 20 |
The registry lists 20 participants at risk for serious adverse events in the oxycodone group and 20 in the placebo group. It records zero participants affected by serious adverse events in each group, and zero deaths in each group. The serious adverse event terms list is empty. These are the registry’s reported counts; they do not establish that no other safety outcomes were assessed.
For other adverse events, the record lists 20 participants at risk in each group and 2 participants affected in the oxycodone group and 2 in the placebo group. These counts should be read separately from the serious adverse event counts. The record does not provide event descriptions or additional detail about the other adverse events, so their nature and timing cannot be characterized from the registry information.
The study is identified as a crossover, but the safety record presents group labels and counts without explaining how participant exposure across conditions was handled. The counts should therefore be reported as recorded, without assuming that the groups represent independent sets of participants or inferring a comparative risk estimate. They also do not answer the primary functional-connectivity question.
12. What the Result Does, and Does Not, Mean
The registry record establishes that a randomized, triple-masked crossover study of oxycodone and placebo was conducted, and it defines a functional-connectivity outcome measured by fMRI. It also describes the intended direction of the transformed score and lists safety counts. These details help readers understand the research question and the kind of measurement planned.
The record does not report a numerical primary outcome result, a treatment contrast, a confidence interval, or a p-value. As a result, it cannot show the observed direction, magnitude, or precision of the functional-connectivity comparison. The absence of a numerical result in the record should not be treated as evidence of no change, and the completed trial status should not be treated as a result.
The safety counts show zero participants affected by serious adverse events in either listed group, with zero deaths recorded; other adverse events were recorded for 2 participants in each group. These counts are limited to what the registry lists. They do not provide detail about the other events, establish comparative safety, or support a conclusion about the primary imaging endpoint.
Even with numerical results, interpretation would depend on the outcome calculation, the handling of repeated measurements in the crossover design, missing data, and any multiplicity approach. These analysis details are not reported in the registry record. General statistical principles can explain why those details matter, but cannot fill in the missing methods or results.
Accordingly, the available record supports a description of what the trial set out to measure, rather than a conclusion about the size or reliability of an oxycodone-placebo difference. Planning calculations, if consulted, are illustrations based on assumptions and should not be mistaken for observed power or for the trial’s outcome estimate.
13. Why This Trial Matters Statistically
This study illustrates an important distinction in clinical-trial reporting: a registered question and a defined endpoint are not the same as a reported result. The record gives the study design, intervention descriptions, outcome scale, and timeframe, but it does not give the numerical estimate needed to evaluate the primary comparison. Readers can identify what the investigators intended to measure without being able to judge what the data showed.
The crossover design also makes the analysis structure important. In general, measurements from the same participant may be related, and an analysis should reflect that dependence when estimating a condition contrast. The registry identifies the design but does not report the statistical model or the way repeated measurements were handled. That gap limits assessment of how the design was translated into an estimate and its uncertainty.
The endpoint’s positive and negative connectivity categories and its stated timeframe raise further questions about which comparison is primary and how multiple observations are handled. The record notes that the primary outcome has several categories or time points and was not reduced to one comparison, yet no analysis or multiplicity approach is reported. This makes it especially important not to infer a single definitive finding from an outcome description.
Finally, the safety counts and planning assumptions answer different questions from an endpoint estimate. Event counts describe recorded safety observations, while planning calculations describe assumptions for hypothetical sample-size requirements. Neither substitutes for a numerical functional-connectivity result with an uncertainty interval. The registry is useful for characterizing the study’s intended design, while its missing outcome and analysis details constrain statistical interpretation.
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 central limitation for statistical interpretation is that the registry record does not report numerical results for the primary functional-connectivity outcome. There is no reported mean, standard deviation, treatment contrast, confidence interval, or p-value. Therefore, neither the magnitude nor the precision of the intended comparison can be evaluated.
The record identifies positive and negative connectivity within the ventral attention network and notes that the primary outcome has several categories or time points. It does not specify the precise contrast used for each category or time point, or how these measures were combined or prioritized. The transformation to a z-score is not described in sufficient detail to reproduce or independently interpret the calculation.
Although the study is listed as a crossover, the registry does not report the sequence structure beyond the named intervention groups, any interval between conditions, the number of scans contributing to each analysis, or the statistical model. It also does not report an analysis population, missing-data handling, or a multiplicity strategy. These omissions prevent assessment of how the design and repeated observations were reflected in the analysis.
The enrollment listing and safety counts do not resolve these outcome limitations. The listed sample size does not provide an outcome estimate, and safety counts are not a substitute for functional-connectivity results. The registry’s completed status likewise does not provide numerical findings. Consequently, conclusions should remain limited to the registered study design, endpoint definition, and recorded safety counts.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Influence of Medication on Functional Connectivity — NCT03612713.
- Registry record last updated 2024-03-08; status last verified 2024-03.
- Results first posted 2024-03-08.
- 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.
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18. Record Summary
NCT03612713, Influence of Medication on Functional Connectivity, is listed as a completed early phase 1 randomized, triple-masked crossover study sponsored by Yale University. The registry lists enrollment of 20 and records a start date of 2018-10-30 and primary completion date of 2022-06-02. The intervention sequences are described as oxycodone first or placebo first, with a single dose given one hour before an fMRI scan.
The primary outcome concerns change in functional connectivity within the ventral attention network, expressed as a transformed z-score. The registry defines 0 as no change and higher scores as increased connectivity, with a timeframe extending up to 4 weeks. Numerical outcome results and analyses are not reported in the registry record. Safety listings record zero serious adverse events and zero deaths in each group, and 2 participants with other adverse events in each group.