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 The Effects of Aripiprazole on the Processing of Rewards in Schizophrenia (NCT00209027), a non-randomized na study. The primary outcome is BOLD Activation During fMRI Scanning During Performance of a Monetary Reward Task.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00209027 |
| Phase | NA |
| Condition | Schizophrenia |
| Allocation | Non-Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 20 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Emory University |
| Results posted | Yes |
2. Clinical Question
The study addressed whether people with negative symptoms of schizophrenia show atypical functioning in brain circuits involved in reward processing, and whether that functioning changes after treatment with aripiprazole. The registry describes a planned comparison of reward-task fMRI activation between schizophrenia subjects and controls at baseline, together with a planned comparison of schizophrenia subjects’ activation at baseline and after a medication switch.
Population
People with schizophrenia, described as having negative symptoms, and a control group. The registry lists enrollment as 20. The primary outcome description states that the planned fMRI comparison was between schizophrenia subjects and controls.
Intervention
Schizophrenia subjects were to switch from their baseline medication to aripiprazole. fMRI during a monetary reward task was the measurement procedure, rather than a drug intervention.
Comparator
Controls were included for the baseline comparison. The schizophrenia group was also intended to serve as its own baseline comparator for the scan after the medication switch. Allocation was non-randomized and masking was none, so the groups are not a like-for-like randomized treatment comparison.
Primary question
Does reward-task BOLD activation differ between schizophrenia subjects and controls at baseline, and does activation in schizophrenia subjects differ between baseline and the scan after switching to aripiprazole? The registry says the prespecified data were not collected because the study was terminated before subjects received aripiprazole.
Consequently, the clinical question remains unanswered by the posted primary outcome. The registry describes an intended investigation, not an observed estimate of change following aripiprazole.
3. Trial Design
NCT00209027 is titled “The Effects of Aripiprazole on the Processing of Rewards in Schizophrenia.” Emory University is listed as the sponsor. The registry records the study as non-randomized, unmasked, and parallel. Its phase is recorded as NA. Enrollment is listed as 20, and the condition is schizophrenia. The study start is recorded as 2005-04, primary completion as 2010-12, and status as terminated.
The described schizophrenia group was to switch from baseline medication to aripiprazole, with fMRI measurements at baseline and after the medication switch. Controls were included in the planned baseline comparison. The registry does not provide a control-group intervention description that would establish an otherwise matched comparison. With no random allocation and no masking, group differences could reflect factors other than the condition being compared; the design does not support treating the groups as equivalent treatment arms.
The primary outcome timeframe is baseline and 12 weeks. The outcome description specifies BOLD activation during a monetary reward task. It describes a baseline comparison between schizophrenia subjects and controls and a within-group comparison of the schizophrenia subjects’ baseline scan with an endpoint scan. These are planned contrasts; they are not reported outcome estimates.
The registry states that prespecified data were not collected because the study was terminated before subjects received aripiprazole. It does not report why the study was terminated, whether any scans were obtained before termination, or whether any participants completed other study procedures. The listed enrollment should therefore not be mistaken for the number who contributed to the primary endpoint. The registry record does not report a detailed protocol, the medication regimens before the planned switch, or the exact recruitment and follow-up procedures.
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 | Schizophrenia Subjects | Controls |
|---|---|---|
| STARTED | 10 | 10 |
| COMPLETED | 0 | 10 |
| NOT COMPLETED | 10 | 0 |
Reasons for not completing this period:
| Reason | Schizophrenia Subjects | Controls |
|---|---|---|
| study terminated | 10 | 0 |
Analysis population for the primary outcome, as defined in the registry: Prespecified data not collected because the study was terminated before subjects received aripiprazole.
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 | Schizophrenia Subjects | Controls | Total |
|---|---|---|---|---|
| Participants analysed | 10 | 10 | 20 | |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 10 | 10 | 20 |
| Age, Categorical: >=65 years | Participants | 0 | 0 | 0 |
| Age Continuous | years | 42.5 (SD 10.9) | 38.6 (SD 7.2) | 40.6 (SD 9.0) |
| Sex: Female, Male: Female | Participants | 0 | 0 | 0 |
| Sex: Female, Male: Male | Participants | 10 | 10 | 20 |
| Region of Enrollment: United States | participants | 10 | 10 | 20 |
6. Primary Endpoint
The registry lists the primary outcome as BOLD Activation During fMRI Scanning During Performance of a Monetary Reward Task, measured over Baseline and 12 weeks.
| Element | Registry entry |
|---|---|
| Result type | N/A |
| Measure of spread | not applicable |
| Unit | not stated |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint was BOLD activation measured with fMRI while participants performed a monetary reward task. BOLD refers to a blood-oxygen-level-dependent signal. In general, fMRI uses changes in this signal as an indirect measure related to brain activity; it is not a direct measurement of reward experience or of a specific psychological process. A reward task offers a structured context in which investigators can examine brain activation associated with reward processing.
The endpoint was selected to address the study’s stated interest in brain circuits relevant to reward processing. The registry describes two intended contrasts: activation in schizophrenia subjects versus controls at baseline, and activation in schizophrenia subjects at baseline versus an endpoint scan after the planned medication switch. The timeframe is baseline and 12 weeks.
The endpoint description does not specify a brain region, task contrast, signal-processing method, or numerical unit. Those details are not reported in the registry record. Most importantly, the registry says the prespecified data were not collected because the study was terminated before subjects received aripiprazole. No primary endpoint values, group difference, change estimate, or uncertainty interval are reported. Thus, the endpoint’s scientific rationale can be described, but its planned comparisons cannot be interpreted as observed findings.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The posted record does not contain a primary outcome result. Although BOLD activation during a monetary reward task was designated as the primary outcome, the registry states that the prespecified data were not collected because the study was terminated before subjects received aripiprazole. No numerical activation values or effect estimates are reported, and the analysis count is zero. As a result, the record does not establish whether baseline activation differed between schizophrenia subjects and controls or whether activation changed after aripiprazole.
The planned comparisons have different interpretations. A baseline comparison between schizophrenia subjects and controls would address whether the groups differed during the task at that time. It would not, by itself, show that schizophrenia caused any difference, because allocation was non-randomized and the groups were not described as matched. A baseline-to-endpoint comparison in schizophrenia subjects would be a within-group change over time. Even if such a change had been observed, without a randomized comparison it could not automatically be attributed to the medication switch; other changes over time or in care could also matter. In this record, neither comparison has a reported primary outcome result.
There is no reported effect estimate with a confidence interval, standard error, or p-value for the primary endpoint. In general, an effect estimate expresses the size and direction of a contrast, while a confidence interval describes the uncertainty around that estimate under the analysis assumptions. A p-value addresses compatibility between the observed data and a specified statistical model; it does not measure clinical importance. None of those quantities can be interpreted for the primary outcome without collected data and a reported analysis.
The adverse-event listing gives zero affected for serious adverse events and zero affected for other adverse events in each listed group, with 10 at risk in each group for each category. These entries describe the registry’s posted safety figures; they do not supply the missing fMRI result. The record does not state the observation period or detailed event definitions for these entries, and deaths are not reported in the registry record.
The study’s termination and absent primary endpoint data are central to interpretation. The enrollment listing does not substitute for endpoint observations. Nor can a planning calculation be taken as evidence that the intended effect was detected: planning illustrations concern hypothetical design requirements, whereas observed results require collected outcome data. Since the primary outcome was not collected, the appropriate conclusion is that the planned question is unresolved in the posted record, not that a treatment effect was present or absent.
9. Statistical Methods Explained
What does the primary endpoint represent?
The outcome is BOLD activation recorded by fMRI during a monetary reward task. In general, BOLD is an indirect signal linked to changes in blood oxygenation that accompany brain activity. It can be used to study patterns of activation during a defined task, but it does not directly measure a participant’s subjective reward response. Interpretation depends on how the task, signal, and brain regions are defined. The registry record names the task and broad signal but does not report the specific region or activation contrast.
The stated comparisons were between schizophrenia subjects and controls at baseline, and between baseline and endpoint scans in the schizophrenia group. Those contrasts answer different questions. A between-group contrast compares group averages at a time point. A within-group contrast compares measurements over time in the same study group. In general, repeated measurements can account for stable characteristics of individuals when the analysis uses the paired structure, but the registry does not report the planned statistical model or confirm that paired observations were collected.
What can be inferred from the design?
The study is recorded as non-randomized, unmasked, and parallel. In general, random allocation helps balance measured and unmeasured characteristics between treatment groups, while masking can reduce some influences on conduct or assessment. Those safeguards are not recorded for this study. The listed control group is relevant to the planned baseline comparison, but the registry says the groups should not be regarded as a like-for-like control comparison. A group difference would therefore need careful interpretation even if endpoint data had been available.
The planned switch comparison also has limits as a causal estimate. A before-and-after difference can reflect the intervention, but it can also reflect time, changes in other care, measurement variation, or other influences. A suitable concurrent comparison and a specified analysis could help address some of these concerns; the record does not describe a randomized treatment comparison. These are general design considerations, not findings about what happened in this study.
What results and uncertainty measures are available?
The primary outcome is explicitly described as not collected because the study was terminated before subjects received aripiprazole. The analysis count is zero. No outcome means, activation differences, changes, uncertainty intervals, or p-values are reported. In general, an estimate should be read together with its uncertainty: a narrow interval indicates greater precision under the model assumptions, while a wide interval indicates less precision. Neither direction nor precision can be assessed for this primary endpoint without a reported estimate and interval.
The registry does not report a statistical analysis plan, a model for the fMRI endpoint, covariate adjustment, handling of repeated measures, or a definition of the analysis population. It is therefore not possible to identify which statistical test or estimator was intended. Describing a possible method would go beyond the record. General methods such as regression or paired comparisons are not evidence that those methods were used or planned.
How should planning calculations be read?
The stated planning assumptions describe illustrations based on an observed effect, rather than the trial’s own design: a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation. The stated effect to detect is a fraction of the observed effect. For time-to-event calculations, the stated output convention is total events using the Schoenfeld approach; for other calculations, it is participants per arm. These are general planning conventions, not reported features of the study design.
In general, a sample-size calculation asks how much information a future study might need to detect a specified effect under stated assumptions. Such an illustration depends on the effect used, variability, allocation, significance level, and statistical model. It is not “observed power,” and it does not show that a treatment effect exists. The registry record does not report a trial-specific sample-size justification or statistical plan. Because the primary fMRI data were not collected, a planning illustration should not be interpreted as a calculation based on a reported primary endpoint effect from this study.
Over-dispersion is a general issue when variation in the data is greater than the model expects. If ignored, uncertainty may be understated and tests may be poorly calibrated. The record does not identify a count outcome or report a model for which over-dispersion was evaluated, so it is not possible to say whether it was relevant to the primary fMRI endpoint or how it was handled. Likewise, there is no reported primary outcome analysis on which to assess model fit or robustness.
In summary, the methods that can be described are the planned measurement and contrasts, the non-randomized and unmasked design, and the stated generic planning assumptions. The statistical analysis itself, its estimates, and its uncertainty are not reported in the registry record.
10. Multiplicity, Missing Data and Analysis Populations
The registry names one primary outcome measure, BOLD activation during fMRI scanning during performance of a monetary reward task, and describes two planned comparisons: schizophrenia subjects versus controls at baseline, and baseline versus endpoint in schizophrenia subjects. It does not report a multiplicity strategy for handling more than one comparison, task contrast, brain region, or outcome. The endpoint description does not specify how many regions or task contrasts would be examined. Any multiplicity adjustment, hierarchy of tests, or distinction between confirmatory and exploratory analyses is not reported in the registry record.
The primary endpoint data were not collected because the study was terminated before subjects received aripiprazole. The analysis count is zero, so no primary endpoint analysis population or missing-data method is described. The registry does not report whether missing observations were to be excluded, imputed, or handled through a model, nor does it provide reasons for individual missing observations. These details cannot be inferred from the enrollment listing.
The record does not define an intention-to-treat, per-protocol, or other analysis population. It also does not say whether controls were included in any planned safety or efficacy analysis beyond the stated baseline fMRI comparison. In general, analysis-population definitions matter because they determine which participants contribute to an estimate; missing-data assumptions matter because conclusions can depend on what is assumed about unobserved outcomes. In this terminated study, no primary outcome estimate is available to evaluate under any such assumptions.
The registry does not report interim analyses, stopping rules, or a statistical analysis plan. The reason for termination is also not reported in the registry record. These omissions limit assessment of how the planned analyses and study conduct were to be managed, but they do not justify guessing why the study ended or what analyses might have been performed.
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 |
|---|---|---|---|
| Schizophrenia Subjects | 0 | 10 | 0.0% |
| Controls | 0 | 10 | 0.0% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Schizophrenia Subjects | 0 of 10 |
| Controls | 0 of 10 |
The registry lists separate safety figures for schizophrenia subjects and controls. For serious adverse events, each group has 10 at risk and zero affected. For other adverse events, each group likewise has 10 at risk and zero affected. These are the posted counts; they should be read as registry entries for the listed categories, not as evidence about the uncollected primary fMRI endpoint.
The record does not report the safety observation period, detailed adverse-event definitions, or the method used to collect and classify events. It also does not provide event terms in the serious-event listing. Deaths are not reported in the registry record. The displayed zero affected counts therefore need to be interpreted within the limited safety information recorded, without assuming a particular follow-up duration or completeness of ascertainment.
In general, a zero count in a study group does not establish that an event cannot occur or fully characterize safety. Counts are more informative when the exposure duration, ascertainment procedures, and event definitions are clear. Those details are not reported. The safety figures also do not alter the central limitation: the study was terminated before subjects received aripiprazole, and its prespecified primary data were not collected.
12. What the Result Does, and Does Not, Mean
The record documents a planned investigation of reward-task brain activation in schizophrenia and a planned medication switch to aripiprazole. It does not document a primary outcome result. The registry specifically states that prespecified data were not collected because the study was terminated before subjects received aripiprazole. Consequently, no conclusion about the direction, size, or precision of a change in BOLD activation can be drawn from the posted primary outcome information.
The planned baseline comparison with controls and the planned baseline-to-endpoint comparison serve different purposes. The first would describe how the groups’ task-related activation compared at baseline; the second would describe within-group change over time after the planned switch. Neither is reported as an observed analysis. Even if such results had been reported, the non-randomized, unmasked design would require caution in attributing group differences or changes to the medication itself.
The zero affected counts in the safety listing are limited observations for the categories recorded. The registry does not specify the observation period or detailed event definitions, and deaths are not reported in the registry record. These safety entries cannot answer the primary question about reward-processing activation.
In general, absence of an estimate is not the same as an estimate showing no effect. A result consistent with little or no difference would require collected outcome data and an estimate precise enough to distinguish that possibility from other values. Here, no primary estimate or uncertainty interval is reported. The proper statistical interpretation is therefore that the planned question remains unresolved in the registry record. The enrollment listing and planning assumptions do not fill that evidentiary gap and should not be read as proof of efficacy, lack of efficacy, or adequate statistical power.
13. Why This Trial Matters Statistically
This study is statistically informative as an example of why a registered research question must be distinguished from a reported result. The record gives a specific scientific aim, a defined fMRI outcome, and planned comparisons, yet also states that the primary data were not collected after the study was terminated before subjects received aripiprazole. The intended analysis therefore cannot be evaluated as an observed treatment effect.
The design also illustrates how the comparison structure affects interpretation. A baseline contrast between schizophrenia subjects and controls is not equivalent to a randomized treatment comparison. A before-and-after contrast in the schizophrenia group would describe change over time, but without random allocation it would not isolate the medication effect from other influences. Clear separation of these questions prevents a planned control comparison from being mistaken for a causal treatment estimate.
Finally, the record distinguishes design-planning assumptions from trial-specific analysis. Generic sample-size illustrations can help explain how assumptions relate to future study planning, but they are not observed power and do not establish that an effect was measured. Since no primary endpoint data were collected, the principal statistical lesson is about limits of inference: a complete description of the intended question and design cannot substitute for estimates, uncertainty, and transparent analysis of collected outcomes.
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 is that the prespecified primary data were not collected because the study was terminated before subjects received aripiprazole. No BOLD activation values or analyses are reported. The reason for termination is not reported in the registry record, and the enrollment listing does not show how many participants contributed any particular measurement.
The design is non-randomized and unmasked, and the registry cautions that the arms are not a like-for-like control comparison. The record does not describe matching, adjustment for baseline differences, or a concurrent control intervention. Thus, even the planned group comparison would require caution, while the intended before-and-after comparison would be vulnerable to changes over time and other factors not separated by randomization.
Important technical details are not reported in the registry record: the brain regions and task contrasts, fMRI processing and quality-control procedures, endpoint summary measure, statistical model, covariate strategy, and missing-data approach. The analysis population and multiplicity plan are also not reported. It is not possible to assess whether the planned endpoint was measured consistently or how uncertainty would have been estimated.
The safety listing lacks a stated observation period and detailed event definitions; deaths are not reported in the registry record. The registry also does not report a trial-specific sample-size justification, interim analyses, or statistical analysis plan. These gaps limit assessment of design adequacy and result interpretation, but they do not support assumptions about the protocol or the reason the study stopped.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: The Effects of Aripiprazole on the Processing of Rewards in Schizophrenia — NCT00209027.
- Registry record last updated 2013-12-06; status last verified 2013-11.
- Results first posted 2012-06-18.
- 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
NCT00209027, sponsored by Emory University, planned to study reward processing in schizophrenia using BOLD activation during a monetary reward task. It was recorded as non-randomized, unmasked, and parallel, with enrollment of 20 and phase listed as NA. The study start is recorded as 2005-04, primary completion as 2010-12, and status as terminated.
The planned comparisons were schizophrenia subjects versus controls at baseline and schizophrenia subjects at baseline versus an endpoint scan after a planned switch to aripiprazole. The primary timeframe was baseline and 12 weeks. The registry states that the prespecified data were not collected because the study was terminated before subjects received aripiprazole; no analysis is reported.
The safety listing records zero affected for serious and other adverse events in both groups, with 10 at risk for each category in each group. The safety observation period and detailed event definitions are not reported, and deaths are not reported in the registry record. The primary clinical question remains unanswered by the posted outcome data.