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 Stimulant Enhancement of Well-Being Therapy for Depression (NCT01478113), a randomized na study. The primary outcome is Change in Hamilton-Depression Rating Scale(SIGH-D)-17 Items.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01478113 |
| Phase | NA |
| Condition | Major Depressive Disorder |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Triple |
| Enrollment | 5 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Massachusetts General Hospital |
| Results posted | Yes |
2. Clinical Question
Population
The study concerned people with major depressive disorder who had residual symptoms while already taking an antidepressant that affects serotonin. The registry describes a planned enrollment of 40 individuals and reports enrollment of 5. The primary outcome record says the population was not able to be analyzed due to small sample size.
Intervention
The active-group plan combined well-being therapy (WBT) with amphetamine/dextroamphetamine. The study description presents WBT as a cognitive-behavioral therapy intended to help participants increase contact with natural rewards and reduce thoughts that interfere with reward. The record does not report treatment results for this group.
Comparator
The comparison group was assigned WBT with pill placebo. Thus, the planned comparison focused on adding amphetamine/dextroamphetamine to WBT, rather than comparing WBT with no therapy. The registry does not report analyzed outcome results for this group.
Primary question
The primary outcome description defines remission as a HAM-D-17 score < 8 at the endpoint visit, identified as visit 11/week 8 of treatment, or at an early termination visit. The stated question is a comparison between groups of the percentage of participants in remission. Although the outcome title refers to change in the Hamilton-Depression Rating Scale, the description specifies remission status as the comparison.
3. Trial Design
The registry describes a randomized, triple-masked, parallel-group study of well-being therapy with amphetamine/dextroamphetamine or with pill placebo. The study condition is major depressive disorder. The sponsor is Massachusetts General Hospital. The phase is listed as NA. The registry reports a start date of 2012-02, a primary completion date of 2014-07, and a status of terminated.
The brief study description states that investigators planned to randomize 40 individuals with residual symptoms of depression who were already taking an antidepressant that affects serotonin. It describes 8 weeks of treatment. The registry reports enrollment of 5, rather than the planned enrollment described in the study summary. The record does not explain the reason for termination or provide a detailed account of how the study proceeded.
The active group was assigned WBT and amphetamine/dextroamphetamine; the comparator group was assigned WBT and pill placebo. Because both groups were to receive WBT, the planned contrast isolates the addition of the stimulant within that therapy setting. Random allocation is intended, in general, to make groups comparable on average with respect to measured and unmeasured characteristics. Masking is intended to limit the influence of treatment knowledge on participants, study staff, or outcome assessment. The record labels masking as triple but does not identify which roles were masked or describe how masking was maintained.
The stated primary outcome concerns remission on the HAM-D-17 at the endpoint visit or early termination visit. Secondary outcomes include changes in psychological well-being, pleasure, behavioral inhibition and activation, positive and negative affect, and functioning. These listed outcome domains describe the planned scope of assessment, not evidence that usable results were obtained. The registry reports that the primary outcome population could not be analyzed because of small sample size.
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 | Well-being Therapy With Amphetamine/Dextroamphetamine | Well-being Therapy With Placebo |
|---|---|---|
| STARTED | 2 | 2 |
| COMPLETED | 1 | 1 |
| NOT COMPLETED | 1 | 1 |
Reasons for not completing this period:
| Reason | Well-being Therapy With Amphetamine/Dextroamphetamine | Well-being Therapy With Placebo |
|---|---|---|
| Withdrawal by Subject | 0 | 1 |
| Physician Decision | 1 | 0 |
Analysis population for the primary outcome, as defined in the registry: not able to analyze due to small sample size
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 | Well-being Therapy With Amphetamine/Dextroamphetamine | Well-being Therapy With Placebo | Total |
|---|---|---|---|---|
| Participants analysed | 2 | 2 | 4 | |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 2 | 2 | 4 |
| Age, Categorical: >=65 years | Participants | 0 | 0 | 0 |
| Age, Continuous | years | 50 (45 to 55) | 54 (53 to 55) | 52 (45 to 55) |
| Sex: Female, Male: Female | Participants | 0 | 1 | 1 |
| Sex: Female, Male: Male | Participants | 2 | 1 | 3 |
| Region of Enrollment: United States | Participants | 2 | 2 | 4 |
6. Primary Endpoint
The registry lists the primary outcome as Change in Hamilton-Depression Rating Scale(SIGH-D)-17 Items, measured over Baseline and visit 11/week 8 of treatment, or between baseline and early termination visit..
| 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 outcome is titled as change in the Hamilton-Depression Rating Scale (SIGH-D)-17 Items. Its description specifies a comparison of the percentage of participants in remission between the groups. Remission is defined as a HAM-D-17 score < 8 at endpoint visit 11/week 8 of treatment or at an early termination visit. The record therefore describes a remission classification at the endpoint, rather than giving an analyzed estimate of mean score change.
A symptom rating scale can provide a structured way to assess depressive symptoms. Converting the endpoint score into a remission category makes the primary question about the proportion of participants meeting the stated threshold. In general, a threshold can make the outcome clinically interpretable as a defined status, but it also discards information about how far scores lie above or below that threshold. A remission comparison does not, by itself, describe the full distribution of symptom scores or change over time.
The registry identifies baseline and the endpoint or early termination visit as the assessment timing. It does not report the actual remission percentages, a between-group estimate, uncertainty intervals, or an inferential test. It states that the population was not able to be analyzed due to small sample size. Consequently, the endpoint definition can be described, but the registry record does not support a conclusion about the observed treatment contrast.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record does not report an analyzable primary outcome result. It describes the primary question and its remission threshold, but gives no group-specific remission percentages, treatment-effect estimate, confidence interval, or p-value. It explicitly states that the population was not able to be analyzed due to small sample size. The planned comparison therefore cannot be interpreted as evidence for or against a difference in remission based on this record.
Enrollment is reported as 5, while the brief study description says that 40 individuals were to be randomized. These figures characterize the enrollment record and the intended enrollment, respectively. They should not be treated as outcome denominators or used to infer how participants were distributed across groups. The registry does not report the analyzed group sizes, participant flow, or reasons for the difference between planned and reported enrollment.
In general, an effect estimate describes the direction and magnitude of a contrast, while a confidence interval describes the range of estimates compatible with the data under the method used. Neither is reported for the primary outcome. A p-value, which can summarize how incompatible data are with a specified null model, is also not reported. Without these statistics, readers cannot assess the estimated contrast, its precision, or the strength of evidence against a null hypothesis. The small enrollment noted by the record is a reason for caution, but it does not reveal what the unobserved or unanalyzed outcome values would have been.
The registry lists several secondary outcome domains, including well-being, pleasure, affect, behavioral activation and inhibition, and functioning. It does not report results for those outcomes in the record. Their inclusion in the study plan does not establish that they were assessed successfully or analyzed. The record reports 7 outcome measures and 0 analyses; it does not explain the scope or status of those analyses beyond the primary outcome note.
The study status is terminated. That status alone does not identify why the study ended, whether termination was related to recruitment, resources, safety, or another factor, or whether any interim review took place. Such details are not reported in the registry record. The stated primary completion date does not substitute for an explanation of study conduct or a completed analysis.
The most defensible reading is therefore descriptive: the registry records a randomized, triple-masked comparison that was intended to assess remission after WBT with stimulant versus WBT with placebo, but it does not provide an analyzable primary result. It is not possible to infer benefit, lack of benefit, equivalence, or harm from the absence of an estimate. Absence of an analyzed finding is not the same as a finding of no difference.
9. Statistical Methods Explained
The registry describes a randomized, parallel-group design and triple masking. These design labels indicate the intended structure of the trial, but they do not provide a statistical analysis plan. The record does not report the method used to generate the random sequence, how allocation was concealed, which roles were masked, or how masking was assessed. These implementation details are not reported in the registry record.
What does randomization contribute?
In general, randomization assigns participants to groups using a chance-based process. Its purpose is to reduce systematic differences in prognostic factors between groups, so a later comparison can more credibly be attributed to assigned treatment. Randomization does not guarantee that groups will be balanced in a small study, and it cannot compensate for missing outcome information or an absent analysis. The record identifies randomized allocation but does not report the sequence-generation or allocation-concealment procedures.
What is the planned treatment contrast?
The active regimen combines WBT with amphetamine/dextroamphetamine. The comparator combines WBT with pill placebo. In general, comparing these groups addresses the added effect of the stimulant when both groups receive WBT, subject to adherence, co-interventions, outcome measurement, and other features of conduct. It is not a comparison of WBT against no therapy. The record does not report adherence, treatment exposure, or deviations from assigned treatment.
How should the primary outcome be understood?
The primary outcome title refers to change in a 17-item Hamilton depression rating scale, while its description defines the comparison as the percentage in remission at the endpoint. The remission criterion is a HAM-D-17 score < 8 at visit 11/week 8 of treatment or at an early termination visit. In general, a binary endpoint classifies each assessed participant according to whether the criterion is met. A comparison of group percentages would then summarize the difference in the prevalence of that endpoint status. The registry does not provide those percentages or specify a statistical model for comparing them.
Using a threshold has interpretive trade-offs. It can provide a clear operational definition of remission, but participants with scores close to the threshold can be classified differently despite similar scores. It also loses information about the amount of score change and the spread of scores within each group. The record does not report whether continuous score change was analyzed as a separate primary or secondary analysis.
What do uncertainty and significance measures normally add?
In general, an effect estimate gives the direction and size of a group contrast on a defined scale. A confidence interval communicates the uncertainty around that estimate under stated assumptions; a narrower interval indicates greater precision, while a wider interval indicates less precision. A p-value describes how unusual the observed data would be under a specified null model and analysis procedure. These measures answer different questions and should be interpreted alongside the design and outcome definition. None is reported for the primary comparison in the registry record, so the contrast and its precision cannot be assessed.
What does a small sample imply?
In general, small samples tend to provide limited information and can produce imprecise estimates. They can also make estimates sensitive to individual observations and make reliable adjustment for multiple prognostic factors difficult. This general point does not establish the direction or size of an effect in this study. The record itself states that the primary outcome population could not be analyzed due to small sample size. It does not report a sample-size justification, a power calculation, or the statistical assumptions behind the planned enrollment.
What is not specified about the analysis?
The registry does not report the primary analysis method, the test or model, covariate adjustment, the analysis population definition, handling of repeated measurements, or a plan for missing outcomes. It also does not report an interim-analysis plan or rules for early stopping. These omissions mean that readers cannot reconstruct a prespecified analysis or judge whether any analysis followed a plan. In general, a prespecified analysis helps reduce the risk that choices made after seeing results influence conclusions; whether such a plan existed is not reported in the registry record.
The record's statement that the primary population could not be analyzed should be kept distinct from an estimated null result. It indicates that the registry does not provide an analyzable primary comparison. It does not provide a basis for calculating a treatment effect, an uncertainty interval, or observed power. Any sample-size illustration based on an observed effect would not be an observed trial result, and no such observed primary effect is reported in the record.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists primary and secondary outcome domains, with 7 outcome measures reported. It also reports 0 analyses. The record does not describe a multiplicity strategy, such as a hierarchy of outcomes, an adjustment to control the chance of false-positive findings across comparisons, or a designation of confirmatory versus exploratory analyses. Such a plan is not reported in the registry record.
In general, examining many outcomes or contrasts can increase the chance that at least one result appears noteworthy by chance. Multiplicity methods address that issue by defining how evidence is evaluated across a family of analyses. Without a stated plan and reported analyses, readers cannot determine whether multiplicity was considered or how any secondary finding should be interpreted. The listed secondary outcomes are changes in psychological well-being, pleasure, behavioral inhibition and activation, positive and negative affect, and functioning; their listing alone is not evidence of analyzed results.
The record says the primary outcome population was not able to be analyzed due to small sample size. It does not report missing-outcome counts, reasons for missingness, participant flow, or methods for handling missing data. The endpoint description allows assessment at an early termination visit, but does not explain how unavailable endpoint assessments were treated. In general, missing-data methods rely on assumptions about why measurements are missing; those assumptions and methods cannot be evaluated when they are not reported.
The analysis population is not described beyond the note that the primary population could not be analyzed. The record does not state whether the intended analysis was based on randomized assignment, treatment received, or another population definition. It does not report an intention-to-treat analysis or a per-protocol analysis. No conclusion about the handling of deviations from assigned treatment or the completeness of follow-up is supported by the registry record.
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 |
|---|---|---|---|
| Well-being Therapy With Amphetamine/Dextroamphetamine | 0 | 2 | 0.0% |
| Well-being Therapy With Placebo | 0 | 2 | 0.0% |
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 |
|---|---|
| Well-being Therapy With Amphetamine/Dextroamphetamine | 1 of 2 |
| Well-being Therapy With Placebo | 0 of 2 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Well-being Therapy With Amphetamine/Dextroamphetamine | Well-being Therapy With Placebo |
|---|---|---|---|
| Insomnia and Headache | Psychiatric disorders | 1 of 2 | 0 of 2 |
The adverse-event record reports serious adverse events affecting 0 participants in the WBT with amphetamine/dextroamphetamine group and 0 participants in the WBT with placebo group. The at-risk figures recorded for serious events are 2 in each group. The record lists no serious-event terms. Deaths are not reported in the registry record.
For other adverse events, the record reports 1 affected participant in the WBT with amphetamine/dextroamphetamine group and 0 in the WBT with placebo group. The at-risk figures recorded for other events are 2 in each group. These are the safety counts as recorded; they are not a basis for calculating comparative rates or drawing a reliable group-level safety conclusion.
In general, safety counts need to be interpreted with attention to the number and duration of participants observed, how events were defined and collected, and whether figures refer to participants or events. The registry does not report additional detail about event definitions, observation time, severity of the other event, or the relationship of that event to treatment. Enrollment is reported as 5, while the adverse-event at-risk figures are recorded separately by group; the record does not explain the relationship between these entries. The small study record and limited reported safety information do not establish that harms were absent.
12. What the Result Does, and Does Not, Mean
The registry documents a randomized, triple-masked study intended to compare WBT with amphetamine/dextroamphetamine against WBT with pill placebo for residual symptoms of major depressive disorder. The primary outcome description defines remission using a HAM-D-17 score < 8 at the endpoint visit or an early termination visit. The record reports enrollment of 5 and states that the primary outcome population could not be analyzed due to small sample size.
What the record does show is the intended design, intervention contrast, endpoint definition, listed outcome domains, study status, and a limited set of adverse-event counts. It does not show an analyzed estimate of the primary comparison. No remission percentages, treatment-effect estimate, confidence interval, or p-value are reported. The registry record therefore cannot establish whether the groups differed, how large any difference might have been, or how precisely it could be estimated.
What the record does not show is equally important. It does not establish that the treatments are equivalent, that neither group changed, or that the intervention had no effect. A missing or unanalyzable result is not evidence for a zero effect. The study's terminated status does not explain why it ended, and cannot by itself be used to infer an outcome or a safety concern.
The registry's planned enrollment of 40 and reported enrollment of 5 should be understood as distinct design and enrollment information, not as evidence about outcomes. No reason for the termination or the reported enrollment is given. The record also does not provide enough detail to assess missing data, participant flow, adherence, analysis populations, or the statistical methods that would have been used.
In general, a randomized comparison can support causal interpretation when allocation, follow-up, outcome assessment, and analysis are conducted and reported appropriately. Those general properties do not create evidence where an outcome analysis is unavailable. The cautious interpretation is that this record describes a planned clinical comparison but does not provide an analyzable efficacy result, and its safety counts are too limited to support broad safety conclusions.
13. Why This Trial Matters Statistically
This trial is statistically notable because its registry record separates a clearly described intended comparison from the absence of an analyzable primary outcome. The planned design randomized participants to WBT with amphetamine/dextroamphetamine or WBT with pill placebo, and defined remission using a HAM-D-17 threshold. Yet the record reports enrollment of 5, compared with a planned enrollment of 40 in the study summary, and states that the primary outcome could not be analyzed due to small sample size.
That distinction matters for evidence synthesis. A study can have a relevant question and a specified endpoint without contributing an effect estimate that can be compared or combined with estimates from other studies. Without group-specific outcome data and an uncertainty measure, the direction, magnitude, and precision of the contrast are unknown. Treating the absence of a result as a null result would confuse non-estimation with evidence of no difference.
The record also illustrates why the endpoint definition and endpoint result should be read separately. The title describes change in a depression rating scale, while the endpoint description specifies a comparison of remission percentages at the endpoint. Those are related but not interchangeable summaries. A threshold-based endpoint can answer a focused classification question, whereas continuous score change retains information about differences across the scale.
Finally, the safety record illustrates the limits of interpreting small counts without context about observation and event ascertainment. The reported adverse-event figures can be stated as recorded, but they do not substitute for a complete safety analysis. Overall, the statistical importance lies not in an effect claim, but in recognizing what the registry does and does not permit readers to estimate.
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 the lack of an analyzable primary outcome. The record explicitly says that the primary population could not be analyzed due to small sample size, and it reports no remission results or treatment-effect estimate. As a result, the intended randomized comparison cannot be quantitatively interpreted from this registry information.
The record reports enrollment of 5, whereas the study summary describes a plan to randomize 40 individuals. It does not explain this difference, give participant flow, show group allocation counts for the primary endpoint, or identify reasons for termination. The status is terminated, but the reason and timing of termination relative to recruitment and outcome collection are not reported in the registry record.
Methods needed to assess bias and precision are also not reported. The registry does not provide a statistical analysis plan, the method of random sequence generation, allocation concealment, the roles masked under triple masking, analysis-population definitions, or handling of treatment deviations. It does not report missing-data amounts or methods, an interim-analysis plan, or a sample-size justification.
The primary outcome title refers to change in a rating scale, while the description defines a remission-percentage comparison. The record does not clarify whether continuous change was also intended as an analysis or how any outcome hierarchy was specified. Although secondary outcome domains are listed, results for them are not reported. Multiplicity handling is also not reported.
Safety information is limited to the recorded adverse-event counts. Deaths are not reported, and the record does not provide event descriptions or sufficient context to assess exposure and ascertainment. These reporting gaps limit interpretation of both efficacy and safety. They do not establish that outcomes were absent or that no events occurred beyond those recorded.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Stimulant Enhancement of Well-Being Therapy for Depression — NCT01478113.
- Registry record last updated 2017-04-26; status last verified 2017-03.
- Results first posted 2017-04-26.
- 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
NCT01478113 is a randomized, triple-masked, parallel-group study sponsored by Massachusetts General Hospital. It concerns major depressive disorder and compares well-being therapy with amphetamine/dextroamphetamine against well-being therapy with pill placebo. The phase is listed as NA. The registry reports a start date of 2012-02, primary completion of 2014-07, terminated status, and enrollment of 5. The brief study description states that 40 individuals were planned for 8 weeks of treatment.
The primary outcome is titled as change in the Hamilton-Depression Rating Scale (SIGH-D)-17 Items. Its description defines a comparison of the percentage in remission, with remission specified as a HAM-D-17 score < 8 at visit 11/week 8 or an early termination visit. The record says the primary outcome population could not be analyzed due to small sample size. It reports 7 outcome measures and 0 analyses, and does not provide primary outcome estimates or a statistical analysis plan.
Adverse-event entries report serious events affecting 0 participants in each group, other events affecting 1 participant in the stimulant group and 0 in the placebo group, and deaths not reported. These limited figures do not provide a complete comparative safety assessment.