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 Lisdexamfetamine's Effect In ADHD in the Brain and Cognition (NCT02170298), a randomized phase 4 study. The primary outcome is Working Memory.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02170298 |
| Phase | Phase 4 |
| Condition | Attention Deficit Hyperactivity Disorder |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Quadruple |
| Enrollment | 6 |
| Arms in the primary outcome | n/a |
| Lead sponsor | University of California, Davis |
| Results posted | Yes |
2. Clinical Question
Population
Adolescents and young adults with attention-deficit/hyperactivity disorder (ADHD). The registry record lists ADHD as the condition and describes the study population in its title and summary. It does not report further eligibility details or a demographic profile for the enrolled participants.
Intervention
Lisdexamfetamine (LDX), given orally once daily and titrated up to 70 mg daily over the course of 9 weeks in the intervention arm. The registry summary also describes a newly added condition involving a single dose of LDX, but does not report results for that comparison.
Comparator
A placebo comparator. The arm description identifies the placebo as a sugar pill titrated up to 70 mg daily over the course of 9 weeks. The registry summary describes the study as placebo-controlled and randomized.
Primary question
Whether LDX is associated with changes in working-memory task performance, measured as the percent of items correct on the Span Working Memory Task. The planned assessment timeframe was baseline and 9 weeks. The registry states that this measure was not analyzed because of early termination and insufficient recruitment; it therefore does not report a treatment comparison for the primary outcome.
3. Trial Design
The registry identifies this as a randomized, parallel-group, Phase 4 study sponsored by the University of California, Davis. It lists quadruple masking. The brief summary describes a double-blind, placebo-controlled randomized trial and a repeated-measures, between-subject design. These descriptions do not fully align: the registry record does not explain the difference between the masking labels, so the exact masking arrangements cannot be resolved from the record.
The record describes oral, once-daily LDX and placebo titrated up to 70 mg daily over the course of 9 weeks. The primary outcome timeframe is baseline and 9 weeks. The summary also says a condition was added involving a within-subject crossover comparison of a single dose of LDX with a single dose of placebo. It does not clarify how that added condition related to the parallel-group design or whether it was implemented. No results for the crossover comparison are reported.
The registry lists an enrollment of 6 and a status of terminated. The start date is 2014-02 and the primary completion date is 2015-06. The stated reason for the absence of primary-outcome analysis is early termination and inability to recruit sufficient participants. The record does not report a detailed recruitment history or further explanation for termination.
The intended scientific focus was cognitive control and reward functioning, with neural and behavioral assessments. The summary names functional MRI (fMRI), a working-memory task, and a reward-delay discounting task. It also describes hypotheses about activity and connectivity in brain regions and networks. The registry record does not establish which assessments were completed or analyzed; the primary working-memory measure was explicitly not analyzed.
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 | Placebo | Lisdexamfetamine |
|---|---|---|
| STARTED | 1 | 5 |
| COMPLETED | 0 | 4 |
| NOT COMPLETED | 1 | 1 |
Reasons for not completing this period:
| Reason | Placebo | Lisdexamfetamine |
|---|---|---|
| Withdrawal by Subject | 0 | 1 |
| unblinded, rerandomized to intervention | 1 | 0 |
Analysis population for the primary outcome, as defined in the registry: Data were not analyzed due to early study termination. Unable to recruit a sufficient number of subjects. Data on this measure is highly variable and low subject numbers will not produce reliable or valid 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.
| Characteristic | Unit | Placebo | Lisdexamfetamine | Total |
|---|---|---|---|---|
| Participants analysed | 1 | 4 | 5 | |
| Age, Categorical: <=18 years | Participants | 0 | 2 | 2 |
| Age, Categorical: Between 18 and 65 years | Participants | 1 | 2 | 3 |
| Age, Categorical: >=65 years | Participants | 0 | 0 | 0 |
| Sex: Female, Male: Female | Participants | 1 | 3 | 4 |
| Sex: Female, Male: Male | Participants | 0 | 1 | 1 |
| Race and Ethnicity Not Collected | Participants | — | — | 0 |
6. Primary Endpoint
The registry lists the primary outcome as Working Memory, measured over Baseline, 9 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 working-memory performance, defined as the percent of items correct on the Span Working Memory Task. The planned measurement occasions were baseline and 9 weeks. This endpoint captures accuracy on a task intended to assess working memory, a component of cognitive control and self-control that is relevant to the study's stated scientific focus.
As a general statistical point, an endpoint needs a clear operational definition so that the outcome being compared is explicit. A task-based accuracy measure gives a direct, task-specific description of performance. It should not be interpreted as a complete measure of everyday functioning or of cognition broadly; the registry describes performance on this particular task.
The registry record says the outcome was not analyzed because the study terminated early, recruitment was insufficient, and the measure was considered highly variable. It further states that the low subject numbers would not produce reliable or valid data. Consequently, the record contains no observed primary-outcome estimate, treatment difference, uncertainty interval, or statistical test. The endpoint's definition and planned timeframe are reported, but the results needed to assess the treatment comparison are not.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The central interpretive point is that the registry does not report an analyzed result for the primary working-memory outcome. Although the trial was intended to compare LDX with placebo, the posted record says the Span Working Memory Task data were not analyzed. It gives no group-level performance values, effect estimate, confidence interval, or test result for that endpoint. A treatment effect cannot be estimated from the primary-outcome information in the record.
The record lists enrollment of 6 and says that insufficient recruitment contributed to the decision not to analyze the endpoint. It also describes the measure as highly variable and says low subject numbers would not produce reliable or valid data. These are the registry's stated reasons, not evidence of a particular direction or size of effect. The record does not report whether any observed task scores favored either arm.
The brief summary includes hypotheses about neural activity, connectivity, and task performance. Hypotheses describe expectations to be tested; they are not findings. The record lists no analyses, and it does not provide outcome results supporting or contradicting those hypotheses. No conclusion about LDX's effect on brain activity, reward response, working memory, or self-control can be drawn from the stated hypotheses alone.
The adverse-event entries are descriptive counts for the groups and at-risk populations listed in the record. They do not substitute for the missing efficacy analysis and, given the small reported at-risk counts, should not be treated as a precise estimate of safety. The registry lists no serious adverse events, other adverse events, or deaths in the recorded groups, but this does not establish that such events would be absent in a larger or differently observed population.
Overall, the posted results document an incomplete trial record rather than a comparative estimate of treatment effect. There is no basis in the registry record for interpreting a nonsignificant finding: no primary-outcome statistical test is reported. Likewise, absence of an analyzed outcome is not evidence that the treatments performed similarly. The study's status, recruitment limitation, and unanalysed primary endpoint determine how narrowly these results can be interpreted.
9. Statistical Methods Explained
The registry describes a randomized parallel-group study and gives a more detailed summary of intended repeated-measures assessments. Randomization is a method for assigning participants to treatment groups by chance; in general, it aims to make groups comparable with respect to measured and unmeasured characteristics. A parallel-group design compares participants assigned to different groups. Repeated measurements can assess change over time within participants as well as differences between groups. The record does not report the allocation procedure or a statistical analysis plan for the primary endpoint.
The record's design descriptions are not entirely consistent. Its metadata lists quadruple masking, while the study summary calls the trial double-blind. Masking is intended to limit the influence of knowledge about treatment assignment on participants, study staff, or outcome assessment. The registry does not clarify who was masked or how the two descriptions relate. The summary also mentions a crossover condition comparing a single dose of LDX with a single dose of placebo, whereas the registry classifies the study as parallel. The record does not explain the implementation or analysis of this added condition.
What was the primary measure?
The primary measure was the percent of items correct on the Span Working Memory Task, with baseline and 9 weeks specified as the assessment timeframe. In general, a repeated-measures analysis can compare change over time while accounting for the fact that measurements from the same participant are related. The registry does not report whether such an analysis was planned for this endpoint, what model would have been used, or how task scores would have been summarized.
The record explicitly says the primary measure was not analyzed. It attributes this to early termination, insufficient recruitment, and high variability in the measure, and states that low subject numbers would not produce reliable or valid data. As a result, there is no reported treatment-effect estimate to interpret. The registry lists zero analyses. It does not report an endpoint-specific model, standard error, confidence interval, or hypothesis-test result.
What analysis methods were described?
The summary says the investigators planned to test hypotheses about fMRI data using linear contrasts of voxel-wise maps of parameter estimates in univariate and connectivity analyses. In general, a linear contrast expresses a planned comparison among model estimates. Voxel-wise analyses assess signals at locations across brain images, while connectivity analyses concern relationships among activity in brain regions or networks. The record does not report results from these analyses, details of model specification, how multiplicity across locations or contrasts would be handled, or whether these analyses were completed.
The hypotheses concerned task-independent locus coeruleus activity; task-related activity in the locus coeruleus and cognitive control network; connectivity with that network; task performance and self-control; and activity in the locus coeruleus and ventral tegmental areas. These are aims and proposed comparisons, not reported findings. The registry does not give numerical estimates or uncertainty measures for them.
How should uncertainty be understood?
General explanation: a confidence interval describes a range of values compatible with an estimate under the assumptions of the analysis. Its width conveys precision; a wider interval indicates less precision. No confidence interval for the primary endpoint is reported in the registry record, so its precision cannot be assessed from an interval. The registry's statement that the task measure was highly variable and recruitment insufficient signals concerns about the reliability and validity of a result from the available data, but it does not quantify uncertainty.
General explanation: over-dispersion occurs when outcome variability is greater than a model assumes. When variability is high, an analysis may be less precise than expected under a simpler variance assumption. The registry describes the task data as highly variable, but it does not report a distribution, variance estimate, or model that would allow readers to assess over-dispersion or its consequences quantitatively.
The record includes assumptions for planning illustrations: a two-sided significance level of 0.05, equal allocation between arms, a normal approximation, and effects defined as stated fractions of an observed effect. These are described as planning assumptions, not as the trial's own design or observed power. No resulting planning values are reported in the registry record. Any planning illustration based on an observed effect would not replace the missing primary-outcome analysis or establish the precision of this terminated study.
10. Multiplicity, Missing Data and Analysis Populations
The registry record does not report a multiplicity strategy. The study summary names several neural hypotheses and refers to univariate and connectivity analyses of fMRI data, alongside behavioral measures. When an analysis includes multiple outcomes, contrasts, or brain locations, the chance of obtaining an apparently notable result can increase if no adjustment or prespecified hierarchy is used. This is a general statistical concern; the record does not say whether or how it was addressed.
Missing-data procedures are not reported in the registry record. The stated reason the primary measure was not analyzed is early termination and insufficient recruitment, along with concern that the measure was highly variable and the available subject numbers would not produce reliable or valid data. The record does not describe missingness by group, reasons for missing measurements at each time, or any method for handling unavailable observations. It is therefore not possible to assess whether missing data could have affected a treatment comparison.
The analysis populations are not reported in the registry record. It does not say whether analyses were intended to follow randomized assignment, include only participants who completed treatment, or use another population definition. Nor does it report protocol deviations, adherence, or how participants would have been handled in the proposed crossover condition.
Because the primary endpoint was not analyzed and no analysis results are listed, there is no reported multiplicity-adjusted or unadjusted primary-outcome inference to interpret. The registry also does not state an interim-analysis plan or sample-size justification. These omissions limit assessment of how the intended analyses would have controlled error rates, used available observations, or supported the planned comparisons.
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 |
|---|---|---|---|
| Placebo | 0 | 1 | 0.0% |
| Lisdexamfetamine | 0 | 4 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Placebo | 0 of 1 |
| Lisdexamfetamine | 0 of 4 |
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 |
|---|---|
| Placebo | 0 of 1 |
| Lisdexamfetamine | 0 of 4 |
The registry lists serious adverse events, other adverse events, and deaths by group. For placebo, the record lists 1 at risk, 0 affected by serious adverse events, 0 affected by other adverse events, and 0 deaths. For LDX, it lists 4 at risk, 0 affected by serious adverse events, 0 affected by other adverse events, and 0 deaths.
These are descriptive counts for the at-risk populations recorded in the registry. The entries indicate that no affected participants or deaths were recorded in these categories for these groups. They do not establish that the risk of an event is zero, and they are not a precise estimate of event frequency in a broader population. The registry record does not provide further detail about how events were collected, the duration of safety observation, or the completeness of reporting.
The small at-risk counts make the safety information especially limited. The figures should be read as a record of reported events during this study, not as evidence that rare or delayed events could be ruled out. They also do not address the unanalysed working-memory endpoint.
12. What the Result Does, and Does Not, Mean
The record documents a randomized, placebo-controlled study of LDX in adolescents and young adults with ADHD, intended to examine neural and behavioral aspects of cognitive control and reward response. It identifies working-memory task accuracy as the primary outcome and baseline and 9 weeks as the planned assessment timeframe. These details describe the research question and the planned measurement, not an observed treatment effect.
The primary outcome was not analyzed. The registry attributes this to early termination, insufficient recruitment, and concern about high variability and the reliability or validity of results with the available subject numbers. No comparative estimate, uncertainty interval, or statistical test is reported. Accordingly, the record does not show whether LDX changed working-memory performance relative to placebo, nor does it show that the groups had equivalent performance.
The hypotheses about fMRI activity, connectivity, reward processing, and self-control likewise remain hypotheses in the posted record. No corresponding results are reported. The registry's adverse-event entries record no affected participants in the listed categories among the stated at-risk groups, but those counts are too limited to establish the absence of risk outside the recorded study experience.
General statistical explanation: a study result is informative not only through its direction, but also through its precision and the methods used to produce it. Here, there is no primary-outcome estimate whose direction or precision can be assessed. The appropriate interpretation is therefore constrained to the study's design, stated aims, termination, and reported event counts. It would go beyond the registry record to claim either benefit or lack of benefit, or to draw a definitive safety conclusion.
13. Why This Trial Matters Statistically
This record illustrates the distinction between a clinical research question and an answer to that question. A trial can be randomized and have a clearly described primary endpoint, yet still fail to report an analyzable comparison. The registry identifies a working-memory measure and a planned assessment timeframe, but states that the data were not analyzed after early termination and insufficient recruitment.
That distinction matters for statistical interpretation. Without an effect estimate and its uncertainty, readers cannot judge the direction, magnitude, or precision of a treatment comparison. The absence of a reported test result should not be mistaken for a null result. A non-significant result would still require an analyzed comparison; no such primary-outcome result is reported.
The registry also demonstrates why design descriptions and analysis reporting are important. It identifies the trial as parallel and quadruple-masked, while the summary describes double-blinding, repeated measures, and an added crossover condition. The record does not reconcile these descriptions. It also outlines planned fMRI contrasts but gives no corresponding analysis results. These gaps limit the ability to reconstruct the intended analysis or evaluate how its outcomes would have been interpreted.
Finally, the event counts provide a useful example of the difference between observed counts and general conclusions about risk. Zero recorded events in the listed groups is a description of this study's record, not proof that an event cannot occur. The overall lesson is that design, measurement, recruitment, analysis, and uncertainty all shape what a clinical trial can support. In this case, the posted information is most informative about why the primary endpoint remains unanswered.
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 is that the primary working-memory outcome was not analyzed. The registry explicitly links this to early termination and insufficient recruitment, and describes the measure as highly variable. It states that the available subject numbers would not produce reliable or valid data. No group-level values or treatment-effect estimate are reported, so the planned efficacy comparison cannot be evaluated.
The registry lists enrollment of 6, but does not provide a participant flow account or clarify the relationship between enrollment and the at-risk counts in the adverse-event record. It does not report how many participants completed each assessment, whether measurements were missing, or why any individual observations might be unavailable. The effect of these unknowns cannot be assessed.
There are unresolved design-description differences. The registry classifies the study as a parallel-group, quadruple-masked trial, while the summary describes double-blinding and a repeated-measures, between-subject design, and mentions an added crossover condition. The record does not explain whether the added condition was implemented or how it related to the main design.
Statistical details are limited. The registry does not report a primary-outcome analysis plan, missing-data procedure, analysis population, multiplicity approach, or interim-analysis plan. It describes intended fMRI contrasts but does not report results or further model details. The safety counts are also limited by the small listed at-risk groups and lack of additional information about event ascertainment and observation. These limitations make the record insufficient for estimating comparative clinical or neural effects.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Lisdexamfetamine's Effect In ADHD in the Brain and Cognition — NCT02170298.
- Registry record last updated 2019-12-26; status last verified 2019-12.
- Results first posted 2019-12-26.
- 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
The registry record describes a randomized, placebo-controlled Phase 4 study of LDX in adolescents and young adults with ADHD, sponsored by the University of California, Davis. It lists a parallel model, quadruple masking, enrollment of 6, a start date of 2014-02, primary completion in 2015-06, and terminated status. The arm descriptions specify oral LDX or placebo titrated up to 70 mg daily over 9 weeks.
The primary endpoint was percent correct on the Span Working Memory Task, assessed at baseline and 9 weeks. The registry states that it was not analyzed because of early termination and insufficient recruitment, with concern about variability and the validity of results at the available subject numbers. The record lists no analyses. It reports zero serious adverse events, other adverse events, and deaths for the at-risk groups listed, but those counts are limited and descriptive.
The study summary also describes planned fMRI and behavioral hypotheses, and an added single-dose crossover condition. Results for these are not reported in the registry record.