Treatment to Enhance Cognition in Bipolar Disorder: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Treatment to Enhance Cognition in Bipolar Disorder (NCT01470781), a randomized na study. The primary outcome is MATRICS Consensus Cognitive Battery (MCCB).

2. Clinical Question

In statistical terms, the central question is whether cognitive scores changed differently across the scheduled assessments for participants assigned to cognitive remediation and participants assigned to computer control. The record describes several assessment occasions, but does not designate one time point or one contrast as the sole primary comparison. A result for a single occasion would not by itself answer every question about change over time, while a broad claim across occasions would require an analysis that accounts for the multiple measurements. The statistical analysis plan is not reported in the registry record, so the exact intended contrast cannot be identified.

3. Trial Design

The registry identifies a randomized, triple-masked, parallel-group study. The two groups were Cognitive Remediation and Computer Control. Parallel-group means that participants were assigned to one of the groups and followed in that assignment, rather than being described as receiving both conditions in sequence. The record does not describe the randomization procedure, the people or roles covered by triple masking, or how masking was maintained; these details are not reported in the registry record.

The enrollment is listed as 72. The cognitive remediation arm was described as computer-based treatment 3 times per week for 24 weeks, with a total of 70 hours. The control arm was described as 70 hours of computer time playing pre-selected games in a similar format. These descriptions identify the intended activities but do not report adherence, attendance, treatment fidelity, or the amount of treatment actually received by participants.

The primary outcome schedule included an assessment within 1 week prior to initiating intervention, a midpoint on average 8 weeks after initiation, a post-treatment assessment on average 24 weeks after initiation, and an assessment after 6 months with no active intervention. These are described as timing points, not as observed participant-level follow-up times. The record lists the study status as completed, with a start date of 2011-06 and primary completion date of 2016-08-01. The phase is recorded as NA. Details of the recruitment process, allocation concealment, protocol deviations, and reasons for the study’s duration are not reported in the registry record.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

Analysis population for the primary outcome, as defined in the registry: 84 participants signed consent and met eligibility criteria; however, 12 discontinued prior to completion of the baseline assessment and therefore were not randomized and no data were available; therefore only randomized participants who completed at least one assessment were able to be included in the analyses.

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.

6. Primary Endpoint

The registry lists the primary outcome as MATRICS Consensus Cognitive Battery (MCCB), measured over within 1 week prior to initiating intervention; midpoint - on average 8 weeks after initiation; post-treatment - on average 24 weeks after initiation; after 6 months no active intervention.

The primary outcome was the MATRICS Consensus Cognitive Battery (MCCB), with results expressed as T-scores. The battery is described as including 10 tasks designed to assess seven cognitive domains: processing speed, attention, working memory, verbal learning, visual learning, problem solving, and social cognition. Subtest and domain scores are combined to yield a cognitive Composite. Higher standardized scores indicate better performance. The registry description states that scores are normed by age and sex and generated using the MCCB scoring software.

A standardized cognitive measure can help researchers assess performance across distinct areas using a common score scale. In general, the composite can provide an overall summary, while domain scores can show whether patterns differ across aspects of cognition. Those summaries answer different questions: a composite may obscure a domain-specific pattern, while examining many domains creates multiple opportunities for comparisons. The record does not identify a single MCCB domain or assessment occasion as the one primary comparison.

The planned assessment schedule spans the period before intervention, during treatment, after treatment, and after a period with no active intervention. That schedule could describe both change during treatment and whether scores are observed again after treatment ends. The registry record does not report any MCCB means, standard deviations, confidence intervals, or comparisons between the groups. It therefore does not establish the size, direction, or precision of any cognitive outcome difference.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The trial is described as randomized, triple-masked, and parallel-group. In general, random assignment is used to make treatment groups comparable on average, including on factors that may not have been measured. It does not guarantee identical groups, particularly in a finite study. The record does not describe the sequence-generation method, allocation concealment, or the details of masking, so those aspects of the implementation cannot be evaluated from the registry entry. The word triple-masked is recorded, but the masked roles are not identified.

What does a continuous outcome mean?

The primary outcome is a continuous measure reported as a mean and standard deviation. In general, a continuous outcome can take a range of values, rather than representing a count of events or a binary status. A group mean describes the central level of the scores; the standard deviation describes how spread out individual scores are around that mean. Neither quantity alone describes the uncertainty in a comparison between groups. That uncertainty depends on the data and the analysis, and is commonly conveyed with a confidence interval.

The MCCB uses standardized T-scores. The registry description says the scores have a mean of 50 and a standard deviation of 10 in the normative scale, and that higher scores reflect better performance. These are properties of the standardized scoring scale, not study results. A study’s observed group mean or the difference between group means could not be inferred from those scale characteristics. No observed MCCB summaries are reported in the registry record.

How should repeated assessments be understood?

Repeated measurements are observations on the same participants at different occasions. In general, scores from one participant may be related to one another, so analyses should account for that within-participant dependence rather than treating each assessment as an unrelated observation. A longitudinal analysis can address change over time and differences in change between groups, but the particular model or method used for this trial is not reported in the registry record.

The listed timing includes an assessment within 1 week prior to initiating intervention, a midpoint on average 8 weeks after initiation, a post-treatment assessment on average 24 weeks after initiation, and an assessment after 6 months no active intervention. Because those timings span different stages, a result at one stage should not automatically be generalized to another. The record does not specify how the assessments were combined into a primary contrast, whether all scheduled time points were analyzed together, or how departures from the planned assessment schedule were treated.

What do confidence intervals and significance tests convey?

In general, a confidence interval describes the range of estimates reasonably compatible with the observed data under the statistical method used. A narrow interval indicates greater precision than a wide interval, but does not by itself establish that an effect is clinically important. A significance test addresses compatibility with a specified null hypothesis under its assumptions; a p-value is not the probability that the null hypothesis is true. Interpreting either requires the estimate, its uncertainty, the analysis approach, and the context of the outcome.

No confidence interval, p-value, or effect estimate for the primary outcome is reported in the registry record. The listed sample-size assumptions describe a planning illustration based on a stated fraction of an observed effect, using a two-sided significance level of 0.05, equal allocation, and a normal approximation. These assumptions describe an illustrative calculation, not the trial’s own design justification. The registry record does not report the trial’s sample-size justification, the observed effect used in that illustration, or numerical planning results. Such planning quantities are not observed power and do not establish the precision of the trial’s actual result.

Why can variation matter?

In general, the standard deviation reflects variation among participants. Greater variability can make an estimated group difference less precise if other aspects of the study remain the same. Some outcomes may also show over-dispersion, meaning that observed variability exceeds what a simple model assumes. Over-dispersion matters because a model that understates variability can produce overly narrow uncertainty intervals or misleading test results. The primary outcome is described as continuous and summarized by means and standard deviations; the registry record does not report a model, a variance assessment, or an over-dispersion evaluation.

For continuous outcomes, assumptions can concern the distribution of scores, the form of the group comparison, and the handling of repeated observations. In general, model diagnostics and sensitivity analyses help assess whether conclusions depend on these assumptions. The registry record does not report these methods. Consequently, it is not possible to evaluate whether the analyses used an appropriate model or whether alternative analytical choices would change the result.

What can be inferred from the design information?

The randomized parallel-group design identifies the intended structure of the comparison, and the active computer control gives context for the intervention contrast. The design description alone does not provide evidence about the magnitude or direction of an outcome difference. A complete statistical interpretation would require the outcome estimates, their uncertainty, the analysis population, and the prespecified analysis approach. Those efficacy details are not reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The registry describes a primary cognitive measure with a Composite and scores for multiple cognitive domains and tasks, assessed at several time points. It also lists secondary outcomes: Young Mania Rating Scale (YMRS), Montgomery-Asberg Depression Rating Scale (MADRS), Positive and Negative Syndrome Scale (PANSS), Multnomah Community Ability Scale (MCAS), and Social and Occupational Functioning Assessment Scale. Looking at multiple outcomes or time points raises a multiplicity issue. In general, if many statistical tests are performed, the chance of at least one apparently notable result can increase unless the analysis accounts for the testing strategy. The registry record does not report a multiplicity adjustment, a hierarchy of outcomes, or which contrasts were prespecified.

The record indicates that 84 participants signed consent and met eligibility criteria, while 12 discontinued before completing the baseline assessment and were not randomized, with no data available. Enrollment is listed as 72. The primary-outcome population description says that only randomized participants who completed at least one assessment were able to be included, but the record does not provide enough information to identify the final analysis population or the number contributing data at each time point.

Missing-data handling is not reported in the registry record. In general, missing follow-up measurements can affect an estimate if the chance of missingness is related to participant characteristics or outcomes. Analyses may use different assumptions and methods to address incomplete follow-up; those choices should be stated because they influence interpretation. The record does not say whether participants were analyzed according to randomized assignment, how partial records were handled, or whether sensitivity analyses were conducted. The analysis plan and interim-analysis procedures are also not reported in the registry record.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

The registry lists the Cognitive Remediation group with 39 participants at risk for serious adverse events and 39 at risk for other adverse events. It reports zero participants affected in each category and zero deaths. The Computer Control group has 33 participants at risk for serious adverse events and 33 at risk for other adverse events, with zero affected in each category and zero deaths. No top serious adverse-event terms are listed.

These entries describe the recorded counts, not a full account of every event or a statistical comparison of safety between groups. Zero recorded events does not establish that no symptoms or problems occurred, and the figures do not quantify the uncertainty around the event frequency. The registry record does not report event definitions, collection procedures, follow-up completeness, or any detailed adverse-event narrative. The participant counts listed as at risk are safety-group counts and should not be assumed to describe the number contributing to every efficacy assessment.

In general, safety counts are interpreted in relation to the participants monitored, the duration of monitoring, the event definitions, and the completeness of reporting. The posted figures can be read as no serious or other adverse events and no deaths recorded in these group summaries. They do not establish that the intervention and control had equivalent safety, nor do they answer the primary cognitive question.

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

This trial’s registry record describes a randomized comparison of computer-based cognitive remediation and an active computer-game control in people with bipolar disorder. The primary cognitive measure was the MCCB, with standardized T-scores and assessments scheduled before, during, and after the intervention period, including a follow-up after 6 months without active intervention. These details clarify what the study set out to measure and how its two conditions were intended to differ.

The record does not report the MCCB outcomes or a group comparison. It therefore does not establish whether scores changed, whether any change differed between groups, how large a difference might have been, or how precise an estimate would be. It also does not report results for the listed secondary measures. The absence of these results from the registry entry should not be read as a null finding or as proof of benefit; neither conclusion is supported by the posted information.

Even if results were available, interpretation would depend on the specific estimate and its uncertainty, the selected outcome and time point, the analysis population, and the approach to repeated measures and multiple comparisons. A statistically detectable difference would not by itself indicate whether the size of a difference matters in practice. Likewise, a non-significant result would not prove that the groups were identical. Those distinctions are general statistical principles; the registry record does not contain the estimates needed to apply them to this trial.

The safety record lists no serious adverse events, other adverse events, or deaths in either group. Those counts are useful descriptive information but do not demonstrate equivalence between groups or establish that no unrecorded events occurred. The most defensible reading is therefore limited: the registry describes the planned comparison and reports these safety counts, but it does not provide the outcome evidence needed to judge the cognitive contrast.

13. Why This Trial Matters Statistically

Statistically, the study is notable for pairing a cognitive remediation program with an active computer-based control rather than describing a comparison with no computer activity. In general, an active control can help distinguish effects associated with the specific remediation program from effects associated with time spent using a computer or taking part in a structured activity. The registry description supports the existence of that intended contrast, but not a claim about what the contrast produced.

The MCCB is described as covering several cognitive domains and generating a Composite score. That structure creates an important measurement question: broad overall performance and specific cognitive skills may not tell the same story. Repeated assessments extend that question across the intervention and follow-up schedule. For researchers, the choice of primary score, time point, and treatment contrast matters because multiple plausible analyses can address different scientific questions.

The trial also illustrates why a design description and a results record should be distinguished. Randomization and masking describe how a comparison was intended to be conducted; they do not supply an effect estimate or show that bias was prevented in practice. Likewise, a completed status does not itself mean that outcome results are available in the registry. Here, the registry reports design and safety information but not the primary cognitive comparison.

For clinical researchers and biostatisticians, the missing outcome estimates, uncertainty measures, analysis population, and multiplicity and missing-data methods are central to judging evidence. Their absence prevents assessment of both the size and precision of any treatment contrast. This is a statistical reporting limitation, not a basis for inferring what the unreported findings would have been.

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 principal limitation of the available registry information is the absence of primary and secondary outcome results. The record names the MCCB and gives its assessment schedule, but reports no group summaries, effect estimates, confidence intervals, or significance tests. As a result, the direction, magnitude, and precision of the cognitive comparison cannot be evaluated. The listed secondary outcomes likewise have no results reported in the registry record.

The statistical analysis plan is not reported in the registry record. In particular, the record does not identify the primary time-point contrast, the model for repeated assessments, the multiplicity strategy, handling of missing observations, or whether analyses followed randomized assignment. It does not describe the sample-size justification, any interim analyses, or methods for checking model assumptions. These omissions limit assessment of how the planned scientific question was translated into an analysis.

The participant information also leaves uncertainty about the efficacy analysis population and follow-up completeness. The outcome description states that 84 participants signed consent and met eligibility criteria and that 12 discontinued before baseline and were not randomized. Enrollment is listed as 72, but the numbers contributing to each outcome assessment and the reasons for missing follow-up measurements are not reported in the registry record. The description that randomized participants with at least one assessment could be included does not by itself identify the final analysis set.

Finally, the safety summary provides event counts but not detailed definitions, monitoring procedures, or event narratives. The record also does not give enough information to assess implementation of masking or adherence to the planned treatment hours. These limitations concern what can be learned from the registry record; they should not be converted into assumptions about unreported trial conduct or findings.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Treatment to Enhance Cognition in Bipolar Disorder — NCT01470781.
• Registry record last updated 2026-04-03; status last verified 2021-08.
• Results first posted 2020-02-26.
• 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.

18. Record Summary

The registry record identifies NCT01470781 as a completed, randomized, triple-masked, parallel-group study of cognitive remediation for bipolar disorder. It lists enrollment of 72 and compares BrainWorks cognitive remediation with a computer-game control. The primary outcome is the MCCB, expressed as standardized T-scores, with assessments planned before intervention, during treatment, after treatment, and after 6 months without active intervention.

The record describes the outcome measure and names several secondary measures, but does not report efficacy results, the statistical analysis plan, or the final analysis population. It reports zero serious adverse events, zero other adverse events, and zero deaths in both groups. These details describe the trial’s registered design and posted safety counts; they do not provide a quantitative estimate of the primary cognitive comparison.