Software Treatment for Actively Reducing Severity of ADHD as Adjunctive Treatment to Stimulant: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Software Treatment for Actively Reducing Severity of ADHD as Adjunctive Treatment to Stimulant (NCT03649074), a na na study. The primary outcome is Impairment Rating Scale, Overall Impairment (Change From Baseline to Posttreatment) in Cohort 1: Stimulant.

2. Clinical Question

In statistical terms, the primary question is descriptive: what change was recorded among participants meeting the stated analysis-population conditions? Without a randomized comparator, a change from baseline cannot by itself separate a treatment-associated change from other influences, such as time, expectations, or changes in circumstances. The record’s stated purpose also includes understanding outcomes in participants not recently on medication, but that is distinct from the primary outcome specified for the stimulant cohort.

3. Trial Design

The registry describes a completed, single-group study of AKL-T01, a device intervention for Attention Deficit Hyperactivity Disorder. Enrollment is listed as 206. The study start is recorded as 2018-12-28 and primary completion as 2019-09-23. The sponsor is Akili Interactive Labs, Inc. The phase and allocation are recorded as NA, and masking is listed as none.

The study summary describes two aims: assessing AKL-T01 with AKL-X01 symptom tracking as an adjunct to stimulant medication, and understanding AKL-T01 treatment with symptom tracking among participants not recently on medication. The outcome descriptions distinguish Cohort 1: Stimulant and Cohort 2: Non-Stimulant. The intervention arm descriptions identify AKL-T01 as a digital treatment. The existence of cohorts does not make this a randomized comparison. The registry explicitly characterizes the study as single-group and flags that its arms are not a like-for-like control comparison.

The primary outcome is the change in the parent-rated IRS Overall Impairment score from Day 0 to Day 28 in Cohort 1: Stimulant. Other registered outcomes include ADHD-RS Total change, CGI-I at posttreatment, and change in the TOVA Attention Composite Score, with cohort-specific entries. The registry lists 8 outcome measures, but the number of posted analyses is 0. This means the record identifies outcomes without providing an analysis result for them.

The record does not report a randomized allocation method, a masking procedure beyond listing none, or a separate control arm. It also does not report a detailed statistical analysis plan, sample-size justification, or interim-analysis plan. The stated planning illustration assumptions describe a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, but these are not a description of the trial’s single-group design. They are not evidence that the trial was designed or analyzed using those assumptions.

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

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Participants in the ITT (all participants who received a device) for whom both Day 0 and Day 28 data was able to be collected in full. For the IRS, this population included all participants for whom the eighth item of the questionnaire was completed. In the Stimulant cohort, two participants had the eighth item incomplete.

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.

Population: All participants who were enrolled in both the Stimulant (n=130) and No Stimulant (n=76) cohorts.

6. Primary Endpoint

The registry lists the primary outcome as Impairment Rating Scale, Overall Impairment (Change From Baseline to Posttreatment) in Cohort 1: Stimulant, measured over Day 0 to Day 28.

The primary endpoint is the change from baseline to posttreatment in the IRS Overall Impairment score for Cohort 1: Stimulant, assessed from Day 0 to Day 28. The IRS is described as a parent-rated measure of individualized areas of difficulty and the degree to which those difficulties affect a child’s functioning across social, family, school, and self-esteem domains. Parents identify primary areas of difficulty and rate their impact on a Visual Analog Scale.

The IRS contains 8 items. The eighth item is the overall impairment rating, the specific item used for this primary endpoint. Its scale runs from 1, described as no problem and not needing treatment or special services, to 7, described as an extreme problem and definitely needing treatment or special services. The registry defines a negative change as a decrease in overall impairment.

This endpoint is used to capture a parent’s overall appraisal of the impact of the child’s difficulties, rather than relying only on a task-based measure or a symptom total. It may therefore provide information about perceived functioning across several domains. As a rating, it remains dependent on the parent’s observations and judgments. The registry record does not report the observed baseline and posttreatment values, the mean change, or its standard deviation. It also does not report a confidence interval or inferential test for this outcome, so the magnitude and precision of any change cannot be assessed.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is continuous: it is a score on a scale, and the planned summary is a mean with a standard deviation. The registry does not report the observed mean change or standard deviation for the primary endpoint. It also lists 0 analyses. Consequently, the statistical methods that can be described from the record are limited to the outcome definition, the stated analysis-population condition, and the general meaning of the statistics named in the endpoint description.

What does a mean change represent? In general, a change score is formed by comparing a participant’s follow-up value with that participant’s baseline value. The mean change summarizes those individual changes across the participants included in the analysis. Here, the outcome is defined from Day 0 to Day 28, and negative change is defined as a decrease in overall impairment. The registry does not state the numerical mean change. Nor does it report the baseline and follow-up summaries needed to examine the distribution of scores separately.

What does the standard deviation describe? In general, a standard deviation describes how much individual observations vary around the mean. For a change outcome, it describes the spread of participant-level changes, not the precision of the estimated mean itself. A larger spread can occur even when the average change is well defined, and a small spread does not by itself establish that the average change is estimated precisely. The registry names standard deviation as the dispersion measure but does not report its value for the primary outcome.

How does an uncertainty interval help? In general, a confidence interval presents a range of estimates compatible with the observed data under the analysis assumptions. Its width reflects statistical precision: a narrower interval indicates greater precision than a wider interval, while neither width nor location alone establishes the importance of an effect. The registry does not report a confidence interval for the primary outcome. A p-value is also not reported. General interpretation of a p-value concerns how compatible the data are with a specified null model, under its assumptions; it does not measure the probability that a treatment works, and it does not describe the size of an effect.

Why does the design matter? The registry classifies the study as single-group, with no masking. In general, a within-participant comparison can describe how scores changed over time, but a before-and-after change is not a randomized estimate of what would have happened without the intervention. Time trends, expectations, measurement conditions, and other changes can contribute to the observed pattern. A randomized comparison can help distinguish those influences when it is appropriately designed and analyzed. The registry does not describe such a comparison for this study. The stimulant and no-stimulant cohorts do not serve as randomized controls; the record specifically cautions that they are not like-for-like comparison groups.

What does the stated planning method mean? General sample-size planning often uses assumptions about a target effect, variability, significance level, allocation, and statistical approximation. The record’s planning assumptions name a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. Those assumptions describe a planning illustration, not the recorded single-group design. Any planning illustration based on an observed effect is a scenario for future planning, not observed power and not evidence that the study had a particular chance of detecting an effect. The registry does not report the trial’s own sample-size justification or a statistical plan showing that these assumptions governed the study.

Why can over-dispersion matter? General explanation: for count outcomes, over-dispersion means that the observed variation is greater than a simple model assumes. If ignored, uncertainty can be understated and inferential conclusions can be too confident. The primary endpoint is a continuous score, not a count outcome, so over-dispersion is not identified as a concern for this endpoint in the registry record. The record does not describe the distributional checks or model diagnostics used for any outcome.

What is known about analysis populations? The primary outcome description says that the analysis population included participants in the ITT population who received a device and had complete Day 0 and Day 28 data. For the IRS, it further specifies completion of the eighth questionnaire item. In general, restricting an analysis to complete records can affect representativeness if missingness is related to outcomes or participant characteristics. The record does not report the number included in the primary analysis, reasons for missing data, or a method for handling missing observations. Its description of the population is truncated, so additional detail is not reported in the registry record.

What should be inferred from no posted analysis? The registry record lists 0 analyses. This does not mean the study collected no data or that a particular analysis was not conducted outside the record. It means that no analysis result is available in the registry entry for statistical interpretation. Without estimates and uncertainty measures, readers cannot assess effect magnitude, precision, or compatibility with a null value. General statistical methods can clarify how such measures would be read, but they cannot replace the unreported trial results.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("AKL-T01 - Stimulant Cohort")
n   <- c(128)
m   <- c(-0.7)
sp  <- c(1.04)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  AKL-T01 - Stimulant Cohort  128  -0.700  1.040  -0.882  -0.518

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 8 outcome measures, including cohort-specific measures of ADHD-RS Total change, CGI-I at posttreatment, and TOVA Attention Composite Score change, alongside the primary IRS outcome. Multiple outcomes create a multiplicity issue when several hypotheses are tested: the more analyses used to make confirmatory claims, the greater the chance of at least one apparently notable result arising by chance. The registry record does not report a multiplicity adjustment, a hierarchy of confirmatory outcomes, or a statistical plan defining which analyses were primary beyond the identified primary outcome. It also lists 0 analyses, so there are no posted results to evaluate for selective reporting or multiplicity handling.

The primary outcome description defines an analysis population that includes participants who received a device and had complete Day 0 and Day 28 data. For the IRS, completion of the eighth item is required. The description says this population is within the ITT population, but the registry does not report how many participants contributed to the primary endpoint. Its description ends mid-sentence after noting two participants, and the remaining detail is not reported in the registry record.

In general, complete-case analysis can be biased if the likelihood of having complete data is related to the outcome or to factors associated with it. The registry does not report the amount or pattern of missing primary-outcome data, reasons for missingness, imputation methods, sensitivity analyses, or comparisons of participants with and without complete records. It is therefore not possible to assess how missing outcomes may have affected the estimate.

The record does not report the statistical analysis plan, prespecified handling of protocol deviations, or a detailed definition of the analysis population beyond the stated conditions. These omissions limit assessment of whether the reported outcome analysis, if any, followed a prespecified approach. Since no analysis is posted, the record also does not allow evaluation of whether outcome-specific decisions were made after examining results.

12. 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.

Most frequent non-serious adverse event terms

The registry lists serious adverse events for the AKL-T01 stimulant cohort as 0 affected among 130 at risk, and for the AKL-T01 no-stimulant cohort as 0 affected among 76 at risk. Deaths are listed as 0 in both cohorts. The registry lists other adverse events affecting 22 among 130 at risk in the stimulant cohort and 15 among 76 at risk in the no-stimulant cohort. These are separate cohort entries and should be read as reported, without combining them into a new total.

Serious adverse events and other adverse events are distinct categories in the registry record. The serious-event entries do not mean that no other adverse events were recorded; the other-event entries are nonzero. Conversely, the other-event counts do not indicate how many events occurred, their severity, duration, or relationship to AKL-T01. The record does not provide serious-event terms in its listed top serious terms.

These counts are descriptive and do not establish that the intervention caused or prevented an event. The record does not report the adverse-event observation window, event-level details, or a randomized control group. Because the study is single-group and the cohorts are not a like-for-like comparison, the cohort entries cannot support a causal safety comparison. A zero count in the registry entry should be interpreted as no event recorded in that category for the listed group, not as proof that risk is absent.

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

The record identifies a clinical question about parent-rated overall impairment in the stimulant cohort and defines how to interpret the direction of the IRS score change. It does not report the primary outcome estimate, standard deviation, confidence interval, or test result. As a result, the posted registry information does not show how much the score changed, how variable individual changes were, or how precisely a mean change was estimated. It cannot support a conclusion about the direction or magnitude of the observed primary outcome.

The design is also important to what any change would mean. This was a single-group, unmasked study, not a randomized comparison. Even if a baseline-to-follow-up change had been reported, that change alone could not establish that AKL-T01 caused it. A concurrent control group can help account for changes that might occur over time or through other influences; no such randomized control is described in the registry. The stimulant and no-stimulant cohorts are not like-for-like controls, according to the record.

The registry lists other symptom and attention outcomes, but it does not post analyses for them. Their presence as registered outcomes is not evidence of an observed result. Likewise, the safety entries report event counts but do not establish whether events were caused by the intervention. The absence of reported serious events in the listed entries should not be read as proof that no safety risk exists.

In general, an outcome estimate is most informative when read alongside its uncertainty, the analysis population, missing-data handling, and the design that generated the comparison. Those elements are incomplete or absent in this record. The appropriate interpretation is therefore narrow: the registry describes what was intended to be measured and gives selected adverse-event counts, but it does not provide the primary statistical results needed to judge the amount or precision of change. It neither establishes benefit nor demonstrates lack of benefit.

14. Why This Trial Matters Statistically

This study is statistically noteworthy because it separates two medication contexts while asking a primary question within the stimulant cohort. That distinction matters: an outcome measured among participants receiving stimulant medication as an adjunctive setting does not answer the same question as an outcome in participants not recently on medication. The registry’s cohort labels reflect that context, but they do not create a randomized comparison between medication groups.

The primary endpoint also illustrates the difference between defining an outcome and reporting its result. The registry gives a clear description of the parent-rated IRS overall impairment item, its scale anchors, and the direction of change. Yet it does not provide the observed mean change or an uncertainty measure, and it lists 0 analyses. A well-described measure is useful for understanding the intended question, but without results readers cannot determine what the study found statistically.

More broadly, the design underscores why change from baseline is not automatically a treatment effect. A single-group before-and-after result, if reported, would describe temporal change among included participants. It would not isolate the intervention’s contribution from other possible influences. This is a general issue in interpreting uncontrolled studies, not a claim about what happened to participants in this trial.

The registry also illustrates why outcome populations and missingness matter. The primary outcome is limited to participants with complete measurements at both stated time points and completion of the IRS overall impairment item. Without the analysis count and missing-data details, readers cannot assess how much information contributed to the estimate or whether complete cases represent the enrolled population. The record’s limited analysis reporting therefore constrains both clinical interpretation and statistical appraisal.

15. 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 primary limitation for interpreting this study is that the registry record does not report the primary endpoint result. It identifies a mean change and standard deviation as the outcome summary but gives no observed values, confidence interval, or inferential test. The record lists 0 analyses. Consequently, neither effect magnitude nor precision can be evaluated from the posted registry information.

The single-group, unmasked design has no randomized control group. Any change from baseline, if it were reported, would not alone distinguish an intervention-associated change from time trends, expectations, or other concurrent influences. The registry explicitly cautions that the stimulant and no-stimulant cohorts are not a like-for-like control comparison. Between-cohort contrasts should therefore not be treated as randomized estimates.

The primary outcome population is described as participants who received a device and had complete Day 0 and Day 28 data, with the IRS eighth item completed. The description is truncated after mentioning two participants. The record does not report the number included in the endpoint analysis, reasons for missing data, or methods for handling incomplete observations. This makes it difficult to judge the representativeness of the analyzed population.

The registry lists 8 outcome measures but does not report a statistical analysis plan, a multiplicity approach, interim analyses, or the trial’s sample-size justification. The planning assumptions mentioned in the record are not evidence of the trial’s design or analysis plan. Finally, the adverse-event entries lack a reported observation window and detailed event descriptions. These limitations restrict interpretation of efficacy-related outcomes and safety reporting without establishing that any unreported result was favorable or unfavorable.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Software Treatment for Actively Reducing Severity of ADHD as Adjunctive Treatment to Stimulant — NCT03649074.
• Registry record last updated 2023-08-09; status last verified 2023-07.
• Results first posted 2023-08-09.
• 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.

19. Record Summary

NCT03649074 is a completed, single-group study of AKL-T01 digital treatment in participants with Attention Deficit Hyperactivity Disorder. Enrollment is listed as 206. The registry records the study start as 2018-12-28 and primary completion as 2019-09-23. Masking is listed as none.

The primary outcome is change in parent-rated IRS Overall Impairment from Day 0 to Day 28 in Cohort 1: Stimulant. A negative change is defined as a decrease in overall impairment. The registry does not report the numerical result, its standard deviation, or an inferential analysis, and lists 0 analyses. The stimulant and no-stimulant cohorts are not randomized, like-for-like controls.

Serious adverse events and deaths are listed as 0 in both cohorts; other adverse events are listed as affecting 22 in the stimulant cohort and 15 in the no-stimulant cohort. These descriptive entries do not establish causation. Missing-data methods, multiplicity handling, and a detailed statistical analysis plan are not reported in the registry record.