Digital Therapeutic Development of Virtual Cognitive-Affective Training for Opioid Use Disorder: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Digital Therapeutic Development of Virtual Cognitive-Affective Training for Opioid Use Disorder (NCT05034276), a na na study. The primary outcome is Number of Participants With Adverse Events and/or Serious Adverse Events.

2. Clinical Question

3. Trial Design

The registry record describes a completed single-group study of MORE-VR for opioid-use disorder. Its official title is “Digital Therapeutic Development of Virtual Cognitive-Affective Training for Opioid Use Disorder.” MORE-VR is described as Mindfulness-Oriented Recovery Enhancement deployed over virtual reality. The study summary characterizes the trial as Phase 1 and says its aims included establishing safety and collecting feasibility, usability, and engagement data for patients receiving medications for opioid use disorder. The formal phase entry is NA.

The intervention was delivered without a listed comparator arm. Allocation is recorded as NA, and masking is listed as none. These design features mean that the posted results describe outcomes in the MORE-VR group; they do not estimate a treatment contrast against a control group. The record lists an enrollment of 34. The safety results, however, report 28 participants at risk. The reason for that difference is not reported in the registry record.

The study start date is 2021-10-04, and the primary completion date is 2022-04-01. The status is completed. The primary safety timeframe runs from baseline through week 8. Secondary outcomes listed in the record are engagement, Numeric Rating Scale of State Craving, and Numeric Rating Scale of State Positive Affect. The record lists 8 outcome measures and 0 analyses. It does not report further details about the intervention schedule, adherence criteria, or how the feasibility and usability outcomes were defined.

Because the study has a single group, its design can describe observed safety events in participants who received MORE-VR, but it cannot by itself distinguish events related to the intervention from events that would have occurred otherwise. The registry record does not report a randomized comparison, a control condition, or a masking procedure.

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.

Before assignment: 34 participants were enrolled but only 28 participants started the intervention and attended the first treatment session. The other 6 participants were lost-to-follow up prior to initiation of the study intervention. This type of dropout is common among patients with opioid use disorder.

Overall Study

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 Number of Participants With Adverse Events and/or Serious Adverse Events, measured over Baseline through week 8.

The primary endpoint is the number of participants who reported adverse events and serious adverse events from baseline through week 8. It is expressed as a count of participants, rather than as a rate per unit of follow-up or a measure of event severity. In the posted safety results, serious adverse events and other adverse events are presented separately.

Counting participants with events is a direct way to describe the safety experience recorded during a study. It can show whether any participants in the listed group were reported to have an event in a category during the specified timeframe. It does not indicate how many total events occurred if one participant could have experienced more than one, and the registry record does not report event-level counts for this endpoint. The record also does not provide definitions of the event categories or details on how events were elicited and classified.

For this single-group study, the endpoint is descriptive. There is no control-group count against which to compare the observed number of participants with events. A count of zero serious adverse events in the posted results describes the reported observations; it does not establish that serious events are impossible or that the intervention caused no risk. Interpretation also depends on the observed safety denominator and follow-up period. The posted results give 28 participants at risk and specify baseline through week 8 as the primary timeframe.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a count of participants with events mean?

A participant count records how many people in a defined group experienced at least one event in a specified category and timeframe. It is different from an event count: a participant may experience multiple events, but a participant-level endpoint generally counts that person once for the category. The primary endpoint is explicitly defined as the number of participants reporting adverse events and serious adverse events. The record does not give event-level counts or clarify whether participants could appear in both categories.

The denominator matters because a count cannot be interpreted independently of the number of participants observed. The posted safety results identify 28 participants at risk for the MORE-VR group. The timeframe is baseline through week 8. Those details define the scope of the reported count, but they do not supply information about individual follow-up duration, event timing, or completeness of ascertainment. Such details are not reported in the registry record.

Why separate serious and other adverse events?

Safety summaries often distinguish serious adverse events from other adverse events because the categories reflect different classifications. Presenting them separately helps readers avoid treating all events as having the same seriousness. Here, the record reports 0 serious adverse events and 2 other adverse events. It does not provide the operational definitions used for either category, event descriptions, severity grades, or judgments about whether events were related to the intervention. The counts can therefore be described, but their clinical details and attribution cannot be reconstructed from the registry record.

What can a single-group study estimate?

A single-group study can describe outcomes observed among participants who received the intervention. It does not provide a concurrent group receiving a different intervention or control condition. Without such a group, the observed event count cannot be used to estimate a comparative difference in safety. Differences in participant characteristics, care, or time would also not be separated from intervention effects by a simple before-and-after interpretation unless the relevant data and analytic plan were available. The registry record does not report such an analysis.

In general, a confidence interval describes the range of values compatible with observed data under a specified statistical model and sampling assumptions. It can communicate uncertainty that a point estimate alone does not convey. No confidence interval is reported for this endpoint. With no comparison estimate and no analysis listed, there is no reported inferential result to interpret for the primary safety count.

How should zero observed events be read?

In general, observing no events in a study does not prove that the underlying event probability is zero. The observed count is influenced by the size of the group, the length and completeness of observation, the event definition, and how events are collected. A limited observation period may not capture uncommon events, and a small count can be imprecise. These are general statistical considerations, not additional findings about this study. The registry reports 0 serious adverse events among 28 participants at risk during the stated timeframe; it does not report an interval that quantifies the uncertainty around that observation.

The same caution applies to the reported count of 2 participants with other adverse events. The count describes the result in the safety group; without a comparison group or a model-based estimate, it does not establish whether the event experience is higher or lower than it would have been under another condition.

What do the planning assumptions mean?

The registry’s planning description refers to a hypothetical two-arm illustration using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It says that the effect to detect is a stated fraction of the observed effect; time-to-event planning uses the total number of events, while other planning outputs are expressed as participants per arm. These are planning assumptions, not a description of the single-group trial design. The record does not report a randomized two-arm comparison for this study, and those planning illustrations should not be read as observed power or as evidence of treatment effect.

In general, power calculations estimate the sample size needed to detect a specified effect under stated assumptions. They do not measure the probability that a finding is true, and calculations based on an observed effect can be unstable when that effect is uncertain. No trial-specific sample-size justification or power target is reported in the registry record. Since the present study is single-group, a hypothetical equal-allocation comparison does not describe its observed design.

What does the analysis listing tell readers?

The record lists 0 analyses. This means there is no registry-listed analysis result to supplement the posted counts. The statistical plan, any interim analyses, and the method used to handle incomplete outcome data are not reported in the registry record. Without those details, readers should not infer that unreported analyses were or were not conducted. The posted descriptive counts remain the basis for interpreting the safety endpoint.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("MORE-VR")
n      <- c(28)
events <- c(2)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  MORE-VR  28  2  7.1  0.9  23.5  2.0  22.6  2.2  22.8

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 8 outcome measures and 0 analyses. It identifies engagement, Numeric Rating Scale of State Craving, and Numeric Rating Scale of State Positive Affect as secondary outcomes, in addition to the primary safety endpoint. The record does not report how the listed outcomes were prioritized beyond identifying the primary endpoint, whether any multiplicity adjustment was planned, or how secondary analyses were to be interpreted. When multiple outcomes are assessed, general statistical practice recognizes that the chance of at least one apparently notable result can increase if many tests are conducted; whether that concern applies to any particular result depends on the actual analyses. No such analyses are listed.

Missing-data methods, analysis populations, and rules for excluding participants from an analysis are not reported in the registry record. The enrollment entry is 34, while the safety results give 28 participants at risk. The record does not explain the difference, describe missing observations, or indicate whether participants without complete follow-up were handled in a particular way. The count should therefore be interpreted using the stated safety denominator, not treated as an analysis of everyone enrolled.

The registry record does not report an interim-analysis plan, a statistical analysis plan, or procedures for imputing missing outcomes. It is not possible to determine from the posted information whether missingness occurred, how much outcome data were available for secondary measures, or whether analysis populations differed across endpoints. These omissions limit assessment of the full analysis strategy, but they do not change the descriptive meaning of the stated safety counts.

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 serious adverse event result is 0 participants among 28 at risk in the MORE-VR group. The other adverse event result is 2 participants among 28 at risk. The primary timeframe is baseline through week 8. These figures describe participant counts in the posted safety results, not the number of all event episodes.

The serious and other adverse event categories are presented separately. The registry record does not report event descriptions for the two participants with other adverse events, the criteria used to classify seriousness, or judgments about whether events were related to MORE-VR. It also does not report a comparison group or a statistical uncertainty interval for these results.

A zero observed serious-event count should be read as no serious adverse events reported in this safety group during the specified timeframe. In general, a zero count does not show that the underlying risk is exactly zero; the observation depends on the group and follow-up observed. The registry lists enrollment of 34, but the safety result uses 28 participants at risk, and the reason for the difference is not reported in the registry record.

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

The posted results describe a safety experience in one group receiving MORE-VR. They report 0 participants with serious adverse events and 2 with other adverse events among 28 participants at risk, from baseline through week 8. This is the direct descriptive finding available for the primary endpoint. The registry does not report an inferential analysis, comparative estimate, or confidence interval for it.

These counts do not show whether the event experience would have been different without MORE-VR or with another intervention. There is no comparator group, and the study is listed as single-group with allocation recorded as NA. Events observed during a study cannot be attributed to the intervention solely because they occurred while participants were receiving it. The record does not report event-level details or causal assessments.

The absence of reported serious adverse events in the observed group does not establish that serious adverse events cannot occur. In general, a study’s observed count is bounded by its participants, follow-up, and event ascertainment. The registry reports the safety denominator as 28 and the timeframe as baseline through week 8, but does not provide a precision interval or detailed information about follow-up completeness.

The result also does not answer the study’s feasibility, usability, or engagement questions. Those aims are described in the study summary, and secondary outcomes include engagement and state ratings of craving and positive affect. The registry record lists these outcomes but does not provide their results in the registry record reported for this analysis. No conclusion about those outcomes follows from the safety counts.

The study summary calls the trial Phase 1, while the formal phase entry is NA. Regardless of that difference in labeling, the posted safety result should be understood as descriptive and limited to this single-group record. It does not establish comparative safety, efficacy, or effects on opioid-use disorder.

14. Why This Trial Matters Statistically

This study illustrates an important distinction between describing safety observations and estimating comparative effects. A single-group count can document the number of participants reported to have events during a stated period. It cannot show whether that count is different from what would have occurred under another condition. Readers should keep the design and the endpoint aligned: the design supports a descriptive safety account, not a controlled treatment contrast.

The denominator is also central to interpretation. The registry reports enrollment of 34, but the posted safety result is based on 28 participants at risk. Because the record does not explain that difference, readers should preserve the denominator attached to the safety result and avoid assuming it represents the full enrollment. Transparent reporting of analysis populations and follow-up would help readers understand who contributed to each outcome.

Separating serious adverse events from other adverse events is useful because it prevents unlike categories from being collapsed into a single count. At the same time, counts alone provide limited detail. Event descriptions, definitions, timing, and attribution can help readers assess what the categories represent, and those details are not reported in the registry record for these results.

The record also demonstrates why planning illustrations should not be mistaken for evidence from the completed study. The listed planning assumptions describe a hypothetical two-arm framework, whereas the trial is single-group. Planning sample sizes are not observed power, and a hypothetical comparison does not create a comparison group in the data. Clear separation of design, planning, and observed results is necessary for sound statistical interpretation.

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 main trial-specific limitation is the absence of a comparator group. The study is listed as single-group, and allocation is NA. The reported event counts therefore cannot estimate a difference in safety between MORE-VR and another condition, nor can they isolate the intervention’s contribution to events.

The registry lists enrollment of 34, while the posted safety results state that 28 participants were at risk. The reason for this difference is not reported in the registry record. The record also does not give details on participant flow, completeness of follow-up, or the analysis population for each outcome. These omissions constrain interpretation of who contributed to the reported safety counts.

Event-level information is limited. The record reports 0 serious adverse events and 2 other adverse events among 28 participants at risk, but does not list the terms for the other events, describe event timing, or provide criteria for event classification or attribution. It is not possible to determine from these counts whether participants experienced multiple events or whether the events were judged related to MORE-VR.

The registry lists 0 analyses and does not report inferential estimates or uncertainty intervals for the primary endpoint. Methods for handling missing data, the analysis plan, and any interim analyses are not reported in the registry record. Secondary outcomes are listed, but results for those outcomes are not included in the registry record reported for this analysis.

The stated safety timeframe is baseline through week 8. Findings should be limited to that observation period and the reported group. The registry record does not provide evidence from longer follow-up or a controlled comparison, so broader conclusions about safety, efficacy, or the intervention’s effects are not supported by these results.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Digital Therapeutic Development of Virtual Cognitive-Affective Training for Opioid Use Disorder — NCT05034276.
• Registry record last updated 2023-07-20; status last verified 2023-07.
• Results first posted 2023-07-20.
• 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

The registry record describes a completed single-group study of MORE-VR, Mindfulness-Oriented Recovery Enhancement deployed over virtual reality, for opioid-use disorder. The study summary calls it Phase 1 and identifies safety, feasibility, usability, and engagement aims; the formal phase entry is NA. The listed enrollment is 34, with a safety denominator of 28 participants at risk. The reason for the difference is not reported in the registry record.

The primary endpoint counts participants reporting adverse events and serious adverse events from baseline through week 8. The posted safety results report 0 serious adverse events and 2 other adverse events in the MORE-VR group. There is no comparator arm, and the record lists 0 analyses. Consequently, the reported counts are descriptive and do not provide a comparative safety estimate. The record does not report event details, uncertainty intervals, missing-data methods, or results for the listed secondary outcomes.