Pragmatic Comparative Effectiveness Trial of Evidence-based, On-demand, Digital Behavioral Treatments for Chronic Pain: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Pragmatic Comparative Effectiveness Trial of Evidence-based, On-demand, Digital Behavioral Treatments for Chronic Pain (NCT04933474), a randomized na study. The primary outcome is Change From Baseline to Week 8 in Daily Pain Intensity.

2. Clinical Question

The study was designed as a pragmatic comparison of two at-home digital approaches rather than a comparison with no treatment. Participants were randomly assigned to one of the programs. The study description says both interventions were delivered to participants’ homes with instructions and remote technical support. Follow-up included patient-reported questionnaires covering functional status, pain levels, and pain-medication use, including opioids; participants were also asked for authorization to access medical records from their treating facility.

The title frames the work around barriers to pain care in rural America. However, the registry record does not report the eligibility criteria or the enrolled participants’ geographic distribution, so it does not establish which rural populations were represented. It also does not report whether the comparative effects were examined in specific patient subgroups. The broad question is whether the two digital programs differed on the stated pain-intensity endpoint; the available registry information describes that question but does not give the result needed to answer it.

3. Trial Design

This was a randomized, parallel-group trial with triple masking listed in the registry. The record does not specify which people or roles were masked, how masking was maintained, or whether it could be assessed during the study. Random assignment supports a planned comparison between the two intervention arms, but the registry information alone does not show how assignment was generated or concealed.

The two arms received different formats of behavioral pain treatment. painTRAINER is described as an eight-week, self-administered mobile health program with weekly sessions and optional practice modules. Skills-Based VR is described as a virtual-reality approach incorporating cognitive behavioral therapy principles, mindfulness, and biofeedback. The programs differ in delivery format as well as their described components, so the comparison concerns the assigned treatment packages rather than a single isolated therapeutic ingredient.

The study description says participants were followed for 12 weeks and completed patient-reported outcome questionnaires. The primary endpoint, however, is specified from baseline to the end of treatment at week 8. Other listed measures include pain interference, anxiety, pain self-efficacy, pain catastrophizing, and weekly opioid use. The registry identifies the study as completed and lists its start as 2022-03-23 and primary completion as 2024-05-12. The phase is listed as NA, and Cedars-Sinai Medical Center is named as sponsor.

Enrollment is listed as 330, but details about recruitment, eligibility, adherence, treatment exposure, and follow-up completion are not reported in the registry record. Nor does the record describe the exact procedures used to deliver each program beyond the general home delivery and support information. These omissions limit interpretation of how closely the study population, treatment use, and analysis followed the intended pragmatic comparison.

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: Of 2,804 participants screened, 367 underwent the informed eConsent process and enrolled in the Screening Week. Of the 367 participants, 330 successfully met inclusion criteria and were randomized to one of two treatment arms.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: All analyses were performed by study arm using an Intent-to-treat (ITT) population defined as all randomized participants across each treatment arm. Participants that provided at least 4 out of 7 possibly daily responses at Week 8 were included in the analysis.

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 Change From Baseline to Week 8 in Daily Pain Intensity, measured over From baseline to end of treatment at Week 8.

The primary endpoint is the change from baseline to week 8 in daily pain intensity, expressed as the proportion of participants reaching a specified threshold. Pain intensity was assessed with an 11-point numeric rating scale using a 24-hour recall. Participants recorded daily ratings for 7-days during baseline and again during the final week of the study. The endpoint is based on the difference between the average daily ratings across those periods, then dichotomized according to whether the minimally clinically important difference of 2 was achieved.

The scale is positively scored: higher values mean worse pain intensity. The registry defines the difference as baseline minus week 8, so a higher difference indicates a reduction in pain intensity. The endpoint therefore translates a continuous change in scores into a binary classification: meeting or not meeting the stated threshold. The registry describes the result as a proportion by arm, although its primary outcome unit is listed as participants.

Using repeated daily ratings to form a weekly average can represent pain across more than one isolated day. In general, dichotomizing a continuous measure makes the result easier to interpret against a threshold, but it discards information about how far participants’ changes fall above or below that threshold. The registry record does not report the underlying arm-level averages, the number meeting the threshold, or the comparative estimate. It therefore does not allow readers to assess the observed size or precision of the primary result.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The trial is described as randomized and parallel-group. Randomization is intended to make assigned groups comparable on average, including characteristics that were measured and those that were not. In general, it does not guarantee identical groups in a particular trial, and it does not by itself resolve missing outcome data or problems with treatment adherence. The registry does not report the randomization procedure, allocation concealment, or the statistical model used for the primary comparison.

The primary measure begins with repeated daily pain ratings at baseline and in the final week of treatment. For each period, the endpoint uses a 7-day average, then takes baseline minus week 8. Because the numeric rating scale is positively scored, a positive shift in the stated direction corresponds to improvement. The analysis then classifies whether the change reaches the threshold of 2. This turns the outcome into a binary event: reaching the threshold or not reaching it. The registry identifies the unit as participants and describes the outcome as the proportion meeting the threshold by arm.

For a binary outcome, a comparative analysis can describe how often the event occurred in each arm and estimate the contrast between those proportions. In general, uncertainty intervals help show how compatible the data are with a range of possible underlying effects. The registry record does not report the primary arm-level event counts, the comparative estimate, its confidence interval, or its p-value. The particular statistical test or model is also not reported, so no method-specific interpretation can be made.

The registry defines the primary analysis population as an intent-to-treat population of randomized participants across the arms, but also states that participants needed at least 4 out of 7 possible daily responses at week 8 to be included in the analysis. This endpoint-specific response requirement means the described analysis population is not simply every randomized participant regardless of outcome availability. The record does not state how missing daily responses were handled, whether baseline data were required for inclusion, or how participants without sufficient week 8 responses were treated in other analyses.

The record lists secondary outcomes for changes in pain interference, anxiety, pain self-efficacy, pain catastrophizing, and weekly opioid use. It also identifies six outcome measures and six analyses. The registry does not report the full analysis specifications for these measures, including which models were used, how repeated measurements were handled, or how the outcome timing was incorporated. The listed outcomes indicate areas assessed, not the results or the analytical details.

Multiplicity concerns arise when multiple outcomes or comparisons are examined. In general, as the number of statistical tests increases, the chance of at least one apparently unusual result can increase if all are treated as independent opportunities for discovery. A prespecified strategy may distinguish a primary test from secondary or exploratory analyses and may control or contextualize multiplicity. The registry record does not report whether such a strategy was used, whether there were planned subgroup analyses, or whether any adjustment was made. It is therefore not possible to determine how multiple outcomes were handled.

General explanation: a confidence interval expresses uncertainty around an estimate under the assumptions of the analysis. A narrow interval indicates greater precision than a wide interval, but its interpretation depends on the design and model. Since no primary estimate or interval is reported in the registry record, precision cannot be evaluated for the main comparison. A p-value, if reported, would address compatibility with a specified null model; it would not by itself describe the size or practical meaning of a difference. No primary p-value is reported.

The record also describes sample-size illustrations based on the observed effect, with a two-sided significance level of 0.05, equal allocation, and a normal approximation. The effect to detect is expressed as a stated fraction of the observed effect. Such values are planning illustrations, not observed power and not evidence that the original trial was designed with those assumptions. The registry does not report the trial’s own sample-size justification or the assumptions behind its original design. The stated illustration method does not replace a reported analysis of the trial outcome.

General explanation: binary outcomes can be sensitive to the event definition and to missing observations, because a participant must be classifiable as meeting or not meeting the threshold. Repeated daily ratings can also vary from day to day; averaging is one way to define a period-level score, but the registry does not report the distribution of daily responses. Over-dispersion matters in count models when variability exceeds what the model assumes; the primary endpoint is described as binary rather than a count model, and no count-model method is reported for it. No model assumption should be inferred beyond the endpoint description.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists multiple outcomes, including the primary pain-intensity threshold and measures of pain interference, anxiety, pain self-efficacy, pain catastrophizing, and weekly opioid use. It identifies six outcome measures and six analyses. The statistical plan for prioritizing or interpreting these outcomes is not reported in the registry record. In particular, the record does not say whether secondary outcomes were treated as confirmatory or exploratory, whether any adjustment for multiple testing was applied, or whether there were planned subgroup comparisons. Without that information, isolated findings across outcomes would require cautious interpretation.

The endpoint description sets a response threshold for week 8: participants with at least 4 out of 7 possible daily responses were included in the analysis. The record calls the population intent-to-treat and defines that population as randomized participants across the arms, while also specifying this endpoint-level response condition. Those descriptions identify the intended randomized population and the requirement for an analyzable week 8 endpoint, but they do not explain how all randomized participants were handled when the response condition was not met.

Missing-data methods are not reported in the registry record. It does not state whether missing daily responses were imputed, whether incomplete weekly averages were otherwise used, or whether sensitivity analyses assessed the impact of missingness. The record also does not provide the number of participants with analyzable primary outcomes by arm or describe missingness in baseline ratings. These details matter because an analysis limited to participants with sufficient responses can differ from an analysis that accounts for all randomized participants under specified assumptions.

The timing of the secondary outcomes and the exact analysis populations for each are not fully described in the available record. Therefore, the primary endpoint’s response rule should not be assumed to apply to every measure. The absence of reported methods does not show that no multiplicity or missing-data procedures were used; it means their use and implications cannot be assessed from 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.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: kidney stones (0.6%), lumbar sprain (0.6%), leg swelling (0.6%), hysterectomy (0.6%), kidney infection (0.6%).

The registry lists serious adverse event counts of 3 for painTRAINER and 4 for Skills-based VR. The corresponding numbers at risk are 161 and 169. It lists other adverse event counts of 13 and 47, with the same respective numbers at risk. Deaths are listed as 0 in each arm. These are registry counts; they are not, by themselves, estimates of causal effects or proof that an event was related to an intervention.

The record names Kidney Stones, Lumbar Sprain, Leg Swelling, Hysterectomy, Kidney Infection, and Hospitalization for pain among the top serious-event terms, each listed as 0.6%. The information does not assign those terms to a particular arm in the description, so they should not be interpreted as arm-specific events. It also does not provide detailed event narratives, timing, severity criteria, or investigator assessments of relatedness.

General explanation: safety counts are most informative when read alongside definitions, follow-up duration, exposure, and consistent ascertainment procedures. A count alone does not establish comparative risk, and a difference between counts should not be interpreted as a treatment effect without an appropriate analysis. The registry record does not report a formal comparative safety estimate, an uncertainty interval, or causal attribution for the listed events. The counts therefore describe what was recorded, not whether either program caused more harm.

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

The registry record defines a direct comparison between two digital behavioral treatments for chronic pain and specifies a threshold-based primary endpoint. It also records follow-up, secondary outcome domains, and adverse-event counts. These details clarify what the trial set out to compare and how the primary pain outcome was constructed. They do not provide the primary result needed to assess whether the arms differed on the endpoint.

Because the primary outcome values and comparison estimate are not reported in the registry record, it is not possible to say which arm had a higher proportion meeting the threshold, how large any difference was, or how precisely it was estimated. The same limitation applies to the secondary outcomes: their names are listed, but their results are not available in the record. No conclusion about comparative effectiveness should be drawn from the intervention descriptions or the trial’s completion status alone.

The endpoint itself represents one way to summarize pain intensity: average daily ratings across two periods are compared, then classified using the stated threshold. In general, this can make threshold attainment easier to communicate, but it does not capture all changes in the underlying score. Nor does it establish whether any observed change persisted beyond the period measured. The registry describes follow-up for 12 weeks, while the primary endpoint is specified through week 8; the later follow-up’s primary analytical role is not reported.

Safety counts are also descriptive. The record lists serious and other adverse events and zero deaths in each arm, but the information does not establish attribution or comparative risk. The counts should not be read as evidence that one program caused more events, or that an intervention is free of risk.

In short, the record supplies a trial design and endpoint definition, but not the outcome estimates needed for conclusions about benefit, comparative performance, or precision. It also leaves important analysis details unreported. The distinction between a clearly defined question and a reported answer is essential when interpreting registry information.

13. Why This Trial Matters Statistically

This trial is statistically notable because its primary outcome converts repeated pain ratings into a binary threshold measure. Daily ratings are averaged over baseline and the final treatment week, and improvement is classified according to whether the specified difference reaches 2. That design choice changes the question from how much scores changed on average to how many participants crossed a chosen threshold. Those are related but not interchangeable summaries.

Comparing two active digital programs also makes the estimand specific: the contrast concerns assignment to the Skills-Based VR package versus assignment to painTRAINER, as described in the registry. It is not a comparison with no treatment, and it does not isolate the contribution of any one component shared or differing between the programs. The random allocation and parallel structure provide the framework for a comparative analysis, but the result still depends on outcome availability and the analysis methods.

The record’s endpoint eligibility rule illustrates how an intent-to-treat label can coexist with an analysis requirement for sufficient outcome data. A reader needs both pieces of information to understand who contributes to the endpoint analysis and how missingness might affect interpretation. The registry does not report missing-data procedures, so this aspect cannot be fully evaluated.

Finally, the difference between a defined endpoint and a reported estimate is consequential. Without arm-level results and uncertainty, neither effect size nor precision can be assessed. The trial description makes the intended statistical question clear, while the outcome reporting available in the registry record is insufficient to answer it. That distinction is central to responsible interpretation of clinical trial evidence.

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.

Several trial-specific details needed to evaluate the primary comparison are not reported in the registry record. These include arm-level primary outcome results, the comparative effect estimate, its uncertainty, and the statistical test or model. The absence of these items prevents assessment of the observed effect’s direction, magnitude, and precision.

The primary endpoint requires at least 4 out of 7 possible daily responses at week 8. The record does not report how many participants met that requirement in each arm, how many were excluded from the endpoint analysis for insufficient responses, or how missing daily ratings were handled. It also does not describe sensitivity analyses for missing outcomes. Thus, the potential influence of incomplete response data cannot be assessed.

The binary threshold outcome does not retain the full range of score changes. The record does not report a continuous-score analysis of the difference between baseline and week 8, which could show how changes were distributed around the cutoff. The endpoint’s threshold is described as the minimally clinically important difference, but the registry record does not provide further details about how that threshold was selected or applied in the analysis.

The registry describes triple masking but does not identify who was masked or how masking was implemented for interventions with visibly different delivery formats. It also does not report adherence, actual treatment exposure, or whether technical support use differed by arm. Eligibility criteria and participant characteristics, including the geographic distribution of enrollment, are not reported in the available information, limiting assessment of how broadly results might apply.

The statistical plan for secondary outcomes, multiplicity, subgroup analyses, and missing data is not reported. Safety counts lack detailed attribution and a comparative analysis. These limitations concern what can be assessed from the registry record; they do not establish that the underlying study lacked methods or analyses not documented there.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Pragmatic Comparative Effectiveness Trial of Evidence-based, On-demand, Digital Behavioral Treatments for Chronic Pain — NCT04933474.
• Registry record last updated 2026-03-27; status last verified 2025-12.
• Results first posted 2025-06-26.
• 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

NCT04933474 is a completed randomized, triple-masked, parallel-group trial comparing Skills-Based VR with painTRAINER for chronic pain. Enrollment is listed as 330, and Cedars-Sinai Medical Center is named as sponsor. The registry lists the study start as 2022-03-23 and primary completion as 2024-05-12.

The primary endpoint is the proportion of participants meeting the stated threshold for improvement in daily pain intensity from baseline to week 8. Daily ratings used an 11-point numeric rating scale, and the endpoint was based on 7-day averages. For the endpoint analysis, participants needed at least 4 out of 7 possible daily responses at week 8.

The registry lists secondary measures concerning pain interference, anxiety, pain self-efficacy, pain catastrophizing, and weekly opioid use. It also reports serious and other adverse event counts and zero deaths in both arms. The primary outcome comparison, uncertainty estimates, statistical plan, and missing-data methods are not reported in the registry record.