EaseVRx-8w+ for the Treatment of Chronic Lower Back Pain: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for EaseVRx-8w+ for the Treatment of Chronic Lower Back Pain (NCT05263037), a randomized na study. The primary outcome is Brief Pain Inventory (BPI) Pain Intensity Questionnaire.

2. Clinical Question

3. Trial Design

The registry describes a decentralized, randomized, controlled trial with a parallel-group model and triple masking. It lists an enrollment of 1093 and four arms: skills-based VR for 56 days, skills-based VR followed by an extended 56-day on-demand period, 56-day Sham VR, and Sham VR followed by an extended 56-day on-demand period. The interventions are identified as EaseVRx and Sham VR.

The active program lasted 8 weeks. In each extended-period arm, participants were offered an additional 8-week on-demand period after the initial program. The arm descriptions state that follow-up was to continue for 24 months after treatment completion. The primary endpoint reported in the record is the Brief Pain Inventory (BPI) pain-intensity questionnaire at Day 56, the end of treatment. The reported outcome counts are 269, 267, 266, and 265, respectively, across the four arms.

The trial status is listed as active, not recruiting. The registry record identifies AppliedVR Inc. as the sponsor. It lists four secondary outcomes: Oswestry Disability Index Score (ODI v2.1b), PROMIS Sleep Disturbance, PROMIS Depression, and PROMIS Anxiety. The record also describes broader aims, including assessing pain interference, physical function, sleep, behavioral skills development, health outcomes, satisfaction, healthcare utilization, and costs. These aims do not establish that results for every listed outcome are posted.

The record does not report the original sample-size justification, detailed randomization procedures, or the operational details of masking. It also does not report the trial’s full statistical analysis plan. Those omissions limit what can be inferred about the original design and analysis decisions from the registry record alone.

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

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 Brief Pain Inventory (BPI) Pain Intensity Questionnaire, measured over Day 56 (end of treatment).

The primary endpoint is mean pain intensity on the Brief Pain Inventory (BPI) pain-intensity questionnaire at Day 56, identified as the end of treatment. The registry describes the BPI pain-intensity questionnaire as a validated instrument with good content validity, construct validity, and reliability in participants with chronic pain. It reports a score range of 0-10, with higher values indicating greater pain intensity. The pain-intensity measure contains a single item related to pain intensity.

A continuous score retains more detail than a simple classification into categories. Reporting a mean describes the group’s average score, while the standard deviation describes how spread out individual scores are around that average. Neither quantity alone shows how many participants improved, how much any individual changed, or whether participants experienced a meaningful change. The registry result is an endpoint comparison at Day 56; no baseline values or individual-level changes are included in the registry record reported for this analysis.

The endpoint is relevant to the stated trial aim of assessing pain intensity in people with chronic lower back pain. It is one outcome among the broader set of outcomes described in the registry, which also includes pain interference, anxiety, depression, physical function, sleep, and other health and utilization measures. The results concern only the posted primary pain-intensity endpoint, not those other outcomes.

7. Results Posted in the Registry

• 56-day Skills-based VR Program: mean 4.51 versus 5.25 on control; difference -0.74 (95% CI -1.11 to -0.37), standardized effect d = -0.34; z-test p = <0.001.
• 56-day Skills-based VR Program Followed by an Extended 56-day On-demand Period: mean 4.83 versus 5.25 on control; difference -0.42 (95% CI -0.78 to -0.06), standardized effect d = -0.20; z-test p = 0.023.
• • 56-day Control (Sham VR Plus 8w Extended On-demand): mean 5.17 versus 5.25 on control; difference -0.08 (95% CI -0.46 to 0.30), standardized effect d = -0.04; z-test p = 0.682.

8. Statistical Interpretation

9. Statistical Methods Explained

The endpoint is continuous: each participant’s BPI pain-intensity score is numeric, and the registry reports the mean and standard deviation for each arm. A mean summarizes the central location of scores within an arm. A standard deviation summarizes the spread of participant scores around that mean. These are different from the standard error, which describes the uncertainty of an estimated mean and is affected by both variability and the number of observations. The posted arm summaries are means with standard deviations, not means with standard errors.

What does a mean difference describe?

The reported mean difference compares an intervention arm with the 56-day Sham VR control. It is expressed as the intervention mean minus the control mean. Thus, a negative difference corresponds to a lower intervention-arm mean on the BPI scale. Since the instrument’s higher scores indicate greater pain intensity, the direction of the mean difference can be understood from the scale definition. A mean difference is an average contrast between groups; it is not an individual participant’s change and does not indicate that every participant had a score in the same direction.

The posted comparisons are unadjusted. In general, an unadjusted comparison uses the group summaries without accounting for covariates such as baseline measurements. An adjusted analysis can address specified covariates, but whether such an analysis was planned or performed is not reported in the registry record. The posted results should not be described as adjusted estimates.

How should the p-values be understood?

A p-value measures how incompatible the observed data are with a specified null model, under the assumptions of the analysis. It is not the probability that the null hypothesis is true, and it does not measure the size or importance of an effect. The p-values reported for these comparisons are unadjusted. They should be considered alongside the estimated mean differences and confidence intervals, rather than treated as a standalone ranking of the arms.

Multiplicity arises when several statistical comparisons or outcomes are considered. If many tests are conducted, the chance of at least one apparently unusual result can increase unless the analysis accounts for that testing structure. This is a general statistical issue; the registry record does not report whether or how multiplicity was addressed. In particular, the presence of several arms and listed secondary outcomes does not, on its own, reveal the planned testing hierarchy or adjustment method.

What does a confidence interval add?

A confidence interval expresses the precision of an estimated contrast under the method used to construct it. A narrower interval indicates greater precision than a wider interval, while the interval’s location indicates which values remain compatible with the estimate and its uncertainty. When an interval for a mean difference includes zero, the range includes no mean difference as well as values on either side. When it lies on one side of zero, the interval’s reported range does not include zero under that interval method. These statements describe statistical uncertainty and do not determine clinical relevance.

Confidence intervals are based on assumptions, including how the outcome distribution and sampling variability are handled. The registry record does not report enough detail to establish the exact model or interval construction beyond the posted comparison summaries. General statistical explanations of intervals should therefore not be mistaken for a claim about unreported modeling details.

Why does variability matter?

Standard deviations of 2.22, 2.11, 2.15, and 2.35 are reported for the four arm means, respectively. In general, more variability makes group means harder to estimate precisely when sample sizes are otherwise similar. In a continuous-outcome comparison, the estimated difference is interpreted in relation to the variation in scores and the number of participants contributing to the comparison. The registry’s arm summaries describe the observed variation; they do not explain its causes.

Over-dispersion is a general concern when data vary more than a chosen statistical model expects. If present and ignored, uncertainty can be understated. The registry record does not report an over-dispersion assessment, and the continuous BPI summaries alone do not establish that such a problem occurred. The appropriate conclusion is limited to the reported means, standard deviations, differences, confidence intervals, and p-values.

The sample-size illustrations use the observed effect as a planning reference and show how estimated requirements change when the effect to detect is reduced. These are prospective planning calculations under stated assumptions, not a reconstruction of the trial’s original design. The original design assumptions and sample-size justification are not reported in the registry record.

10. Confidence Intervals and Precision

The estimated mean difference for the skills-based VR program versus the 56-day Sham VR control is -0.74, with a confidence interval from -1.11 to -0.370. The interval lies below zero, indicating that the reported range of values for the mean difference is negative under the interval method. It also shows that the estimate is not a single exact value: a span of differences is compatible with the data and method used.

For the skills-based VR program followed by an extended on-demand period versus the same control, the estimate is -0.42 and the confidence interval runs from -0.782 to -0.058. This interval also lies below zero, though its upper endpoint is closer to zero than the first comparison’s. For the Sham VR arm with an extended on-demand period versus the Sham VR control without an extension, the estimate is -0.08, with a confidence interval from -0.463 to 0.303. That interval includes zero and extends to values on either side of it.

Precision is not the same as clinical importance. The registry record does not report a threshold for a clinically important difference on this endpoint, and the intervals do not establish what score change participants would consider meaningful. They also do not show the distribution of individual responses. The reported confidence intervals concern mean differences between arms at Day 56, rather than changes within individuals or effects at the later follow-up time points described in the trial design.

The posted arm sizes range from 265 to 269 for the primary outcome summaries. A confidence interval’s width reflects both the amount of information and the variability in the data, along with the method used to construct it. The exact confidence level and detailed interval method are not reported in the registry record. The confidence intervals should therefore be read as the posted uncertainty ranges, without attributing unreported analysis settings to them.

11. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The displayed planning figures are participants per arm, not total events. The registry record’s planning assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect to detect is set to the stated fraction of the observed effect. These figures are planning illustrations and are not observed power.

The 80% power column gives the estimated participants per arm for a design with an 80% chance of detecting the specified effect under those assumptions, if that effect were the true difference and the model assumptions held. The 90% power column gives the corresponding estimate for a design with a 90% chance. Power is a property of a planned study under a set of assumptions; it does not report the probability that the trial’s result is correct.

Each comparison has planning rows for 100%, 75%, and 50% of the observed effect. For the skills-based VR program comparison, the estimates are 137 participants per arm for 80% power and 184 for 90% power when planning for 100% of the observed effect; for 75%, they are 244 and 326; for 50%, they are 548 and 734. For the skills-based VR program followed by an extended on-demand period, the corresponding estimates are 404 and 541 for 100%, 718 and 961 for 75%, and 1,616 and 2,163 for 50%. For the extended Sham VR control comparison, they are 12,440 and 16,654 for 100%, 22,115 and 29,606 for 75%, and 49,759 and 66,613 for 50%.

The pattern illustrates a general planning principle: smaller effects require more participants to detect under otherwise unchanged assumptions. Because these estimates are based on the observed effects, they should not be read as the trial’s original sample-size target or justification. The original design assumptions are not reported in the registry record.

12. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = -0.740; pooled standard deviation σ = 2.185.
2. n = 2 × (1.96 + 0.842)² × 2.185² / -0.740² = 136.9, rounded up to 137 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
delta <- -0.74                      # observed difference in means
sigma <- 2.18547726636566                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(5263037)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 137 (80% power), 184 (90% power)
 75% of observed effect: n per arm = 244 (80% power), 326 (90% power)
 50% of observed effect: n per arm = 548 (80% power), 734 (90% power)
power.t.test: 137.9 
Simulated power at n = 137 per arm: 0.798 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

13. Multiplicity, Missing Data and Analysis Populations

Multiplicity concerns can arise when a trial reports several treatment comparisons and several outcomes. This record includes four arms and lists four secondary outcomes in addition to the primary outcome. The posted primary results include comparisons of three arms with the 56-day Sham VR control. The registry record does not report whether these comparisons were organized in a testing hierarchy, whether a family of hypotheses was defined, or whether p-values were adjusted to account for multiple testing.

The p-values described for the primary comparisons are unadjusted. They should not be interpreted as though a particular multiplicity correction had been applied. The record does not report a prespecified primary contrast beyond identifying the primary endpoint, nor does it report how the comparisons among the four arms were prioritized. Without those details, the relationship between the posted comparisons and the trial’s full inferential plan cannot be established.

Missing-data handling is also not reported in the registry record. The arm counts for the primary outcome are 269, 267, 266, and 265, but these counts alone do not explain whether every randomized participant contributed an outcome, how absent measurements were handled, or whether any imputation or sensitivity analysis was used. The registry record also does not report reasons for missing endpoint data.

The analysis population is not reported in the registry record. It is therefore not possible to determine from these registry entries whether the posted analysis used all randomized participants, participants who completed treatment, or another defined population. The treatment of adherence, withdrawals, protocol deviations, and participants with incomplete follow-up is also not reported.

These missing details matter because analysis choices can affect the interpretation and precision of estimates. The registry results support describing the posted arm summaries and unadjusted comparisons, but they do not establish the complete statistical plan, the handling of missing observations, or the population used for every analysis.

14. 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 reports zero serious adverse events and zero other adverse events for each of the four arms. The numbers listed as at risk are 269 for the skills-based VR program, 267 for that program with extended on-demand access, 266 for 56-day Sham VR, and 265 for Sham VR with extended on-demand access. The registry also reports zero deaths in each arm and no top serious-event terms.

These figures describe the adverse-event counts recorded in the registry for the groups and reporting period represented there. They do not establish that no adverse events occurred outside what was reported, nor do they establish that an intervention is safe. The registry record does not provide further detail about event definitions, collection procedures, duration of safety follow-up for this summary, or how adverse events were assessed for relatedness.

Counts should be read with their group sizes and reporting context in mind. A zero count is a statement about the recorded events, not proof of zero risk. These summaries also do not compare the likelihood of events using an adjusted statistical analysis.

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

The posted results describe mean BPI pain-intensity scores at Day 56 in four randomized arms. Both skills-based VR arms had lower reported mean scores than the 56-day Sham VR control at that time point, with unadjusted mean differences of -0.74 and -0.42. The extended Sham VR control arm had a mean close to that of the Sham VR control without the extension, with a reported difference of -0.08 and a confidence interval that includes zero.

Those comparisons do not show how much individual participants’ scores changed from baseline, because baseline results and individual trajectories are not included in the registry record reported for this analysis. A group mean can conceal variation in response, and the standard deviations indicate that participant scores varied within each arm. The registry record does not report a clinically important difference threshold, so the estimates cannot be classified against such a threshold from these registry entries.

The result is specific to pain intensity on the BPI at Day 56. It does not establish results for pain interference, anxiety, depression, physical function, sleep, satisfaction, healthcare utilization, costs, or other outcomes in the trial’s aims. The registry lists secondary outcome measures, but the results do not provide estimates for them. Nor should a Day-56 endpoint comparison be treated as evidence about the 24-month follow-up period.

Unadjusted p-values and confidence intervals describe statistical evidence and uncertainty under the analysis represented in the posted results. They do not prove a causal mechanism, determine clinical importance, or resolve possible multiplicity and missing-data concerns. The registry record does not report the full statistical plan or analysis population. The appropriate reading is therefore limited to the posted group summaries and comparisons, with these design and reporting details in mind.

16. Why This Trial Matters Statistically

This trial is statistically interesting because it has four randomized arms that separate two program features: skills-based VR content and an extended on-demand period. The primary comparison results include two skills-based VR arms against the same Sham VR control, as well as a comparison between Sham VR with and without an extended on-demand period. Keeping these contrasts distinct helps avoid treating all arms as interchangeable versions of one intervention.

The BPI endpoint is continuous, and its reported means are accompanied by standard deviations. That combination gives readers information about both the average score and the variability among participants. The mean differences and confidence intervals then describe the group contrasts and their uncertainty. Reading all of these together is more informative than relying only on whether an unadjusted p-value crosses a threshold.

The estimates also illustrate how the size of an observed effect is relevant to planning. The planning figures rise as the effect assumed for detection becomes smaller. This is a general consequence of aiming to distinguish a smaller difference from random variation under otherwise unchanged design assumptions. These calculations are illustrations based on the observed effects, not a substitute for the trial’s original planning rationale, which is not reported in the registry record.

Finally, the registry’s limited reporting of multiplicity, missing data, analysis populations, and detailed statistical methods makes transparent distinctions important. Readers can describe the Day-56 means and unadjusted contrasts, but should not infer an unreported adjustment procedure or a broader conclusion about the full range of outcomes and follow-up.

17. 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 registry record identifies the endpoint and reports arm means, standard deviations, mean differences, confidence intervals, and unadjusted p-values. It does not report the original sample-size justification or the assumptions used when the trial was designed. The planning illustrations based on observed effects should not be confused with that original rationale.

Details of the statistical analysis plan are not reported in the registry record. This includes the planned treatment contrasts, any multiplicity procedure, the model used for the primary analysis, and the exact confidence-interval method. The analysis population is also not reported. Without those details, the posted comparisons cannot be placed within a fully specified analysis framework.

The registry entries do not include baseline BPI scores, individual participant changes, distributions beyond the means and standard deviations, or the number and reasons for missing Day-56 measurements. Missing-data methods and sensitivity analyses are not reported. The available summaries therefore do not establish how incomplete outcomes or departures from treatment were handled.

The primary results concern Day 56, while the arm descriptions state that follow-up was to continue for 24 months after treatment completion. Longer-term endpoint results are not included in the registry record. Although the registry lists secondary outcome measures and broader trial aims, estimates for those outcomes are not described in the primary results. The registry record also does not report a threshold for a clinically important BPI difference, which limits interpretation of the size of the observed contrasts.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: EaseVRx-8w+ for the Treatment of Chronic Lower Back Pain — NCT05263037.
• Registry record last updated 2025-01-29; status last verified 2025-01.
• Results first posted 2023-12-20.
• 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.

21. Record Summary

The registry describes a decentralized, randomized, controlled, parallel-group trial with triple masking and an enrollment of 1093. Four arms compare skills-based VR, skills-based VR with an extended on-demand period, Sham VR, and Sham VR with an extended on-demand period. The primary endpoint is mean BPI pain intensity at Day 56, with higher scores indicating greater pain intensity.

The skills-based VR arms had means of 4.51 and 4.83, compared with 5.25 in the Sham VR control. Their unadjusted mean differences were -0.74 and -0.42. The extended Sham VR control mean was 5.17, with a difference of -0.08 versus the Sham VR control. The registry reports zero serious adverse events, zero other adverse events, and zero deaths in each arm.

Multiplicity procedures, missing-data methods, analysis populations, detailed statistical methods, and the original sample-size justification are not reported in the registry record.