Pain, Inflammation and Opioid Craving: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Pain, Inflammation and Opioid Craving (NCT04190563), a randomized na study. The primary outcome is Craving.

2. Clinical Question

3. Trial Design

The registry describes a randomized, single-masked, parallel-group behavioral study. Participants were assigned to Pain De-Catastrophizing or Pain Education. In a parallel design, each participant is assigned to one group, and outcomes are compared between groups. The record does not specify who was masked, how the random sequence was generated, or how allocation was concealed; these details are not reported in the registry record.

The study is listed as completed, with an enrollment of 83. The listed start date is 2021-05-04, and the primary completion date is 2025-07-31. The phase is listed as NA. The sponsor is Mclean Hospital. The condition listed is opioid-use disorder.

The registry describes each intervention as brief behavioral education. Pain De-Catastrophizing addressed modifying the interpretation of pain, while Pain Education provided education about pain. The record does not report session duration, delivery procedures, adherence, or whether participants received other care alongside the sessions. Those details should not be inferred from the group names.

The posted outcome data include 38 participants in Pain De-Catastrophizing and 45 in Pain Education. These are the group counts attached to the craving outcome; the record does not explain whether all enrolled participants contributed outcome data or how any unavailable observations were handled. The trial’s original sample-size justification, target enrollment rationale, and design assumptions are not reported in the registry record. The separate sample-size illustrations are based on the observed group difference and should not be mistaken for the trial’s original planning.

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 Craving, measured over immediately after the intervention.

The primary endpoint is the mean score on the Opioid Craving Scale immediately after the intervention. It is a participant-reported measure of opioid craving. The total score averages the measure’s 3 items and ranges from 0-10; higher scores reflect more craving. The registry identifies the endpoint as a continuous measure and reports a group mean and standard deviation for each intervention.

A continuous score retains gradations in reported craving rather than classifying participants into categories. Comparing group means provides a summary of the average score in each group at the specified time point. The standard deviations describe the spread of participants’ scores around those means. They are not confidence intervals for the means, and they do not show the range of individual scores.

Craving is relevant to the study’s stated interest in opioid-use disorder and responses to pain. A score measured immediately after the session captures a short-term outcome at that specific time. It does not, by itself, describe later craving, opioid use, or changes in clinical status. The record does not report a longer-term primary assessment or a separate primary measure of pain response. Interpretation should therefore stay focused on the posted immediate post-intervention craving scores.

7. Results Posted in the Registry

• Pain Education: mean 4.93 versus 4.21 on control; difference 0.72 (95% CI -0.59 to 2.03), standardized effect d = 0.24; z-test p = 0.280.

8. Statistical Interpretation

9. Statistical Methods Explained

The posted group summaries are means and standard deviations for a continuous outcome. A mean is the arithmetic average of observed scores in a group. A standard deviation describes how dispersed those scores are around their group mean. A larger standard deviation indicates more spread, but it does not indicate uncertainty in the mean by itself. The registry reports a mean of 4.21 and standard deviation of 3.1 for Pain De-Catastrophizing, and a mean of 4.93 and standard deviation of 2.93 for Pain Education.

What does a mean difference describe?

For the unadjusted re-calculation, the mean difference is the Pain Education mean minus the Pain De-Catastrophizing mean. Its reported estimate is 0.72. A positive value means the observed group mean is higher in Pain Education for this chosen subtraction order. The estimate is a comparison of group averages, not a change score for each participant and not an estimate of the difference for every individual. It does not adjust for other variables.

The re-calculation uses the posted summary statistics and is described as a simple, unadjusted comparison. It is distinct from the sponsor’s reported ANCOVA. Because the registry does not describe the ANCOVA covariates or other model details, its adjusted estimate and test cannot be reconstructed from the information in the record. The record also does not report whether the sponsor analyzed a particular subset of participants or used any additional modeling choices.

What does the confidence interval add?

A confidence interval gives a range of values that are compatible with the estimate under the statistical method and its assumptions. It communicates uncertainty around the estimated group difference, whereas the point estimate alone gives only one value. The unadjusted interval includes values on both sides of no difference. That means the summary data do not pin down whether the underlying mean difference is positive or negative with high precision. The interval is not a range containing a stated proportion of individual participants’ scores.

What does the p-value mean?

In general, a p-value measures how unusual data at least as incompatible with a specified null hypothesis would be if that hypothesis and the model assumptions were true. It is not the probability that the null hypothesis is true, nor a measure of the size or importance of an effect. The unadjusted re-calculation reports p = 0.28. The sponsor’s ANCOVA reports p < .05. These values come from different analyses and should not be treated as if they were generated by the same model. The record does not provide enough detail to identify all reasons for their difference.

Why can an adjusted analysis differ?

In general, ANCOVA compares group outcomes while accounting for selected covariates in a model. Depending on the covariates and model specification, an adjusted comparison can differ from a comparison based only on group means. The registry identifies the sponsor’s method as ANCOVA but does not name the covariates, report adjusted group means, or give a confidence interval for the analysis. It is therefore possible to describe the method and reported test, but not to explain the result in terms of particular adjustments.

The trial is described as randomized and parallel. In general, randomization is intended to support comparable groups at the start of a study, while a parallel design assigns each participant to one group. The registry does not report the randomization procedure, concealment method, or masking details beyond listing the study as single-masked. These missing details limit assessment of how assignment and masking were implemented, but they do not justify assuming that either was inadequate.

The posted outcome is a single continuous score assessed immediately after intervention. The record lists one outcome measure and one analysis, but does not report a statistical analysis plan, a formal multiplicity strategy, the approach to missing outcomes, model diagnostics, or analysis populations. Those omissions matter when interpreting inferential results and reproducibility. The general statistical concepts above explain the reported quantities; the specific details of the trial’s analysis beyond those explicitly posted are not reported in the registry record.

10. Confidence Intervals and Precision

The unadjusted mean difference is 0.72, with a confidence interval whose lower bound is -0.586 and upper bound is 2.026. The interval crosses zero, the value corresponding to no mean difference. It therefore includes possibilities in which the Pain Education mean is lower, as well as possibilities in which it is higher. The point estimate alone should not be read as a precise determination of the direction or magnitude of the group difference.

A confidence interval represents uncertainty in an estimated quantity under the method used to calculate it. It is not the range of scores for participants, nor does it mean that the true value has a particular probability of falling within the calculated interval. The group standard deviations—3.1 and 2.93—describe variability among observed scores, a different kind of uncertainty from the interval around the mean difference.

The interval’s breadth relative to the point estimate signals limited precision for the unadjusted comparison: it allows a range of materially different mean differences, including no difference. The unadjusted p-value of 0.28 is consistent with the interval crossing zero. Precision is not the same as statistical significance, and neither alone indicates practical importance. The registry does not define a threshold for a meaningful change in craving, so the clinical importance of values within the interval cannot be determined from the record.

The sponsor’s ANCOVA result has no confidence interval posted. Its reported F statistic and p-value provide evidence from that analysis, but without an interval or further model details, the precision of its adjusted effect estimate cannot be assessed from the registry record.

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 sample-size illustrations are planning calculations based on the observed effect, not the trial’s original design. The registry does not report the original sample-size justification or the assumptions used to select the study enrollment. These illustrations assume a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. They consider detecting the stated fraction of the observed effect.

The listed figures are participants per arm, not total participants or total events. For the observed effect, the illustration lists 275 participants per arm for 80% power and 367 participants per arm for 90% power. For planning at 75% of the observed effect, it lists 488 participants per arm for 80% power and 653 participants per arm for 90% power. For planning at 50% of the observed effect, it lists 1,097 participants per arm for 80% power and 1,468 participants per arm for 90% power.

In plain terms, power is the chance that a specified analysis would identify a difference at the chosen significance level if the assumed effect and other planning conditions held. The 80% column describes a design with an 80% chance under those assumptions; the 90% column uses a higher target chance. Planning for a smaller effect requires more participants to achieve either target, as the listed rows illustrate.

These are not observed power calculations and do not describe the probability that the completed study’s result is correct. They are prospective planning illustrations tied to an effect estimated from this study, which itself is uncertain. Their assumptions may not match the trial’s design or sponsor analysis. The curve should be read as a planning aid under those stated assumptions, not as evidence about enrollment adequacy under an unreported protocol.

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 = 0.720; pooled standard deviation σ = 3.009.
2. n = 2 × (1.96 + 0.842)² × 3.009² / 0.720² = 274.1, rounded up to 275 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 <- 0.72                      # observed difference in means
sigma <- 3.0088462166677                     # 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(4190563)
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 = 275 (80% power), 367 (90% power)
 75% of observed effect: n per arm = 488 (80% power), 653 (90% power)
 50% of observed effect: n per arm = 1,097 (80% power), 1,468 (90% power)
power.t.test: 275.1 
Simulated power at n = 275 per arm: 0.805 (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. Analyses Reported by the Sponsor

The sponsor’s posted analysis compares the two groups using ANCOVA and reports F = 6.69 with p < .05. The registry does not report a confidence interval, adjusted group means, or the covariates used in that model. The result can therefore be described as the sponsor’s reported ANCOVA test, but its adjusted effect size and precision cannot be recovered from the record.

The re-calculation uses the posted means and standard deviations to make an unadjusted comparison. It reports a mean difference of 0.72, a confidence interval spanning negative and positive values, and p = 0.28. Because this calculation does not account for covariates, it is not a reproduction of the ANCOVA. In general, adjustment can change an estimate or its uncertainty, but the specific explanation for the difference cannot be established without the sponsor’s model details.

The registry does not flag a discrepancy between the sponsor analysis and the re-calculation. Both results should be reported with their methods identified: one is the sponsor’s ANCOVA, and the other is an unadjusted calculation from the group summaries. The record does not provide enough information to adjudicate their difference or to claim that one is a corrected version of the other.

14. Multiplicity, Missing Data and Analysis Populations

The registry lists one outcome measure and one analysis, and no secondary outcomes are posted. This limited set of posted results reduces the number of reported comparisons that can be examined, but it does not establish how many outcomes or analyses were planned or conducted. A formal multiplicity strategy, including whether any adjustment was planned, is not reported in the registry record. It is also not reported whether the posted primary outcome or analysis was selected before results were examined.

Multiplicity matters when several hypotheses are tested: in general, conducting more tests can increase the chance that at least one result appears statistically significant by chance. The available record does not establish that multiple tests were performed, and it would be inappropriate to assume either that they were or that they were not. The sponsor’s ANCOVA is the one analysis described for the posted comparison; details of any analysis plan are not reported.

Missing-data handling is also not reported in the registry record. The posted outcome counts are 38 and 45, while overall enrollment is 83. The record does not state whether these counts represent all randomized participants, all participants with observed scores, or an analysis population defined in another way. It does not describe missingness, imputation, exclusions, or sensitivity analyses. Thus the available summaries cannot establish whether missing data affected the comparison.

The analysis population is not reported in the registry record. It is not specified whether the sponsor used all randomized participants, participants who completed the intervention, or another group. The registry also does not report protocol deviations, adherence, or model diagnostics. These omissions limit assessment of the analysis and its reproducibility; they do not, on their own, demonstrate that the analysis was biased or invalid.

15. 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 in Pain De-Catastrophizing among 38 participants at risk, and zero in Pain Education among 45 participants at risk. It also reports zero other adverse events in each group, with the same group counts at risk, and zero deaths in both groups. No serious adverse-event terms are listed.

These entries describe the adverse-event counts posted in the registry. They do not mean that no participant experienced any symptom or event beyond the categories recorded, and they do not establish that an event was impossible. The record does not provide event definitions, collection procedures, observation duration, or detail on whether events were assessed systematically. The number of participants at risk identifies the group sizes used for the adverse-event reporting, but does not supply information about the intensity or duration of monitoring.

With zero events recorded in the listed categories, there is no event count to compare between groups. The results should be read as the registry’s reported counts, not as proof of an absence of risk. This summary concerns reported adverse events in this study and does not support conclusions about safety outside the study setting.

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

The posted results establish that the study compared immediate post-intervention opioid-craving scores between two groups that received different brief education sessions. The unadjusted group means were 4.21 for Pain De-Catastrophizing and 4.93 for Pain Education, with an unadjusted mean difference of 0.72. The confidence interval crosses zero, and the unadjusted p-value is 0.28. The sponsor separately reports an ANCOVA result with F = 6.69 and p < .05.

These are statistical summaries, not a complete account of what happened to each participant. The endpoint is self-reported craving on a scale ranging from 0-10, with higher scores reflecting more craving. The assessment was immediately after the intervention, so it does not answer questions about later outcomes. The registry does not post a separate estimate relating pain response to craving, despite that broader association being part of the study’s stated aim.

The comparison also does not include a no-session group. It therefore does not estimate the effect of either education session relative to no intervention. Nor do the posted scores establish whether the sessions changed pain responses, opioid use, or longer-term outcomes. The record does not give a threshold for a clinically meaningful difference, so the practical importance of the observed estimates cannot be determined from these data alone.

Random assignment is listed, but details of the assignment procedure, masking, and analysis population are not reported. Such information is relevant to assessing how well a group comparison supports causal interpretation. The sponsor’s adjusted analysis and the unadjusted re-calculation use different methods, and the ANCOVA details are insufficient to explain their different inferential results. A careful reading keeps each result attached to its method and outcome, rather than treating either as a universal conclusion about pain education or opioid craving.

17. Why This Trial Matters Statistically

This trial illustrates why a clinical result should be read together with its endpoint, comparison, time point, and analysis method. The primary outcome is a continuous participant-reported craving score immediately after the intervention. The study’s broader aim concerns the association between response to pain and opioid craving, but the posted primary outcome is a between-group comparison of craving. Keeping those questions distinct prevents a group difference from being mistaken for an estimate of an association.

The record also offers an example of how an adjusted sponsor analysis and an unadjusted re-calculation can yield different reported inferences. The ANCOVA result is reported with p < .05; the re-calculation from the group summaries gives p = 0.28 and an interval that crosses zero. Those results cannot be compared as if they used the same model. Because adjustment details are absent, readers cannot identify which covariates were included or reconstruct the sponsor estimate. Reporting both the estimate and its method is essential for transparent interpretation.

Finally, the planning illustrations make clear that sample-size needs depend on the effect a study aims to detect. Smaller assumed effects require more participants under the stated planning assumptions. These calculations are not the original protocol’s justification, and they are not observed power. Together, the posted results and missing methodological details demonstrate the value of separating observed data, sponsor analyses, and planning assumptions when evaluating a clinical trial statistically.

18. 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 posted primary outcome is limited to one assessment immediately after the intervention. The registry does not report follow-up craving outcomes, a separate primary pain-response measure, or an estimate of the stated association between pain response and craving. As a result, the posted outcome cannot establish whether any relationship persists over time or how pain response relates to craving.

The groups received different education sessions, with no untreated or usual-care comparator listed. The comparison therefore concerns the two sessions as described, not either session against no intervention. The record does not report the full session content, duration, delivery, adherence, or concurrent care, so the intervention contrast cannot be characterized in greater detail.

The sponsor’s ANCOVA is not fully specified: covariates, adjusted estimates, confidence intervals, diagnostics, and the analysis population are not reported. Missing-data procedures, exclusions, and handling of protocol deviations are also absent. This makes the sponsor analysis difficult to reproduce and limits interpretation of its relationship to the unadjusted calculation. The registry lists a single-masked design but does not identify who was masked or describe the randomization procedure or allocation concealment.

The outcome is self-reported, and the registry does not provide participant-level score distributions or characteristics that would help readers assess how broadly the results apply. The posted adverse-event counts are zero, but definitions and monitoring details are not reported. Finally, the registry does not report the original sample-size justification, multiplicity plan, or threshold for a meaningful craving-score difference. These limitations identify what cannot be assessed from the record; they do not demonstrate that any unreported procedure was inadequate.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Pain, Inflammation and Opioid Craving — NCT04190563.
• Registry record last updated 2026-08-13; status last verified 2026-08.
• Results first posted 2026-08-13.
• 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.

22. Record Summary

The registry record describes a completed randomized, single-masked, parallel-group study of brief behavioral education for adults with opioid-use disorder. Participants were assigned to Pain De-Catastrophizing or Pain Education. Enrollment is listed as 83, and the primary completion date is 2025-07-31.

The primary outcome is mean Opioid Craving Scale score immediately after the intervention. The posted means are 4.21 and 4.93, and the unadjusted mean difference is 0.72 with a confidence interval spanning zero and p = 0.28. The sponsor reports an ANCOVA result of F = 6.69 with p < .05; details of that model are not reported. Serious adverse events, other adverse events, and deaths are each listed as zero in both groups.

The record does not report the original sample-size rationale, missing-data approach, analysis population, or full statistical plan. Its planning illustrations are based on the observed effect and stated assumptions, not the trial’s original design.