Nonopioid Analgesia After Rotator Cuff Repair: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Nonopioid Analgesia After Rotator Cuff Repair (NCT03818919), a randomized phase 2 study. The primary outcome is Pain Levels.

2. Clinical Question

3. Trial Design

The registry describes a randomized, single-blinded, parallel-group, phase 2 clinical trial comparing two postoperative pain protocols for rotator cuff repair. One arm received the nonopioid protocol and the other received a traditional opioid protocol. The registry record labels the study completed and reports enrollment of 70. It lists Henry Ford Health System as sponsor.

The posted primary outcome data include 17 patients for the nonopioid protocol and 23 for the traditional protocol. These outcome counts differ from the enrollment figure. The registry record does not explain the difference, so it should not be attributed to withdrawal, missing measurements, exclusions, or any other particular reason. Nor does the record describe whether the outcome counts represent all randomized participants or a subset defined by an analysis rule.

The trial is described as single blinded, but the registry record does not identify who was blinded or explain how blinding was maintained. It also does not report allocation concealment, the method used to generate the random assignment, or the protocol details needed to assess treatment delivery. The record gives a start date of 2019-01-22 and a primary completion date of 2020-12-31; it does not provide further context about recruitment or follow-up.

Randomization can help balance factors that might affect pain outcomes, but it does not guarantee balance in a particular trial, especially when the analyzed groups are limited in size. A parallel-group comparison evaluates the outcomes in separately assigned groups. The available registry information supports describing the design and posted arm summaries, but it does not support assumptions about details that the record leaves unreported.

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 Pain Levels, measured over day 10 post-operative.

The primary endpoint is pain level at day 10 post-operative. Patients recorded pain using visual analog scales over 10 days after surgery, and the registry says an average daily pain score was calculated for each patient. The scale ranges from 0 for no pain to 10 for worst pain. A higher score represents worse pain control. The posted outcome is continuous and is summarized by a mean and standard deviation in each arm.

A pain scale provides a way to represent a patient-reported experience numerically. Averaging daily scores gives a summary of pain over the recorded period for each patient, rather than focusing on a single daily observation. Comparing arm means then describes the difference in average scores between the assigned protocols. This type of summary is useful for assessing the direction and magnitude of an average group contrast, while the standard deviations describe how much individual scores vary within each arm.

The endpoint should be interpreted according to its stated measurement and timing. The posted comparison concerns the average daily pain outcome summarized at the day 10 post-operative timeframe. It does not report every participant's daily trajectory, a separate estimate for each of the 10 days, or another outcome such as function or medication use. Further details about how incomplete daily records were handled are not reported in the registry record.

7. Results Posted in the Registry

• Post-Operative Traditional Pain Protocol: mean 3.00 versus 2.40 on control; difference 0.60 (95% CI -0.64 to 1.84), standardized effect d = 0.31; z-test p = 0.343.

8. Statistical Interpretation

9. Statistical Methods Explained

The posted comparison uses a mean difference for a continuous outcome. A mean is the arithmetic average of the patient-level average pain scores in an arm. The difference is calculated by subtracting the nonopioid-arm mean from the traditional-arm mean, giving 0.6. With this ordering, a positive value indicates a higher average score in the traditional arm; because higher scale values correspond to worse pain control, the direction is straightforward to interpret. This is a description of the observed contrast, not an adjusted estimate.

What does the standard deviation describe?

In general, a standard deviation describes the spread of individual observations around a mean. It is not the same as the uncertainty in the mean itself: the standard deviation reflects variability among patient scores, while the standard error reflects uncertainty in an estimated mean or contrast. The posted arm standard deviations are 2.1 and 1.8. The registry record does not report individual-level data, so the distribution, outliers, and shape of scores cannot be assessed from these summary statistics alone.

How is a mean difference interpreted?

In general, a mean difference is most directly interpretable when the compared measurements use the same scale and are summarized over comparable populations and timeframes. Here the arms share the stated visual analog scale and the day 10 post-operative timeframe. The mean difference of 0.6 is expressed in scale units. Its sign reflects the subtraction order, and its magnitude is an estimate subject to sampling uncertainty. The record does not report a threshold for a clinically important difference, so statistical estimates cannot be translated into a judgment about clinical importance from this record alone.

What does the confidence interval add?

In general, a confidence interval presents a range of values compatible with the data and the method used to estimate uncertainty. The posted 95% confidence interval for the mean difference is -0.64 to 1.84. It communicates uncertainty around the point estimate rather than a range containing a known proportion of individual patient scores. It also does not mean that every value in the interval is equally plausible, or that values outside it are impossible. Its interpretation depends on the statistical assumptions and the analysis used.

What does the p-value say?

In general, a p-value measures how unusual results at least as discrepant as the observed result would be under a specified null hypothesis and statistical model. The posted unadjusted p-value is 0.343. It is not the probability that the null hypothesis is true, and it does not measure the size or clinical importance of an effect. A p-value should be considered alongside the estimate and confidence interval, rather than used alone to summarize the result. The registry record does not report a sponsor statistical analysis to compare with the posted unadjusted result.

Why do sample sizes and variation matter?

In general, uncertainty in a group comparison depends on the amount of information in each arm and the variation in the outcome. More variability makes an average harder to estimate precisely, while additional observations can improve precision if the other conditions are comparable. Here, the posted outcome counts are 17 and 23, and the arm standard deviations are 2.1 and 1.8. These features help explain why the point estimate should be read together with its interval. They do not allow reconstruction of unreported participant-level results or analysis choices.

What can and cannot be inferred from the posted summary?

The posted estimate is a comparison of arm means. It does not show whether pain scores changed over time in either arm, because the arm-specific daily trajectories are not reported. It does not establish that treatment assignment was followed in every case, because adherence information is not reported. The record does not describe adjustment for covariates, missing-data methods, an intention-to-treat analysis, or another analysis population. Those details are important to evaluating the analysis and should not be inferred from a mean, standard deviation, confidence interval, or p-value.

All statistical interpretations also depend on the analysis methods being appropriate for the data. General statistical practice considers features such as the distribution of the outcome, the independence of observations, and the handling of missing measurements. The registry record does not report diagnostics or detailed methods for assessing these features. The available summary supports a cautious reading of the reported mean contrast and its uncertainty, but not a more detailed reconstruction of the analysis.

10. Confidence Intervals and Precision

The mean-difference estimate is 0.6 points, with a 95% confidence interval from -0.64 to 1.84. This interval is the most direct guide to the precision of the estimated contrast. It is broad enough to include zero and values on either side of zero, so the point estimate does not pin down the direction of the underlying difference. The interval also includes differences larger in magnitude than the observed estimate.

In general, a confidence interval reflects both the estimated effect and its uncertainty under a statistical method. It is not a prediction interval for individual pain scores, and it does not say that each value inside the interval is equally likely. The posted interval concerns the difference between group means, not the range of scores among patients. The group standard deviations, 2.1 and 1.8, describe that within-arm spread separately.

Precision and clinical importance are different questions. The registry record does not report a threshold defining a clinically important mean difference, so the interval cannot be classified against such a threshold from the available information. Nor does the interval establish that the protocols are equivalent. A wide interval can leave uncertainty about effects in either direction even when a single point estimate is available.

The estimate is based on the posted outcome counts of 17 and 23. The registry record does not describe whether missing observations or exclusions affected these counts, or whether any adjusted analysis was performed. Such unreported details matter when assessing how well the interval captures uncertainty for the intended trial population. The confidence interval should therefore be read as the uncertainty accompanying the posted unadjusted summary comparison, not as a complete account of every possible source of uncertainty.

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 figures are planning illustrations expressed as participants per arm, not total event counts. They use the observed mean difference as a reference and show how the number of participants per arm changes when planning to detect the full observed effect or a smaller fraction of it. For the observed effect, the illustrations list 163 participants per arm for 80% power and 218 participants per arm for 90% power. For planning for 75% of the observed effect, they list 290 participants per arm for 80% power and 388 participants per arm for 90% power. For planning for 50% of the observed effect, they list 652 participants per arm for 80% power and 872 participants per arm for 90% power.

The calculations assume a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The registry record does not report the trial's original design assumptions or sample-size justification; these illustrations are based on the observed effect and are not a report of the original plan. This is not observed power.

In general, the 80% power column represents the planning size associated with an 80% chance of detecting the specified effect under the stated assumptions if that effect is present. The 90% power column uses a higher target chance of detection and therefore calls for more participants per arm in these illustrations. Smaller effects need more participants to distinguish them from sampling variation, which is why the listed requirements increase when the target is a smaller fraction of the observed effect. These numbers are hypothetical planning aids, not evidence that the trial had those group sizes or that its observed result had a particular probability of being correct.

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 = 0.600; pooled standard deviation σ = 1.932.
2. n = 2 × (1.96 + 0.842)² × 1.932² / 0.600² = 162.8, rounded up to 163 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 <- 0.6                      # observed difference in means
sigma <- 1.93200196142431                     # 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(3818919)
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 = 163 (80% power), 218 (90% power)
 75% of observed effect: n per arm = 290 (80% power), 388 (90% power)
 50% of observed effect: n per arm = 652 (80% power), 872 (90% power)
power.t.test: 163.7 
Simulated power at n = 163 per arm: 0.795 (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

The registry lists 2 outcome measures, but it posts no secondary outcomes. It lists 0 analyses. The posted primary comparison is unadjusted, and no sponsor-reported statistical analysis is included in the registry information. The record does not report whether the primary comparison was prespecified in a statistical analysis plan, whether other analyses were conducted, or whether there was any adjustment for multiple comparisons.

In general, multiplicity arises when researchers evaluate multiple outcomes, timepoints, subgroups, or statistical tests. Repeated opportunities to identify a result can increase the chance of at least one apparently notable result, and statistical plans may address that issue in different ways. The registry information does not permit assessment of whether or how multiplicity was considered. Although pain was collected over 10 days, the posted primary comparison is tied to the stated day 10 post-operative timeframe; the record does not provide separate daily comparisons or explain selection among timepoints.

The registry record does not report how missing pain measurements were handled, whether any imputation was used, or how patient-level daily records were combined when records were incomplete. It also does not specify whether the analysis followed an intention-to-treat, per-protocol, or other population definition. The outcome counts are 17 in the nonopioid arm and 23 in the traditional arm, but the reason these counts differ from the registry enrollment figure is not reported. No explanation should be inferred from the counts alone.

Interim analyses, stopping rules, and the handling of protocol deviations are also not reported in the registry record. These omissions do not change the arithmetic of the posted arm summaries, but they limit the ability to evaluate the full analysis process and the risk of selective reporting. A complete statistical interpretation would require those details; in their absence, the posted comparison is best treated as an unadjusted summary with unresolved questions about the analysis population and missing data.

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 5% reporting threshold.

Most frequent non-serious adverse event terms

The posted serious adverse event counts are 0 in the nonopioid-protocol arm and 0 in the traditional-protocol arm. The deaths count is also 0 in each arm. The registry lists no serious adverse event terms. These are counts recorded in the registry, not proof that no serious events occurred outside the reported information or that the protocols have identical safety profiles.

For other adverse events, the registry reports 8 affected participants among 17 at risk in the nonopioid arm, and 10 affected participants among 23 at risk in the traditional arm. These are counts of participants affected, rather than a description of event severity or event types. The record does not list which non-serious events occurred, how many events each participant experienced, their timing, or whether investigators considered them related to a protocol.

In general, adverse-event counts are interpreted in light of how events were defined, collected, and followed up. The registry record does not provide those details or a comparative statistical analysis of adverse events. The counts therefore describe the posted safety information and should not be treated as a definitive comparison of risk.

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

The posted data describe average pain scores in the two trial arms at the day 10 post-operative timeframe. The nonopioid-protocol arm had a mean of 2.4, while the traditional-protocol arm had a mean of 3.0. The estimated mean difference, traditional minus nonopioid, was 0.6 points. The 95% confidence interval, -0.64 to 1.84, shows substantial uncertainty about the direction and size of the underlying mean contrast. The unadjusted p-value was 0.343.

These results do not establish equivalence between the protocols. Demonstrating equivalence requires a prespecified margin and an analysis designed to evaluate whether the uncertainty lies within that margin; such a margin and analysis are not reported in the registry record. The results also do not establish that one protocol is superior. The estimate is compatible with differences in either direction, and the record does not provide a clinical-importance threshold for judging the size of possible differences.

The comparison is limited to the stated pain outcome and timeframe. It does not answer questions about pain on each individual day, longer-term outcomes, function, medication consumption, or other aspects of recovery. Those outcomes are not reported as results in the registry record. The posted adverse-event counts provide limited descriptive safety information and do not resolve comparative safety.

Random assignment is a design feature that can support causal comparisons when the trial is conducted and analyzed as intended. However, information about the randomization process, analysis population, missing data, adherence, and statistical plan is not reported. The posted summary therefore should not be stretched into claims about all patients undergoing rotator cuff repair or about treatment effects outside the measured trial context. It describes the available registry results, with the precision and limitations stated, rather than giving a recommendation for care.

16. Why This Trial Matters Statistically

This trial illustrates why an estimated difference should be interpreted together with its uncertainty. The arm means point in one direction, but the confidence interval includes zero and values on both sides. The p-value alone would not convey that range of compatible estimates, while the point estimate alone would conceal the uncertainty. Reading the estimate, interval, and within-arm variation together gives a more complete statistical account.

It also highlights the distinction between an observed effect and a planning assumption. The sample-size illustrations use the observed difference as a reference and show that planning for a smaller effect requires more participants per arm under the stated assumptions. These calculations are useful for understanding how effect size and precision relate, but they do not reveal the trial's original design rationale or constitute evidence of observed power.

The posted outcome counts are smaller than the enrollment figure, and the registry record does not explain why. This makes transparent reporting of analysis populations and missing-data handling particularly relevant. Without those details, readers cannot determine whether outcome availability, exclusions, or another process accounts for the difference. Recognizing this uncertainty is part of evaluating the evidence rather than filling gaps with assumptions.

Finally, the comparison shows the limits of registry-level summaries. Mean scores and adverse-event counts communicate important information, but they cannot substitute for a full statistical analysis plan, participant-level data, or detailed reporting of outcome collection. The result is most informative when kept tied to its measured endpoint, posted analysis, and confidence interval.

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 leaves several trial-specific uncertainties. It reports enrollment of 70 but gives primary outcome counts of 17 and 23; it does not explain the difference. As a result, the relationship between enrolled participants and those represented in the posted pain summaries cannot be established from the record. Details about eligibility, participant characteristics, and the analysis population are not reported, limiting assessment of how representative the outcome groups are.

The study is described as single blinded, but the record does not identify who was blinded or how blinding was maintained. Allocation concealment and the randomization procedure are also not reported. Medication doses, timing beyond the postoperative description, protocol adherence, and co-interventions are not reported in detail. These omissions limit evaluation of how consistently the assigned protocols were implemented.

The endpoint summarizes average daily pain scores, but the record does not describe missing daily measurements or the method used to handle them. It does not report an analysis plan, covariate adjustment, interim analyses, or a prespecified threshold for clinical importance. No sponsor analysis is posted. The unadjusted summary comparison therefore cannot be evaluated against a fuller protocol-defined analysis using the available registry information.

Safety reporting is also limited: the registry provides counts for serious and other adverse events, but does not give event types for the other category, collection methods, follow-up details, or a comparative analysis. Finally, results concern the stated postoperative pain measure and timeframe. The registry does not report further outcome results that would support broader conclusions about recovery.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: Nonopioid Analgesia After Rotator Cuff Repair — NCT03818919.
• Registry record last updated 2024-04-02; status last verified 2024-03.
• Results first posted 2024-04-02.
• 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 record describes a completed, randomized, single-blinded, parallel-group, phase 2 trial sponsored by Henry Ford Health System. It compares a postoperative nonopioid protocol with a traditional hydrocodone-acetaminophen protocol after rotator cuff repair. Registry enrollment is 70.

The primary outcome is average daily pain measured on a visual analog scale from 0 to 10 at the day 10 post-operative timeframe. Posted means are 2.4 for the nonopioid protocol and 3.0 for the traditional protocol. The unadjusted mean difference is 0.6, with a 95% confidence interval from -0.64 to 1.84 and an unadjusted p-value of 0.343. The posted serious adverse event and death counts are 0 in each arm.

The registry record does not report the sponsor's statistical analysis, the original sample-size rationale, missing-data methods, or the analysis population. The posted comparison is therefore best read as a summary-level result with uncertainty and reporting limitations.