Corticosteroid/Ropivacaine Versus Corticosteroid/Saline Injections for Knee Osteoarthritis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Corticosteroid/Ropivacaine Versus Corticosteroid/Saline Injections for Knee Osteoarthritis (NCT02576249), a randomized phase 4 study. The primary outcome is The Knee Osteoarthritis Outcome Score (KOOS) Pain Subscale.

2. Clinical Question

The registry describes the study as a comparison of corticosteroid with local anesthetic against corticosteroid with normal saline. Its stated rationale is that anesthetic is commonly included in joint injections, while its clinical benefit in this setting was described as uncertain. The trial’s primary outcome was the KOOS Pain Subscale, recorded three months after injection. The posted means were 63.1 for the ropivacaine and methylprednisolone group and 67.2 for the saline and methylprednisolone group. The reported mean difference, expressed as saline and methylprednisolone minus ropivacaine and methylprednisolone, was 4.1 units. This is a comparison of group averages, not a description of every participant’s experience. The registry record does not report a threshold for a clinically important difference, so the statistical result alone cannot establish whether the observed difference would be important to participants.

3. Trial Design

The registry describes NCT02576249 as a randomized, parallel-group, phase 4 trial sponsored by Mayo Clinic. Its status is completed. The record lists enrollment of 29 and study start in 2015-10, with primary completion in 2016-07. It identifies osteoarthritis as the condition under study and describes knee joint injections as the treatments being compared.

One arm received 0.2% ropivacaine with methylprednisolone. The other received 0.9% normal saline with methylprednisolone. Because methylprednisolone appears in both arm descriptions, the contrast is between adding ropivacaine and adding saline, rather than between corticosteroid and no corticosteroid. The record identifies the allocation as randomized and the model as parallel. It describes masking as single, but which people were masked is not reported in the registry record.

The primary outcome was the KOOS Pain Subscale at three months after injection. The registry also names Pain Scale Score and Tegner Activity Level Scale as secondary outcomes. It lists three outcome measures overall, while the posted results identify two secondary outcomes. Results for those secondary measures are not included in the recorded results presented for this comparison.

Further details about the randomization procedure, allocation concealment, injection administration, participant eligibility, and the original statistical analysis plan are not reported in the registry record. The record also does not report the trial’s original sample-size justification or its intended analysis population. The posted outcome information gives group summaries and an unadjusted comparison, but does not describe a model-based or covariate-adjusted analysis.

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 The Knee Osteoarthritis Outcome Score (KOOS) Pain Subscale, measured over 3 months after the injection.

The primary endpoint was the Knee Osteoarthritis Outcome Score (KOOS) Pain Subscale, measured three months after the injection. KOOS contains 42 items divided among five separately scored subscales: Pain, other Symptoms, Function in daily living, Function in Sport and Recreation, and knee-related Quality of Life. The primary endpoint concerns the Pain subscale specifically, not the combined score across all five subscales.

The registry describes responses as using a five-option Likert scale. Items are scored from 0, described as “No Problems,” to 4, described as “Extreme Problems.” The subscale scores are calculated from the items in the relevant subscale and transformed to a 0–100 scale. On the transformed scale, zero represents extreme knee problems and 100 represents no knee problems. This direction matters when interpreting a mean: a higher score corresponds to fewer knee problems according to the registry’s scale description.

A continuous score can summarize the distribution of reported pain-related problems across a group and allows the registry to report a mean and standard deviation. Comparing group means gives a simple description of the average outcome in each randomized arm. It does not show the spread of individual experiences in full, and it does not indicate how many participants experienced a particular degree of change. The record does not report a clinically important difference threshold or a baseline KOOS Pain Subscale result, so those aspects cannot be used to contextualize the three-month means.

7. Results Posted in the Registry

• Saline and Methylprednisolone: mean 67.20 versus 63.10 on control; difference 4.10 (95% CI -7.00 to 15.20), standardized effect d = 0.27; z-test p = 0.469.

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is a continuous score, and the registry reports its mean and standard deviation in each arm. A mean describes the arithmetic average of the observed scores. A standard deviation describes how dispersed individual scores are around that average. These are different quantities: the standard deviation describes participant-level variability, while the uncertainty interval for a mean difference describes uncertainty about the comparison between group averages.

What does the mean difference represent?

The reported comparison is saline and methylprednisolone minus ropivacaine and methylprednisolone. The corresponding arm means are 67.2 and 63.1, and the reported mean difference is 4.1 units. The sign therefore indicates which arm has the higher average on the registry’s score scale. Since higher KOOS Pain Subscale scores represent fewer knee problems, the positive estimate favors the higher mean as a score description; it is not, by itself, proof of a meaningful treatment effect. The record does not state a threshold for clinical importance.

A mean difference focuses on an average contrast. It does not show the full distributions, whether scores were skewed, or whether the average reflects a broadly shared pattern or a smaller number of particularly high or low scores. The registry does not report individual-level data or a distributional summary beyond the standard deviations. Thus, the group means and standard deviations are informative summaries, but they cannot reconstruct the range of individual outcomes.

How should the interval be read?

A confidence interval expresses a range of values for the underlying mean difference that are reasonably compatible with the observed data under the method used. The reported interval runs from -7.003 to 15.2. Because it crosses zero, it includes the possibility of no average difference and also allows for differences in either direction. Its breadth indicates limited precision: the point estimate alone should not be treated as a settled estimate of the effect’s direction or size.

The confidence level and the exact method used to construct this interval are not reported in the registry record. The record also does not explain whether the comparison used a particular distributional assumption, adjustment, or handling of missing outcome data. These details matter when assessing the interval’s statistical properties, so interpretation should stay close to what is posted rather than infer a specific analysis procedure.

What does the p-value add?

The unadjusted p-value is 0.469. In general, a p-value describes how unusual data at least as discrepant as those observed would be under a specified null model, if that model and its assumptions were correct. It is not the probability that the null hypothesis is true, and it does not measure the probability that the result is due to chance. Nor does a p-value indicate the size or clinical importance of a difference. Here, the p-value and interval both point to substantial uncertainty about the mean contrast; neither establishes equivalence.

The term “unadjusted” means the posted p-value is not described as adjusted for multiple comparisons or other factors. The registry record does not report a multiplicity procedure, covariate adjustment, or a more detailed analysis plan. Because several outcome measures are listed, the absence of a reported multiplicity strategy makes it inappropriate to assume that the primary comparison was evaluated within a particular family of tests. No formal analysis entries are listed in the record, although the primary outcome results and comparison statistics are posted.

Why can over-dispersion matter in other kinds of outcomes?

In general, over-dispersion refers to count data varying more than a statistical model expects. If a count model assumes less variability than the data actually contain, standard errors may be too small and intervals may be too narrow. That concept is not the central issue for this primary endpoint: KOOS Pain Subscale is reported as a continuous score, with group means and standard deviations. The registry does not report a count-based primary outcome or a model for over-dispersed counts.

Randomization supports a comparison between groups, but it does not eliminate uncertainty in a small trial. Chance imbalances can remain, and the record does not report baseline outcome values or adjustment for baseline. Without those details, the posted unadjusted contrast should be read as the registry’s reported comparison of follow-up group means, rather than as a claim about change from baseline or an adjusted causal estimate. Further information about the original design assumptions, missing-data handling, analysis populations, and interval construction is not reported in the registry record.

10. Confidence Intervals and Precision

The reported mean difference was 4.1 KOOS Pain Subscale units, with an interval from -7.003 to 15.2. The interval is the most direct indication of precision for the comparison: it spans values below and above zero, so the observed data do not pin down the direction of the underlying difference. Its lower end allows a mean score favoring the ropivacaine arm, while its upper end allows a mean score favoring the saline arm. On this scale, higher scores indicate fewer knee problems.

The point estimate should therefore be read alongside the interval, not in isolation. The value 4.1 is the estimated difference in the observed group means, but the interval indicates that other mean differences remain compatible with the data under the interval’s method. The unadjusted p-value of 0.469 is consistent with this uncertainty; it is not evidence that the groups are equivalent, and it does not quantify the probability that the observed difference is real.

The group standard deviations, 16.1 and 14.4, describe observed variation in scores within the arms. They are not confidence intervals and do not directly state how precisely the arm means or their difference have been estimated. The arm sizes are 15 and 14, so each group summary is based on a small number of observations. The registry does not report the confidence level or interval-construction method, and does not provide baseline scores or a clinically important difference threshold. Those omissions limit further assessment of statistical and clinical precision. The result supports a cautious description of the observed averages, not a precise conclusion about the size or importance of a difference.

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 planning figures are participants per arm, not total events. They are illustrations based on the observed effect rather than the trial’s original design. The assumptions listed for these calculations 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 at the stated fraction of the observed effect. The trial’s own original sample-size assumptions and justification are not reported in the registry record.

For planning around 100% of the observed effect, the illustration gives 219 participants per arm for 80% power and 293 participants per arm for 90% power. For 75% of the observed effect, it gives 389 participants per arm for 80% power and 521 participants per arm for 90% power. For 50% of the observed effect, it gives 875 participants per arm for 80% power and 1,172 participants per arm for 90% power. These are hypothetical planning scenarios, not observed trial results.

In general, power is the probability that a study will detect an effect of a specified size under the assumptions of its statistical model and design. The 80% column gives the participant count per arm in the illustration for an 80% chance of detecting the specified effect; the 90% column gives the count per arm for a 90% chance. Higher power generally requires more participants when the other assumptions remain fixed. The figures also show that smaller effects need more participants: planning for a smaller fraction of the observed effect produces larger per-arm requirements.

These calculations are not observed power. They are planning illustrations, and their inputs depend on the observed effect, which is uncertain in a small trial. They should not be read as evidence that a future study will have exactly the stated power or as a recommendation for a particular design. The registry record does not report the investigators’ original planned effect size, target power, or recruitment assumptions.

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 = 4.100; pooled standard deviation σ = 15.305.
2. n = 2 × (1.96 + 0.842)² × 15.305² / 4.100² = 218.7, rounded up to 219 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 <- 4.1                      # observed difference in means
sigma <- 15.3050705710619                     # 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(2576249)
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 = 219 (80% power), 293 (90% power)
 75% of observed effect: n per arm = 389 (80% power), 521 (90% power)
 50% of observed effect: n per arm = 875 (80% power), 1,172 (90% power)
power.t.test: 219.7 
Simulated power at n = 219 per arm: 0.800 (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 a primary KOOS Pain Subscale outcome and names Pain Scale Score and Tegner Activity Level Scale as secondary outcomes. It also reports three outcome measures overall. Considering multiple outcomes can create a multiplicity issue: when several statistical tests are performed, the chance of finding at least one apparently unusual result can increase. In general, investigators may address this by identifying a primary endpoint in advance, adjusting for multiple testing, or treating secondary analyses as exploratory. The registry record does not report a multiplicity adjustment, a family of tests, or details of a prespecified testing hierarchy.

The posted comparison for the primary endpoint is described with an unadjusted p-value of 0.469. It should not be assumed to have been adjusted for the secondary outcomes. The record does not report statistical results for the named secondary outcomes in the results. Nor does it report whether additional outcome analyses were conducted outside the posted entries. The original analysis plan and the timing of any analysis decisions are not reported in the registry record.

Missing-data methods are also not reported in the registry record. The arm counts for the primary outcome are 15 and 14, but the record does not describe whether these represent all randomized participants with available endpoint data, an analysis subset, or another analysis population. It does not report the number or reasons for missing KOOS measurements, how missing values were handled, or whether any sensitivity analyses were performed. The reported group summaries should therefore be interpreted without assuming complete follow-up or a particular imputation method.

The record identifies randomized allocation but does not describe an intention-to-treat analysis, a per-protocol analysis, or another named analysis population. It also does not report baseline outcome adjustment or a model for repeated measurements. These absences do not demonstrate that such procedures were not used; they mean that the registry record does not document them. Consequently, readers cannot determine from the posted record how missingness, multiplicity, or analysis-population choices may have affected the estimate. The most transparent reading is to treat the reported values as the posted outcome summaries and unadjusted comparison, without extending them to undocumented analyses.

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 safety counts separately by arm. In the ropivacaine and methylprednisolone group, 15 participants were listed as at risk for serious adverse events and zero serious adverse events were recorded; the same group had 15 at risk for other adverse events and zero such events recorded. In the saline and methylprednisolone group, 14 were listed as at risk for serious adverse events and zero serious adverse events were recorded; 14 were listed as at risk for other adverse events and zero other adverse events were recorded. The record lists zero deaths in each group.

These figures describe events recorded in the registry’s reported categories. A zero count means no event in that category was recorded for the stated group; it does not prove that the risk is zero or that no symptoms or other experiences occurred. The registry does not report detailed event definitions, the safety follow-up period, or the methods used to collect adverse events. With small arm sizes, the absence of recorded events also leaves substantial uncertainty about uncommon harms. The safety counts should be interpreted as descriptive rather than conclusive evidence about comparative safety.

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

The primary result is a comparison of average KOOS Pain Subscale scores three months after injection. The saline and methylprednisolone arm had a mean of 67.2, while the ropivacaine and methylprednisolone arm had a mean of 63.1. The reported mean difference was 4.1 units in the direction of the saline arm. Because higher values on the transformed KOOS scale represent fewer knee problems, the observed mean was higher in the saline arm. This describes the posted group averages; it does not establish that the difference was clinically important.

The interval from -7.003 to 15.2 includes zero and allows differences in either direction. The unadjusted p-value of 0.469 likewise does not provide strong evidence against a zero-difference null under the test used, but it cannot establish that the treatments have identical effects. A failure to establish a difference is not the same as evidence of equivalence. The registry does not report an equivalence margin, a non-inferiority margin, or a clinically important difference threshold.

The outcome is measured at one reported follow-up time. The record does not provide baseline KOOS values or a change-from-baseline comparison, so the scores cannot be used to infer how much participants improved or worsened after injection. Group means also do not describe every participant’s response. The posted summaries do not identify how many participants had better or worse scores, nor do they indicate the distribution of individual changes.

The trial compares two injection mixtures in which methylprednisolone is included in both arms. The result therefore pertains to the contrast between adding ropivacaine and adding normal saline in this study, rather than to corticosteroid versus no corticosteroid. It should not be generalized beyond the population, treatment conditions, outcome, and follow-up documented in the registry. Further eligibility details and the original analysis plan are not reported in the registry record.

The safety entries record zero serious adverse events, zero other adverse events, and zero deaths in each arm. These counts are limited to the record’s reported categories and cannot rule out events that were not observed, recorded, or captured in the stated follow-up. Taken together, the posted results show uncertain evidence about the difference in average pain-subscale scores and no recorded events in the reported safety categories. They do not prove equal effects, determine clinical importance, or establish the absence of risk.

16. Why This Trial Matters Statistically

This trial illustrates why a point estimate should be read with its uncertainty interval. The observed mean difference is 4.1 units, but the interval extends from -7.003 to 15.2. The point estimate gives one summary of the observed contrast; the interval shows that the data do not precisely identify the direction or size of the underlying average difference. A p-value alone would not convey that range of plausible estimates.

It also illustrates the distinction between statistical evidence and clinical importance. The p-value is 0.469, and the interval includes zero, but these findings do not demonstrate equivalence. Conversely, the numerical difference between group means does not by itself establish a clinically meaningful advantage. The registry does not report a clinically important difference threshold or an equivalence margin, so those judgments cannot be made from the posted statistics alone.

Small randomized comparisons can produce informative estimates while still leaving wide uncertainty. The arm counts are 15 and 14, and the standard deviations show substantial variation in scores within each group. The planning illustrations reinforce the general relationship between the effect size a study aims to detect and the participant count required, but they are based on the observed effect and are not the trial’s original design justification.

Finally, interpretation depends on transparent reporting beyond the headline outcome. The registry does not report the confidence-interval method, missing-data handling, analysis population, multiplicity strategy, or baseline KOOS results. These details would help readers assess how the estimate was generated and how robust it is to analytic choices. The study’s value statistically lies not in a definitive answer, but in showing the observed contrast and the substantial uncertainty that remains in the posted results.

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 details unclear. It identifies the study as randomized, single-masked, and parallel-group, but does not say who was masked or describe the randomization and allocation-concealment procedures. It does not provide detailed eligibility criteria or a fuller description of the enrolled population beyond osteoarthritis and the knee-injection context. These omissions limit assessment of how the trial was conducted and to whom its results may apply.

The primary outcome is reported at three months after injection, but baseline KOOS Pain Subscale results and change-from-baseline estimates are not reported in the registry record. The record does not state whether the posted group means include all randomized participants, how missing outcome data were handled, or whether the analysis was adjusted for baseline values. It also does not report the confidence-interval construction method or confidence level. Those gaps make it difficult to assess the sensitivity of the estimate to analytic decisions.

The original sample-size rationale and intended statistical plan are not reported. Although planning illustrations are available based on the observed effect, those calculations do not establish what the investigators planned before the trial. The registry lists secondary outcomes, but their results are not included in the posted comparison, and a multiplicity approach is not reported. A clinically important difference threshold is also absent, limiting interpretation of the score difference in practical terms.

The safety record lists no events in the reported categories, but does not describe event definitions, collection procedures, or the duration of safety monitoring. The small group sizes and limited posted details mean the zero counts should not be treated as proof that adverse events cannot occur. These are limitations of the information documented in the registry record; they do not establish that unreported procedures or analyses were not performed.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: Corticosteroid/Ropivacaine Versus Corticosteroid/Saline Injections for Knee Osteoarthritis — NCT02576249.
• Registry record last updated 2017-08-21; status last verified 2017-07.
• Results first posted 2017-07-21.
• 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

NCT02576249 is a completed randomized, parallel-group, phase 4 trial sponsored by Mayo Clinic. The registry lists enrollment of 29 and compares knee joint injections containing methylprednisolone with either 0.2% ropivacaine or 0.9% normal saline. Masking is described as single, but the masked parties are not reported in the registry record.

The primary outcome was the KOOS Pain Subscale at three months after injection. The mean was 63.1 in the ropivacaine and methylprednisolone arm and 67.2 in the saline and methylprednisolone arm. The reported mean difference was 4.1, with an interval from -7.003 to 15.2 and an unadjusted p-value of 0.469. The interval includes zero and indicates uncertainty about the direction and size of the difference.

The registry lists Pain Scale Score and Tegner Activity Level Scale as secondary outcomes. It records zero serious adverse events, zero other adverse events, and zero deaths in each arm. Details about the original design assumptions, missing-data procedures, analysis population, and statistical plan are not reported in the registry record.