Efficacy of Cooled and Monopolar Radiofrequency Ablation of the Geniculate Nerves for the Treatment of Chronic Osteoarthritic Knee Pain: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Efficacy of Cooled and Monopolar Radiofrequency Ablation of the Geniculate Nerves for the Treatment of Chronic Osteoarthritic Knee Pain (NCT02260869), a randomized na study. The primary outcome is Evidence of Change in Knee Pain.

2. Clinical Question

3. Trial Design

The registry describes a prospective, randomized, parallel-group trial at a single center. Participants were assigned to cooled radiofrequency ablation or conventional monopolar radiofrequency ablation. The study is listed as triple masked, although the record does not identify which individuals were masked or describe how masking was maintained. Allocation concealment procedures are not reported in the registry record.

The registry lists enrollment of 79 and a terminated status. Its brief summary describes an intended enrollment of approximately 102; the reason for termination and the circumstances behind the difference between intended and recorded enrollment are not reported in the registry record. The record lists a start date of 2015-01 and a primary completion date of 2018-10-15. It identifies the sponsor as Millennium Pain Center and lists the phase as NA.

The summary describes eligibility based on chronic knee pain, moderate to severe osteoarthritis according to the Kellgren-Lawrence scale, symptoms for at least 6 months, and failure of conservative therapy. It also says enrollment depended on reporting at least 50% pain relief after a fluoroscopic guided diagnostic block using local anesthetic. Further eligibility criteria, including any exclusions, are not reported in the registry record.

Baseline data were to be collected, with outcomes scheduled at 1, 4, 12, 24, and 52 weeks. The primary outcome reported for comparison is pain change at 24 weeks, and the posted secondary outcome is the Oxford Knee Score at 24 weeks. The registry does not report whether all planned follow-up visits were completed or how many participants contributed data at other time points.

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 Evidence of Change in Knee Pain, measured over 24 weeks.

The primary endpoint measures change in knee pain from baseline to 24 weeks using a 100 mm visual analogue scale. The registry defines the scale as a line from 0, meaning no pain, to 100 mm, meaning the worst pain imaginable. Each participant’s change is defined as the 24-week score minus the baseline score. Consequently, a negative change denotes a reduction in the recorded pain score over that interval.

Comparing mean change between randomized groups addresses whether the average recorded change differed between the two procedures over the specified follow-up. A change score incorporates both the starting and follow-up measurements in a single outcome, but group means alone do not show each participant’s experience or the distribution of individual changes. The registry reports group means and standard deviations, rather than individual observations.

This endpoint is used because pain is the trial’s stated central outcome and the VAS gives a numerical measure that can be summarized and compared statistically. The record does not report a threshold for a clinically important difference, so the statistical contrast cannot by itself establish whether a difference would be meaningful to participants. Nor does the registry record explain the rationale for selecting 24 weeks as the primary assessment point.

7. Results Posted in the Registry

• Monopolar Radiofrequency Ablation: mean -38.60 versus -40.70 on control; difference 2.10 (95% CI -10.26 to 14.46), standardized effect d = 0.08; z-test p = 0.739.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Evidence of Functional Changes

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Monopolar Radiofrequency Ablation: mean 12.70 versus 10.70 on control; difference 2.00 (95% CI -2.43 to 6.43), standardized effect d = 0.20; z-test p = 0.376.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Monopolar Radiofrequency Ablation and the control. The interval gives the range of effects that remain compatible with the data.

The registry posts one secondary outcome, Evidence of Functional Changes, measured with the Oxford Knee Score at 24 weeks. Its group summaries and between-group comparison are available alongside the primary pain outcome. The secondary contrast is numerically positive, and its confidence interval includes zero. The record does not provide a scale-direction explanation or a clinical-importance threshold for this score, so the numerical direction alone does not establish whether the contrast represents a favorable difference.

At a broad level, the primary and secondary comparisons both have confidence intervals that include zero. This means neither posted comparison precisely resolves whether there is an average difference between the randomized groups. The secondary result does not overturn or independently settle the primary result; it is an additional outcome that may inform a broader view of the trial, subject to its own uncertainty and reporting limitations.

The secondary p-value is unadjusted. When several outcomes, time points, or analyses are examined, the chance of at least one apparently notable result can increase. In general, multiplicity procedures can address that issue, but the registry record does not report a correction or a hierarchy governing how secondary findings should be interpreted. This is why an unadjusted secondary result ordinarily carries less confirmatory weight than a clearly designated primary endpoint analyzed under a prespecified plan.

The registry summary lists several follow-up times for outcome measurement, while the posted secondary comparison pertains to 24 weeks. It does not report a full set of secondary analyses across all scheduled visits or explain whether other measures listed in the summary were analyzed but not posted. The available secondary result is therefore one part of the reported evidence, not a comprehensive account of every planned functional or patient-reported assessment.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Evidence of Functional Changes

9. Statistical Interpretation

10. Statistical Methods Explained

The main reported quantities are means and standard deviations for continuous outcomes. A mean describes the average recorded value or change in a group. A standard deviation describes how dispersed individual observations are around that group’s mean; it is not the uncertainty interval for the mean and does not imply that every participant had a result close to the average. Here, the primary endpoint is a change score in millimetres, and the secondary endpoint is an Oxford Knee Score.

What does the mean difference represent?

The primary comparison is expressed as a mean difference between monopolar and cooled radiofrequency ablation. The reported estimate is 2.1 mm. Its sign follows the comparison’s stated ordering: the monopolar group’s mean change is compared with the cooled group’s mean change. Because the primary endpoint is defined as follow-up minus baseline, negative values indicate a reduction in VAS score. The estimate is a difference in group averages, not a change experienced by every participant.

The confidence interval gives a range of values compatible with the observed data under the statistical method used and its assumptions. It is useful for judging both the estimated direction and the precision of the contrast. An interval that includes zero does not establish equality; it indicates that no difference remains among the values compatible with the interval. The registry’s comparison interval runs from -10.26 to 14.46 mm, so it includes negative, zero, and positive differences. The record does not report the model specification or all assumptions used to construct the interval.

How should the p-value be read?

The unadjusted p-value for the primary contrast is 0.739. In general, a p-value describes how unusual data at least as inconsistent with a specified null hypothesis would be if that hypothesis and the statistical model were correct. It is not the probability that the null hypothesis is true, nor a measure of the probability that the procedures differ. It also does not measure clinical importance. Since the registry labels the value unadjusted, it should not be treated as accounting for possible testing across outcomes or analyses.

The secondary comparison also has an unadjusted p-value, 0.376. The same general interpretation applies. Neither value supplies information about missing outcomes, masking success, or the suitability of the analysis population. Those matters require information about study conduct and analysis that is not reported in the registry record.

Why do sample-size illustrations depend on an assumed effect?

Planning calculations ask how many participants a future study would need, under specified assumptions, to have a chosen probability of detecting an effect of a given size using a particular test. The registry’s planning illustration uses the observed effect and also considers planning for 75% and 50% of the observed effect. It specifies a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. These are assumptions for the illustration, not evidence about the trial’s original design.

For the continuous outcomes in this record, the planning figures are participants per arm. The calculation uses a fraction of the observed contrast as the effect to detect. Smaller target effects require more participants, all else equal, because they are harder to distinguish from random variation. These figures are planning illustrations, not observed power, and they do not explain why the trial enrolled or stopped at its reported enrollment.

What can and cannot be inferred from aggregate summaries?

Group means, standard deviations, and a reported comparison are useful for understanding the average contrast and its uncertainty. They do not reveal the shape of the outcome distributions, outliers, participant-level changes, or the relationship between baseline and follow-up measurements. Nor do they show whether the comparison was adjusted for baseline values or other variables. Such details are not reported in the registry record.

In general, statistical results depend on the design, analysis model, and completeness of outcome data. Randomization supports a between-group comparison, but interpretation still depends on how assignment was implemented, whether participants remained in their assigned groups for analysis, and how missing observations were handled. The registry identifies randomized allocation but does not describe these analysis details. As a result, the reported group summaries should be interpreted as the posted aggregate results, not as a substitute for a complete statistical analysis plan or participant-level reporting.

11. Confidence Intervals and Precision

Precision concerns how tightly the data locate an estimated difference. The primary mean difference is 2.1 mm, and its 95% confidence interval extends from -10.26 to 14.46 mm. The interval includes zero, so the posted result is compatible with no average difference as well as with differences in either direction. The range is broad relative to the point estimate, which limits how specifically the trial can locate the primary contrast.

A confidence interval is not a guarantee that the true effect lies within its endpoints. In general, it is a method-based range that would capture the underlying value in a stated proportion of repeated studies if the model and its assumptions held. For one study, the interval is best read as expressing uncertainty around the estimate, not as a set of equally likely values. The registry does not report additional sensitivity analyses that would show how the interval changes under different assumptions.

The group standard deviations, 26.8 mm and 27.8 mm, describe variation in participant-level changes around the respective means. They help convey that the individual changes vary, but they are not confidence limits for the group means. The reported sample sizes are 38 and 37; the record does not explain whether these represent all randomized participants with available endpoint data or a different analysis population.

The secondary endpoint also has an interval that includes zero: its mean difference is 2.0 points, with a 95% confidence interval from -2.427 to 6.427. No clinical-importance threshold is reported for either endpoint. Therefore, precision can be discussed statistically, but the registry alone does not establish which values would matter to participants or clinicians.

12. 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 assumptions. For these continuous outcomes, the figures are participants per arm, not total events. The stated planning assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The target effect is the stated fraction of the observed effect. The trial’s own sample-size justification and original design assumptions are not reported in the registry record.

The 80% power column describes the number of participants per arm that the calculation estimates would give an 80% chance of detecting the assumed effect under those planning conditions, if that effect and the model assumptions were correct. The 90% power column describes the corresponding number for a 90% chance. These are prospective planning quantities, not probabilities that the completed trial’s result is correct or that a treatment has an effect. The figures are not observed power.

The illustrations include planning for 100%, 75%, and 50% of the observed effect. As the assumed target effect gets smaller, the required number of participants per arm increases. This reflects a general feature of study planning: smaller differences are more difficult to distinguish from random variation, so greater sample sizes are needed when other assumptions remain fixed.

The planning figures should not be read as a reconstruction of why enrollment was 79 or why the study was terminated. The record does not report the original target’s justification, any changes to that target, or reasons for stopping. A graphical presentation of the calculations should be read under the same assumptions as the listed planning figures, rather than as a forecast of the results of this trial.

13. 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 = 2.100; pooled standard deviation σ = 27.298.
2. n = 2 × (1.96 + 0.842)² × 27.298² / 2.100² = 2,652.5, rounded up to 2,653 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 <- 2.1                      # observed difference in means
sigma <- 27.2977293450803                     # 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(2260869)
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 = 2,653 (80% power), 3,551 (90% power)
 75% of observed effect: n per arm = 4,716 (80% power), 6,313 (90% power)
 50% of observed effect: n per arm = 10,610 (80% power), 14,204 (90% power)
power.t.test: 2653.4 
Simulated power at n = 2,653 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.

14. Multiplicity, Missing Data and Analysis Populations

Multiplicity arises when a study tests more than one outcome, time point, subgroup, or statistical comparison. Repeated testing can increase the chance of finding at least one result that appears statistically notable by chance alone. General approaches include adjusting significance thresholds or specifying a testing hierarchy in advance. Whether such methods are needed and how they should be applied depend on the protocol and analysis plan.

The registry identifies pain change as the primary outcome and lists Evidence of Functional Changes as a secondary outcome. It also describes several scheduled follow-up times and several measures in its summary. The posted comparisons include unadjusted p-values, and no multiplicity adjustment, prespecified hierarchy, or complete family of planned tests is reported in the registry record. The effect of any multiplicity strategy on the reported findings is therefore not available.

Missing-data handling is also not reported in the registry record. The record does not state how participants without a 24-week measurement were handled, whether any observations were imputed, or whether a sensitivity analysis examined the influence of missing outcomes. It gives enrollment of 79 and endpoint group summaries of 38 and 37 participants, but does not explain the relationship between those counts and the number assigned, followed, or included in each analysis. The result should not be assumed to represent a particular intention-to-treat or per-protocol population.

Analysis populations are not described. The record does not say whether participants were analyzed according to randomized assignment, whether crossover or deviations were handled, or which prespecified covariates entered any adjusted analysis. It also does not report the statistical analysis plan or interim analyses. These absences do not establish that such procedures were or were not used; they mean that the registry record does not document them. As a result, interpretation is limited to the posted aggregate outcomes and comparisons, without a basis for assessing how missingness, analysis-set choices, or multiplicity may have influenced them.

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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: pneumonia (2.7%), hypokalemia (2.7%), acute kidney injury (2.7%), worsening of reflux esophagitis (2.7%), broken left femur (2.6%).

The registry lists serious adverse events affecting 2 of 38 participants in the cooled group and 4 of 37 in the monopolar group. It reports zero deaths in each group. Other adverse events are listed as affecting 18 of 38 participants in the cooled group and 20 of 37 in the monopolar group. These are counts of participants recorded in the respective categories, not measures of whether an event was caused by the procedure.

The registry also lists serious-event terms with percentages: Pneumonia, 2.7%; Hypokalemia, 2.7%; Acute kidney injury, 2.7%; Worsening of reflux esophagitis, 2.7%; and Broken Left Femur, 2.6%. The record does not explain whether these terms are related to treatment, nor does the listed summary clearly map each term to a particular randomized group. They should not be interpreted as evidence of a causal relationship.

Safety counts are descriptive. They do not by themselves establish comparative risk, especially without details about event definitions, follow-up completeness, attribution, and statistical analysis. Those details are not reported in the registry record.

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

The posted results describe average outcomes among participants summarized in each randomized group. The primary endpoint shows a negative mean pain change in both groups at 24 weeks, and the estimated difference between group means is 2.1 mm. The confidence interval ranges from -10.26 to 14.46 mm and includes zero. The data therefore do not precisely establish the direction or size of an average difference between the procedures.

This result does not mean that the procedures are equivalent. Demonstrating equivalence or non-inferiority requires a prespecified margin and an analysis designed for that question; such a margin and design are not reported in the registry record. Nor does a p-value of 0.739 prove that the two procedures have the same effect. It describes the test result under its statistical assumptions, not the probability that the groups are identical.

The within-group mean changes also do not show what would have happened without either procedure. Both groups received an intervention, and the reported comparison is between those interventions. A change from baseline can reflect more than the intervention itself, and the registry does not report a no-treatment or usual-care group in this comparison.

The record does not report a threshold for clinically important change in pain or function. Statistical uncertainty can therefore be described, but the practical importance of values within the confidence interval cannot be determined from the registry alone. Participant-level outcomes, missing-data handling, detailed analysis populations, and a complete account of planned analyses are also not reported.

These results apply to the study population and conduct described in the registry, including the stated selection based on chronic knee pain, osteoarthritis, conservative-therapy history, and response to a diagnostic block. The record does not establish how well the findings apply to people outside those selection features or to other settings. The findings are a statistical description of the posted data, not medical advice or a recommendation about treatment choice.

17. Why This Trial Matters Statistically

This trial presents a direct randomized comparison of two radiofrequency procedures for chronic osteoarthritic knee pain, with a clearly identified primary pain outcome and a specified assessment at 24 weeks. The registry also identifies a functional outcome and gives group-level estimates, uncertainty intervals, and adverse-event counts. These features allow readers to distinguish the estimated contrast from the precision with which it was measured.

The primary estimate is small relative to the uncertainty around it, and its confidence interval includes values in both directions. This makes precision central to interpretation: the point estimate alone would give an incomplete account. The result illustrates why an interval and group variability are important alongside a p-value, particularly when a comparison is not statistically conclusive.

The record also shows why planning calculations need careful framing. Illustrative sample sizes based on an observed effect are not a retrospective explanation of enrollment, nor do they establish the original design’s adequacy. The registry reports termination and an intended enrollment of approximately 102 in its summary, while recording enrollment of 79; it does not give the reason for termination or the original planning rationale. Those gaps matter when judging what the study could resolve.

Finally, registry results are most informative when their analysis populations, missing-data methods, multiplicity strategy, and protocol context are documented alongside the estimates. Their absence limits assessment of how robust the posted comparisons are. The trial remains statistically informative as a report of randomized-group summaries, while also showing how incomplete analysis reporting constrains conclusions about precision and interpretation.

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.

Several trial-specific uncertainties limit interpretation. The registry status is terminated, and enrollment is 79, while the brief summary describes an intended enrollment of approximately 102. The reason for termination and the point at which the decision was made are not reported in the registry record. Without that context, it is difficult to assess whether termination affected recruitment, follow-up, or the availability of outcomes.

The primary comparison includes 38 participants in the cooled group and 37 in the monopolar group. The record does not explain whether these are all randomized participants with observed 24-week outcomes, or how any missing outcome data were handled. It does not identify analysis populations or report sensitivity analyses. Thus, the relationship between enrollment, randomization, follow-up, and the posted summaries is not fully documented.

The record describes triple masking but does not say which parties were masked or how masking was assessed. It also does not report allocation concealment procedures, the detailed protocol, or the statistical analysis plan. These omissions prevent assessment of those design and analysis safeguards from the registry record alone.

The summary lists multiple measures and follow-up visits, but the registry does not report a complete set of analyses across them or a multiplicity plan. Only one secondary outcome is posted. A clinically important threshold for either endpoint is not reported, and the Oxford Knee Score’s direction is not explained in the posted outcome details. Finally, the trial is described as single center, so the record alone does not establish how results may generalize to other settings or participant groups.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Efficacy of Cooled and Monopolar Radiofrequency Ablation of the Geniculate Nerves for the Treatment of Chronic Osteoarthritic Knee Pain — NCT02260869.
• Registry record last updated 2022-04-26; status last verified 2022-04.
• Results first posted 2022-04-26.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

22. Record Summary

The registry record identifies NCT02260869 as a randomized, triple-masked, parallel-group trial comparing cooled with conventional monopolar radiofrequency ablation of the geniculate nerves for chronic osteoarthritic knee pain. It lists Millennium Pain Center as sponsor, enrollment of 79, status as terminated, a start date of 2015-01, and a primary completion date of 2018-10-15. The summary describes a single-center study and an intended enrollment of approximately 102.

The primary posted outcome is mean change in VAS pain score from baseline to 24 weeks. The mean difference comparing monopolar with cooled ablation is 2.1 mm, with a 95% confidence interval from -10.26 to 14.46 mm and an unadjusted p-value of 0.739. The secondary posted outcome is the Oxford Knee Score at 24 weeks. Important details about missing data, analysis populations, multiplicity, and reasons for termination are not reported in the registry record.