Durolane Versus Phosphate Buffered Saline (PBS) in Knee Osteoarthritis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Durolane Versus Phosphate Buffered Saline (PBS) in Knee Osteoarthritis (NCT01753830), a randomized na study. The primary outcome is Average Change in WOMAC VAS Pain Score From Week 6 to Week 30.

2. Clinical Question

The registry describes the study’s purpose as determining whether a single Durolane injection is superior to a single PBS injection for relief of joint pain in knee osteoarthritis. The primary outcome is the average change in WOMAC pain score, measured on a 0-100 mm visual analogue scale. On that scale, lower scores mean less pain. The reported group changes are negative, indicating lower scores over the stated change interval; the comparative estimate describes the difference between the group means.

The posted comparison is expressed as PBS minus Durolane. Its positive estimate therefore corresponds to a numerically greater reduction in the Durolane group on this change scale. The estimate is uncertain, however, and its confidence interval includes differences in either direction. This statistical comparison alone does not establish whether any difference is clinically important. A threshold for clinical importance is not reported in the registry record.

3. Trial Design

This was a randomized, double-blind, parallel-group study comparing Durolane with PBS. The official title describes it as a multicenter, saline-controlled study. The registry lists Galderma R&D as the sponsor, knee osteoarthritis as the condition, and the study status as terminated. The recorded start was 2012-12, and primary completion was 2014-02. The reason for termination is not reported in the registry record.

The registry lists enrollment of 75. The outcome results give group sizes of 37 for Durolane and 38 for PBS. Each group received a single intra-articular injection of its assigned intervention. The intervention records classify both as devices. The registry identifies the study as randomized and double blind, but further information about sequence generation, allocation concealment, implementation of blinding, and any assessment of whether blinding was maintained is not reported in the registry record.

The posted primary outcome is average change in WOMAC VAS pain score from Week 6 to Week 30, with a timeframe described as up to 30 weeks. The record reports group means and standard deviations for this continuous outcome, as well as a comparative estimate and confidence interval that can be recalculated from the group summaries. No secondary outcome results are posted. The original statistical analysis plan, including the planned analysis population, handling of missing outcomes, and any adjustments to the comparison, is not reported in the registry record. The study’s own sample-size assumptions and justification are also not reported.

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 Average Change in WOMAC VAS Pain Score From Week 6 to Week 30, measured over Up to 30 weeks.

The primary endpoint is the average change in WOMAC VAS pain score from Week 6 to Week 30. WOMAC is the Western Ontario and McMaster Universities Osteoarthritis Index. The pain score is recorded on a 0-100 mm visual analogue scale, and lower scores mean less pain. The registry describes the measure as a continuous outcome and reports its mean and standard deviation in each group.

A change score focuses on how the measured pain score differs across the specified interval, rather than only on the score at a single assessment. Comparing average change between randomized groups can describe whether their mean trajectories over that interval differed. In this record, the reported mean changes are -32.3 for Durolane and -26.8 for PBS. The comparative estimate is 5.5 for PBS minus Durolane. These figures describe the posted results; they do not by themselves establish the clinical importance of the difference.

WOMAC VAS pain is used as a patient-reported measure relevant to the stated study question about joint pain. A patient-reported scale can capture a person’s own assessment of pain, while the mean summarizes the group’s average change. The registry record does not report the rationale for selecting this measure, a threshold for a clinically meaningful change, or further details about how endpoint data were collected. The outcome population is not reported in the registry record.

7. Results Posted in the Registry

• Phosphate Buffered Saline (PBS): mean -26.80 versus -32.30 on control; difference 5.50 (95% CI -3.51 to 14.51), standardized effect d = 0.28; z-test p = 0.232.

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is continuous, and its group results are reported as means with standard deviations. A mean gives the average observed change within a group. A standard deviation describes how dispersed individual observations are around that mean: a larger standard deviation indicates more variability in the observed scores. The Durolane mean is -32.3 with a standard deviation of 19.64; the PBS mean is -26.8 with a standard deviation of 20.17.

What does the mean difference represent?

The comparison is defined as PBS minus Durolane. The estimated mean difference is 5.5. Because the outcome is a change score and lower WOMAC VAS scores mean less pain, the positive value indicates that the PBS group’s mean change was higher than the Durolane group’s mean change on the reported scale. This direction is a description of the estimate, not a judgment about clinical importance. The registry does not report a threshold for deciding whether a given difference matters clinically.

The comparison uses the group means and their variability to estimate the uncertainty in the contrast. The pooled standard deviation is 19.91. Pooling provides a common variability estimate for the recalculated comparison; it does not imply that every participant had similar scores or that the group means capture each person’s outcome. The posted standard errors are 3.229 for Durolane and 3.272 for PBS. A standard error describes the estimated sampling variability of a statistic, rather than the spread of individual outcomes.

How should the confidence interval be read?

The 95% confidence interval for the mean difference runs from -3.51 to 14.51. In general, a confidence interval gives a range of effect estimates compatible with the observed data under the method’s assumptions. Its width communicates precision: a wider interval leaves more uncertainty about the size and direction of the difference. Here, the interval includes zero and extends to both negative and positive values. It therefore does not pin down the direction of the underlying group difference with precision. The interval is for the mean difference, not a range expected to contain the outcomes of individual participants.

What does the p-value say?

The unadjusted p-value is 0.232. In general, a p-value is calculated under a null hypothesis and describes the probability of results at least as incompatible with that hypothesis as the observed result, if the null model and its assumptions hold. It is not the probability that there is no effect, and it does not indicate the probability that the result will replicate. The p-value does not quantify clinical importance. It should be interpreted alongside the estimated difference and confidence interval rather than as a stand-alone decision rule.

The comparison and p-value are unadjusted recalculations from the posted group summaries. The registry record does not report a model-based sponsor analysis, covariate adjustment, or other planned inferential method. The displayed comparison should therefore be understood as a simple summary-statistic comparison, not as evidence that a particular analysis plan was followed. The registry record lists one primary outcome measure and no posted secondary outcome results, but does not report a plan for controlling multiplicity.

Why does variability matter?

Variation among participants affects how precisely a group mean and between-group difference can be estimated. When individual outcomes vary considerably relative to the difference between group means, the data may leave a broad range of plausible differences. That general principle helps explain why the estimate and interval should be read together. The observed standard deviations describe variability in this study; they do not identify its causes, and the registry record does not provide individual-level results with which to examine the distribution of scores.

All statistical methods rely on assumptions. The original analysis method and its assumptions are not reported in the registry record. The planning illustration uses a normal approximation, but that is an assumption for the separate sample-size illustration and should not be treated as confirmation of the trial’s own analysis method. The record does not report diagnostic checks, transformations, or sensitivity analyses.

What can be inferred from the posted summaries?

The group summaries support a description of the observed mean changes, their variability, and an unadjusted comparison with estimated uncertainty. They do not reveal how missing outcomes were handled, which participants were included in the analysis, or whether any protocol deviations affected the results. Those details are not reported in the registry record. Nor do the summaries establish the cause of any observed changes or show whether the difference would be meaningful to patients. These are limits on interpretation, not evidence that a particular unreported procedure was or was not used.

10. Confidence Intervals and Precision

The estimated mean difference is 5.5 for PBS minus Durolane. Its 95% confidence interval is -3.51 to 14.51. The interval is broad enough to include zero, as well as negative and positive differences. Thus, the point estimate alone should not be read as a precise determination of the direction or size of the underlying difference.

A confidence interval expresses uncertainty around an estimated effect under the statistical method used. In general, a narrower interval indicates greater precision, while a wider interval indicates that the data are consistent with a broader range of values. The interval does not describe the range of individual participants’ outcomes, and it does not mean that there is a 95% probability that the true effect lies within this particular interval.

The unadjusted recalculated p-value is 0.232. Its interpretation is consistent with the interval’s uncertainty: the posted results do not sharply distinguish a zero difference from some differences in either direction. This is not proof that the groups are identical. Nor does the interval establish that all values it includes are clinically plausible or important; the registry record does not report a threshold for clinical importance.

Precision is affected by both the amount of information and variability in outcomes. The observed standard deviations are 19.64 and 20.17, and the group sizes in the outcome record are 37 and 38. The available summaries do not show whether missing data, exclusions, or other analysis choices affected precision. Those methods are not reported in the registry record. The confidence interval therefore communicates uncertainty for the recalculated comparison, but it cannot resolve the unreported details of the original analysis.

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 display is a planning illustration based on the observed effect, not a report of the trial’s original design assumptions. Its figures are participants per arm, not total events. The assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect to detect is set to the stated fraction of the observed effect. The original trial’s sample-size assumptions and justification are not reported in the registry record.

For the planning scenario using 100% of the observed effect, the illustration gives 206 participants per arm for 80% power and 276 participants per arm for 90% power. For 75% of the observed effect, it gives 366 participants per arm for 80% power and 490 participants per arm for 90% power. For 50% of the observed effect, it gives 823 participants per arm for 80% power and 1,102 participants per arm for 90% power.

In plain language, the 80% power column describes the planned number per arm under which the calculation would have an 80% chance of detecting the specified effect using the listed assumptions, if that effect and assumptions held. The 90% column uses a higher probability of detecting that specified effect, and therefore gives larger planning requirements in these scenarios. The curve presents the same general relationship between the assumed effect size and the planning requirement. Smaller effects need more participants to detect them under the same assumptions.

These values are not observed power. They are planning illustrations derived from the observed effect and do not show what the trial was designed to achieve or what its actual power was.

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 = 5.500; pooled standard deviation σ = 19.910.
2. n = 2 × (1.96 + 0.842)² × 19.910² / 5.500² = 205.7, rounded up to 206 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 <- 5.5                      # observed difference in means
sigma <- 19.9103934103127                     # 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(1753830)
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 = 206 (80% power), 276 (90% power)
 75% of observed effect: n per arm = 366 (80% power), 490 (90% power)
 50% of observed effect: n per arm = 823 (80% power), 1,102 (90% power)
power.t.test: 206.7 
Simulated power at n = 206 per arm: 0.802 (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 record lists one primary outcome measure and no posted secondary outcome results. It does not report whether the study prespecified additional outcomes that were not posted, how multiple comparisons were to be handled, or whether any multiplicity adjustment was planned. Without that information, the unadjusted p-value should be read as the result for the reported comparison, not as evidence that a broader family of tests was controlled.

Missing-outcome handling is not reported in the registry record. The record does not say whether participants with unavailable Week 6 or Week 30 scores were excluded, whether values were imputed, or whether another method was used. It also does not report the number of missing outcome observations or reasons for missingness. These details matter because an analysis based only on observed outcomes can be affected if missingness is related to participant outcomes or group assignment. This is a general statistical concern; the record does not establish that such a problem occurred in this trial.

The analysis population is not reported in the registry record. It is therefore unclear from the record whether the posted outcome summaries refer to all randomized participants, participants who received the injection, participants with complete outcome data, or another defined group. The outcome group sizes are 37 for Durolane and 38 for PBS, but the record does not describe the rules used to arrive at those analysis counts.

The registry record also does not report interim analyses, stopping rules, protocol deviations, or a statistical analysis plan. The study status is terminated, but the reason for termination and any relationship to the analysis are not reported. These missing details limit assessment of how closely the posted summaries follow an original analysis plan; they do not, on their own, indicate that the analysis was biased or that a particular method was used.

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 serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: cardiac arrest (2.7%), cardiac failure congestive (2.7%), pulmonary embolism (2.7%), abdominal pain lower (2.6%), pneumonia (2.6%).

The registry’s serious adverse event summary lists 2 affected participants among 37 at risk in the Durolane group and 1 among 38 at risk in the PBS group. Deaths are listed as 1 in the Durolane group and 0 in the PBS group. These are counts as recorded; the summary does not establish that an event was caused by the assigned injection. No causal interpretation should be drawn from the counts alone.

The serious-event terms listed in the record are cardiac arrest (2.7%), cardiac failure congestive (2.7%), pulmonary embolism (2.7%), abdominal pain lower (2.6%), and pneumonia (2.6%). The registry summary does not specify an arm for each listed term in this list, so the terms should not be assigned to either group on that basis. Their percentages should be read as recorded, without inferring a denominator or relationship that the record does not describe.

Adverse-event counts are descriptive safety information, not a randomized comparison with an estimate of uncertainty. The registry record does not provide further detail about event timing, severity grading, relatedness assessment, or whether events were recurrent. The presence of a listed serious event does not by itself establish a treatment effect, and a count of zero deaths in a group does not establish absence of risk.

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

The posted results describe mean change in WOMAC VAS pain score from Week 6 to Week 30 in a randomized, double-blind comparison of a single Durolane injection with a single PBS injection. The group means were -32.3 and -26.8, respectively. The estimated mean difference, expressed as PBS minus Durolane, was 5.5. The confidence interval from -3.51 to 14.51 indicates substantial uncertainty about the direction and size of the difference, and the unadjusted recalculated p-value is 0.232.

These findings do not establish that the groups had identical outcomes. They also do not establish that one injection was superior, or that any observed difference was clinically important. The registry record does not provide a threshold for clinical importance. Statistical uncertainty and clinical importance are different questions: the first concerns the range of effects compatible with the data and method, while the second concerns whether a difference matters in the clinical context.

The reported outcome captures average change on a pain scale, not every participant’s experience or every aspect of knee osteoarthritis. The record does not post secondary outcome results, and it does not report the analysis population, missing-data methods, or details of the original statistical plan. Those omissions mean that interpretation should remain tied to the posted summary and its stated endpoint.

The safety summaries list serious adverse events and deaths by group, but they do not establish causation. The record also lists serious-event terms without providing an arm assignment for each term in that list. The trial is marked terminated, and the reason is not reported. Consequently, the results should be understood as a limited account of the recorded comparison, not as a complete explanation of the trial’s conduct or outcome.

16. Why This Trial Matters Statistically

This trial illustrates why an estimated effect should be considered together with its uncertainty. The difference in mean change is 5.5, but the 95% confidence interval spans -3.51 to 14.51. The estimate gives a single summary of the observed contrast; the interval shows that the data do not determine the contrast precisely. Reporting only the point estimate would hide that uncertainty, while relying only on the p-value would omit the estimated size and range of compatible effects.

The outcome also shows how direction depends on the measure’s definition. The comparison is PBS minus Durolane, and lower WOMAC VAS scores mean less pain. Keeping the subtraction order and score direction explicit makes it possible to interpret the positive difference without confusing it with a direct measure of pain level. A change score and a between-group difference in change answer a different question from a single group’s score at one assessment.

The planning illustration offers a further statistical lesson: required sample size depends on the effect one aims to detect, the desired power, and the stated assumptions. Smaller target effects require more participants per arm in the displayed scenarios. Those calculations are not evidence of the trial’s original planning, and the registry record does not report the original design justification.

Finally, interpretation depends on more than the outcome estimate. Missing-data methods, analysis populations, multiplicity plans, and the reason for termination are not reported in the registry record. Those gaps matter when assessing the completeness and context of a result. They should be treated as unanswered questions, rather than filled in with assumptions about what the investigators did.

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 interpretation is limited by the information recorded about the outcome analysis. The registry gives group means, standard deviations, group sizes, and a recalculated unadjusted comparison, but does not report the original statistical analysis plan or the population used for the analysis. It also does not describe whether any covariates were considered or whether sensitivity analyses were performed.

The registry record does not report missing-data methods, the number of missing outcome measurements, or reasons for missingness. Without those details, it is not possible to assess from the record whether missing outcomes could have affected the comparison. The record also does not report a clinically important difference threshold, which limits interpretation of the estimated difference in terms of practical relevance.

The study is listed as terminated, but the reason is not reported in the registry record. No inference about the cause or consequences of termination is warranted from the status alone. The record describes the study as multicenter, randomized, double blind, and parallel-group, but does not provide further operational details about randomization, concealment, blinding, or protocol adherence.

The serious adverse event summary is limited to recorded counts and a list of terms with percentages. The list does not identify the group for each term, and the record does not give further context about timing, relatedness, or event-level details. These limitations mean that the safety summary should be read descriptively. The posted data do not establish whether reported events were caused by treatment or how complete the event reporting was.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: Durolane Versus Phosphate Buffered Saline (PBS) in Knee Osteoarthritis — NCT01753830.
• Registry record last updated 2022-08-26; status last verified 2020-09.
• Results first posted 2020-09-30.
• 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 randomized, double-blind, parallel-group trial of a single intra-articular Durolane injection versus a single PBS injection for knee osteoarthritis. Galderma R&D is listed as sponsor, enrollment is 75, and study status is terminated. The recorded start was 2012-12, with primary completion in 2014-02.

The primary outcome is average change in WOMAC VAS pain score from Week 6 to Week 30. The group means are -32.3 for Durolane and -26.8 for PBS. The unadjusted recalculated mean difference for PBS minus Durolane is 5.5, with a 95% confidence interval from -3.51 to 14.51 and p = 0.232.

The registry record does not report the reason for termination, the original sample-size justification, the analysis population, or missing-data and multiplicity methods. No secondary outcome results are posted.