Efficacy of Flavocoxid 500 mg Compared With Naproxen 500 mg in Subjects With Moderate-severe Osteoarthritis of the Knee: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Efficacy of Flavocoxid 500 mg Compared With Naproxen 500 mg in Subjects With Moderate-severe Osteoarthritis of the Knee (NCT00790985), a randomized na study. The primary outcome is Western Ontario and McMaster Universities Arthritis (WOMAC) Composite Score: Percent Change From Baseline to Week 12..

2. Clinical Question

3. Trial Design

The registry describes a completed, randomized, triple-masked, parallel-group trial comparing flavocoxid with naproxen in subjects with moderate-to-severe osteoarthritis of the knee. Enrollment is recorded as 223. The registry lists the start as 2008-01 and primary completion as 2008-08. The study phase is recorded as NA. The sponsor is Primus Pharmaceuticals.

A parallel-group design assigns participants to a treatment group and compares outcomes between groups. Random allocation is intended to reduce systematic differences between groups at the point of assignment. The record identifies the trial as triple-masked, but does not specify which groups of people were masked or how masking was maintained. Further details about allocation procedures, concealment, treatment delivery, follow-up, and protocol adherence are not reported in the registry record.

The posted primary outcome summaries include 106 participants in the naproxen arm and 114 in the flavocoxid 500 mg arm. These are the group counts attached to the reported outcome, not a full account of participant flow. Reasons for nonparticipation, withdrawals, or any difference between enrollment and the outcome counts are not reported in the registry record. The record lists one outcome measure and no posted analysis entries.

The primary outcome was measured at baseline and Week 12. The registry does not report the trial's original sample-size justification, its planned statistical model, or the originally specified approach to missing outcome data. Although the posted comparison provides a mean difference, confidence interval, and unadjusted p-value, those results do not supply the missing protocol-level details. The description of the trial design should therefore be limited to the registry's recorded features and the posted endpoint summaries.

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 Western Ontario and McMaster Universities Arthritis (WOMAC) Composite Score: Percent Change From Baseline to Week 12., measured over As measured at Baseline and Week 12.

The primary endpoint was percent change from baseline to Week 12 in the Western Ontario and McMaster Universities Arthritis (WOMAC) composite score. WOMAC combines responses about pain, stiffness, and physical function. Its questions use ordered response options from none to extreme difficulty or symptoms. The component scores are added to form a raw total, then normalized to a 0-to-100 scale, with higher scores indicating a better outcome.

For each participant, the registry defines percent change as 100 multiplied by the Week 12 score minus the baseline score, divided by the baseline score. Under that definition, a higher percent change represents a better outcome. The endpoint therefore describes change relative to each participant's baseline rather than simply the Week 12 score alone. Group means summarize the average participant-level percent changes in each treatment arm.

A composite measure can capture several related dimensions of a condition in one outcome, instead of focusing on only pain or only physical function. That makes it useful for an overall comparison, while also meaning that the composite does not show which component drove a group result. The registry does not post separate results for the pain, stiffness, or physical-function subscales. Nor does it report participant-level data or other details needed to assess the distribution of individual changes.

7. Results Posted in the Registry

• Flavocoxid 500 mg: mean 69.97 versus 85.75 on control; difference -15.78 (95% CI -18.09 to -13.47), standardized effect d = -1.83; z-test p = <0.001.

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is continuous: the registry reports a mean and standard deviation for the percent change in WOMAC composite score. A mean gives the arithmetic average of the recorded outcome within an arm. A standard deviation describes how dispersed participant values are around that arm's mean. It does not describe uncertainty in the mean itself, and it does not show the shape of the outcome distribution. The posted standard deviations are 9.83 for naproxen and 7.34 for flavocoxid 500 mg.

What does the mean difference represent?

The comparison is expressed as flavocoxid minus naproxen. The posted means are 69.97 and 85.75, respectively, and the reported difference is -15.78. A negative value means the mean percent change was lower in the flavocoxid arm under this subtraction order. The estimate is on the scale of the reported percent change; it is not a difference in normalized WOMAC points. The registry defines larger percent changes as better outcomes.

A mean difference is an absolute contrast on the endpoint scale. It differs from a ratio, which would describe a relative contrast between quantities. Here, the posted comparison is a mean difference. Avoid interpreting its magnitude as a percent improvement between groups: the endpoint itself is a percent change from baseline, but the contrast between the group means is the difference of those endpoint values.

What does the p-value tell the reader?

The unadjusted p-value is <0.001. In general, a p-value assesses how compatible the observed data are with a specified null hypothesis, given a statistical model. It is not the probability that the null hypothesis is true, nor the probability that the result occurred by chance in an ordinary-language sense. The posted p-value is unadjusted; the registry does not report whether any multiplicity adjustment was planned or applied. Because the record lists one outcome measure but no analysis entries, details of the test and analysis model are not reported in the registry record.

Why use a confidence interval?

A confidence interval gives a range of estimates compatible with the observed data and the method's assumptions. The posted interval for the mean difference is -18.09 to -13.47. It is centered on the estimated contrast subject to rounding. If a confidence interval for a difference includes zero, values indicating either direction may remain compatible with the data under that method; this interval does not include zero. That feature does not determine clinical importance, rule out bias, or address missing data by itself.

What role do the standard deviations play?

Variation among participants affects the precision of an estimated group mean and of a between-group contrast. In general, more variability makes a group mean less precise when other features are held constant. The posted record reports standard deviations for both arms and a comparison interval. The comparison's calculations use an unadjusted summary-statistic approach; the registry does not report an adjusted model, covariates, or a detailed analysis specification. The reported standard deviations alone cannot reveal whether the outcome distribution was symmetric, contained unusual observations, or met any particular model assumptions.

What does over-dispersion mean in general?

For count outcomes, over-dispersion means the observed variation exceeds what a chosen count model expects. A model that ignores this extra variation can produce uncertainty estimates that are too small. That general issue is not the main structure of this primary endpoint, which is continuous and reported as a mean with standard deviation. It is therefore not appropriate to infer a count-model analysis for the primary result. The registry does not describe a model for the adverse-event counts.

The posted summary comparison and its interval are useful for describing the numerical contrast, but they do not establish the exact analysis procedures used by the trial investigators. The original statistical analysis plan, handling of missing values, analysis population, and adjustment strategy are not reported in the registry record. Those details matter because estimates and uncertainty can depend on choices about participant inclusion, outcome handling, and model specification. The calculation should be read as the posted unadjusted comparison, with these documentation limits kept in view.

10. Confidence Intervals and Precision

The posted mean difference is -15.78 for flavocoxid 500 mg minus naproxen, with a 95% confidence interval from -18.09 to -13.47. The interval describes the precision of the estimated contrast under the method's assumptions. Its endpoints are both below zero, so the range of values compatible with this unadjusted comparison points in the same direction as the estimate: a lower mean percent change for flavocoxid than for naproxen.

A confidence interval is not a range containing a fixed proportion of individual participants' outcomes. It concerns uncertainty in the estimated group contrast, not the spread of participant values. That spread is described separately by the arm standard deviations, which are 7.34 for flavocoxid 500 mg and 9.83 for naproxen. Nor is the interval a guarantee that the true value falls within its endpoints. Its usual interpretation depends on the statistical method and assumptions.

The interval's precision does not resolve whether the difference is clinically meaningful. The registry does not report a threshold for clinical importance, nor does it provide results for the separate WOMAC components. The record also does not describe missing-data handling or an adjusted analysis. These omissions limit what the confidence interval can address: it quantifies uncertainty for the posted comparison, not uncertainty from every possible source of bias or analysis choice.

The unadjusted p-value of <0.001 is consistent with the interval's separation from zero, but it answers a different question and should not replace reading the interval's direction and span. Precision is also distinct from representativeness: a relatively focused estimate does not show that the enrolled participants reflect all people with knee osteoarthritis. The registry record does not report enough information to assess that broader issue.

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, not the trial's original design justification. The stated assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. Each row uses a stated fraction of the observed effect as the effect to detect. The trial's own original design assumptions and sample-size justification are not reported in the registry record.

The 80% power column gives the planned participants per arm for a design with 80% power under those assumptions and for the effect size specified in that row. The 90% power column gives the corresponding participants per arm for 90% power. Power is a design property under assumed conditions; it is not a guarantee that a study will detect an effect or that its estimate will be accurate. Smaller effects need more participants to detect, all else equal.

For planning for 100% of the observed effect, the figures are 5 participants per arm for 80% power and 7 participants per arm for 90% power. For planning for 75% of the observed effect, the figures are 9 participants per arm for 80% power and 12 participants per arm for 90% power. For planning for 50% of the observed effect, they are 19 participants per arm for 80% power and 26 participants per arm for 90% power. These are planning illustrations, not observed power.

The curve should be read as a visual representation of how required planning size changes with the effect being targeted under the same assumptions. It does not reconstruct the trial's actual design process, and it should not be used to infer the investigators' intended effect size. The figures rely on the posted observed effect, which may be uncertain and may differ from an effect chosen before a trial begins.

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 = -15.780; pooled standard deviation σ = 8.629.
2. n = 2 × (1.96 + 0.842)² × 8.629² / -15.780² = 4.7, rounded up to 5 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 <- -15.78                      # observed difference in means
sigma <- 8.62947192937184                     # 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(790985)
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 = 5 (80% power), 7 (90% power)
 75% of observed effect: n per arm = 9 (80% power), 12 (90% power)
 50% of observed effect: n per arm = 19 (80% power), 26 (90% power)
power.t.test: 5.8 
Simulated power at n = 5 per arm: 0.722 (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 one outcome measure, the Week 12 percent change in WOMAC composite score, and no posted analysis entries. The record does not report a statistical analysis plan or say whether the primary outcome was tested alongside additional planned outcomes that were not posted. It also does not report whether multiplicity was considered. When several hypotheses are tested, the chance of at least one apparently strong result can increase; methods to account for multiple testing can address that issue. Whether such methods were relevant or used in this trial is not reported in the registry record.

The posted p-value is explicitly unadjusted. It should be read as an unadjusted result rather than evidence that any family of tests has been accounted for. The record does not identify the test used, whether covariates were included, or whether the reported comparison followed a prespecified analysis. Details of endpoint hierarchy and any secondary outcome analyses are also not reported in the registry record.

Missing-data handling is not reported. The record does not state how missing baseline or Week 12 values were treated, whether participants with incomplete measurements were excluded, or whether any imputation method was used. The posted outcome counts are 106 for naproxen and 114 for flavocoxid 500 mg, while enrollment is recorded as 223. Without participant-flow information, these entries cannot establish why the counts differ from enrollment or whether missingness could have influenced the comparison.

The analysis population is not reported in the registry record. It is therefore not possible to determine whether the summary uses all randomized participants, participants who received treatment, participants with available endpoint measurements, or another defined set. These distinctions can affect interpretation, particularly when adherence, withdrawal, or outcome availability differs between arms. The registry also does not report sensitivity analyses addressing missing values or alternative analysis populations.

These reporting gaps do not change the arithmetic description of the posted means and confidence interval. They do limit assessment of whether the analysis was prespecified, how robust it is to missing data, and whether the unadjusted inference accounts for the full set of planned comparisons. Those questions remain unresolved by the registry record.

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 safety record reports serious adverse events among 108 participants at risk in the flavocoxid 500 mg group and 115 at risk in the naproxen 500 mg group. The serious adverse event count is zero for each group. Deaths are also recorded as zero for each group. These are the registry's reported counts; the record does not provide serious-event terms because none are listed.

For other adverse events, the record reports 21 affected participants among 108 at risk in the flavocoxid group and 39 among 115 at risk in the naproxen group. These counts are not the same as the serious adverse event counts. The registry does not list the event types, timing, severity beyond the category distinction, or whether events were considered related to treatment. No comparative statistical analysis for these safety counts is posted.

Read the figures as descriptive safety summaries, not as proof that an event was caused by a treatment or that a treatment is safer. The record does not describe how adverse events were collected, whether all participants were followed for the same duration, or how missing safety information was handled. No rates or additional comparisons are inferred from these counts.

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

The posted primary result is a comparison of mean percent change in WOMAC composite score from baseline to Week 12. Higher percent changes were defined as better outcomes. The naproxen mean was 85.75, while the flavocoxid 500 mg mean was 69.97. The mean difference for flavocoxid minus naproxen was -15.78, with a 95% confidence interval from -18.09 to -13.47 and an unadjusted p-value of <0.001. In this recorded comparison, the mean percent change was lower in the flavocoxid group.

That statement is limited to the primary endpoint, its stated time point, and the posted summary. It does not show the groups' baseline WOMAC values or their Week 12 values separately. It also does not show which of the pain, stiffness, or physical-function components contributed to the composite result. The registry does not report a threshold that would establish whether the numerical difference is clinically important.

The result does not establish that every participant had a change resembling the group mean. Means summarize group averages, while individual responses can vary. The arm standard deviations indicate dispersion, but the registry does not provide the full outcome distributions. The result also does not establish what would happen in populations or settings not described in the record.

The unadjusted p-value and confidence interval quantify statistical evidence and uncertainty under the comparison's method; they do not address every possible source of bias. The record does not report the analysis population, missing-data methods, the original statistical plan, or multiplicity procedures. Those omissions matter when assessing how robustly the posted estimate represents the randomized comparison.

The safety counts are separate descriptive results. Zero serious adverse events and deaths are recorded in both arms, while other adverse events affected participants in both arms. These figures do not determine causality or provide a complete account of safety. Taken together, the posted data describe the reported outcome and safety summaries, but do not support broader claims beyond those measures and the available registry information.

16. Why This Trial Matters Statistically

This trial is statistically informative because it reports a direct randomized comparison and an interpretable continuous primary endpoint. The direction of the endpoint is clearly specified: higher percent changes in the WOMAC composite are better. That definition makes it possible to interpret the signs of the group difference without treating the result as a raw-score contrast.

The comparison also illustrates why an estimate, confidence interval, and p-value answer related but distinct questions. The mean difference describes the size and direction of the contrast on the endpoint scale. The confidence interval describes uncertainty around that estimate under the method's assumptions. The unadjusted p-value describes compatibility with a null difference under its test assumptions. None alone establishes clinical importance, and the record does not provide a clinical-importance threshold.

The registry includes group counts, means, standard deviations, and a comparison interval, which support a clear account of the posted endpoint. At the same time, the analysis plan and analysis population are not reported, and the registry contains no posted analysis entries. This contrast highlights a general reporting issue: numerical results can be readable while key context needed to judge their robustness remains unavailable.

The sample-size illustrations also demonstrate the dependence of planning requirements on the effect targeted. Smaller target effects require more participants per arm under the stated planning assumptions. Because the calculations use the observed effect rather than a prospectively chosen target, they should not be mistaken for the trial's design rationale or for observed power.

Finally, the safety summaries distinguish serious events and deaths from other adverse events, but the counts do not convey event type, attribution, or comparative uncertainty. Together, the endpoint and safety information show why statistical interpretation depends not only on numerical estimates, but also on definitions, uncertainty, analysis details, and the limits of what the record reports.

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 provides limited context for evaluating how the trial was conducted and how the primary result was analyzed. It identifies randomization, triple masking, and a parallel design, but does not describe the allocation method, concealment, or which parties were masked. Further information about eligibility criteria, baseline characteristics, treatment adherence, and follow-up is not reported in the registry record.

The primary outcome is a percent change, but the posted summary does not include arm-specific baseline or Week 12 WOMAC scores. Because percent change is calculated relative to baseline, those component values would help readers understand the underlying score patterns. Separate pain, stiffness, and physical-function results are not posted. The record also does not report a clinical-importance threshold for the endpoint.

The analysis population, missing-data approach, and original analysis plan are not reported. The record does not explain why the primary outcome counts differ from enrollment, and no participant-flow account is posted. The comparison is unadjusted, while the registry does not describe covariate adjustment, model checks, or sensitivity analyses. The record lists one outcome measure and no analysis entries, limiting evaluation of prespecification and multiplicity.

The safety information is also limited: event types, attribution, timing, collection procedures, and comparative analyses are not reported. These registry limitations do not negate the posted numerical summaries, but they constrain assessment of their context and robustness. The results should therefore be interpreted as the reported Week 12 comparison and safety counts rather than as a complete account of trial evidence.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: Efficacy of Flavocoxid 500 mg Compared With Naproxen 500 mg in Subjects With Moderate-severe Osteoarthritis of the Knee — NCT00790985.
• Registry record last updated 2022-11-01; status last verified 2015-10.
• Results first posted 2022-11-01.
• 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 identifies a completed randomized, triple-masked, parallel-group trial of flavocoxid 500 mg compared with naproxen in subjects with moderate-to-severe osteoarthritis of the knee. Enrollment is recorded as 223. The primary endpoint was percent change in WOMAC composite score from baseline to Week 12, with higher values defined as better outcomes.

The posted mean percent changes were 69.97 for flavocoxid 500 mg and 85.75 for naproxen. The unadjusted difference, flavocoxid minus naproxen, was -15.78, with a 95% confidence interval from -18.09 to -13.47 and p <0.001. The registry also records zero serious adverse events and zero deaths in each arm, alongside other adverse event counts.

Details about the original statistical plan, analysis population, missing-data handling, and clinical-importance threshold are not reported in the registry record. The numerical interpretation is therefore limited to the posted endpoint comparison and safety summaries.