Diclofenac Sodium Topical Gel to Reduce Injection Site Discomfort in Patients Taking Glatiramer Acetate: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Diclofenac Sodium Topical Gel to Reduce Injection Site Discomfort in Patients Taking Glatiramer Acetate (NCT01454791), a randomized phase 4 study. The primary outcome is Local Injection Site Reaction (0-6) Scale at Baseline, 2 Weeks.

2. Clinical Question

The primary measure was the Local Injection Site Reaction scale, which ranges from 0 to 6, with zero described as best and 6 as worst. The registry says participants completed a daily diary rating reaction elements that included pain and inflammation. The primary outcome was defined as a comparison between interventions at 2 weeks, not as a comparison at another timepoint.

The registry describes a randomized, double-blind crossover trial. In a crossover design, participants receive interventions in sequence, so the treatment comparison may involve measurements from the same participant under both interventions. The record lists two sequences, active treatment followed by placebo and placebo followed by active treatment, with 1:1 randomization. The record does not report whether the primary comparison accounted for the paired nature of the observations or for possible sequence effects.

The practical statistical question is whether the observed difference in average scores is precise enough to distinguish a difference from no difference, and how the registry’s own analysis relates to a simple recalculation from posted summaries. These are questions about the posted results and their uncertainty, not a judgment about clinical benefit.

3. Trial Design

The registry describes this as a completed phase 4, randomized, double-blind crossover trial. It studied diclofenac sodium topical gel and placebo in people with multiple sclerosis taking glatiramer acetate. The recorded enrollment is 40. The study began in 2011-01 and primary completion was recorded as 2013-03.

Participants were randomized 1:1 to one of two sequences: diclofenac sodium topical gel first and placebo second, or placebo first and diclofenac sodium topical gel second. Each treatment phase is described as lasting 2 weeks. The registry identifies the primary comparison as the difference between interventions at 2 weeks. It does not describe the length of any interval between treatment phases, whether there was a washout period, or how the analysis handled treatment sequence or possible carryover.

A crossover design differs from a parallel-group design because participants move between interventions rather than remaining in one intervention group throughout. This can make within-participant comparisons informative when the analysis uses the paired measurements appropriately. At the same time, the interpretation depends on details such as the timing of measurements and how sequence and period are handled. Those statistical details are not reported in the registry record.

The record lists 40 observations for each intervention in the posted primary outcome summaries. That does not establish how many separate people contributed to each summary or how the analysis treated repeated measurements. The posted summaries should therefore be read as intervention-specific outcome summaries, not as evidence that the trial had separate parallel groups of that size.

The registry lists a t-test, 2 sided, for its reported primary analysis and gives a mean difference in final values. It does not report a fuller statistical analysis plan, an analysis population definition, or a sample-size justification. The posted record does not describe interim analyses. These omissions limit the ability to assess whether the reported analysis follows a prespecified plan or whether the assumptions suited the crossover structure.

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

Analysis population for the primary outcome, as defined in the registry: The primary outcome is looking at between-intervention differences at 2 weeks of intervention. Not a comparison at any other timepoint

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 Local Injection Site Reaction (0-6) Scale at Baseline, 2 Weeks, measured over 2 weeks.

The primary endpoint is the mean Local Injection Site Reaction score at 2 weeks, comparing diclofenac sodium topical gel with placebo. The scale runs from 0 to 6; the registry describes zero as best and 6 as worst. Participants were asked to complete a daily diary that rated reaction elements including pain and inflammation. The posted outcome is a mean, with standard deviation as its measure of spread.

A scale-based endpoint turns a set of ratings into a numerical summary that can be compared between interventions. The mean describes the average recorded score, while the standard deviation describes how much scores vary around that average. Neither statistic alone gives the full distribution of responses or indicates whether individual participants changed in the same way.

The registry’s stated primary comparison is specifically between interventions at 2 weeks. It is not a comparison of baseline with follow-up, nor does the record define the primary question as a change over time. That distinction matters: the posted mean difference represents the contrast between the two intervention summaries at the stated timepoint.

The scale’s direction helps interpret the sign of the contrast: a lower score is closer to the scale’s stated best value. The observed intervention means were 3.39 for diclofenac sodium topical gel and 3.47 for placebo, with a posted mean difference of -0.08. This small numerical contrast must be considered alongside the uncertainty and the registry’s own analysis. The record does not report a threshold for a clinically important difference, so the clinical importance of a difference of this size is not established by the registry.

7. Results Posted in the Registry

• Diclofenac Sodium Topical Gel: mean 3.39 versus 3.47 on control; difference -0.08 (95% CI -0.16 to 0.00), standardized effect d = -0.42; z-test p = 0.060.

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.

Subject Global Impression at 2 Weeks

• 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:
  • Diclofenac Sodium Topical Gel: mean 4.68 versus 4.50 on control; difference 0.18 (95% CI 0.11 to 0.25), standardized effect d = 1.06; z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically higher for Diclofenac Sodium Topical Gel than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

The posted secondary outcome is Subject Global Impression at 2 Weeks, measured on a Likert scale from 1 to 7, with 7 described as best. Its recalculated mean difference is 0.18 in favor of the higher mean for diclofenac sodium topical gel, and the unadjusted p-value is < 0.001. The registry’s own analysis gives the same mean difference and p = 0.705. The difference between those p-values means the secondary result also has a distinction between the registry analysis and the summary-based recalculation.

Across the posted primary and secondary outcomes, the estimated directions are not identical: the primary reaction-score contrast is lower for diclofenac gel, while the secondary global-impression contrast is higher for diclofenac gel. The registry’s own analyses report p = 0.45 for the primary outcome and p = 0.705 for the secondary outcome. The unadjusted recalculations yield different p-values. These patterns should not be compressed into a single overall claim because the outcomes measure different things and the analyses differ.

A secondary result can add context, but it does not replace the primary question or resolve uncertainty about it. The registry does not report a multiplicity adjustment or a prespecified strategy for interpreting secondary outcomes. In general, when multiple outcomes are assessed, unadjusted results carry less weight because the chance of an apparently notable result by chance can increase. The registry record also lists 3 outcome measures and 3 analyses, while only 1 secondary outcome is posted in the record summarized for interpretation. The status and analysis details of other measures are not reported in the registry record.

Accordingly, the secondary finding is best treated cautiously. Its scale, direction, and p-value belong to that outcome and should not be used as confirmation of the primary contrast without a prespecified analysis plan and adequate control of multiplicity.

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

• Subject Global Impression at 2 Weeks

9. Statistical Interpretation

10. Statistical Methods Explained

Several statistical ideas help put these results in context: means describe average scores, standard deviations describe spread, a mean difference expresses a contrast, and confidence intervals convey uncertainty. The crossover design also raises a question about whether the comparison used the relationship between measurements from the same participant.

What does a mean difference describe?

The mean is the arithmetic average of the scores in an outcome summary. The posted primary mean was 3.39 for diclofenac sodium topical gel and 3.47 for placebo. The mean difference is reported as -0.08, with the comparison expressed as diclofenac gel minus placebo. A negative value therefore indicates a lower average score in the diclofenac summary. Since lower scores are closer to the scale’s stated best value, the direction can be described, but direction alone does not establish importance or certainty.

The standard deviation is a measure of how dispersed individual scores are around the mean. Both primary summaries have a standard deviation of 0.19. It is not the uncertainty in the difference itself, and it does not tell how many participants had a better or worse score. A mean and standard deviation can be useful concise summaries, but they do not show the complete distribution or reveal whether the same participants had similar scores under both interventions.

What does a p-value say?

In general, a p-value describes how compatible data are with a specified null model, under the assumptions of the analysis. It is not the probability that the null hypothesis is true, and it does not measure the size or clinical importance of an effect. The unadjusted recalculation gives p = 0.06. The registry’s own 2-sided t-test reports p = 0.45. These values come from different presentations of the analysis and should be kept distinct. Neither by itself answers whether the observed contrast matters to participants.

The p-value depends on the estimate, its uncertainty, the statistical model, and the analysis procedure. In a crossover trial, the measurements under the two interventions may be related because they come from the same participants. A method that uses this pairing can have different uncertainty from a comparison that treats the intervention summaries as independent. The registry record does not report enough detail to establish how the sponsor’s analysis handled pairing. The recalculation is an unadjusted re-analysis of posted summary statistics and should not be mistaken for the original crossover analysis.

Why does the crossover structure matter?

As a general statistical principle, a paired analysis can use within-participant differences. When measurements from the same person tend to move together, accounting for that relationship can change the standard error of the treatment contrast. The relevant relationship is not recoverable from separate means and standard deviations alone. The registry record does not report participant-level paired differences or the covariance between measurements. The posted summary-based recalculation therefore cannot fully represent all information that might be available in an appropriately specified crossover analysis.

Crossover results may also depend on treatment period and sequence. For example, a participant’s response in a later period could be influenced by period-related changes or by the preceding intervention. These are general design considerations, not claims that such effects occurred in this trial. The registry record does not report a washout interval or analyses of period, sequence, or carryover effects, so their handling cannot be assessed.

How should the confidence interval be understood?

In general, a confidence interval gives a range of values reasonably compatible with the data and the calculation’s assumptions. A narrower interval indicates greater precision; a wider interval indicates more uncertainty. The recalculated primary interval includes zero, meaning that the posted summary statistics do not pin down the direction of the mean contrast with high precision under that recalculation. The registry’s reported analysis has no confidence interval posted. No interval should be read as a range containing a fixed proportion of individual participants’ scores.

Confidence intervals are conditional on their method and assumptions. Here, the recalculated interval is not a substitute for an interval from the trial’s own crossover analysis. The record’s lack of paired-data and analysis details limits what can be inferred from it. The endpoint’s standard deviations describe score spread; they should not be confused with the uncertainty around the treatment difference.

What is the difference between the registry analysis and recalculation?

The registry lists a 2-sided t-test of mean difference in final values and reports -0.08 with p = 0.45. The unadjusted recalculation also gives a mean difference of -0.08, but p = 0.06. The estimate is the same as posted; the uncertainty calculation differs. Since the registry record does not explain the discrepancy, the recalculation is best understood as a separate statistical reading of the summary values, not as a correction to the trial’s analysis.

In general, different analysis methods can yield different p-values even when their point estimates match, because their standard errors and assumptions may differ. That possibility is particularly relevant when a trial uses a crossover design but only separate intervention summaries are available. The record does not report whether the sponsor used a paired method, adjusted for other factors, or applied another analysis detail that would explain the p-value. The observed details support noting the difference, not guessing at its cause.

What do the secondary results add?

Subject Global Impression at 2 Weeks is the posted secondary outcome. It uses a Likert scale from 1 to 7, with 7 described as best. As a general principle, a secondary outcome can provide complementary information, but it does not replace the primary outcome. If several outcomes or analyses are examined, the chance of finding an apparently notable result by chance can rise unless multiplicity is addressed. The registry record does not report a multiplicity adjustment or a plan defining how secondary findings were to be interpreted.

Unadjusted secondary p-values should therefore be treated as exploratory evidence rather than as independent confirmation. The registry record also does not report missing-data methods, the analysis population, or a sample-size justification. These omissions make it difficult to judge whether the posted summaries represent all randomized participants under a prespecified strategy. Statistical interpretation is strongest when the design, estimand, analysis method, uncertainty, and missing-data handling are described together; several of those details are not reported in the registry record.

11. Confidence Intervals and Precision

The recalculated primary mean difference is -0.08. Its confidence interval includes zero, indicating that the summary-based estimate is not precise enough to rule out no difference under that recalculation. The interval also allows values on either side of zero, so the direction is uncertain from this calculation alone. The interval is a statement about uncertainty in the estimated mean difference, not a range describing individual diary scores.

The registry’s own analysis reports the same mean difference, -0.08, but does not include a confidence interval. Its p-value is 0.45. The summary-based recalculation gives p = 0.06. Because the registry record does not describe enough analysis detail to reconcile those p-values, the recalculated interval should not be attributed to the sponsor’s analysis. The record’s own interval is not reported in the registry record.

Precision depends on the amount of information and on the method used to analyze it. The posted standard deviation is 0.19 for each intervention summary, but these values do not establish the uncertainty of a paired crossover contrast. Separate means and standard deviations do not show the correlation between each participant’s scores under the two interventions. That relationship can matter to the precision of a crossover estimate.

The registry does not report a clinically important threshold for the reaction scale. Consequently, the interval cannot be used to decide whether all values it spans would be clinically negligible or important. Nor does an interval that includes zero establish equivalence. It describes uncertainty around an estimate under its calculation method; it does not prove the absence of an effect.

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 planning figures are participants per arm, not total events. They are illustrations based on the observed effect, not a report of the trial’s original sample-size calculation. The listed assumptions are a 2-sided significance level of 0.05, equal allocation between the two arms, a normal approximation, and an effect to detect equal to a stated fraction of the observed effect. The registry’s own original design assumptions and sample-size justification are not reported in the registry record.

The 80% power column describes the planned number of participants per arm for a hypothetical study to have an 80% chance of detecting the chosen effect under those assumptions, if that effect and model were correct. The 90% power column gives the corresponding planning target for a 90% chance. These are design probabilities, not probabilities that the trial result is true and not measures of the probability that this completed study detected an effect.

The rows use the observed effect in full, 75% of the observed effect, and 50% of the observed effect. Planning for a smaller effect requires more participants per arm because a smaller contrast is harder to distinguish from random variation. For example, the posted planning illustrations for 100% of the observed effect are 89 participants per arm for 80% power and 119 for 90% power; for 50% of the observed effect, they are 355 and 475, respectively.

These values are planning illustrations, not observed power. They rely on the listed assumptions and on the observed effect as a starting point. They do not reproduce the original trial’s design calculation, and they should not be read as evidence that the trial was or was not adequately designed for its own objectives.

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 = -0.080; pooled standard deviation σ = 0.190.
2. n = 2 × (1.96 + 0.842)² × 0.190² / -0.080² = 88.5, rounded up to 89 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
delta <- -0.0800000000000001                      # observed difference in means
sigma <- 0.19                     # 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(1454791)
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 = 89 (80% power), 119 (90% power)
 75% of observed effect: n per arm = 158 (80% power), 211 (90% power)
 50% of observed effect: n per arm = 355 (80% power), 475 (90% power)
power.t.test: 89.5 
Simulated power at n = 89 per arm: 0.794 (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. Analyses Reported by the Sponsor

The registry’s own primary analysis is listed as a 2-sided t-test of mean difference in final values. It reports a mean difference of -0.08 and p = 0.45. The unadjusted recalculation from the posted summary statistics also gives a mean difference of -0.08, but its p-value is 0.06. Thus, the contrast itself matches while the reported uncertainty differs.

The registry record does not explain why the p-values differ. The recalculation uses posted summary statistics and is not a reconstruction of the complete trial analysis. Because this was a crossover trial, the sponsor’s analysis may have used features of the design that cannot be recovered from separate means and standard deviations; however, the registry record does not report enough detail to say whether that is the explanation. No particular cause should be assumed.

The sponsor’s result is the trial’s reported analysis, and the recalculation is a separate unadjusted statistical check. Both should be presented with their methods and limitations rather than treated as interchangeable. The registry record does not report a confidence interval for the sponsor’s estimate. The recalculated confidence interval belongs only to the summary-based recalculation and should not be attributed to the sponsor.

15. Multiplicity, Missing Data and Analysis Populations

The registry record does not report whether the trial used a multiplicity adjustment, how it prioritized secondary outcomes, or whether a formal hierarchy of hypotheses was prespecified. It lists 3 outcome measures and 3 analyses, and identifies Subject Global Impression at 2 Weeks as a secondary outcome. With more than one outcome or analysis, unadjusted p-values can overstate the strength of evidence if they are interpreted as though only one hypothesis had been tested. This is a general statistical concern, not evidence that any particular result is false.

The record does not report how missing outcome values were handled, whether participants with incomplete diaries were included, or how the analysis population was defined. These details matter because the observed means and p-values can depend on which measurements are available and how incomplete records are treated. The registry record does not describe an intention-to-treat population, a per-protocol population, imputation, or a sensitivity analysis. Their use cannot be assumed.

The crossover structure also makes analysis-population details important. The posted summaries give an n of 40 for each intervention, but do not clarify whether those counts refer to complete paired observations, intervention-period records, or another summary convention. They should not be added or interpreted as separate parallel groups. The record does not report how participants who did not complete both treatment phases were handled.

Other design and analysis details are also absent: the registry does not report the original sample-size justification, interim analyses, a full statistical analysis plan, treatment-period or sequence effects, or a washout description. The absence of these details does not establish that the procedures were not used; it means that they are not reported in the registry record. As a result, the posted results can be described, but their consistency with a prespecified plan and the influence of missing data or multiplicity cannot be fully assessed.

16. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent non-serious adverse event terms

The registry lists serious adverse events for 20 at risk in each intervention group, with 0 affected in the diclofenac sodium topical gel group and 0 affected in the placebo group. These are the serious-event figures recorded for the groups; the registry does not list any serious adverse-event terms.

For other adverse events, the record lists 20 at risk in each group. It records 0 affected in the diclofenac gel group and 1 affected in the placebo group. These counts describe the posted event record, not comparative rates from a detailed safety analysis. The registry does not define the “other” event category further in the information recorded here, so its scope should not be expanded beyond the label.

Death counts are not reported in the registry record. The adverse-event summaries do not establish that no events occurred outside the recorded categories or periods, and they do not show event severity, timing, relatedness, or recurrent events. The group figures are limited to the registry’s posted at-risk counts and affected counts. They should be read as descriptive safety information, not as a definitive comparison of safety between interventions.

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

The primary result describes a mean difference of -0.08 in the Local Injection Site Reaction score at 2 weeks, with lower scores closer to the scale’s stated best value. The recalculated interval includes zero, and the registry’s own analysis reports p = 0.45. These findings indicate uncertainty about the size and direction of the primary contrast; they do not establish that the interventions are equivalent or that there is no difference.

The estimate also cannot, by itself, determine whether any difference would matter to participants. The registry does not report a minimally important difference for the reaction scale. A numerical contrast should not be called clinically meaningful or unimportant without an appropriate threshold and context. The diary-based score summarizes a particular measure of local reaction and does not represent every possible treatment outcome.

The secondary global-impression outcome has a different pattern, but it is not a replacement for the primary endpoint. Its p-value differs between the registry’s own analysis and the unadjusted recalculation, and the record does not report a multiplicity plan. It therefore cannot settle the uncertainty in the primary result.

Interpretation is further limited by the crossover design and the lack of reported detail about paired analysis, missing data, treatment sequence, or period effects. The simple recalculation uses posted summary statistics and cannot recover all information needed to assess a crossover comparison. The trial’s own reported analysis should be distinguished from that recalculation, and neither should be read without its uncertainty and methods.

Overall, the registry supports a description of the posted group summaries and analyses, but not a broad claim that one intervention is effective, ineffective, equivalent, or clinically preferable. Those conclusions would require a fuller account of the analysis plan, data completeness, clinical importance, and the trial’s design-specific statistical handling.

18. Why This Trial Matters Statistically

This trial is statistically informative because its crossover structure makes the unit of comparison important. The posted outcome summaries are organized by intervention, but the registry record does not describe whether the primary analysis used within-participant pairing. In general, that relationship can affect the precision of a treatment contrast. Separate means and standard deviations cannot recover the paired information, so an unadjusted recalculation is necessarily limited.

The record also illustrates why an effect estimate and a p-value should be considered separately. Both the registry analysis and the recalculation give a primary mean difference of -0.08, but their p-values differ: 0.45 in the registry and 0.06 in the recalculation. The point estimate alone does not reveal the analysis uncertainty, and the p-value alone does not describe the size or clinical importance of the contrast. The registry does not provide enough analysis detail to explain the difference.

Another useful lesson is that a nonsignificant result is not evidence of equivalence. The primary recalculated interval includes zero, but the registry does not report an equivalence margin or a minimally important difference. Without those elements, the data cannot answer whether the interventions are sufficiently similar for a clinical purpose.

Finally, the secondary result demonstrates why multiple endpoints require a clear interpretation plan. A secondary outcome may offer additional perspective, but unadjusted findings can be less conclusive when several outcomes are examined. The missing information about multiplicity, analysis populations, and missing data limits how confidently the full set of posted outcomes can be interpreted. These are practical considerations for reading trial registries, especially when a concise record does not include the complete protocol or statistical analysis plan.

19. 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 main trial-specific limitation is that the registry does not report the details needed to assess a crossover analysis fully. It identifies two treatment sequences and 2-week phases, but does not report a washout interval or how the analysis handled within-participant pairing, period, sequence, or carryover. The posted means and standard deviations do not provide the participant-level relationship between intervention measurements.

The sponsor’s primary analysis is reported as a 2-sided t-test, but the record does not provide a confidence interval or fuller model description. Its p-value differs from the unadjusted recalculation despite the same mean difference. The reason is not reported in the registry record. That makes it difficult to determine which analysis details account for the difference, or how well either summary reflects the crossover design.

The record does not report a sample-size justification, a prespecified statistical analysis plan, interim analyses, multiplicity handling, the analysis population, or methods for missing data. It also does not report a clinically important difference for the primary scale. These absences prevent assessment of whether the study was planned to detect a meaningful contrast or how robust the results are to incomplete data and multiple outcome testing.

The posted safety figures are limited to the recorded at-risk and affected counts. Death counts are not reported in the registry record, and the event summaries do not describe timing, severity, relatedness, or recurrence. The secondary outcome’s analysis also has a difference between the registry p-value and the recalculation. Together, these limitations favor a cautious, descriptive interpretation rather than a definitive conclusion.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: Diclofenac Sodium Topical Gel to Reduce Injection Site Discomfort in Patients Taking Glatiramer Acetate — NCT01454791.
• Registry record last updated 2015-03-05; status last verified 2015-01.
• Results first posted 2015-02-13.
• 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.

23. Record Summary

The registry record describes a completed phase 4, randomized, double-blind crossover trial of diclofenac sodium topical gel versus placebo in people with multiple sclerosis taking glatiramer acetate. Enrollment was 40. Participants were randomized to active treatment followed by placebo or placebo followed by active treatment, with each phase lasting 2 weeks.

The primary endpoint was the Local Injection Site Reaction score at 2 weeks on a scale from 0 to 6, with zero best. The posted means were 3.39 for diclofenac gel and 3.47 for placebo; the mean difference was -0.08. The registry’s own analysis reports p = 0.45, while an unadjusted recalculation gives p = 0.06 and an interval that includes zero.

The registry also posts Subject Global Impression at 2 Weeks as a secondary outcome. Important analysis details—including the crossover handling, missing-data methods, multiplicity plan, and sample-size justification—are not reported in the registry record. The results are therefore best read as descriptive estimates with important uncertainty about analysis methods and precision.