An Investigator Initiated, Within-Subject, Proof of Concept Study to Assess the Efficacy and Safety of Voltaren Gel in Subjects With DOMS: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for An Investigator Initiated, Within-Subject, Proof of Concept Study to Assess the Efficacy and Safety of Voltaren Gel in Subjects With DOMS (NCT02087748), a randomized phase 4 study. The primary outcome is Mean Reduction in SPID Scores of DOMS on Walking Over 24 Hours.

2. Clinical Question

3. Trial Design

This completed Phase 4 study was sponsored by Lotus Clinical Research, LLC. The registry lists randomized allocation, triple masking, enrollment of 24, a start date of 2014-03, and primary completion in 2014-04. The title describes an investigator-initiated, within-subject proof-of-concept study, and the official title also calls it within-subject. At the same time, the registry’s model field says parallel. These descriptions do not align, and the record does not resolve the inconsistency.

The treatment descriptions indicate that each comparison concerned a leg receiving diclofenac gel and a leg receiving placebo. Each outcome arm has 24 observations. These values should not be added to infer a total number of unique participants: the study is described as within-subject, and the registry enrollment is 24. The record does not provide a participant flow or an account of how many participants contributed complete data to each analysis.

Diclofenac and placebo were each applied topically as 4 grams every six hours for 48 hours. The record identifies the study as randomized and triple-masked, but does not describe the randomization procedure, who was masked, or how masking was maintained. The original protocol’s statistical plan, sample-size justification, interim analyses, and analysis populations are not reported in the registry record. The outcome descriptions give a 24-hour assessment period, while the timeframe field says 7 days; the record does not explain that difference.

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.

Population: One group will use 1% diclofenac sodium gel on the left leg and placebo on the right leg for the treatment duration. The other group will use the same products, but on opposite legs.

6. Primary Endpoint

The registry lists the primary outcome as Mean Reduction in SPID Scores of DOMS on Walking Over 24 Hours, measured over 7 days.

The primary endpoint is the mean reduction in SPID scores for DOMS pain while walking over 24 hours. SPID is a summary of pain-intensity differences across the scheduled assessments, rather than a single pain rating at one time. The registry describes pain-intensity differences as post-baseline Numeric Rating Scale values minus the baseline value. It gives a theoretical SPID24 range from -50, indicating an increase in pain, to 50, indicating a decrease in pain.

Repeated ratings capture how pain changes across the early post-treatment period. Summarizing those ratings can represent the overall pattern over that period, while a mean allows a direct comparison of average scores between the treatment conditions. The walking condition is the primary activity context; the record also lists rest and standing as secondary contexts.

The outcome description says the comparison of interest is between the leg receiving diclofenac gel and the leg receiving placebo during the first 24 hours after treatment. It calls the endpoint a mean reduction, but the record does not explain in further detail how the summary score was constructed or how incomplete ratings were handled. The endpoint timeframe field is listed as 7 days despite the stated 24-hour outcome period, and that discrepancy is not explained in the registry record.

7. Results Posted in the Registry

• 1% Diclofenac Sodium Gel: mean 34.87 versus 23.62 on control; difference 11.25 (95% CI -0.74 to 23.24), standardized effect d = 0.53; z-test p = 0.066.

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.

Mean Reduction in SPID Scores of DOMS at Rest Over 24 Hours

• 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:
  • 1% Diclofenac Sodium Gel: mean 28.06 versus 24.81 on control; difference 3.25 (95% CI -9.43 to 15.93), standardized effect d = 0.14; z-test p = 0.616.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between 1% Diclofenac Sodium Gel and the control. The interval gives the range of effects that remain compatible with the data.

Mean Reduction in SPID Scores of DOMS While Standing Over 24 Hours

• 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:
  • 1% Diclofenac Sodium Gel: mean 33.90 versus 21.62 on control; difference 12.28 (95% CI 0.31 to 24.25), standardized effect d = 0.58; z-test p = 0.044.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically higher for 1% Diclofenac Sodium Gel than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

The secondary outcomes assess pain at rest and while standing, complementing the primary walking measure. Across the two contexts, the recalculated results are not uniform: the standing comparison has a positive estimated difference, while the rest comparison is smaller and its interval includes zero. This suggests that the pattern depends on the activity context in the posted summaries. The registry also reports a separate sponsor test for each secondary outcome, but does not provide sponsor estimates or intervals for those comparisons.

The standing result’s direction is consistent with the primary recalculated direction, whereas the rest result offers less evidence of a separated mean. That broad pattern does not establish that the treatment contrast truly differs by activity. Demonstrating such a difference would require an analysis comparing the treatment effects across contexts, which is not reported in the registry record.

Secondary outcomes commonly add context, but their results carry less weight when many outcomes or comparisons are examined without a stated multiplicity approach. Each additional test creates another opportunity for a result to appear noteworthy by chance. The registry does not report whether these outcomes were confirmatory, how they were prioritized, or whether the sponsor adjusted for multiple testing. Their p-values are therefore best treated as exploratory signals rather than independent confirmation of the primary finding.

Because the record does not report participant-level data, paired contrasts, or detailed analysis methods, the secondary recalculations have the same interpretive limits as the primary recalculation. They describe posted summaries, not a substitute for the sponsor’s analysis or a complete account of uncertainty across outcomes.

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

• Mean Reduction in SPID Scores of DOMS at Rest Over 24 Hours
• Mean Reduction in SPID Scores of DOMS While Standing Over 24 Hours

9. Statistical Interpretation

10. Statistical Methods Explained

What does a mean comparison describe?

A mean is the arithmetic average of the observed outcome values. For the primary outcome, the registry reports the mean SPID score for each arm and a recalculated mean difference. A difference is expressed in the same units as the underlying measure. A positive difference in this comparison means the diclofenac-arm mean is higher than the placebo-arm mean; it does not, by itself, establish why the means differ or how reliable the difference is.

The reported standard deviations describe the spread of participant outcome values around each arm’s mean. They are not standard errors and do not directly describe uncertainty in the mean. Standard errors describe the sampling uncertainty of an estimate, while an interval around an estimate expresses a range of values compatible with the analysis and its assumptions. General statistical interpretation of such an interval depends on the sampling model and design.

What does the t-test test?

A two-sided t-test evaluates evidence against a null hypothesis of no mean difference, allowing departures in either direction. A p-value is the probability, under the test’s null model and assumptions, of a test result at least as extreme as the one observed. 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 registry reports two-sided t-tests for the outcomes, but does not give the complete analysis specification.

The recalculated p-values are unadjusted comparisons derived from posted summary statistics. They are not the sponsor’s test results. For the primary outcome, the sponsor’s reported p-value differs from the recalculated p-value, and the sponsor’s analysis takes precedence. The registry does not report enough detail to identify the source of the difference. It does not state whether the sponsor’s analysis used a paired test, a particular analysis population, or other adjustments.

Why does the within-subject description matter?

In a within-subject design, a participant contributes outcomes under both conditions, so the two measurements are related. A paired analysis uses the within-participant differences and their variability. By contrast, an analysis treating the two sets of observations as independent does not use that pairing. The relationship between a participant’s two outcomes can affect the uncertainty estimate. This is a general design principle, not a claim about the sponsor’s method: the registry’s title describes a within-subject study, but its model field says parallel, and the posted summary does not report the paired differences or their variability.

The recalculated comparisons use the posted arm means and standard deviations. They cannot recover the participant-level pairing from those summaries. The recalculation should therefore be read as an unadjusted summary-statistic comparison, not as evidence that the sponsor used the same method. The registry’s labels and summary statistics do not resolve which design model or variance calculation governed the sponsor analysis.

What does the standardized effect add?

The recalculated primary standardized difference is 0.531. A standardized effect expresses a mean difference relative to a measure of outcome spread, making it unitless. It can help describe the scale of a contrast relative to observed variability, but it does not replace the mean difference in the outcome’s original units. Its interpretation depends on the design and on how the spread was calculated. The record does not report this standardized effect as part of the sponsor’s analysis.

Effect-size estimates from a small study can be imprecise. A value calculated from the observed difference is not a guarantee that the same effect would appear in another study. This is particularly important when the study is described as proof of concept and the observed estimate is used for planning illustrations: an effect estimated in one small study may not be a dependable target for a future design.

How should the outcome scale be read?

The Numeric Rating Scale records pain intensity, and the SPID24 summary combines changes at the listed post-baseline assessments. The registry says pain-intensity differences were calculated as post-baseline ratings minus baseline ratings, and that the theoretical SPID24 range runs from -50 to 50. Under the registry’s description, the negative end represents increased pain and the positive end represents decreased pain. The scale’s direction is essential when interpreting the sign of a mean difference. The record does not describe the handling of missing time points or the exact procedure used to form an individual’s SPID24 value.

In general, a repeated-measure summary can retain information about change across several scheduled times, but it can also conceal the shape of that change. The same overall summary could arise from different patterns across assessments. The registry does not report separate estimates at each time point, so the posted SPID summary should not be interpreted as showing a particular time course.

What limits the statistical interpretation?

The registry does not report the original sample-size justification, assumptions for the sponsor’s analysis, a prespecified multiplicity approach, an interim-analysis plan, or the treatment of missing observations. It also does not report the sponsor’s primary effect estimate and interval. These omissions limit independent evaluation of how the analysis followed the original plan and how robust the reported findings are. They do not establish that a particular method was or was not used; those details are not reported in the registry record.

11. Confidence Intervals and Precision

The recalculated primary mean difference is 11.25 units, with an interval from -0.74 to 23.24. The interval spans zero and includes both a small negative contrast and positive contrasts of greater size. It therefore reflects substantial uncertainty about the direction and magnitude of the difference in this summary-statistic recalculation. The registry does not state the interval’s confidence level, so it should not be assigned a level that is not reported.

A confidence interval, in general, is a range constructed by a method that has a stated long-run coverage under its assumptions. It is not a guarantee that the true value lies within the particular interval, nor is it a range of individual participant outcomes. Its width is affected by the amount of information, variability, design, and analysis method. In a within-subject study, the pairing can matter to precision; the posted summaries do not provide the paired variation needed to assess that contribution independently.

The sponsor reports a p-value for the primary comparison but no sponsor estimate or interval in the registry record. A p-value cannot communicate the full range of plausible effect sizes or the precision of an estimate. The sponsor’s reported analysis takes precedence over the recalculation because the two differ, but its estimate and precision cannot be characterized from the reported p-value alone.

Both the recalculated interval and the limited sponsor reporting counsel against treating one test result as a complete account of the evidence. The size of the mean contrast, its uncertainty, the design, and the analysis must be considered together. Neither the interval nor the p-value describes how much participants differed from one another or whether individual effects were consistent.

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 computed from the observed effect, not the original trial’s design calculation. The stated assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; each planning scenario targets the stated fraction of the observed effect. The original design assumptions and sample-size justification are not reported in the registry record.

The 80% power column gives the illustrative number of participants per arm for a design with an 80% chance of detecting the specified effect if that effect were the true one and the planning assumptions held. The 90% column uses a higher probability of detection under those same conditions, and consequently requires more participants. These are planning probabilities, not probabilities that the study’s finding is true.

The scenarios use the full observed effect and smaller fractions of it. A smaller effect is harder to distinguish from random variation at the same significance level, so more participants are needed to achieve the same target power. The displayed counts are not observations from the completed trial and should not be read as evidence that the study had a particular probability of obtaining its result. This is not observed power.

These calculations are sensitive to the chosen effect size and assumptions. In particular, the trial is described as within-subject, while the registry model field says parallel. The planning assumptions describe equal allocation between two arms, but the registry does not explain how the illustrative calculations account for the within-subject description. They should be interpreted only as planning illustrations, not as a reproduction of the sponsor’s original design process.

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 = 11.250; pooled standard deviation σ = 21.192.
2. n = 2 × (1.96 + 0.842)² × 21.192² / 11.250² = 55.7, rounded up to 56 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 <- 11.25                      # observed difference in means
sigma <- 21.1915549217135                     # 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(2087748)
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 = 56 (80% power), 75 (90% power)
 75% of observed effect: n per arm = 100 (80% power), 133 (90% power)
 50% of observed effect: n per arm = 223 (80% power), 299 (90% power)
power.t.test: 56.7 
Simulated power at n = 56 per arm: 0.797 (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

For the primary outcome, the registry reports a sponsor two-sided t-test p-value of 0.032. The unadjusted recalculation from the posted arm summaries gives a mean difference of 11.25 units, an interval from -0.74 to 23.24, and p = 0.066. These are not the same analysis result. The sponsor’s own analysis takes precedence; the recalculation is a separate, simple summary-statistic calculation and should not be presented as correcting or replacing the sponsor’s result.

The registry does not report the sponsor’s estimated primary mean difference, its interval, or enough analytical detail to explain the discrepancy. The study’s within-subject description makes the handling of paired observations potentially relevant in general, but the record does not state whether that accounts for the difference. No conclusion about the reason for the discrepancy can be drawn from the available information.

The sponsor’s p-value alone gives no direct estimate of the size or precision of the sponsor’s contrast. It should be read alongside the endpoint definition and the limits of the registry record, rather than treated as a complete statistical summary. The separate recalculated figures are useful for describing what follows from the posted arm summaries, with the distinction from the sponsor’s result kept explicit.

15. Multiplicity, Missing Data and Analysis Populations

The registry lists one primary outcome and two secondary outcomes, each with a reported analysis. It does not report a multiplicity strategy, such as a hierarchy among outcomes or an adjustment to account for testing more than one outcome. Without that information, the separate p-values should not be treated as if each arose from a single, isolated confirmatory test. Considering several tests increases the chance of at least one apparently unusual result under a collection of null hypotheses. This is a general statistical concern; the record does not say which approach, if any, was used by the sponsor.

The outcome descriptions give the assessment schedule and the 24-hour period of interest, but the endpoint timeframe field says 7 days. The record does not explain the difference. It also does not provide a detailed protocol for selecting analysis populations, handling missing ratings, or managing deviations from assigned treatment. Those details are not reported in the registry record, so it is not possible to assess their effects on the estimates.

The registry reports arm sample sizes for the outcomes, but does not report a participant flow, the number with missing observations, or an account of which participants were included in each sponsor analysis. It does not say whether all randomized participants were analyzed, whether analyses used another population definition, or how incomplete participant records were treated. These omissions matter because exclusions and missing outcome data can affect both the estimate and its uncertainty.

Nor does the record report interim analyses or stopping rules, so no claim can be made about whether results were examined during the study or how that might have influenced inference. The registry’s design descriptions are also inconsistent: the titles describe a within-subject study, while the model field says parallel. The record does not resolve how that design was represented in the sponsor’s statistical analysis. These missing details limit assessment of multiplicity, analysis choices, and the relationship between the posted summaries and the original plan.

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.

The registry lists 24 participants at risk in each treatment condition for serious adverse events and reports zero serious adverse events in each. It also lists 24 at risk in each condition for other adverse events and reports zero in both. The deaths count is not reported in the registry record. No serious adverse event terms are listed.

These figures describe the adverse-event entries posted for this study; they do not establish that no adverse events of any kind occurred beyond the categories recorded. The registry does not give further details about adverse-event collection, duration of follow-up for safety, or the handling of missing safety information. The treatment period is described as 48 hours, but the record does not explain the safety observation period.

With a small enrolled study, zero reported events should be read as an observation from this study, not as proof that an event cannot occur. The figures do not support broad comparisons of safety risk or conclusions about other populations and treatment durations.

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

The posted data describe average pain-summary scores for diclofenac gel and placebo in a randomized, triple-masked study of subjects experiencing DOMS. For the primary walking outcome, the recalculated mean is higher in the diclofenac arm, but the recalculated interval includes zero. The sponsor reports a different two-sided test result, and its own analysis takes precedence. Since no sponsor estimate or interval is reported, the registry does not give a complete account of the size and precision of the sponsor’s primary contrast.

These findings do not establish that the treatment works or does not work. A test result is not a direct measure of clinical importance, and a p-value does not give the probability that a treatment effect is real. The mean comparison also does not show individual responses or the distribution of changes. The study’s proof-of-concept description, small enrollment, unclear design-model entry, and incomplete reporting of analysis details all limit the conclusions that can be drawn from the registry record.

The pain measure is a summary across prespecified assessments over 24 hours. It does not disclose the pattern at each time point, and the record does not state how missing ratings were handled. The secondary outcomes broaden the measured contexts, but multiple testing and the absence of a reported adjustment mean they should not be taken as independent confirmation.

The results apply to the recorded study conditions: topical gel applied every six hours for 48 hours, and pain associated with DOMS. The registry does not supply participant characteristics sufficient to evaluate generalizability, nor does it report detailed methods that would allow a full independent reconstruction. The findings should therefore be understood as a limited statistical description of this study, not a recommendation or a conclusion about other settings, regimens, or groups.

18. Why This Trial Matters Statistically

This trial illustrates why the design description and the statistical comparison need to be read together. The study titles describe a within-subject comparison, in which observations from the same participant may be related, while the registry’s model field says parallel. That difference matters because paired and independent-group analyses can estimate uncertainty differently. The summary information does not resolve which approach underlies the sponsor’s result.

It also illustrates the distinction between a sponsor-reported test and a recalculation from posted summaries. The primary p-values differ, while the registry does not include the sponsor’s effect estimate or interval. Reporting only a p-value leaves readers without a direct description of the sponsor’s estimated contrast and its precision. A transparent account of the analysis method and paired data would help readers understand how the result was obtained.

The three outcome contexts show why outcomes should be prioritized and interpreted as a family. A primary endpoint provides a focal question, while secondary measures can offer useful context. Without a reported multiplicity plan, however, separate secondary p-values should not be treated as if each were a standalone confirmatory result.

Finally, planning illustrations based on the observed effect can be informative about how sample size depends on the target effect, but they are not the original design rationale. Keeping planning assumptions distinct from the trial’s actual design assumptions is important when interpreting small proof-of-concept studies.

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 registry record has several limitations specific to this study. Its titles identify a within-subject design, but its model field identifies a parallel model. The arm summaries list 24 observations per condition, while enrollment is 24; without participant-level linkage or a description of the analysis, the relationship between these summaries and the within-subject design cannot be checked independently.

The primary sponsor analysis is reported only as a two-sided t-test p-value. The sponsor’s estimate and interval are absent, and the recalculation from posted arm summaries yields a different p-value. The record does not explain the discrepancy or provide enough detail to reconstruct the sponsor’s analysis. The posted endpoint timeframe is also listed as 7 days even though the outcome description concerns the first 24 hours; that difference is unexplained.

Participant characteristics and eligibility details are not reported in the outcome information. The record does not describe the randomization procedure, masking implementation, analysis populations, missing-data handling, or participant flow. It also does not report the original sample-size justification, interim analyses, or multiplicity plan. These omissions prevent a fuller assessment of generalizability, precision, and whether the reported analyses followed a prespecified plan.

Safety entries report no serious or other adverse events in either condition, but death counts are not reported and the safety observation details are not given. The short treatment description and absent follow-up detail limit interpretation of those entries. These are limits of the registry record and should not be interpreted as proof that the underlying study lacked such procedures or information.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: An Investigator Initiated, Within-Subject, Proof of Concept Study to Assess the Efficacy and Safety of Voltaren Gel in Subjects With DOMS — NCT02087748.
• Registry record last updated 2014-12-10; status last verified 2014-12.
• Results first posted 2014-12-10.
• 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

NCT02087748 is a completed Phase 4 randomized, triple-masked study sponsored by Lotus Clinical Research, LLC, with enrollment listed as 24. The study titles describe a within-subject comparison of topical 1% diclofenac sodium gel and placebo in subjects experiencing DOMS; the model field says parallel. Each gel was applied as 4 grams every six hours for 48 hours.

The primary outcome was mean reduction in SPID scores while walking over 24 hours. The registry reports arm means and a sponsor two-sided test, alongside summaries that support a separate unadjusted recalculation. Those primary statistical results differ, and the sponsor’s own analysis takes precedence. Two secondary outcomes assess pain at rest and while standing. The record does not report a multiplicity plan, the original sample-size justification, or several details needed to reconstruct the analyses. Safety entries list zero serious and zero other adverse events in each condition; deaths are not reported in the registry record.