Administration of Two Injections for Multiple Dupuytren's Contractures: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Administration of Two Injections for Multiple Dupuytren's Contractures (NCT01407068), a na phase 3 study. The primary outcome is Percent Change From Baseline in Total Fixed Flexion.

2. Clinical Question

3. Trial Design

This is a Phase 3, open-label, single-group study of concurrent administration of two injections of AA4500 into the same hand of subjects with multiple Dupuytren's contractures. The intervention is listed as AA4500 collagenase clostridium histolyticum. The registry record lists 60 enrolled participants and marks the study as completed. Its recorded study dates are 2011-09 for start and 2012-02 for primary completion.

Because the design is single group and allocation is NA, the study does not have a randomized control arm in the registry record. The observations are intended to describe outcomes after the intervention within the treated group. They cannot, by themselves, distinguish changes associated with treatment from changes that might occur over time or from other influences. The open-label status also means that masking was none. This is relevant when interpreting outcomes that involve assessment or judgment, although the record does not report how individual assessments were conducted.

The primary endpoint was assessed 30 days after the last injection. The efficacy population is defined in the record as enrolled subjects who received two injections and had at least one post-injection measurement. That definition should not be confused with the enrollment count: the number included in the primary outcome analysis is not reported in the registry record.

The record lists five outcome measures and zero analyses. It describes the primary measure and lists secondary outcomes concerning subject satisfaction, investigator assessment of improvement, and clinical success by joint type. Numerical results for these outcomes are not reported in the registry record. Details of the statistical analysis plan, including any adjustment methods, are not reported in the registry record.

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: Efficacy analysis is based of the intent-to-treat population (ITT). The population is defined as all enrolled subjects who received two injections of AA4500 and had at least one-post-injection measurement.

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 Percent Change From Baseline in Total Fixed Flexion, measured over 30 days after last injection.

The primary endpoint is percent change from baseline in total fixed flexion, with the assessment made 30 days after the last injection. The registry defines total fixed flexion as the sum of fixed flexion contractures in the two joints receiving treatment. It describes change in fixed-flexion contracture as measured in degrees and states that a decrease of 100% would correspond to a reduction in contracture to 0 degrees.

This is a continuous outcome: it represents a measurement along a scale rather than a simple event count or yes-or-no status. The record specifies the mean as the summary parameter and standard deviation as the dispersion measure. In general, a mean describes the central value of a group, while a standard deviation describes how spread out individual measurements are around that mean. Both can help readers understand the group outcome and its variability, but neither is reported numerically in the registry record.

Using change from baseline focuses the endpoint on how the measured contracture differs from its baseline value. The specified assessment time gives the outcome a defined point after treatment. The endpoint is clinically relevant to the study's stated objective because it measures contracture in the treated joints. However, the registry record does not give a numerical change, a confidence interval, or an analysis result, so the size and precision of the observed endpoint cannot be assessed from the posted results.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The statistical interpretation begins with the distinction between the study design and the outcome measure. The design is single group and open label, with allocation listed as NA and masking listed as none. The primary outcome is continuous and is summarized, according to the registry record, by a mean and standard deviation. These registry entries define the broad setting for interpretation, but they do not specify the complete analysis method. The statistical plan is not reported in the registry record.

What does the mean describe?

In general, the mean is a summary of the central tendency of measured values. For this endpoint, the registry specifies the mean of the percent change from baseline in total fixed flexion. A mean can be useful for describing the overall direction and size of change in a group, but it does not show how each participant's measurement changed. Participants may have outcomes that differ from the group average. The standard deviation provides a general description of that spread, but it is not a measure of how precisely the group mean is estimated.

Neither the primary mean nor its standard deviation is reported numerically in the registry record. There is also no reported confidence interval or test result. Thus, the endpoint's specified summary format should not be mistaken for a posted estimate. The record identifies what was intended to be summarized, but does not give the values needed to interpret the group outcome.

What does a confidence interval add?

In general, a confidence interval expresses the uncertainty around an estimated quantity under the assumptions of the statistical method used. A narrower interval indicates greater precision, while a wider interval indicates more uncertainty. An interval for a group mean would help readers judge which values are compatible with the observed data and method. It would not remove design limitations, establish a causal effect in a single-group study, or guarantee that the true value lies within any one calculated interval. No confidence interval for the primary endpoint is reported in the registry record.

A p-value, if reported, would address how compatible the observed data are with a specified null hypothesis under the test's assumptions. It would not describe the size of an effect or its clinical importance. The registry record does not report a p-value or identify a primary-outcome hypothesis test. As a result, the posted information cannot support a test-based interpretation of the endpoint.

Why does the single-group design matter?

In a randomized comparison, a treatment contrast can be estimated by comparing outcomes across assigned groups, subject to the design and analysis assumptions. This study is listed as single group, so no such contrast is available from its design description. A before-and-after outcome, if reported, would describe within-group change. In general, within-group change may reflect intervention-related change as well as time trends, measurement variation, or other influences. Without a concurrent comparator, those explanations cannot be separated by a randomized between-group contrast.

The open-label designation means masking was none. In general, knowledge of treatment assignment can affect some assessments or reported outcomes, particularly when judgment or participant report is involved. The record lists subject satisfaction and investigator assessment among the secondary outcomes, but does not provide numerical results or detailed assessment procedures for them. This observation is a design consideration, not evidence that any particular assessment was biased.

How should the planning illustration be understood?

The planning illustration uses a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It considers an effect to detect expressed as a stated fraction of the observed effect. These are planning assumptions, not a description of the trial's single-group design. The illustration is not the trial's own design and is not observed power. Sample-size planning values describe hypothetical requirements under assumptions; they do not show how many participants were analyzed or establish the probability that the completed study detected an effect.

Because the actual trial is single group, the equal-allocation, two-arm planning setup should not be read as evidence that the trial included two arms. The record does not report a randomized comparison. Nor should a planning illustration be treated as a retrospective assessment of success. The registry record does not report a trial-specific sample-size justification, and the planning assumptions do not establish what rationale was used when the study was designed.

What can be concluded from the reported methods?

The record gives a primary endpoint, its measurement time, the mean and standard deviation as summary measures, and a definition of the efficacy population. It does not report the outcome estimate, its dispersion, an uncertainty interval, a hypothesis test, or the number included in the analysis. The statistical analysis plan and details such as adjustment for baseline values are not reported in the registry record. No method should be presumed from the endpoint definition alone.

In general, interpreting a continuous endpoint requires attention to the outcome scale, the population analyzed, the handling of incomplete measurements, the summary statistic, and the uncertainty around the estimate. The endpoint definition addresses some of these elements, but the posted record does not provide enough analysis detail to evaluate the others. The safest statistical reading is therefore descriptive: the registry specifies the question and measurement framework, while the result and its precision are not reported in the registry record.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("AA4500")
n   <- c(60)
m   <- c(75.5)
sp  <- c(24.11)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  AA4500  60  75.500  24.110  69.272  81.728

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists one primary outcome, Percent Change From Baseline in Total Fixed Flexion, and lists secondary outcomes for subject satisfaction with treatment, investigator assessment of improvement with treatment, and clinical success by joint type. It reports five outcome measures and zero analyses. Numerical results for the primary and secondary outcomes are not reported in the registry record.

When multiple outcomes or multiple analyses are considered, the chance of at least one apparently notable result can increase. In general, a statistical analysis plan may specify which outcome is primary, how secondary outcomes will be interpreted, and whether any adjustment for multiple testing is planned. The registry record does not report an approach to multiplicity, any hierarchy among secondary outcomes, or any multiplicity adjustment. It would not be appropriate to assume that an adjustment was or was not performed.

The record defines the efficacy analysis population as enrolled subjects who received two AA4500 injections and had at least one post-injection measurement. It does not report the number of participants in that population or the number contributing to the primary outcome. The enrollment count of 60 does not establish the analyzed count. The handling of missing measurements, withdrawals, or participants without qualifying post-injection measurements is not reported in the registry record.

In general, missing-data methods can affect the estimate and its uncertainty, especially when the availability of measurements is related to participants' outcomes. The record does not describe imputation, exclusion rules beyond the efficacy-population definition, or sensitivity analyses. It also does not report whether an intention-to-treat analysis was implemented beyond the stated population description. These omissions limit assessment of the analysis population and the robustness of any result; no numerical outcome is available in the registry record to evaluate.

12. 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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: pain in extremity (1.7%), tendonitis (1.7%), tendon rupture (1.7%), ligament injury (1.7%).

The registry record lists one AA4500 group, with 60 at risk in the serious adverse-event field and 3 affected in that field. It lists 60 at risk in the other adverse-event field and 60 affected there. These are the registry's recorded figures for the respective fields. They should not be combined or treated as a measure of the primary efficacy outcome. The record does not provide further detail in these entries about event timing, severity grading, or how repeated events were handled.

The serious adverse-event terms listed are pain in extremity, tendonitis, tendon rupture, and ligament injury. Each is accompanied by a percentage of 1.7%. The record does not provide additional information in these entries that would explain how the term-specific figures relate to the group-level affected count. The percentages should therefore be quoted as recorded rather than used to infer a count or a relationship among events.

No deaths figure is given; deaths are not reported in the registry record. These safety entries describe what the registry records, not a comparative safety estimate. Since the study is single group and has no like-for-like control comparison, the listed values cannot provide a randomized comparison of adverse-event risk. The registry record does not report further information on safety analysis methods.

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

The record supports a clear description of what the trial set out to assess: concurrent administration of two AA4500 injections into the same hand in subjects with multiple Dupuytren's contractures, with percent change from baseline in total fixed flexion as the primary endpoint 30 days after the last injection. It also identifies a mean and standard deviation as the intended summary measures and defines the efficacy population.

However, the record does not report the primary outcome value, its standard deviation, a confidence interval, or a statistical test. It therefore does not show the magnitude of the observed change or how precisely that change was estimated. The study's completed status and enrollment count do not substitute for a reported outcome result. Nor can the record's endpoint definition be taken as evidence of a particular observed outcome.

The single-group, open-label design also limits what a result could establish. In general, a within-group change would describe the course of outcomes among the treated participants, but without a concurrent comparator it would not isolate the effect of the intervention from other explanations for change. The design does not support a randomized treatment contrast, and the registry record does not describe another comparison group.

The safety entries report serious and other adverse-event fields, along with selected serious-event terms. They should be interpreted as registry entries rather than as a comparative assessment. The listed information does not supply a control-group contrast, and deaths are not reported in the registry record.

In short, the posted record establishes the trial's question, design, endpoint definition, efficacy-population rule, and selected safety figures. It does not provide the primary efficacy result or the analysis details needed to judge its statistical precision. The record therefore cannot establish from the posted results how large the measured change was, or whether any change was attributable to the intervention.

14. Why This Trial Matters Statistically

This trial is statistically informative as an example of how an endpoint definition and a design description are not the same as an analyzable result. The registry identifies a continuous primary outcome, its measurement time, and the intended group summaries. Those details help readers understand what the study was designed to measure. But without the numerical estimate, dispersion, or uncertainty interval, the outcome cannot be quantified or assessed for precision.

The single-group design is another important statistical feature. It can describe outcomes in participants who received the intervention, but it does not include the randomized control comparison needed to estimate a between-group treatment contrast. This distinction matters even when an outcome is measured from baseline: a change over time is not, on its own, a controlled estimate of what the intervention caused.

The record also illustrates why analysis-population definitions need to be separated from enrollment. It states that the efficacy population consists of enrolled subjects who received two injections and had at least one post-injection measurement. The number meeting that definition is not reported in the registry record. Consequently, the enrollment count cannot be used as the number analyzed.

Finally, the record's zero analyses and absence of numerical outcome results leave important questions unanswered about uncertainty, missing data, and multiplicity. Recognizing these gaps prevents the design description or safety entries from being mistaken for evidence about the size of the primary outcome. The statistical value of the record lies in clarifying the intended question and identifying which results cannot be evaluated from the posted information.

15. 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 for interpretation is the single-group design. The registry record describes no control group or randomized comparison, so there is no between-group contrast with which to separate change over time from change associated with the intervention. The open-label status, with masking none, is also relevant when considering subjective or judgment-based assessments, including the listed satisfaction and investigator-assessment outcomes.

The registry record does not report a numerical primary outcome result, standard deviation, confidence interval, or test result. It lists zero analyses. As a result, the size and precision of the primary endpoint cannot be assessed. Numerical results for the secondary outcomes are also not reported in the registry record.

The efficacy population is defined, but its size is not reported. The number with missing measurements, the handling of missing data, and any sensitivity analyses are not reported in the registry record. The statistical analysis plan and multiplicity approach are also not reported. These gaps prevent evaluation of how analysis choices may have influenced results.

The safety entries provide group-level at-risk and affected fields and selected serious-event terms, but the registry record does not report additional detail on event timing or repeated events. Deaths are not reported in the registry record. The planning illustration's stated two-arm assumptions should not be confused with this trial's single-group design, nor with the trial's own sample-size justification, which is not reported in the registry record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Administration of Two Injections for Multiple Dupuytren's Contractures — NCT01407068.
• Registry record last updated 2017-10-05; status last verified 2017-09.
• Results first posted 2015-02-20.
• 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.

19. Record Summary

NCT01407068 is a completed Phase 3, open-label, single-group study of concurrent administration of two AA4500 injections into the same hand for multiple Dupuytren's contractures. The registry record lists 60 enrolled participants. The primary endpoint was percent change from baseline in total fixed flexion, assessed 30 days after the last injection, with the mean and standard deviation specified as summary measures.

The efficacy population is defined as enrolled subjects who received two injections and had at least one post-injection measurement, but its size is not reported in the registry record. The record lists five outcome measures and zero analyses. A numerical primary outcome estimate, uncertainty interval, statistical test, analysis plan, and missing-data methods are not reported in the registry record.

The safety entries list 3 affected in the serious adverse-event field and 60 affected in the other adverse-event field, with 60 at risk in each. Four serious-event terms are listed, each at 1.7%. Deaths are not reported in the registry record. The single-group design does not provide a randomized comparator.