Evaluation of Xiaflex: Trial of Effectivenss iN Dupuytren's: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Evaluation of Xiaflex: Trial of Effectivenss iN Dupuytren's (NCT02725528), a randomized phase 3 study. The primary outcome is Health-related Quality of Life (HRQL) Using the Michigan Hand Outcomes Questionnaire (MHQ).

2. Clinical Question

3. Trial Design

NCT02725528 is a completed, phase 3, randomized, single-masked, parallel trial sponsored by McMaster University. Its official title describes a multi-centre comparison of the clinical effectiveness and cost-effectiveness of collagenase injection and palmar fasciectomy in Dupuytren's Disease. The registry characterizes the study as prospective and pragmatic. Enrollment was 22. The recorded start date is 2017-07-08, and the primary completion date is 2021-12-17.

The two treatment groups were collagenase injection and limited palmar fasciectomy. In a parallel design, participants are assigned to one treatment group and outcomes are compared between groups. Random allocation is intended to reduce systematic differences between treatment groups at entry, although it does not ensure that every characteristic is balanced, particularly in a small trial. The registry says the trial was single-masked, but which participants, clinicians, or assessors were masked is not reported in the registry record.

The pragmatic description indicates that treatment delivery could follow surgeons' routine practice. For collagenase, the registry allows administration in a minor procedure room or hand clinic, with or without local anesthesia. For fasciectomy, it describes possible settings and anesthetic approaches that depend on disease complexity and routine practice. This approach reflects variation in ordinary care, but the full procedural protocol and the extent of variation are not reported in the registry record.

The primary endpoint was MHQ-based Health-related Quality of Life at 1 year. The registry also lists secondary outcomes involving other health-related quality-of-life instruments, quality-adjusted life years, recurrence, and loss of extension at MCP, PIP, and DIP joints. The design description alone does not establish how those secondary outcomes were analyzed or whether all were reported. The completed status indicates that the registry lists the trial as completed; it does not, by itself, resolve the uncertainty associated with the small posted outcome groups or missing analysis details.

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

Reasons for not completing this period:

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 participant in the limited palmar fasciectomy (LPF) group dropped out immediately after randomization, before baseline outcomes were measured, thus the size of the LPF group is 13, not 14.

6. Primary Endpoint

The registry lists the primary outcome as Health-related Quality of Life (HRQL) Using the Michigan Hand Outcomes Questionnaire (MHQ), measured over 1 year.

The primary endpoint was Health-related Quality of Life measured with the Michigan Hand Outcomes Questionnaire. The score was converted to a 0-100 scale, with higher scores representing better function, and the registry specifies a 1 year timeframe. The posted result is expressed as a group mean with a standard deviation, so it describes the average score and the spread of participant scores within each treatment group.

Patient-reported outcomes can complement clinical assessments because they capture participants' reported experience of function and health-related quality of life. A standardized questionnaire also gives the study a defined way to quantify that experience for comparison between groups. This is a general explanation of the role of patient-reported measures; the registry does not report which particular questionnaire domains or scoring components contributed to the posted result beyond its stated scale interpretation.

The endpoint is relevant to the stated trial objective because the study description emphasizes quality of life as an outcome of interest. It is not the same as recurrence, joint extension, complications, or cost-effectiveness. Those are separate outcomes listed in the registry and cannot be inferred from an MHQ score. The posted primary result therefore addresses the reported MHQ measure at the specified follow-up, rather than every clinical or economic question raised in the trial description.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does the randomized parallel design contribute?

Random allocation is a design method intended to make treatment assignment independent of participant characteristics, on average. It supports a fair comparison by limiting deliberate or systematic assignment according to prognosis. Randomization does not guarantee identical groups, and chance imbalance can remain, especially when the number of participants is limited. The registry identifies randomized allocation and a parallel model, but does not report the allocation sequence method, concealment procedure, or detailed implementation.

In a parallel trial, each participant receives an assigned treatment and contributes outcome information to that group. The comparison concerns the outcomes observed across groups rather than a within-person change between treatments. The record calls the study single-masked but does not identify who was masked or how masking was maintained. Those details are not reported in the registry record.

What do the mean and standard deviation describe?

For a continuous outcome, the mean is the arithmetic average of observed scores in a group. The standard deviation describes how dispersed individual scores are around that average. Together, they summarize the location and variability of the observed MHQ scores. They do not describe every participant's result, and they do not show how uncertain the treatment-group contrast is. A confidence interval for a contrast would address uncertainty in the estimated comparison; none is posted for the ANCOVA result.

The MHQ score is on a 0-100 scale, and higher scores represent better function according to the registry description. That direction makes the descriptive means interpretable, but a difference in group means is not automatically a causal or clinically important effect. The trial's randomized design is relevant to causal comparison, while the completeness of the analysis, outcome data, and uncertainty reporting also matters.

What does ANCOVA mean in this comparison?

Analysis of covariance, or ANCOVA, is a regression-based approach that compares group outcomes while adjusting for specified covariates. In general, adjustment can account for baseline measures or other prespecified variables and may improve precision when used appropriately. The registry reports ANCOVA for the primary comparison, but the covariates, model specification, adjusted estimate, standard error, and confidence interval are not reported in the registry record. Consequently, the exact adjusted comparison cannot be interpreted from the posted p-value alone.

The reported p-value is 0.05. In general, a p-value is calculated under a null hypothesis and model assumptions; it indicates how unusual data at least as incompatible with that null would be under those assumptions. It is not an effect-size measure and is not a direct probability that the null hypothesis is true. The value does not convey the full range of plausible treatment contrasts. An effect estimate with a confidence interval would help readers evaluate both the direction and precision of the comparison, but neither is posted for this analysis.

How should the secondary outcomes be considered?

The registry lists secondary outcomes that include health-related quality of life measured by HUI3, URAM, and SDSS; quality-adjusted life years measured with HUI3; recurrence; and loss of extension at MCP, PIP, and DIP. These endpoints differ in scale and meaning. A continuous score, an event such as recurrence, and a joint-extension measure require outcome-appropriate summaries and analyses. The methods used for these outcomes, their estimates, and their uncertainty are not reported in the registry record in the registry record for this analysis.

When a trial examines multiple outcomes or multiple time points, the chance of at least one apparently notable result can increase if every comparison is treated as independent evidence without considering multiplicity. This is a general statistical concern, not a claim about the trial's actual analysis. Whether the investigators adjusted for multiple testing, designated a hierarchy of outcomes, or interpreted secondary analyses as exploratory is not reported in the registry record. The primary endpoint should therefore be distinguished from the listed secondary outcomes.

What can planning illustrations tell readers?

Sample-size calculations are planning tools that describe the number of participants needed under stated assumptions to detect a specified effect with a chosen significance level and power. In general, the result depends on assumptions about the target effect, variability, allocation, and analysis. A planning calculation based on an observed effect is illustrative rather than a record of the trial's design rationale. It is not observed power and does not show how likely the completed trial was to detect an effect after the results were known.

The registry record does not report the trial's sample-size justification or the assumptions used by investigators when planning enrollment. It also does not report whether interim analyses were planned or conducted. The planning assumptions described for illustrations use a two-sided significance level of 0.05, equal allocation, and a normal approximation, with effects expressed as fractions of an observed effect. Those are planning conditions, not evidence that the trial itself used those design assumptions. For non-time-to-event outcomes, such illustrations refer to participants per arm; time-to-event illustrations refer to total events. No interpretation of a planning illustration should replace the observed enrollment or posted outcome counts.

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("Collagenase Injection", "Limited Palmar Fasciectomy")
n   <- c(7, 9)
m   <- c(78.1, 68.3)
sp  <- c(14.9, 15.7)
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  Collagenase Injection  7  78.100  14.900  64.320  91.880
CARM  Limited Palmar Fasciectomy  9  68.300  15.700  56.232  80.368

11. Analyses Reported by the Sponsor

The registry reports the sponsor's primary comparison as ANCOVA with p = 0.05. It does not post the adjusted effect estimate or confidence interval. The arm-level summaries are a mean of 78.1 with standard deviation 14.9 for 7.0 collagenase participants, and a mean of 68.3 with standard deviation 15.7 for 9.0 participants assigned to limited palmar fasciectomy. Those summaries describe observed scores, but they are not a recalculation of the adjusted ANCOVA contrast.

A simple unadjusted recalculation from summary statistics cannot reproduce an adjusted ANCOVA analysis when the adjustment variables and their data are unavailable. No recalculated comparative estimate or confidence interval is reported for this continuous endpoint in the registry information used for this analysis. The posted sponsor analysis is therefore the available inferential result, while the arm means remain descriptive. The discrepancy indicator is false, so the record does not identify a disagreement requiring the sponsor's analysis to take precedence over a conflicting recalculation. The absence of a recalculated result should not be mistaken for confirmation of the sponsor's estimate; the adjusted estimate itself is not posted.

12. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary MHQ endpoint and several secondary outcomes, including other health-related quality-of-life measures, quality-adjusted life years, recurrence, and measures of loss of extension. Considering several endpoints can create multiplicity: if many statistical tests are conducted, some results can appear notable by chance even when no corresponding effect exists. This is a general statistical issue. The registry record does not report whether a multiplicity adjustment, testing hierarchy, or other prespecified strategy was used.

The analysis populations are not reported in the registry record. It is not stated whether the primary analysis included all randomized participants, participants with an observed 1 year MHQ score, or another defined population. The posted outcome group sizes are 7.0 for collagenase injection and 9.0 for limited palmar fasciectomy, while overall enrollment was 22. The record does not explain the relationship between enrollment and the number contributing to the primary outcome summaries, so the reasons for the difference are not established.

Missing-data methods are also not reported in the registry record. There is no information about the amount or reasons for missing MHQ data, any imputation approach, or sensitivity analyses assessing the effect of missingness. A complete-case summary can be affected if the participants with observed outcomes differ systematically from those without them; this is a general concern, not a statement about what happened in this trial.

The registry does not report whether the analysis plan prespecified covariates, transformations, or procedures for handling departures from model assumptions. It also does not report interim analyses. These omissions limit the ability to assess how firmly the posted p-value and endpoint summaries correspond to a prespecified analysis strategy. They do not establish that a particular method was or was not used; the details are simply not reported in the registry record.

13. 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 0% reporting threshold.

For collagenase injection, the registry reports 0 serious adverse events among 8 participants at risk and 0 other adverse events among 8 participants at risk. For limited palmar fasciectomy, it reports 0 serious adverse events among 13 participants at risk and 0 other adverse events among 13 participants at risk. Deaths are reported as 0 in each group. No serious adverse event terms are listed.

These figures describe the adverse-event information posted in the registry, using the recorded at-risk counts. A zero count means no events of that category were recorded in the reported group data; it does not establish that the underlying risk is absent. With limited group sizes, an absence of observed events cannot precisely characterize uncommon events or exclude risks that were not observed during the reporting period.

The record does not provide further detail about adverse-event definitions, collection procedures, follow-up duration for safety, severity grading, or whether events were assessed as related to treatment. The serious and other adverse-event counts should therefore be read as registry summaries, not as a complete account of all possible harms or as a comparison adjusted for differences in exposure or follow-up. These figures alone do not establish a safety advantage for either intervention.

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

The posted primary outcome gives a descriptive account of MHQ scores at 1 year in the two treatment groups. The mean score was 78.1 for collagenase injection and 68.3 for limited palmar fasciectomy; higher scores represent better function on the registry's 0-100 scale. The registry also reports an ANCOVA p-value of 0.05. Taken together, these registry entries describe the observed group scores and identify the sponsor's reported inferential result, but they do not provide the size or precision of the adjusted comparison.

The result does not establish how large an adjusted difference might be, because no adjusted estimate or confidence interval is posted. A p-value alone cannot show whether an estimated contrast is clinically important, nor can it show the range of values reasonably compatible with the data. The arm-level standard deviations describe participant-level variation; they are not confidence limits for the comparison.

The posted endpoint is not a direct result for recurrence, cost-effectiveness, complications, or loss of joint extension. Although these outcomes appear in the trial description or secondary outcome list, their results are not reported in the registry record in the information. The primary MHQ result cannot be used as a substitute for those outcomes.

The groups contributing to the primary summaries were small, and the registry does not explain the analysis population or missing-data handling. These limits matter when considering how representative the observed scores may be and how much uncertainty surrounds the comparison. Randomized allocation supports the design of a group comparison, but it does not remedy incomplete reporting of the estimate, its precision, or the analysis details.

Accordingly, the result should be interpreted as a limited statistical record: it reports descriptive MHQ values, a standard deviation for each group, and an ANCOVA p-value. It does not by itself establish a treatment effect of a particular magnitude, demonstrate a clinically meaningful difference, resolve uncertainty, or answer the trial's broader clinical and economic questions.

15. Why This Trial Matters Statistically

This trial is statistically notable as a randomized comparison of a drug intervention and a surgical procedure using a patient-reported quality-of-life endpoint. The pragmatic design description also recognizes that treatment delivery may vary according to routine practice. Such comparisons can raise important questions about how to interpret outcomes that are meaningful to participants while care is delivered in clinical settings.

The posted primary result illustrates why an inferential p-value is not enough to understand a treatment comparison. The registry gives arm means and standard deviations and reports an ANCOVA p-value, but does not post the adjusted effect estimate or its confidence interval. Readers can see the direction of the descriptive mean ordering, yet cannot judge the magnitude and precision of the adjusted contrast from the p-value alone. Reporting an estimate with an uncertainty interval would make the inferential result more interpretable.

The small outcome groups also make transparent reporting of analysis populations, missing data, and model details especially important. Those details help readers understand who contributed to the estimate and whether the analysis reflects the randomized groups as intended. The record does not report these details, and their absence should be kept distinct from a claim that the methods were inadequate.

The trial also lists several secondary outcomes with different statistical forms and interpretations. Distinguishing the primary endpoint from secondary outcomes, and explaining any multiplicity strategy, would help readers assess the strength of evidence across a broad set of questions. The registry's posted primary result thus offers a useful example of the difference between a study's design, its descriptive data, and the information needed to evaluate an adjusted comparison.

16. 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 primary outcome summaries involve 7.0 participants in the collagenase injection group and 9.0 in the limited palmar fasciectomy group, compared with overall enrollment of 22. The registry does not explain why the primary outcome group counts differ from total enrollment. It does not report participant flow, exclusions, withdrawals, or the number of participants with missing endpoint data. These omissions limit assessment of how the posted summaries relate to the randomized population.

The ANCOVA result is reported only as p = 0.05. The adjusted effect estimate, confidence interval, model covariates, and model specification are not reported in the registry record. Without these, it is not possible to evaluate the size and precision of the adjusted comparison or to determine how the reported model relates to the arm-level summaries. The reported means and standard deviations are descriptive and cannot recover an adjusted result.

The registry describes single masking but does not say who was masked. It does not report the allocation concealment procedure, the detailed analysis populations, the handling of missing data, or sensitivity analyses. It also does not report whether multiple testing was addressed for the primary and secondary outcomes, or whether interim analyses occurred. These are reporting limits; they do not show that a particular procedure was omitted.

The pragmatic treatment descriptions allow variation in setting and anesthesia, but the registry record does not provide complete procedural protocols or detail how treatment variation was captured. The safety summaries do not provide event definitions, follow-up detail, or relatedness assessments. Results for the listed secondary outcomes are not reported in the registry record for this analysis. Together, these limitations mean the primary finding should be read narrowly and the wider clinical and economic aims cannot be assessed from this result alone.

17. Related Tutorials

18. Related Statistical Calculators

19. Sources

• ClinicalTrials.gov: Evaluation of Xiaflex: Trial of Effectivenss iN Dupuytren's — NCT02725528.
• Registry record last updated 2023-07-18; status last verified 2023-06.
• Results first posted 2023-07-18.
• 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.

20. Record Summary

NCT02725528 is a completed phase 3, randomized, single-masked, parallel, multi-centre pragmatic trial sponsored by McMaster University. It compared collagenase injection with limited palmar fasciectomy for Dupuytren's Disease. Enrollment was 22. The recorded study start date is 2017-07-08 and primary completion date is 2021-12-17.

The primary endpoint was MHQ-based Health-related Quality of Life at 1 year, scored on a 0-100 scale with higher scores representing better function. The posted means were 78.1 with standard deviation 14.9 among 7.0 collagenase participants and 68.3 with standard deviation 15.7 among 9.0 fasciectomy participants. The registry reports an ANCOVA p-value of 0.05 but does not post its adjusted effect estimate or confidence interval. Analysis population, missing-data procedures, and multiplicity methods are not reported in the registry record. Safety counts report 0 serious adverse events and 0 other adverse events in each group, with deaths reported as 0 in both groups.