Controlled Study to Evaluate the Safety and Efficacy of Azficel-T for Vocal Fold Scarring and Age-Related Dysphonia: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Controlled Study to Evaluate the Safety and Efficacy of Azficel-T for Vocal Fold Scarring and Age-Related Dysphonia (NCT02120781), a randomized phase 2 study. The primary outcome is Number of Participants With Any Improvement From Baseline in Mucosal Wave Grade.

2. Clinical Question

The study set out to assess the safety of azficel-T and evaluate its efficacy for dysphonia related to vocal fold function. The primary endpoint focuses on a change in the mucosal wave, an observable feature of vocal fold motion during phonation. The registry reports 14 of 15 participants in the azficel-T arm and 5 of 6 in the control arm as having any improvement from baseline. Those are descriptive arm counts. The registry record does not report an estimated treatment contrast, a confidence interval, or a statistical test for this endpoint, so the posted counts alone do not quantify how precisely the arms differ. Details of eligibility, baseline clinical features, and the way participants were allocated to unilateral or bilateral treatment are not reported in the registry record.

3. Trial Design

This was a randomized, triple-masked, parallel-group phase II study, with azficel-T compared with control. The registry lists a total enrollment of 21. The posted primary outcome includes 15 participants in the azficel-T arm and 6 in the control arm. The record does not explain the allocation procedure or why the enrolled arm sizes differed. It also does not identify which study roles were masked or describe the steps used to maintain masking.

Azficel-T is described as autologous fibroblasts. The intervention description specifies injections into the vocal fold or folds three times at two-week intervals. Participants in the control group were to receive sterile saline injections on the same schedule. The record does not describe additional treatment procedures or details of how the study intervention was prepared or administered.

The study began in 2014-03 and reached primary completion in 2016-04; its status is completed. The primary endpoint timeframe is four months after final treatment, or up to a total of 25 weeks from baseline with unilateral treatment and 27 weeks from baseline for bilateral treatment. The record does not state how many participants received unilateral versus bilateral treatment.

The registry lists 8 outcome measures, but no secondary results are posted. It records no analyses for the primary result. The protocol’s sample-size justification, planned statistical methods, analysis populations, and interim-analysis plan are not reported in the registry record. These omissions limit assessment of how the posted endpoint counts relate to the study’s original design and prespecified analysis.

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.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Any Improvement From Baseline in Mucosal Wave Grade, measured over Four months after final treatment, or up to a total of 25 weeks from baseline with unilateral treatment and 27 weeks from baseline for bilateral treatment.

The primary endpoint is the number of participants with any improvement from baseline in mucosal wave grade. Videostroboscopy is used to assess vocal fold pliability; the mucosal wave is visualized on the vocal fold surface while a participant phonates a sustained vowel. The endpoint therefore records whether an improvement was observed, rather than the size or degree of improvement.

A mucosal wave is relevant to vocal fold function, which is the subject of this study. Recording the number of participants who improve gives a simple, interpretable summary of the observed outcome in each arm. It also reduces a graded assessment to an event count: a participant is classified according to whether any improvement from baseline was present. That simplicity comes with a limitation. The count does not convey how large an improvement was, and participants with different degrees of change can be represented alike if both meet the improvement criterion.

The assessment was scheduled four months after final treatment, or up to a total of 25 weeks from baseline with unilateral treatment and 27 weeks from baseline for bilateral treatment. The registry description does not report the grading scale’s categories, the threshold for a change to count as improvement, or details of assessor training and reliability. The posted result is 14 of 15 participants in the azficel-T arm and 5 of 6 in the control arm. No comparative estimate or uncertainty interval is reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The posted primary outcome is a count of participants who met an event definition: any improvement from baseline in mucosal wave grade. For this kind of endpoint, each participant is classified according to whether the specified event occurred. The arm-level count is meaningful only alongside the number of participants represented in that arm. The registry reports 14 of 15 participants for azficel-T and 5 of 6 for control.

What does a count show?

A count conveys how many participants were recorded as meeting the endpoint, but it does not by itself describe the uncertainty around that result. A statistical comparison would typically estimate how the event occurrence differs between treatment groups and indicate the precision of that estimate. A confidence interval is a range expressing uncertainty around an estimated quantity under a specified statistical method. The registry record does not report a confidence interval or an estimated between-arm contrast for this endpoint.

The distinction between an arm-level result and a treatment contrast matters. The arm-level values describe participants within each group. A treatment contrast is designed to address how outcomes differ between groups. The registry reports the former but no analysis of the latter. No new comparison can be inferred from the posted counts without making additional statistical choices, and no such calculation is reported in the registry record.

Why can small groups limit precision?

When an endpoint is observed in a limited number of participants, the estimated event pattern can be sensitive to the outcomes of individual participants. Uncertainty intervals and suitable inferential methods help convey that imprecision. The registry’s arm sizes are 15 and 6, and it does not post an interval or test for the primary endpoint. This means the precision of any comparative interpretation cannot be assessed from the reported analysis, because no comparative analysis is posted.

Random allocation is a design feature intended to make treatment groups comparable on average. It does not guarantee identical groups, particularly in a study with limited enrollment, and it does not replace reporting the method of analysis. The allocation method and any adjustments to the analysis are not reported in the registry record. The study is described as triple-masked, but the identities of the masked roles and the procedures used to maintain masking are not reported.

What is the endpoint’s measurement scale?

The endpoint treats improvement as an event, rather than retaining the amount of change in mucosal wave grade. This approach can make a result easier to summarize, but it discards information about the degree of change. The registry description identifies videostroboscopy as the assessment method and refers to vocal fold pliability and mucosal waves during sustained-vowel phonation. It does not report the grading categories, the rule used to decide that an improvement occurred, or measurement reliability.

The timeframe also matters to interpretation. The endpoint was assessed four months after final treatment, or up to a total of 25 weeks from baseline with unilateral treatment and 27 weeks from baseline for bilateral treatment. This is the registry’s stated endpoint timing; it should not be read as evidence about outcomes at other times. The record does not report the distribution of unilateral and bilateral treatment or other endpoint assessment details.

What does a recalculation mean?

A recalculated result, when shown for a trial, is a simple unadjusted calculation from posted summary statistics. It is not a substitute for the sponsor’s prespecified analysis, and its validity depends on the available summaries and assumptions. In this record, the registry indicates that values are missing or not estimable for a two-arm comparison of the binary endpoint. No recalculated comparison is reported. The sponsor’s own analysis takes precedence if a discrepancy is identified; no discrepancy is recorded for this trial.

Planning illustrations based on an observed effect are also distinct from results of the trial. Such illustrations describe hypothetical design requirements under specified assumptions; they do not indicate the study’s observed power. The registry record does not report a sample-size justification or planned power calculation. Any sample-size illustration should therefore be understood as a planning exercise, not evidence that the study was adequately or inadequately powered.

What is not available for evaluating the analysis?

The registry record does not report the planned statistical model, the primary analysis population, how missing endpoint data were handled, whether any covariate adjustment was planned, or how the analysis accounted for the endpoint’s assessment process. It also does not report an interim-analysis plan. Without those details and a posted inferential result, the primary outcome can be described but not fully evaluated as a treatment comparison.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Azficel-T (Autologous Fibroblasts)", "Control")
n      <- c(15, 6)
events <- c(14, 5)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Azficel-T (Autologous Fibroblasts)  15  14  93.3  68.1  99.8  70.2  98.8  69.8  98.4
ARM  Control  6  5  83.3  35.9  99.6  43.6  97.0  42.1  96.3

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 8 outcome measures, while no secondary results are posted and no analyses are recorded. The record identifies the mucosal-wave improvement count as the primary endpoint. It does not report whether the other outcomes were prespecified as secondary, how hypotheses across outcomes were prioritized, or whether any adjustment for multiple comparisons was planned. When several outcomes or statistical tests are considered, the chance of at least one apparently unusual finding can increase; multiplicity procedures are used in some analyses to address that issue. The registry record does not describe such a plan.

Missing-data methods and analysis populations are also not reported in the registry record. The posted primary counts account for 15 participants in the azficel-T arm and 6 in the control arm, but the record does not describe whether these are all randomized participants, all treated participants, or a defined analysis population. It does not state whether any endpoint assessments were missing, how missing outcomes were classified, or whether participants who did not complete treatment or follow-up were included in the analysis.

These details matter because the handling of unavailable measurements can affect an outcome count and the meaning of a group comparison. A complete-case analysis, an imputation method, and a conservative event rule can answer different questions and rely on different assumptions. None of these approaches is specified in the registry record. The record also does not identify whether the analysis followed assigned treatment regardless of treatment received. Consequently, the reported counts can be described, but the population and missing-data assumptions behind them cannot be independently assessed.

12. Safety Results

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

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: intestinal obstruction (6.7%), breast cancer (6.7%), arthralgia (6.7%).

The registry reports serious adverse events for 3 of 15 participants in the azficel-T arm and 0 of 6 in the control arm. It reports other adverse events for 13 of 15 participants in the azficel-T arm and 4 of 6 in the control arm. No deaths are reported in either arm. These figures are counts among the participants at risk listed in the record, not estimates of comparative risk with uncertainty intervals.

The registry lists intestinal obstruction, breast cancer, and arthralgia among the top serious adverse-event terms, each recorded as 6.7%. The record does not provide further detail about timing, severity, duration, clinical course, or whether an event was judged related to treatment. A listed event occurring during a trial does not by itself establish that the intervention caused it.

The arm counts are descriptive and involve limited numbers of participants. The registry record does not report a statistical comparison of serious adverse events, an exposure-adjusted analysis, or a formal assessment of causality. The absence of reported deaths does not resolve other safety questions, and the event counts should not be interpreted as a complete account of all possible risks.

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

The posted primary result describes the number of participants recorded as having any improvement in mucosal wave grade at the stated follow-up: 14 of 15 in the azficel-T arm and 5 of 6 in the control arm. This is a descriptive finding for the study groups. It is not a reported estimate of the treatment effect, and it is not accompanied by a confidence interval or statistical test in the registry record.

The result does not state how much participants’ mucosal wave grades changed, whether changes persisted beyond the assessment timeframe, or how the endpoint relates to other aspects of dysphonia. The registry’s endpoint description focuses on videostroboscopic assessment of mucosal waves. It does not report details needed to assess the threshold for improvement or the reliability of grading.

The trial was randomized and triple-masked, but important operational and analysis details are not reported in the registry record. The posted group counts cannot, on their own, resolve the role of chance, differences in participant characteristics, missing assessments, or other factors that could affect interpretation. Nor do the counts establish whether the observed pattern reflects a treatment effect.

The study’s stated objectives included safety and efficacy assessment. The serious and other adverse-event counts provide descriptive safety information, but the record does not report causal assessments or a comparative safety analysis. Taken together, the registry entries describe observed outcomes in a phase II study; they do not provide a complete inferential evaluation of benefits and harms. No medical conclusion should be drawn from the posted counts alone.

14. Why This Trial Matters Statistically

This trial illustrates the distinction between reporting an outcome and reporting an analysis. The registry gives arm-level counts for the primary binary endpoint, but it records no analyses and no estimated comparison. For clinical researchers, that distinction is important: descriptive results help show what was observed, while an inferential analysis addresses the size and precision of a between-group contrast under stated assumptions.

The outcome also shows how endpoint definition shapes interpretation. “Any improvement” classifies participants according to whether they crossed an improvement threshold, but it does not express the amount of change. A binary endpoint can be straightforward to communicate, yet it may conceal differences in the degree of response. The registry record does not specify the grading rule or threshold used to classify improvement, limiting independent assessment of the outcome’s measurement properties.

The study’s randomized, triple-masked, parallel-group design is relevant context, but design labels cannot replace reporting of allocation, masking procedures, analysis populations, missing-data handling, and statistical methods. Those details are not reported in the registry record. Their absence makes it difficult to judge how fully the posted counts reflect the intended comparison.

Finally, the safety results illustrate why event counts require context. Counts without a comparative analysis, exposure information, or attribution details can identify what was reported, but they do not establish causation or quantify comparative risk. Clear reporting of both outcome definitions and analysis methods is essential for interpreting clinical-trial registry results responsibly.

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 limitation for interpreting this trial’s primary outcome is that the registry reports arm-level counts without a two-arm analysis. It provides no comparative estimate, confidence interval, or p-value. The observed counts therefore cannot be used to assess the precision of a treatment contrast from the registry record alone.

The endpoint is recorded as any improvement from baseline, but the registry does not report the mucosal-wave grading scale, the threshold for improvement, assessor reliability, or the handling of borderline assessments. It also does not describe whether assessors knew treatment assignments, despite the trial being labeled triple-masked.

The enrollment is 21, with 15 participants in the azficel-T outcome group and 6 in control. The record does not explain the arm-size difference or report whether all randomized participants contributed endpoint data. Eligibility criteria, baseline characteristics, treatment completion, and missing assessments are not reported in the registry record. These omissions prevent fuller assessment of comparability and completeness.

The primary endpoint was assessed at the stated post-treatment timeframe, but outcomes at other time points are not described in the posted primary result. The registry lists 8 outcome measures but posts no secondary results. It does not report the statistical analysis plan, multiplicity approach, analysis population, sample-size justification, or interim-analysis plan.

Safety reporting is also limited: event counts are posted, but details of timing, exposure, severity, attribution, and comparative analysis are not reported. These limitations do not show that a particular bias or problem occurred; they identify information unavailable in the registry record that is needed for a more complete interpretation.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Controlled Study to Evaluate the Safety and Efficacy of Azficel-T for Vocal Fold Scarring and Age-Related Dysphonia — NCT02120781.
• Registry record last updated 2021-06-03; status last verified 2021-05.
• Results first posted 2021-06-03.
• 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

NCT02120781 is a completed phase II randomized, triple-masked, parallel-group study of azficel-T for dysphonia related to vocal fold scarring or age-related dysphonia. The registry lists enrollment of 21 and compares azficel-T, described as autologous fibroblasts, with sterile-saline control injections.

The primary endpoint is the number of participants with any improvement from baseline in mucosal wave grade. The posted result is 14 of 15 participants in the azficel-T arm and 5 of 6 in control. The registry records no analyses and does not report a comparative estimate or uncertainty interval for the primary endpoint.

The record reports serious adverse events for 3 of 15 participants in the azficel-T arm and 0 of 6 in control, other adverse events for 13 of 15 and 4 of 6, and no deaths. Details needed to assess the comparative analysis, endpoint measurement, missing data, and event attribution are not reported in the registry record.