IMPACT: Safety and Feasibility of a Single-stage Procedure for Focal Cartilage Lesions of the Knee.: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for IMPACT: Safety and Feasibility of a Single-stage Procedure for Focal Cartilage Lesions of the Knee. (NCT02037204), a na phase 1, phase 2 study. The primary outcome is Safety: Adverse Events.

2. Clinical Question

3. Trial Design

The registry identifies the study as Phase 1 and Phase 2 and lists an enrollment of 35. Its design is single-group, with allocation recorded as NA and masking listed as none. The intervention is a single-stage cartilage repair procedure using autologous chondrons and allogeneic mesenchymal stromal cells in a fibrin glue carrier. It was applied once during a surgical procedure.

The study is titled as an evaluation of safety and feasibility for focal cartilage lesions of the knee. The record describes a rationale for combining chondrons with mesenchymal stromal cells and delivering the cell mixture during one procedure. Those statements describe the treatment rationale; they do not establish a clinical benefit. The registry lists cartilage repair surgery as the intervention and does not identify a separate control arm.

The primary outcome is safety, with an 18-month timeframe. The description says patients were monitored for inflammation and signs of a foreign-body response by an independent physician, using standardized clinical measures, pain assessment by numeric rating scale, and blood analysis including serum C-reactive protein. The registry also lists clinical improvement measured by the Knee Injury and Osteoarthritis Outcome Score as a secondary outcome.

The record lists the study status as completed. The start is recorded as 2013-03 and primary completion as 2016-04. The exact recruitment period, detailed eligibility criteria, participant flow, and reasons for any missing outcome observations are not reported in the registry record. A statistical analysis plan and detailed methods for analyzing the outcomes are also 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.

Before assignment: Four patients were excluded based on MRI scans showing multiple cartilage defects and/ or osteochondral defects. Inclusion was continued until n = 35 was reached

Overall Study

Analysis population for the primary outcome, as defined in the registry: All patients were monitored for the duration of the studie for inflammation and signs of a foreign body response by an independent physician using standardized clinical measures, pain assessment by numeric rating scale for pain and blood analysis including serum C-reactive protein, erythrocyte sedimentation rate and leukocyte count.

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 Safety: Adverse Events, measured over 18 months.

The primary endpoint is titled “Safety: Adverse Events” and is described as an adverse events rate, with participants as the unit and an 18-month timeframe. The posted summary gives counts of participants with events. It reports zero serious adverse events among 35 participants at risk and other adverse events among 18 participants at risk. These are separate categories in the registry’s safety summary and should not be conflated.

Adverse events are used in clinical studies to describe unwanted medical occurrences observed during or after treatment. In a safety and feasibility study, tracking them helps characterize the types of safety events recorded during the study period. The registry description gives particular attention to inflammation and signs of a foreign-body response, monitored by an independent physician using clinical measures, pain assessment, and blood analysis including serum C-reactive protein.

The outcome label does not by itself clarify how events were defined, graded, attributed to the procedure, or counted when a participant experienced more than one event. Those details are not reported in the registry record. The outcome is therefore best read as the registry’s recorded participant counts, rather than as a complete account of event severity, timing, or causality. The record also lists the Knee Injury and Osteoarthritis Outcome Score as a secondary clinical improvement outcome, but the results for that measure are not included in the registry record for this account.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a single-group study rather than a randomized comparison. Allocation is listed as NA, masking as none, and the model as single-group. These design features mean that the posted safety counts can describe what was recorded among participants who received the procedure, but they cannot isolate the procedure’s effect by comparing outcomes against a control group. General statistical principle: a comparison group helps distinguish treatment-associated differences from background events and other influences. Without one, observed events cannot be attributed to the intervention on the basis of the group count alone.

What do the event counts represent?

The primary outcome uses participants as its unit, and the registry’s result is described as participants with an event. The serious-event summary reports zero participants with a serious adverse event among 35 at risk. The other-event summary reports 18 participants with an event among 35 at risk. These counts do not tell readers how many individual events occurred if a participant could have experienced more than one. The registry record does not report whether repeat events were counted separately, how event severity was classified, or how attribution to the procedure was assessed.

General statistical principle: a count is a direct description of observations, while an estimated rate or comparative effect requires a clear definition of the event, follow-up, denominator, and analysis method. The registry labels the outcome as an adverse events rate but reports participant counts in the posted safety summary. No additional calculation is needed to interpret those counts, and no unreported rate or comparison should be inferred from them.

Why does uncertainty matter?

General statistical principle: an estimate from a study group is subject to sampling uncertainty. A confidence interval, when reported, describes a range of values compatible with the data and the method used to calculate it. No confidence interval for these safety counts is reported in the registry record. The zero count should therefore be read as the observed count, not as a claim that the underlying chance of a serious event is zero. The other-event count is also a description of this group, not a prediction for every future group.

The registry entries do not provide a statistical analysis plan for the primary endpoint. They do not state whether the investigators planned a hypothesis test, a confidence interval, a formal feasibility threshold, or a particular event-rate model. Such choices can affect how uncertainty is summarized. The record’s title and phase designation do not supply those missing methods.

What can a planning illustration say?

General statistical principle: sample-size calculations are planning tools whose meaning depends on assumptions about the comparison, target effect, significance level, allocation, and statistical model. The registry record describes a planning illustration based on an observed effect, with two-sided significance level 0.05, equal allocation between two arms, and a normal approximation. It says that the effect to detect is a stated fraction of the observed effect. These assumptions describe an illustration, not the design of this single-group study. They do not constitute observed power, and they do not establish that the trial was designed with those assumptions. The registry record does not report the trial’s own sample-size justification.

For event outcomes, general statistical principle: sparse counts can make estimates imprecise, and conventional approximations may be less suitable when events are uncommon. The record does not describe which method, if any, was used to quantify uncertainty for the safety results. No method should be inferred from the event counts alone.

How should the outcome instruments be understood?

The primary safety description includes standardized clinical measures, pain assessment by numeric rating scale, and blood analysis including serum C-reactive protein. These are described as monitoring approaches, not as separate primary endpoints in the registry record. The registry lists the Knee Injury and Osteoarthritis Outcome Score as a secondary outcome for clinical improvement. The record does not report the score’s analysis method, timing, or results. Therefore, the event counts do not answer questions about changes in knee symptoms or function.

Overall, the statistical information supports a descriptive reading of safety observations in one group. It does not support a comparative treatment estimate, a causal conclusion, or a detailed assessment of uncertainty. More complete methods and outcome reporting would be needed to interpret these dimensions.

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("Cartilage Repair Surgery")
n      <- c(35)
events <- c(0)
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  Cartilage Repair Surgery  35  0  0.0  0.0  10.0  0.0  9.9  0.1  9.7

11. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary safety outcome and a secondary outcome of clinical improvement measured by the Knee Injury and Osteoarthritis Outcome Score. It also states that there are four outcome measures and one analysis, but the registry entries available do not identify all outcome measures or explain how the listed analysis relates to them. The statistical analysis plan, including any hierarchy among outcomes or adjustment for multiple testing, is not reported in the registry record.

Multiplicity matters when a study tests several outcomes or makes several comparisons: considering many results can increase the chance of a seemingly notable result arising by chance. General statistical principle: investigators may address this through a prespecified outcome hierarchy or an adjustment method, but no such approach can be inferred. The posted safety counts are descriptive, and the registry entries do not report a hypothesis test or multiplicity adjustment for them.

The registry entries do not report missing-data methods, the number of participants with complete follow-up, or whether all participants contributed data to every outcome. Although the safety summary lists 35 participants at risk, that figure alone does not establish that all planned observations were available at all times. The registry describes monitoring during the study, but does not explain how incomplete visits or unavailable measurements were handled.

The analysis population is also not fully specified. The safety description refers to all patients being monitored, but the registry record does not provide a separate definition of the population used for the posted analysis or explain exclusions. These omissions limit assessment of the analysis denominator, potential missingness, and whether the outcome reporting followed a prespecified plan.

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 0% reporting threshold.

Most frequent non-serious adverse event terms

The serious adverse-event summary reports zero participants with a serious adverse event among 35 at risk. The separate other-adverse-event summary reports 18 participants with an event among 35 at risk. These are the posted participant counts for the study group and should be read as safety observations, not as a comparison between treatments.

A zero count is not proof that the underlying risk is absent. It means that no serious adverse event is recorded in this summary for the observed group. The registry record does not report a confidence interval, event-classification criteria, or detailed information about monitoring completeness, so the precision of the estimate cannot be fully assessed from these registry entries.

The other-event count does not specify event types, severity, timing, duration, or whether events were judged related to the procedure. The registry lists no serious-event terms, which is not equivalent to a complete narrative of all safety events. The monitoring description mentions inflammation and signs of a foreign-body response, clinical measures, pain assessment, and blood analysis including serum C-reactive protein. No conclusions about specific event causes or clinical consequences are reported.

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

The posted results provide a descriptive account of safety observations after single-stage cartilage repair surgery in the study group. The registry reports zero serious adverse events among 35 participants at risk and other adverse events among 18 participants at risk, with an 18-month primary-outcome timeframe. The study is listed as completed and as Phase 1 and Phase 2.

These counts can help readers understand what was recorded in this group, but they do not establish whether the procedure changes the likelihood of adverse events. There is no comparison group, so the study does not provide a direct estimate of how its safety experience differs from another treatment or from care without this procedure. Nor do the counts establish that an event was caused by the procedure. The registry record does not describe event attribution or a formal comparative analysis.

The absence of a serious event in the posted summary should not be read as proof that serious events are impossible. It is an observed finding from this study group. Likewise, the count of other adverse events does not indicate what those events were or how serious they were, because that detail is not reported in the registry record. A reader cannot use these counts alone to assess event duration, clinical consequences, or treatment-relatedness.

The record also lists clinical improvement measured by the Knee Injury and Osteoarthritis Outcome Score as a secondary outcome. No results for that outcome are included in the registry record, so the safety summary does not establish whether knee symptoms or function improved. The title and treatment rationale describe why the procedure was studied; they are not results demonstrating clinical benefit.

The most supportable interpretation is therefore limited: the registry records the specified safety counts in a single-group study, while comparative safety, causal attribution, event detail, and clinical improvement remain unresolved by these registry entries.

14. Why This Trial Matters Statistically

This study is statistically informative in part because it illustrates the difference between describing an observed safety experience and estimating a comparative treatment effect. The registry records a single-group design and no comparator. The event counts can therefore summarize what was observed among participants in this study, but cannot show whether the procedure leads to more or fewer events than another approach.

Safety studies need careful definitions as well as counts. A participant count does not necessarily reveal the number of individual events, their timing, their severity, or whether they were considered treatment-related. Those details are not reported in the registry entries. Clear event definitions and complete follow-up information are important for interpreting both a zero serious-event count and a count of other adverse events.

The study is identified as Phase 1 and Phase 2 and is titled as an assessment of safety and feasibility. That makes it important to distinguish the study’s purpose and design from evidence of comparative effectiveness. The registry lists a secondary clinical outcome, the Knee Injury and Osteoarthritis Outcome Score, but no result for it is included in the registry record. Safety observations alone cannot answer a question about clinical improvement.

The registry also describes a sample-size planning illustration based on an observed effect and two-arm assumptions, while the trial itself is single-group. This is a reminder that planning calculations depend on their design assumptions and should not be mistaken for evidence of observed power or for the rationale used to choose the study’s enrollment. The trial’s own sample-size justification is not reported in the registry record.

For clinical researchers, the key statistical lesson is to align interpretation with design and reporting. A descriptive count can be useful, but it cannot replace a comparator, clear outcome definitions, or transparent methods for missing data and uncertainty.

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 central limitation for interpreting the safety results is the single-group design. With no comparator, observed events cannot be contrasted with events under another treatment or care condition. The registry’s allocation entry is NA, and masking is listed as none. These registry entries limit comparative interpretation and leave the possibility of observer or reporting influences unaddressed in the available record.

Important details about adverse-event ascertainment are not reported in the registry record. The registry entries do not define serious events, describe grading, identify whether events were judged related to the procedure, or explain how repeat events were counted. The summary contains participant counts, but not event narratives or individual event types. The record lists no serious-event terms; that does not provide a full account of events not classified as serious.

The registry states an 18-month timeframe for the primary outcome, but the registry entries do not specify visit timing, follow-up completeness, or how missing observations were handled. The analysis population and statistical analysis plan are not reported in the registry record. No interval estimate or formal test for the primary safety outcome is included in the registry record.

The listed secondary outcome is clinical improvement measured by the Knee Injury and Osteoarthritis Outcome Score, but its results are not included. The full set of outcome measures and the relationship between the listed analysis and those outcomes are not explained. These omissions limit assessment of outcome selection and multiplicity.

Finally, the registry’s sample-size illustration uses assumptions for a two-arm comparison, whereas the study design is single-group. It is not the trial’s reported design justification and should not be used to infer the precision or power of the observed safety results.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: IMPACT: Safety and Feasibility of a Single-stage Procedure for Focal Cartilage Lesions of the Knee. — NCT02037204.
• Registry record last updated 2019-01-02; status last verified 2018-06.
• Results first posted 2019-01-02.
• 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

The registry record describes IMPACT, a Phase 1/Phase 2, single-group study of single-stage cartilage repair surgery for focal knee cartilage lesions. Enrollment is listed as 35; the study status is completed. Allocation is NA and masking is none.

The intervention used autologous chondrons and allogeneic mesenchymal stromal cells in a fibrin glue carrier. The primary outcome was safety through adverse events over an 18-month timeframe. The posted summary reports zero serious adverse events among 35 participants at risk and other adverse events among 18 participants at risk. Clinical improvement measured by the Knee Injury and Osteoarthritis Outcome Score is listed as a secondary outcome, but its results are not included in the registry record.

Because the study has no comparison group, its safety counts are descriptive rather than comparative. Detailed event definitions, missing-data methods, and the statistical analysis plan are not reported in the registry record.