Safety and Effectiveness of BIOSURE RG in Cruciate Ligaments Reconstruction in Chinese: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety and Effectiveness of BIOSURE RG in Cruciate Ligaments Reconstruction in Chinese (NCT04012567), a randomized na study. The primary outcome is Lysholm Knee Scoring Scale 12 Months After Operation.

2. Clinical Question

The stated objective was to compare the safety and effectiveness of the two screws in patients undergoing cruciate ligament reconstruction. The primary efficacy endpoint was the Lysholm score at 12 months. The record describes a non-inferiority test, which asks whether the investigational device’s outcome is not worse than the control outcome by more than a prespecified margin. That margin is essential to judging the stated question, but it is not reported in the registry record.

The posted means are 92.49 for Biosure Regenesorb and 94.14 for BIOSURE HA. These are group averages, not individual outcomes. The comparison estimate is expressed as BIOSURE HA minus Biosure Regenesorb, so its positive direction indicates a higher observed mean in the control group. The estimate alone does not establish whether the study met its non-inferiority objective.

3. Trial Design

This was a prospective, multicenter, randomized clinical study with a parallel-group design. The registry lists single masking, but whose identity was masked is not reported in the registry record. The study status is completed, and the recorded enrollment is 140. The listed phase is NA.

The two groups received different devices: Biosure Regenesorb Interference Screw as the investigational device and BIOSURE HA Interference Screw as the control device. Both are described as absorbable biocomposite screws used in knee surgery to fix ligaments, tendons, soft tissues or bone-tendon-bone grafts. The investigational screw is additionally described as having an open structure. Details about the surgical technique, allocation concealment, masking procedures, and treatment adherence are not reported in the registry record.

The primary endpoint was the Lysholm Knee Scoring Scale score 12 months after operation. The primary efficacy analysis population is described as the Full Analysis Set, including participants with at least one effectiveness evaluation that provided data for the stated time frame. The registry lists secondary assessments of Lysholm scores before operation and at 6 and 24 months, the International Knee Documentation Committee score, anterior and posterior drawer tests, the Lachman test, and X-ray, CT and MRI evaluations.

The study began on 2019-12-17, and the primary completion date is 2021-09-11. The registry record does not report the original sample-size justification, the planned allocation ratio, the detailed statistical analysis plan, the formal non-inferiority margin, or the procedures used to handle missing observations. The posted group sizes for the primary endpoint are 69 and 70; these endpoint counts need not represent every enrolled participant or every analysis population.

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: One participant enrolled in the study was excluded because their cruciate ligament was found to be unbroken during operation.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Full Analysis Set (FAS) included participants with at least one effectiveness evaluation that provided data for the time frame indicated.

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 Lysholm Knee Scoring Scale 12 Months After Operation, measured over 12 months.

The primary endpoint is the Lysholm Knee Scoring Scale score 12 months after operation. It is a continuous measure of knee function based on eight items: limp, support, interlocking, pain, instability, swelling, stair climbing and squatting. The score ranges from 0 to 100, with 100 indicating the best outcome and 0 the worst. Pain and instability account for a higher proportion of the score.

The registry describes scores of 95-100 as excellent, 84-94 as good, 65-83 as fair, and less than 65 as poor. These categories provide a clinical description of score levels, while the primary comparison is between group means. A mean can summarize a group but does not show the full distribution of individual scores or how many participants fell within any category.

The Lysholm scale is used to represent knee function after cruciate ligament reconstruction, making it relevant to the study’s stated effectiveness question. Comparing scores at a specified follow-up time also gives a common outcome for the randomized groups. However, the registry record does not report a minimally important difference or the non-inferiority margin. Without those thresholds, the clinical importance of a difference and the formal non-inferiority conclusion cannot be determined from the posted means alone.

7. Results Posted in the Registry

• The BIOSURE HA Interference Screw: mean 94.14 versus 92.49 on control; difference 1.65 (95% CI -1.36 to 4.66), standardized effect d = 0.18; z-test p = 0.283.

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is continuous, so the registry reports the group mean and standard deviation at 12 months. A mean represents the average score in a group. A standard deviation describes how dispersed participant scores are around that average. These statistics answer different questions: the standard deviation concerns variability among participants, while a confidence interval for a mean difference concerns uncertainty about the group comparison.

What does the mean difference represent?

The comparison is defined as the BIOSURE HA mean minus the Biosure Regenesorb mean. With this direction, a positive estimate indicates a higher observed average score in the BIOSURE HA group; a negative estimate would indicate a higher observed average in the Biosure Regenesorb group. The reported estimate is 1.65 points. This is a difference between group averages, not a change from baseline and not a difference for every participant.

The posted group means are 94.14 for BIOSURE HA and 92.49 for Biosure Regenesorb. Their standard deviations are 7.13 and 10.61. The comparison also reports a pooled standard deviation of 9.027 and a standardized difference of 0.183. A standardized difference expresses the mean contrast relative to a measure of score variability. It can help describe the size of a contrast on a scale that is less dependent on the original measurement units, but it does not replace clinical interpretation of the score itself.

How should the p-value be read?

The unadjusted p-value is 0.283. In general, a p-value summarizes how compatible the observed data are with a specified null hypothesis under the assumptions of the analysis. It is not the probability that the null hypothesis is true, nor does it measure the probability that a result occurred by chance. The registry’s brief summary describes a non-inferiority hypothesis, but the formal margin and complete statistical procedure are not reported. Therefore, the unadjusted p-value should not be treated as a complete test of the stated non-inferiority objective.

A conventional difference test and a non-inferiority test address different questions. A difference test asks whether evidence indicates a nonzero contrast. A non-inferiority test asks whether the investigational result can be ruled out as worse than control by more than a chosen margin. A nonsignificant difference test does not establish non-inferiority or equivalence. The margin is necessary to identify the boundary that the confidence interval must clear.

Why does the confidence interval matter?

The 95% confidence interval for the mean difference extends from -1.359 to 4.659. In general, a confidence interval gives a range of values compatible with the data and the method’s assumptions, and conveys precision as well as direction. The interval includes zero, so the posted estimate does not isolate a direction of difference at this level. Its interpretation for non-inferiority depends on comparing the lower limit with the prespecified margin. Since that margin is not reported in the registry record, the interval cannot settle the primary non-inferiority question by itself.

The confidence interval is described as an unadjusted recalculation from posted summary statistics. It is not an adjusted estimate from a model that accounts for baseline scores, site, or other covariates. The record does not report whether such an adjusted analysis was part of the planned primary analysis. Any formal sponsor analysis may therefore differ in method and interpretation from this simple summary-based comparison.

What does the Full Analysis Set mean?

The record defines the Full Analysis Set as including participants who had at least one effectiveness evaluation providing data for the indicated time frame. This definition identifies who contributed to the endpoint summary, but the registry record does not give a fuller account of exclusions, missing follow-up scores, imputation, or sensitivity analyses. In general, missing-outcome methods can affect estimated group means if participants without follow-up differ systematically from those with observed scores.

For non-inferiority studies, analysis population choices can be especially consequential. General statistical practice often examines whether conclusions are robust across appropriate analysis sets and missing-data assumptions, but the registry record does not report which such analyses were planned or conducted. It also does not report a protocol-specific analysis plan or whether an intention-to-treat analysis was used.

What can the planning calculations say?

The sample-size figures are planning illustrations based on fractions of the observed effect, with a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation. They show the participants per arm associated with 80% or 90% power under those assumptions. General power calculations describe the chance of detecting a specified effect under a defined statistical model and assumptions. They do not establish the probability that the observed trial result is true, and they do not replace the original design justification, which is not reported in the registry record.

Over-dispersion is a general concern when outcome variability exceeds what a chosen model assumes, because standard errors may be underestimated and confidence intervals may be too narrow. The outcome is a score, and the posted summary uses means and standard deviations. The registry record does not report diagnostics or model checks that would show whether any particular distributional assumption was evaluated. Accordingly, no claim about such diagnostics can be made from the reported summaries.

10. Confidence Intervals and Precision

The 95% confidence interval for the mean difference, defined as BIOSURE HA minus Biosure Regenesorb, is -1.359 to 4.659 points. Its width indicates that the comparison is not precise enough to confine the plausible mean contrast to a narrow range. The interval includes zero, so both a modest contrast favoring Biosure Regenesorb and a contrast favoring BIOSURE HA are compatible with the unadjusted summary-based estimate.

A confidence interval is not a range containing 95% of individual participant scores. It is an uncertainty interval for the estimated group contrast, interpreted under the statistical method and its assumptions. The group standard deviations, 7.13 for BIOSURE HA and 10.61 for Biosure Regenesorb, describe participant-level variation and should not be confused with the interval’s limits.

For the stated non-inferiority objective, precision must be judged in relation to the non-inferiority margin. The lower confidence limit is relevant to whether a sufficiently large disadvantage can be excluded, but the margin is not reported in the registry record. The interval therefore cannot be classified as meeting or failing the non-inferiority criterion from the available information. The record also does not report whether the sponsor’s primary analysis used this same interval method or included adjustment.

The unadjusted p-value is 0.283, but a p-value alone does not show how precisely the mean difference has been estimated. The confidence interval is more informative about the range of contrasts compatible with the observed summaries, while still not resolving the margin-dependent non-inferiority question.

11. 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 stated as participants per arm, not as total events. They use a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect to detect is set at the stated fraction of the observed effect. The original trial’s own sample-size assumptions and justification are not reported in the registry record.

The 80% power column gives the number of participants per arm that the planning calculation associates with an 80% chance of detecting the chosen effect under its assumptions. The 90% power column gives the corresponding per-arm planning number for a 90% chance. These are conditional design calculations: their meaning depends on the assumed effect size, variability, allocation, significance level, and statistical model. They are not observed power.

The scenarios consider planning for 100% of the observed effect, 75% of the observed effect, and 50% of the observed effect. As the effect specified for detection becomes smaller, more participants are needed to distinguish it from random variation at the same power level. This pattern is a general feature of power calculations, not evidence that the original trial was designed around the observed result.

The figures are illustrations based on the observed effect and stated assumptions. They should not be read as the trial’s intended enrollment target, proof that the completed study was adequately powered, or a substitute for the missing original design rationale. They also do not establish whether the study met its non-inferiority objective, which requires the formal margin and planned analysis.

12. 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 = 1.650; pooled standard deviation σ = 9.027.
2. n = 2 × (1.96 + 0.842)² × 9.027² / 1.650² = 469.8, rounded up to 470 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 <- 1.65000000000001                      # observed difference in means
sigma <- 9.02658235718785                     # 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(4012567)
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 = 470 (80% power), 629 (90% power)
 75% of observed effect: n per arm = 836 (80% power), 1,119 (90% power)
 50% of observed effect: n per arm = 1,880 (80% power), 2,516 (90% power)
power.t.test: 470.8 
Simulated power at n = 470 per arm: 0.798 (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.

13. Multiplicity, Missing Data and Analysis Populations

The registry lists several secondary outcomes in addition to the primary 12-month Lysholm score. These include Lysholm scores before operation and at 6 and 24 months, the IKDC score, anterior and posterior drawer tests, the Lachman test, and imaging assessments by X-ray, CT and MRI. The record indicates eight secondary outcomes posted. These measures cover different aspects of knee function, examination findings and imaging, and should not be treated as interchangeable with the primary endpoint.

When many outcomes or time points are examined, the chance of at least one apparently notable result can increase. General statistical approaches to multiplicity include prespecifying a primary comparison, adjusting inference across selected comparisons, or clearly labeling secondary findings as exploratory. The registry record does not report whether multiplicity adjustments were planned or used, which outcomes were formally tested, or whether a hierarchy was specified. The posted summary lists no analyses, so detailed secondary estimates and inferential results are not reported in the registry record.

The primary endpoint population is the Full Analysis Set, defined as participants with at least one effectiveness evaluation providing data for the relevant time frame. That definition does not explain how missing 12-month scores were addressed. The registry record does not report the extent or reasons for missingness, imputation methods, sensitivity analyses, or whether participants were analyzed according to randomized assignment.

These omissions matter because missing outcomes and selective emphasis among many measures can affect how confidently findings are interpreted. General statistical practice uses a prespecified analysis plan and transparent reporting of outcome availability, analysis populations, and multiplicity methods to make these risks assessable. Such details are not reported in the registry record, so the posted primary summary cannot be used to reconstruct them.

14. 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.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: prepuce balanitis, prepuce too long (1.4%), left knee anterior cruciate ligament rupture,lateral meniscus root tear (1.4%), foreign body reaction (1.4%), thrombosis:middle & lower left superficial femoral, popliteal, posterior tibial,& intermuscular vein (1.4%), meniscus injury of the right knee (1.4%).

The safety summary reports serious adverse events in 3 participants in the Biosure Regenesorb group and 3 participants in the BIOSURE HA group. It reports 0 deaths in each group. For other adverse events, the reported affected counts are 30 for Biosure Regenesorb and 26 for BIOSURE HA.

The registry also lists serious adverse-event terms, each with a reported frequency of 1.4%: prepuce balanitis, prepuce too long; left knee anterior cruciate ligament rupture, lateral meniscus root tear; foreign body reaction; thrombosis involving the middle and lower left superficial femoral, popliteal, posterior tibial, and intermuscular vein; meniscus injury of the right knee; and pharyngeal disorder. These terms are reproduced as registry descriptions and do not establish causation by a device.

Counts alone do not provide a complete comparison of safety. The registry record does not report exposure-adjusted rates, event timing, seriousness criteria, duration, relatedness assessments, or a statistical comparison of the groups. The counts should therefore be read descriptively, not as evidence that one device has a safer profile.

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

The posted results describe average Lysholm scores at 12 months that are high relative to the scale’s full range, with a mean of 92.49 for Biosure Regenesorb and 94.14 for BIOSURE HA. The observed mean contrast is 1.65 points in the direction of a higher average in the control group. The interval around that contrast is broad enough to include zero and values favoring either group.

Those findings do not establish that the devices are equivalent. Equivalence requires a prespecified range of differences considered acceptably small and an analysis designed to show that the contrast lies within that range. Nor do the summaries establish non-inferiority: the registry describes that objective, but the non-inferiority margin and formal sponsor conclusion are not reported in the registry record.

The values are group summaries, not individual predictions. They do not show how each participant’s score changed from before operation, whether a particular person improved, or how many participants achieved a score in each descriptive category. The record lists secondary assessments, but detailed results for those assessments are not reported in the registry record.

The safety summaries likewise describe counts rather than causal conclusions. Equal serious-event counts and no reported deaths do not prove equal safety, and differences in other adverse-event counts do not by themselves establish a device-related difference. Event context and comparative analysis are not reported in the registry record.

In general, randomized allocation supports a fair comparison when the planned analysis is appropriate and follow-up and outcome reporting are adequately handled. Here, the registry record does not report enough detail about missing data, analysis populations, masking, or the formal statistical plan to assess those issues fully. The result is best read as a description of posted endpoint summaries and their uncertainty, not as a definitive answer to every effectiveness or safety question.

16. Why This Trial Matters Statistically

This study raises a useful statistical distinction between testing for a difference and testing for non-inferiority. A non-inferiority question requires a clinically justified margin fixed in advance, as well as an analysis that compares uncertainty in the estimate with that margin. The registry describes a non-inferiority hypothesis, but does not report the margin or the formal conclusion. The available mean contrast and confidence interval therefore illustrate why an effect estimate alone cannot answer the study’s stated primary question.

The score is continuous and clinically interpretable, while its group summaries conceal variation between participants. Reporting both means and standard deviations gives context for the observed averages; the confidence interval adds information about uncertainty in the group contrast. Together, they are more informative than a p-value alone, but still do not describe individual trajectories or establish clinical importance without a relevant threshold.

The record also highlights how analysis-population definitions and missing outcomes matter in a randomized study. The Full Analysis Set definition is limited to participants with at least one effectiveness evaluation for the time frame. More detail about missing follow-up, sensitivity analyses, and the planned analysis is not reported. These details are particularly important when the aim is to rule out an unacceptable disadvantage.

Finally, safety counts require context. Serious-event counts, other-event counts, event descriptions and deaths address different aspects of safety, and none alone establishes a comparative causal effect. A fuller interpretation would require event definitions, exposure and follow-up context, relatedness assessment, and the prespecified comparative approach. The record’s limits make careful separation of descriptive observations from confirmatory conclusions central to interpreting this trial.

17. 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 comparison is available as group means and standard deviations, but the registry record does not report the non-inferiority margin or the sponsor’s formal primary analysis conclusion. Without the margin and planned decision rule, the stated non-inferiority objective cannot be independently evaluated from the posted comparison alone.

The record does not identify who was masked or describe allocation concealment, surgical standardization, adherence, or protocol deviations. These are trial-specific details relevant to judging how the randomized comparison was implemented. The record also does not report the original sample-size justification, so the planning figures based on the observed effect should not be mistaken for the study’s design rationale.

The Full Analysis Set is defined by having at least one effectiveness evaluation contributing data at the stated time frame. However, the number and reasons for missing 12-month scores, how missing observations were treated, and whether sensitivity analyses were conducted are not reported in the registry record. These gaps limit assessment of attrition and robustness.

The registry lists secondary assessments but does not report detailed results or the approach to multiple comparisons. The posted comparison is unadjusted and based on summary statistics; the record does not state whether the formal primary analysis adjusted for baseline score or other factors. The safety summary likewise lacks exposure-adjusted rates, event timing and a formal comparative analysis. These limitations are specific to the information recorded and do not establish that unreported procedures were not performed.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: Safety and Effectiveness of BIOSURE RG in Cruciate Ligaments Reconstruction in Chinese — NCT04012567.
• Registry record last updated 2025-03-25; status last verified 2024-08.
• Results first posted 2025-03-25.
• 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.

21. Record Summary

The completed study, NCT04012567, was a prospective, multicenter, randomized, single-masked, parallel-group comparison of Biosure Regenesorb Interference Screw with BIOSURE HA Interference Screw in cruciate ligament reconstruction. Recorded enrollment was 140.

The primary endpoint was Lysholm Knee Scoring Scale score 12 months after operation in the Full Analysis Set. The posted means were 92.49 for Biosure Regenesorb and 94.14 for BIOSURE HA. The unadjusted mean difference, defined as control minus investigational, was 1.65, with a 95% confidence interval from -1.359 to 4.659 and an unadjusted p-value of 0.283.

The registry describes a non-inferiority objective, but the margin, detailed analysis plan, missing-data procedures, and formal sponsor conclusion are not reported in the registry record. Safety summaries report 3 serious adverse events in each group and 0 deaths in each group.