Electrical Stimulation and Eccentric Exercise for Anterior Cruciate Ligament (ACL) Injury: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Electrical Stimulation and Eccentric Exercise for Anterior Cruciate Ligament (ACL) Injury (NCT01555567), a non-randomized na study. The primary outcome is Quadriceps Strength.

2. Clinical Question

The clinical motivation in the registry record is that quadriceps weakness after ACL injury may reflect both neural inhibition and muscle atrophy. The study is intended to assess interventions addressing these potential contributors and their relation to quadriceps function and biomechanics. The record also lists Central Activation Ratio as a secondary outcome. It does not report results for either outcome.

3. Trial Design

The study is listed as a completed, non-randomized, parallel trial sponsored by the University of Michigan. The registry record lists an enrollment of 43 and describes four groups: electrical stimulation, standard of care, eccentric exercise, and combined stimulation and eccentric exercise. A parallel design means participants are assigned to a group and the groups are considered alongside one another, rather than each participant receiving every intervention in sequence. The record does not specify how group assignment was made beyond stating that it was non-randomized.

Masking is listed as none. This means the registry record does not describe a masked design; it does not provide further detail about who knew group assignments or how outcome assessment was conducted. The phase is listed as not applicable. The study start is recorded as 2009-08 and primary completion as 2014-07; the status is completed.

The intervention descriptions indicate that the study concerns treatment following ACL reconstruction. The eccentric exercise description places training between week 6 and week 12 after reconstruction, while the electrical stimulation and combined intervention descriptions are truncated in the registry record. Further delivery details for those groups are therefore not reported in the registry record. Standard of care is described as standard ACL rehabilitation.

Non-random allocation is an important feature when interpreting group comparisons. In a randomized trial, random assignment is intended to balance measured and unmeasured participant characteristics across groups on average. That protection is not established by this record. Differences in outcomes between groups, if reported, could reflect baseline differences or other factors as well as intervention effects. The registry record reports no outcome analyses, so no such comparison can be described.

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.

12 Week

Return to Activity

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 Quadriceps Strength, measured over Time of return to activity (~6 months following surgery).

The primary endpoint is quadriceps strength, expressed in Nm/kg as a mean with standard deviation. The timeframe is time of return to activity, approximately 6 months following surgery. The unit expresses torque relative to body mass; in general, this normalization can make strength measurements more interpretable across people of different body sizes. The registry record does not give a more detailed description of the measurement procedure, the specific return-to-activity definition, or the population included in the endpoint analysis.

Quadriceps strength is relevant to the study's stated objective because the interventions are intended to address quadriceps weakness and improve muscle function. The registry record identifies weakness as a concern after ACL injury and describes neural inhibition and atrophy as possible contributors. A continuous strength measure can describe the amount of measured strength and allow group means to be compared, provided the analysis and its assumptions are appropriate.

The registry record does not report the mean strength, standard deviation, number assessed, or a between-group estimate at the stated timeframe. It therefore supplies no observed endpoint result to interpret. Central Activation Ratio is listed as a secondary outcome, but its results are also not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does the outcome scale represent?

The primary outcome is a continuous measurement of quadriceps strength in Nm/kg. The registry record specifies that results are to be represented as a mean and standard deviation. In general, a continuous outcome can take a range of measured values rather than only categories such as event or no event. A group mean gives a summary of the measurements, while the standard deviation describes how dispersed participant measurements are around that mean. These statistics answer different questions: the mean locates the group average, and the standard deviation describes variation among observations.

Neither statistic is reported for the primary outcome in the registry record. The record also does not give an analysis method, a group contrast, or an uncertainty interval. It is therefore not possible to assess the observed strength distribution or to reproduce an outcome comparison from the registered results.

Why does allocation matter?

Allocation is listed as non-randomized. In general, random allocation helps guard against systematic differences between groups by using chance to assign participants. With non-random allocation, the reasons participants enter particular groups may be related to their characteristics, treatment preferences, timing, or clinical circumstances. Those are general possibilities, not documented explanations for assignment in this study; the basis for allocation is not reported in the registry record.

For a non-randomized comparison, a statistical adjustment can sometimes address measured group differences, but it cannot automatically remove bias from unmeasured factors or incorrect measurement. The registry record does not report a statistical analysis plan, covariate adjustment, or any outcome analysis. It is therefore not possible to determine whether adjustment was intended or used, or whether a reported comparison accounted for group differences.

What would an estimate and confidence interval add?

In general, an effect estimate gives the size and direction of a comparison, while a confidence interval communicates its statistical uncertainty under the assumptions of the analysis. A narrow interval indicates greater precision than a wide interval, but precision is not the same as freedom from bias. In a non-randomized study, a precisely estimated association can still be affected by differences between groups. No estimate or confidence interval for quadriceps strength is reported in the registry record, so neither magnitude nor precision can be assessed.

A p-value, in general, describes how compatible the data are with a specified null model and analysis assumptions. It does not measure the probability that a treatment works, nor does it give the size or clinical importance of an effect. The registry record reports no p-value or inferential analysis. No conclusion about statistical significance is available.

How should planning illustrations be understood?

Planning illustrations based on an observed effect are not observed trial outcomes and are not observed power. The stated illustration assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is a stated fraction of the observed effect. For non-time-to-event outcomes, such illustrations refer to participants per arm. Their purpose is to show how planning requirements would vary under assumptions about the target effect. They do not establish that the study enrolled enough participants, and they do not substitute for a trial's own sample-size justification.

The registry record does not report an observed effect estimate for quadriceps strength or numerical planning results. It also does not report the trial's sample-size justification. Therefore, a reader cannot use the registry information to assess whether the original enrollment target was based on a prespecified clinically relevant difference or whether a planned power target was met.

What can be inferred from the listed enrollment?

Enrollment is reported as 43. In general, the overall number enrolled is not necessarily the number analyzed for an endpoint. Participants may lack a measurement, may not contribute at the specified time, or may be excluded from a particular analysis under a prespecified rule. The number with a recorded primary endpoint and the analysis population are not reported in the registry record. The group-specific safety denominators should not be treated as group-specific primary-outcome sample sizes.

The reported primary-outcome timeframe is approximately 6 months following surgery, but details of the measurement schedule and any allowable window are not reported in the registry record. Without those details, the consistency of measurement timing cannot be assessed. The record also does not state whether the reported mean, if any, would be adjusted for baseline strength or other characteristics.

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("Neuromuscular Electrical Stimulation", "Standard of Care", "Eccentric Exercise", "Combination of NMES and Eccentric Exercise")
n   <- c(10, 10, 8, 8)
m   <- c(2.1, 2.1, 2.8, 2.9)
sp  <- c(0.6, 0.6, 0.9, 0.6)
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  Neuromuscular Electrical Stimulation  10  2.100  0.600  1.671  2.529
CARM  Standard of Care  10  2.100  0.600  1.671  2.529
CARM  Eccentric Exercise  8  2.800  0.900  2.048  3.552
CARM  Combination of NMES and Eccentric Exercise  8  2.900  0.600  2.398  3.402

11. Multiplicity, Missing Data and Analysis Populations

Multiplicity arises when a study evaluates multiple outcomes, groups, timepoints, or statistical comparisons. In general, making many comparisons can increase the chance that at least one appears noteworthy by chance, so a statistical plan may specify a primary comparison or an adjustment approach. This record lists quadriceps strength as the primary outcome and Central Activation Ratio as a secondary outcome, and it describes four study groups. It does not report which contrasts were planned, whether multiple timepoints or additional analyses were considered, or whether any multiplicity procedure was used. Those details are not reported in the registry record.

The registry record reports no analyses. It does not provide an analysis population, endpoint counts, missing-data amounts, or a method for handling missing measurements. It is not possible to determine whether all enrolled participants were included, whether analyses were based on participants with observed outcomes, or whether an imputation or other method was used. No missing-data assumptions should be inferred from the enrollment figure.

The record also does not report a statistical analysis plan, interim analyses, or a sample-size justification. These omissions prevent assessment of whether the presented analytic choices were prespecified or how incomplete outcome information might have affected an estimate. Since no primary or secondary outcome results are reported, multiplicity-adjusted or unadjusted interpretations are unavailable.

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.

The safety record lists serious adverse events and other adverse events separately for four groups. For neuromuscular electrical stimulation, 0 serious and 0 other adverse events are reported among 10 participants at risk for each category. For standard of care, the corresponding figures are 0 and 0 among 10 at risk. For eccentric exercise, 0 and 0 are reported among 8 at risk. For the combination of NMES and eccentric exercise, 0 and 0 are reported among 8 at risk.

These are the adverse-event figures recorded for the stated groups; they are not evidence that every possible harm was assessed or that no event occurred outside the reporting categories or observation period. The time period used for safety follow-up and the event-collection procedures are not reported in the registry record. Death counts are not reported in the registry record. The safety figures should also not be used as the denominators for the quadriceps-strength analysis, whose group counts are not reported.

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

The registry record establishes that a non-randomized study was designed to examine interventions addressing quadriceps weakness after ACL injury and reconstruction. Its primary outcome is quadriceps strength at return to activity, approximately 6 months following surgery. It also identifies Central Activation Ratio as a secondary outcome and records adverse-event counts for the listed groups.

It does not report observed values for either outcome, a between-group comparison, or an inferential analysis. As a result, the record does not show whether group outcomes were similar or different, how large any difference may have been, or how precisely it could be estimated. The study's stated expectations are aims, not evidence of an outcome. No conclusion about intervention efficacy follows from those expectations alone.

Even a reported difference would need careful interpretation because the allocation was non-randomized. Differences in participant characteristics, care, or other factors could contribute to group outcomes. The record does not explain allocation or provide adjustment details, so it cannot establish that a comparison would isolate an intervention effect.

The safety entries show zero reported serious and other adverse events in each listed group for the specified at-risk counts. They do not provide the safety follow-up duration or enough detail to characterize the scope of event monitoring. Overall, the record is useful for understanding the study question, group structure, and intended endpoint, but it does not provide clinical outcome evidence with which to judge the interventions.

14. Why This Trial Matters Statistically

This trial is statistically notable because it addresses several interventions and a continuous functional outcome in a non-randomized, parallel design. The structure makes the distinction between a study question and a treatment comparison especially important. Multiple groups create choices about which contrasts are of interest, while non-random allocation means that group comparability cannot be assumed. The registry record does not specify the planned contrasts or an adjustment strategy.

The primary outcome is presented as a mean with standard deviation, an appropriate descriptive framework for a continuous measurement. But descriptive summaries alone would not answer whether groups differed, and a difference alone would not establish causation in a non-randomized study. Interpretation would require the actual outcome values, an explicit analysis, uncertainty estimates, and information about participant characteristics and missingness. These are not reported in the registry record.

The enrollment figure and safety counts also illustrate why denominators must be interpreted in context. Overall enrollment is not necessarily the number contributing to the primary endpoint, and the safety risk counts do not establish the outcome-analysis sample sizes. Because endpoint counts and analyses are absent, neither statistical precision nor the practical importance of any outcome can be evaluated.

The record therefore supports a careful account of the intended design and measurement, but not a conclusion about comparative outcomes. This is a useful statistical distinction for clinical research: a completed status and an articulated hypothesis do not replace reported results, and a planning illustration is not evidence of observed power or treatment effect.

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 from the registry record is the absence of primary and secondary outcome results. No group means, standard deviations, participant counts for outcome analyses, treatment contrasts, confidence intervals, or p-values are reported. The primary endpoint is named and timed, but the measurement procedure and return-to-activity definition are not described in detail.

Allocation is non-randomized and masking is listed as none. The registry record does not explain how participants entered groups, whether baseline characteristics were assessed, or whether analyses accounted for differences between groups. These omissions limit the ability to assess comparability and potential confounding. The record also does not report the analysis plan, planned contrasts, adjustment for multiple comparisons, sample-size justification, or any interim analyses.

Enrollment is recorded as 43, but endpoint-specific group counts and the analysis population are not reported. Missing-data amounts, reasons for missingness, and handling methods are also not reported in the registry record. The intervention descriptions for electrical stimulation and the combined approach are incomplete in the registry record, so some delivery details cannot be evaluated.

Safety counts are recorded, but safety follow-up duration and event-collection methods are not reported. Death counts are not reported in the registry record. These limitations mean that the design and selected safety entries can be described, but neither efficacy nor a comprehensive safety profile can be assessed from the registry information.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Electrical Stimulation and Eccentric Exercise for Anterior Cruciate Ligament (ACL) Injury — NCT01555567.
• Registry record last updated 2015-06-08; status last verified 2015-05.
• Results first posted 2015-05-14.
• 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

NCT01555567 is a completed, non-randomized, parallel study sponsored by the University of Michigan, with enrollment listed as 43. It concerns electrical stimulation and eccentric exercise for quadriceps weakness after ACL injury and reconstruction. The listed groups are electrical stimulation, standard of care, eccentric exercise, and combined stimulation and eccentric exercise; masking is listed as none.

The primary outcome is quadriceps strength in Nm/kg, recorded as a mean with standard deviation at return to activity, approximately 6 months following surgery. Central Activation Ratio is listed as a secondary outcome. The registry record does not report outcome values or analyses. It records zero serious and zero other adverse events in each group, with group-specific at-risk counts, but does not report safety follow-up duration. The basis for allocation, analysis plan, endpoint-specific participant counts, and missing-data methods are not reported in the registry record.