Human Amniotic Tissue-derived Allograft, NuCel, in Posteriolateral Lumbar Fusions for Degenerative Disc Disease: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Human Amniotic Tissue-derived Allograft, NuCel, in Posteriolateral Lumbar Fusions for Degenerative Disc Disease (NCT02070484), a randomized na study. The primary outcome is Oswestry Disability Index.

2. Clinical Question

3. Trial Design

This was a randomized, single-masked, parallel-group trial sponsored by OhioHealth. It compared NuCel, described as a stemcell allograft, with demineralized bone matrix (DBM), described as a bone graft substitute. Both interventions were classified as biological. The registry record lists the study phase as not applicable. The stated purpose was to compare the effect and safety of NuCel and DBM in patients undergoing posteriolateral lumbar spinal fusion for degenerative disc disease.

The registry record reports enrollment of 6 and a terminated status. The study start is listed as 2014-02, and primary completion as 2017-03-24. The reason for termination is not reported in the registry record. Nor does the record explain whether termination was related to recruitment, operational circumstances, safety, or another consideration. The planned or achieved allocation by arm before losses is not reported in the registry record.

The primary outcome was ODI at 12 months, reported as a mean and standard deviation. The record says one of three NuCel patients withdrew before 12 months; the primary analysis therefore comprised two NuCel patients and three DBM patients. A secondary outcome listed in the registry record was computed tomography scans to assess lumbar bone fusion. One secondary outcome is posted, but its results are not included in the registry record for interpretation. The record lists seven outcome measures overall, while providing no analysis results. Details such as the masking role, randomization method, treatment schedule, and analysis plan are 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.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: One of three NuCel patients withdrew before 12 months; therefore, analysis comprises two NuCel patients and three DBM patients.

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 Oswestry Disability Index, measured over 12 months.

The primary endpoint was the Oswestry Disability Index (ODI) at 12 months. The ODI measures disability on a scale from 0 to 100; higher scores correspond to greater disability. As a continuous measure, it can capture a range of reported disability rather than limiting the result to a binary classification. Its use makes the primary outcome a measure of disability, rather than a direct measurement of bone fusion or a safety event.

The registry record reports the endpoint as a mean and standard deviation for each group. The NuCel group had a mean ODI of 8.0 units on the scale, with a standard deviation of 11.3; the DBM group had a mean of 15.3, with a standard deviation of 17.2. These are descriptive summaries from the participants included at the 12-month assessment. A mean gives the group’s average score, while the standard deviation describes the spread of individual scores around that average. Neither statistic, on its own, establishes whether a difference between groups is distinguishable from chance or is clinically important.

The registry record does not report a threshold for a meaningful change in ODI, a confidence interval, or a statistical test for the group comparison. It also does not report individual participant scores. Consequently, the posted summaries describe the observed groups but do not establish the precision of the estimated difference or how scores changed within individuals.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a mean describe?

For a continuous outcome such as ODI, a mean is the arithmetic average of the recorded scores in a group. It gives a compact description of the group’s central value, but it does not show the full distribution of scores. Participants can have different scores even when their group mean is the same. In this trial, the posted means are 8.0 for NuCel and 15.3 for DBM. Because the ODI scale is oriented so that higher scores indicate greater disability, these averages describe lower observed disability scores in the NuCel group. This is a descriptive statement about the analyzed participants, not a causal conclusion about the assigned interventions.

What does the standard deviation describe?

The standard deviation describes how dispersed observations are around a group mean. A small standard deviation indicates scores are relatively close to the mean; a larger one indicates more spread. The posted standard deviations are 11.3 for NuCel and 17.2 for DBM. These values must be considered alongside the group sizes: two NuCel patients and three DBM patients contributed to the reported primary analysis. In groups this small, a single observation can strongly affect both the mean and the estimate of spread. The standard deviation is not a confidence interval and does not directly give the precision of the estimated group mean.

What would an inferential comparison add?

An inferential analysis would estimate how different the groups are and quantify the uncertainty in that estimate under an explicit statistical model. Common presentations include an estimated treatment contrast with a confidence interval, and a test with a p-value. A confidence interval describes a range of values compatible with the data and model at a stated confidence level; a p-value summarizes how surprising data at least as incompatible with a null hypothesis would be under that hypothesis and the test’s assumptions. These concepts are general explanations. The registry record does not report a confidence interval, p-value, or other inferential comparison for the primary endpoint.

The available continuous-outcome comparison is marked as not estimable, and no analyses are posted. Accordingly, there is no sponsor-reported inferential result to interpret. A recalculated comparison is also not available in the registry entries. Without such an estimate, the difference between the displayed averages should not be treated as a tested effect, and no conclusion about statistical significance can be drawn from the means and standard deviations alone.

Why does the sample size matter?

The primary analysis includes only two NuCel patients and three DBM patients. Small groups provide limited information about the range of outcomes in the population, and estimates can be especially sensitive to one person’s score. Random allocation can help make groups comparable in expectation, but it cannot ensure balance in every small realized sample. The registry record identifies the study as randomized but does not report the allocation procedure or details of baseline comparability. It would therefore be inappropriate to assume that the groups were balanced on prognostic characteristics.

The record includes planning assumptions for an illustrative sample-size calculation based on the observed effect, with a two-sided significance level of 0.05, equal allocation, and a normal approximation. Such calculations are planning illustrations, not evidence about the trial’s actual design or its ability to detect an effect. Their assumptions are not a substitute for an inferential result. The registry record does not report the trial’s own sample-size justification, and the planning illustrations must not be interpreted as observed power.

Why can over-dispersion matter?

In general, over-dispersion means that outcome variability is greater than a statistical model assumes. When variability is underestimated, uncertainty estimates can be too narrow and tests can appear more decisive than warranted. The registry record reports standard deviations for the continuous ODI measure, but does not identify a fitted model or report a dispersion assessment. For a continuous outcome, the relevant issue is whether the analysis appropriately accounts for the observed variability and the very small group sizes. No such analysis is reported, so no model-based conclusion about this trial can be assessed.

What do the posted results allow?

The posted figures allow readers to describe the observed group averages and their spread at 12 months. They do not reveal individual scores, within-person changes, a treatment contrast with uncertainty, or the assumptions of an inferential model. The primary outcome is summarized as a mean with standard deviation; the record does not state whether adjustment for baseline ODI or other covariates was planned or conducted. It also does not report interim analyses, a prespecified statistical analysis plan, or methods for multiple outcomes. These items are not reported in the registry record.

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("NuCel", "Demineralized Bone Matrix (DBM)")
n   <- c(2, 3)
m   <- c(8, 15.3)
sp  <- c(11.3, 17.2)
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  NuCel  2  8.000  11.300  -93.526  109.526
CARM  Demineralized Bone Matrix (DBM)  3  15.300  17.200  -27.427  58.027

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists seven outcome measures, with one secondary outcome posted: computed tomography scans to assess lumbar bone fusion. It does not report results for that secondary outcome in the registry record. The primary endpoint is ODI at 12 months. Since multiple outcomes can create multiple opportunities for apparently notable results, a prespecified approach to multiplicity can help clarify how evidence across endpoints is interpreted. The registry record does not report a multiplicity adjustment or a hierarchy of outcomes beyond identifying the primary endpoint.

The record states that one of three NuCel patients withdrew before the 12-month assessment. The primary analysis contains two NuCel patients and three DBM patients. It does not report the reason for withdrawal, the timing of withdrawal, or whether any ODI information was collected from that participant before withdrawal. The missing-data assumptions and handling method are not reported in the registry record. For example, it is not stated whether the analysis used only observed cases, imputation, or another approach; the reported population description indicates the analyzed group sizes but does not explain a broader missing-data procedure.

The registry record does not describe an intention-to-treat analysis population, a per-protocol population, or sensitivity analyses for missing outcomes. Nor does it report interim analyses or a statistical analysis plan. These omissions matter because analysis choices can affect how a small randomized comparison is interpreted. With no reported inferential analysis and incomplete information about missing-data handling, the registry record supports a description of the five observed 12-month outcomes but not a complete evaluation of the planned analysis strategy.

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 0% reporting threshold.

Most frequent serious adverse event terms

Serious events with the highest arm-level rate: prolonged hospitalization (33.3%).

The registry record reports serious adverse events for three participants at risk in each group. No serious adverse events were recorded among the three NuCel participants at risk; one was recorded among the three DBM participants at risk. The listed serious adverse event term was prolonged hospitalization, reported as 33.3%. No deaths were recorded in either group. Other adverse events were recorded for zero of three participants at risk in each group.

These are event counts from very small groups. They describe what was recorded during the study, but they do not provide a precise estimate of how often such events might occur in a larger population. A count of zero in a small group does not establish that an event cannot occur, and one recorded event does not by itself establish that an intervention caused it. The registry record does not provide further details about event timing, severity beyond the serious classification, relatedness assessment, or the criteria used to attribute events to an intervention.

The serious-event figures should therefore be read as descriptive safety reporting, not as a definitive comparison between NuCel and DBM. The terminated status and small enrollment further limit what can be inferred. The registry record does not report a causal safety analysis or enough information to assess differences in risk with precision.

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

The result has a limited descriptive meaning. Among the participants included in the 12-month primary analysis, the NuCel group had a mean ODI of 8.0, with a standard deviation of 11.3, while the DBM group had a mean of 15.3, with a standard deviation of 17.2. Since higher ODI scores indicate greater disability, the group averages describe lower observed scores in the NuCel arm. The analysis included two NuCel patients and three DBM patients.

Those summaries do not establish that assignment to NuCel caused lower disability scores. The registry record reports no inferential analysis for the comparison and no confidence interval or p-value. It also does not provide a threshold for a clinically meaningful ODI difference. As a result, readers cannot determine from the posted summaries how precisely a group contrast is estimated or how important any contrast would be to patients.

The result also does not answer whether the interventions differed in lumbar bone fusion. Computed tomography scans to assess lumbar bone fusion are listed as a secondary outcome, but corresponding results are not reported in the record. Nor do the ODI summaries provide a full account of safety: the adverse-event counts are descriptive and come from three participants at risk per arm.

The trial’s enrollment was 6, and its status is terminated. One of three NuCel patients withdrew before the 12-month assessment. The withdrawal reason and the missing-data method are not reported in the registry record. Taken together, these registry entries mean that the posted outcome should be treated as an observation from a very small analyzed sample, not as a conclusive estimate of comparative effectiveness or safety. The findings cannot determine what would happen in a larger group or resolve uncertainty about the cause of any observed score pattern.

14. Why This Trial Matters Statistically

This trial illustrates why a randomized label does not, by itself, make a result precise. Randomization is a design feature intended to support fair comparison, but this record reports enrollment of 6 and primary outcome data for only five participants. With such limited information, group averages can change substantially with individual observations, and the record does not provide an inferential estimate to quantify uncertainty around the comparison.

It also shows why endpoint summaries and treatment-effect estimates are different. Means and standard deviations describe the observed ODI scores within each analyzed group. A comparative estimate would directly express the contrast between assignments and ordinarily include an assessment of uncertainty. The registry record does not report that analysis. Readers should therefore distinguish the visible descriptive pattern from evidence that supports a treatment-effect conclusion.

The missing 12-month observation is another statistical concern. The withdrawal occurred in the NuCel group, and the record does not state why it happened or how missingness was addressed. When information is absent, assumptions about the unobserved outcome can affect interpretation. In a very small trial, the influence of one missing participant can be especially consequential, but the record does not provide enough information to evaluate that influence.

Finally, the listed secondary outcome and safety counts demonstrate that a clinical trial can collect several types of information while still leaving major uncertainty about comparative effects. This record reports a secondary fusion assessment but not its results, as well as a small number of adverse-event observations. The statistical lesson is not that a particular intervention should be preferred; it is that design labels, descriptive summaries, incomplete follow-up, and absent inferential results must be considered together before drawing conclusions.

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.

Several trial-specific limitations constrain interpretation. Overall enrollment was 6, and only two NuCel patients and three DBM patients contributed to the primary outcome at 12 months. One of three NuCel patients withdrew before the assessment. The reason for withdrawal, the outcome information available before withdrawal, and the handling of missing data are not reported in the registry record. The observed-case group summaries may therefore not represent all enrolled participants.

The registry record identifies the study as randomized and single-masked, but does not report how the allocation sequence was generated or concealed, who was masked, or whether masking was maintained. Baseline characteristics and the allocation counts before withdrawal are also not reported in the registry record. These omissions prevent assessment of the comparability of the analyzed groups and of how the design was implemented.

The primary endpoint is summarized by group mean and standard deviation, but no inferential comparison, confidence interval, or p-value is posted. The record also does not report an ODI threshold for clinical importance, baseline ODI results, or within-person changes. The reason for study termination, the trial’s sample-size justification, and the detailed statistical analysis plan are not reported in the registry record. It is not possible to assess whether the posted analysis followed a prespecified plan.

Although computed tomography scans to assess lumbar bone fusion are listed as a secondary outcome, its results are not included in the registry entries. The registry record lists seven outcome measures but gives no analysis results. Safety information consists of counts in small groups and does not include further detail on event timing or relatedness. Together, these limitations mean the record provides only a narrow account of observed 12-month disability scores and recorded adverse events.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Human Amniotic Tissue-derived Allograft, NuCel, in Posteriolateral Lumbar Fusions for Degenerative Disc Disease — NCT02070484.
• Registry record last updated 2018-09-28; status last verified 2018-08.
• Results first posted 2018-08-27.
• 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 a randomized, single-masked, parallel-group comparison of NuCel and demineralized bone matrix in patients undergoing posteriolateral lumbar fusion for degenerative disc disease. OhioHealth is listed as sponsor. The study phase is listed as not applicable; enrollment was 6, and the status is terminated. The study start is listed as 2014-02 and primary completion as 2017-03-24. The reason for termination is not reported in the registry record.

The primary outcome was ODI at 12 months. The analysis comprised two NuCel patients and three DBM patients after one NuCel patient withdrew before the assessment. The reported group means were 8.0 and 15.3, with standard deviations of 11.3 and 17.2, respectively. No inferential analysis is reported. One secondary outcome concerns computed tomography assessment of lumbar bone fusion, but its result is not reported in the registry record. Safety reporting records one serious adverse event in the DBM group, none in the NuCel group, and no deaths in either group.