A Clinical Trial to Evaluate the Safety, Tolerability and Preliminary Effectiveness of Single Administration Intradiscal rhGDF-5 for the Treatment of Early Stage Lumbar Disc Degeneration: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Clinical Trial to Evaluate the Safety, Tolerability and Preliminary Effectiveness of Single Administration Intradiscal rhGDF-5 for the Treatment of Early Stage Lumbar Disc Degeneration (NCT01158924), a na phase 1, phase 2 study. The primary outcome is Neurological Assessment for Motor Function and Reflexes/Sensory.

2. Clinical Question

The study is described as a Phase I/IIa, multicenter, open-label clinical trial evaluating safety, tolerability and preliminary effectiveness. Its primary endpoint is a safety-oriented neurological assessment, while the listed secondary outcomes cover change from baseline in disability, pain and quality of life at 12 months. The record does not give numerical results for those secondary outcomes either. This means the posted information identifies the questions the study was designed to address, but does not establish the size or direction of changes in those measures.

3. Trial Design

This completed study is described in its official title as a Phase I/IIa, multicenter, open-label clinical trial. It evaluated a single administration of intradiscal rhGDF-5 in subjects with early lumbar disc degeneration. The registry record lists enrollment of 40 and identifies DePuy Spine as the sponsor. The recorded study start is 2010-03, and primary completion is listed as 2014-03.

The study used a single-group model, with treatment groups receiving Intradiscal rhGDF-5 at 1.0mg or 2.0mg. Allocation is listed as not applicable, and masking is listed as none. The record therefore does not describe randomized assignment or blinding. It also does not describe a concurrent untreated, placebo or active-comparator group. Any contrast between the dose groups should be read as a comparison between groups in this non-randomized study, not as a controlled estimate of treatment effect.

The registry describes the primary outcome as the number of participants with clinically significant abnormal results on neurological assessment at 12 months. The safety population is specified, and the record notes that the assessment was conducted on 13 subjects from the 1.0mg group and 25 subjects from the 2.0 mg group. The group totals are listed as 14 and 26, respectively, in the adverse-event information; reasons for the smaller neurological assessment counts are not reported in the registry record.

Listed secondary outcomes are changes from baseline in the Oswestry Disability Index, pain measured with a visual analog scale, and the physical component summary of the Short-Form 36, each at 12 months. The registry lists five outcome measures overall, but does not report numerical results for these secondary measures. Details of eligibility criteria, dose-selection rationale, recruitment procedures and follow-up beyond the stated endpoint time 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: Safety Population The Neurological Assessment at 12 months was only conducted on 13 subjects from the 1.0mg group (out of 14 total subjects) and 25 subjects from the 2.0 mg group (out of 26 total).

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 Neurological Assessment for Motor Function and Reflexes/Sensory, measured over 12 months.

The primary endpoint counts participants with clinically significant abnormal results at 12 months on neurological assessments covering motor function and reflexes or sensory function. It is recorded as a number of participants, rather than as a continuous score or a change from baseline. The registry describes motor function grading from 0= No Movement through 4= Active Movement against gravity and resistance. Whether a motor result is clinically significant is determined by the surgeon investigator. Reflexes and sensory findings are also judged clinically significant by the surgeon investigator, based on examinations of the knee, ankle, L3-L5 dermatome and S1 dermatome. Tension signs are evaluated with a straight leg raise to identify when sciatic pain occurs.

As a general statistical concept, a count of participants with a defined safety finding can summarize how often that finding was observed in the assessed group. The count is meaningful only alongside its population, assessment timing and definition. Here, the record specifies the 12-month time point and notes that the neurological assessment was conducted on 13 subjects in the 1.0mg group and 25 subjects in the 2.0 mg group. It does not report the numbers who had clinically significant abnormalities. The endpoint definition alone therefore cannot show the observed frequency or how findings were distributed between dose groups.

The endpoint is used as a safety measure because it focuses on clinically significant changes in neurological examination findings. The registry does not provide further information about how investigator judgments were standardized, adjudicated or evaluated for consistency, so those aspects cannot be assessed from the posted record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

For a binary endpoint, the basic descriptive result is a count of participants who meet the event definition, considered in relation to the participants assessed. The primary endpoint is such a count: participants with clinically significant abnormal neurological findings at 12 months. The record describes who was assessed and how findings are classified, but does not report the event counts. Without those counts, neither the observed event frequency nor a comparison between the dose groups can be read from the primary endpoint description.

As a general statistical concept, a confidence interval represents uncertainty around an estimate. A narrow interval indicates greater precision under the method used, while a wide interval indicates less precision. The registry record does not report a primary endpoint estimate or confidence interval, so the precision of the neurological result cannot be judged. It also does not report p-values or other inferential results for the primary endpoint. An endpoint definition and an assessment time point are not substitutes for the result itself.

The study is open-label, has no randomized allocation listed and uses a single-group model. In general, randomization helps balance measured and unmeasured participant characteristics between groups, while masking can reduce the influence of expectations on assessment or reporting. Those protections are not described. The neurological outcome involves investigator judgment about clinical significance, making the assessment process especially relevant to interpretation. The registry identifies the surgeon investigator as the person determining clinical significance, but does not report masking, independent adjudication or reproducibility procedures. These details should not be assumed.

The dose groups also do not function as a conventional control comparison. A contrast between the groups could reflect dose, but could also reflect differences in who entered each group or other factors. The registry does not describe randomized assignment or statistical adjustment to address those possibilities. Therefore, even if group-specific results are shown elsewhere on the page, they should be read as descriptive results from this study, not as proof that dose caused a difference.

General statistical methods for continuous outcomes, such as change in disability, pain or quality-of-life scores, typically summarize the amount and variability of change. Interpretation depends on the measurement scale, the baseline and follow-up observations, and the analysis population. The registry lists these measures as secondary outcomes at 12 months but does not give their results, analysis methods or measures of variability. It is not possible to infer whether the analyses used raw change, adjusted change, or another approach.

The registry lists zero analyses. This indicates that analysis results are not represented in the registry record; it does not establish what analyses investigators conducted outside the record. The statistical analysis plan, including any model choices, handling of repeated observations, hypothesis tests, covariate adjustments or interim analyses, is not reported in the registry record. No particular method should be attributed to this trial on the basis of the endpoint descriptions alone.

The accompanying sample-size material is a planning illustration, not a description of the trial's original design justification. Its stated assumptions include a two-sided significance level of 0.05, equal allocation between two arms and a normal approximation, with the effect to detect expressed as a fraction of an observed effect. The illustration is not the same as observed power and does not demonstrate that the trial was adequately powered. The record does not report the trial's own sample-size justification. In addition, the study was not a randomized comparison, so assumptions used for a hypothetical two-arm planning calculation should not be mistaken for the actual study design.

Over-dispersion is a general issue for count data when variability exceeds what a simple statistical model expects. It matters because a model that understates variability can produce confidence intervals that are too narrow and tests that appear more decisive than warranted. The primary endpoint is a participant count, but no model or variance estimate is reported, and the posted record does not show that an over-dispersion adjustment was used. This is a general consideration, not a claim about the trial's analysis.

For safety outcomes, counts should be interpreted with the number at risk, the event definition and the observation period in view. The registry gives group totals and counts of participants affected by serious and other adverse events, but details of event timing, recurrent events and exposure-adjusted rates are not reported in the registry record. Counts of affected participants do not show how many episodes occurred, and they do not establish that treatment caused an event.

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("Intradiscal rhGDF-5 (1.0mg)", "Intradiscal rhGDF-5 (2.0mg)")
n      <- c(13, 25)
events <- c(0, 2)
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  Intradiscal rhGDF-5 (1.0mg)  13  0  0.0  0.0  24.7  0.0  22.8  0.2  23.2
ARM  Intradiscal rhGDF-5 (2.0mg)  25  2  8.0  1.0  26.0  2.2  25.0  2.4  25.1

11. Multiplicity, Missing Data and Analysis Populations

The registry lists five outcome measures and identifies a primary neurological assessment at 12 months, alongside secondary outcomes for disability, pain and quality of life. It does not report how multiple outcomes were handled statistically. In general, examining multiple outcomes can increase the chance of a chance finding if each is tested separately. Adjustment procedures, a hierarchy of testing or a prespecified strategy for interpreting secondary outcomes are not reported in the registry record, so it is not possible to determine whether or how multiplicity was addressed.

The record lists zero analyses. This means that the registry record does not present analysis results or detail an analysis plan. It does not show whether investigators performed analyses outside the registry. The statistical analysis plan, including any interim analyses, is not reported in the registry record; none should be assumed.

The primary endpoint population is identified as the safety population. The registry notes that neurological assessments at 12 months were conducted on 13 subjects from the 1.0mg group and 25 subjects from the 2.0 mg group. The reason these assessment counts differ from the group totals of 14 and 26 is not reported in the registry record. The record does not describe imputation, exclusion rules, sensitivity analyses or how missing outcome observations were handled. It is therefore not possible to judge whether missing assessments could have affected the endpoint interpretation.

Analysis-population definitions for the secondary outcomes are not reported in the registry record. The record does not state whether all enrolled participants, participants who received treatment, or another defined population contributed to those outcomes. The population and missing-data approach should be considered unresolved when interpreting any displays of posted results.

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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: angina pectoris (7.1%), prostate cancer (3.8%), small cell lung cancer (3.8%), guillain-barre syndrome (3.8%), migraine (3.8%).

The adverse-event information is organized by dose group. For Intradiscal rhGDF-5 (1.0mg), the record lists 1 participant affected by serious adverse events among 14 at risk, and 12 affected by other adverse events among 14 at risk. For Intradiscal rhGDF-5 (2.0mg), it lists 4 participants affected by serious adverse events among 26 at risk, and 18 affected by other adverse events among 26 at risk. These are participant counts, not a measure of the number of event episodes.

The registry also lists serious-event terms with percentages: Angina Pectoris, 7.1%; Prostate Cancer, 3.8%; Small cell lung cancer, 3.8%; Guillain-Barre Syndrome, 3.8%; Migraine, 3.8%; and Back Pain, 3.8%. The record does not clearly assign these terms and percentages to a specific dose group in the information. They should not be treated as a complete account of all events or as evidence that rhGDF-5 caused them. Death counts are not reported in the registry record.

As a general principle, safety counts describe what was recorded during a study; they do not establish causality. Because this study has no reported control group, the counts cannot show whether events occurred more often than they would have without treatment. The registry does not report event timing, severity details beyond the serious-event classification, or exposure-adjusted rates. The assessment counts and adverse-event counts also answer different questions and should not be conflated.

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

This record describes a completed, open-label study of intradiscal rhGDF-5 in people with early lumbar disc degeneration. It documents the intended safety, tolerability and preliminary effectiveness questions, specifies a neurological safety endpoint at 12 months, and lists secondary measures of disability, pain and quality of life. It also gives participant counts for serious and other adverse events by dose group.

What the record does not provide is the numerical result for the primary neurological endpoint. It does not report the number of participants with clinically significant abnormal findings at 12 months, nor does it provide the numerical results for the listed secondary outcomes. Therefore, this registry information cannot show the magnitude, direction or precision of changes in those outcomes. It cannot establish whether a difference between the dose groups was present or meaningful.

The non-randomized, open-label design without a reported control group also limits causal interpretation. The dose groups are not a substitute for a randomized control group, and descriptive differences between them would not isolate the effect of dose. The record does not report methods to adjust for group differences, or provide enough information to assess the handling of missing neurological assessments.

The adverse-event counts are useful as descriptive safety information, but they do not establish that treatment caused any listed event or that the observed counts differ from what would occur in a comparison population. The registry record does not report death counts.

In short, the posted information describes the study structure and some safety counts, but leaves the primary endpoint results and the listed effectiveness results unavailable. Conclusions about outcome changes, comparative effects or statistical precision cannot be drawn from this record alone.

14. Why This Trial Matters Statistically

This trial illustrates why a well-defined endpoint and a reported endpoint result are different things. The registry gives a detailed description of the neurological assessment, its timing and the population assessed. Those details help readers understand what investigators intended to measure. However, without the number of participants who met the clinically significant abnormality definition, the primary endpoint cannot be quantitatively interpreted.

It also demonstrates how design features shape the questions that data can answer. The study is open-label, has no randomized allocation listed and is described as a single-group model. The dose groups can contribute descriptive safety information, but they are not a randomized control comparison. This distinction is important when reading any apparent separation between groups: a difference in observed outcomes does not by itself identify a causal dose effect.

The difference between the group totals and the neurological assessment counts is another reason to examine analysis populations and missing data. The registry identifies the assessment counts but does not explain why assessments were unavailable for some participants relative to the group totals. Without reasons or a missing-data strategy, readers cannot assess whether the assessed participants represent the full groups.

Finally, the record underscores the importance of complete results reporting. Statistical methods, confidence intervals, analysis populations and multiplicity plans would help readers understand both the uncertainty and the limits of the findings. They are not reported. For statisticians and clinical researchers, the key lesson is to separate the protocol question, the observed data and the strength of any inference—and not to treat a detailed endpoint description as evidence of an unreported result.

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 limitations are specific to the information available for this trial. The primary endpoint is described, but its numerical findings are not reported in the registry record. Numerical results for the listed secondary outcomes are also not reported. This prevents assessment of the direction and size of outcome changes, as well as their statistical precision.

The trial is open-label and has no randomized allocation listed. It has no reported concurrent control group, so the dose groups cannot supply a like-for-like control comparison. Any difference between those groups could reflect factors other than dose. The registry does not report adjusted comparisons that might address group differences.

The primary endpoint is based on surgeon-investigator judgments of clinical significance. The record does not describe independent adjudication, masking of assessors or procedures to assess consistency. It also does not report the reasons that neurological assessments were conducted on 13 subjects from the 1.0mg group and 25 subjects from the 2.0 mg group, rather than the full group totals listed in the safety information. Missing-data methods and sensitivity analyses are not reported.

The analysis plan, sample-size justification, interim analyses, statistical models and multiplicity strategy are not reported in the registry record. The record lists zero analyses, but this is a statement about what the registry presents, not evidence that no analyses were conducted. The serious-event terms and percentages are not clearly assigned to dose groups in the information shown, and death counts are not reported. These limitations constrain both efficacy interpretation and detailed safety assessment.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Clinical Trial to Evaluate the Safety, Tolerability and Preliminary Effectiveness of Single Administration Intradiscal rhGDF-5 for the Treatment of Early Stage Lumbar Disc Degeneration — NCT01158924.
• Registry record last updated 2016-02-26; status last verified 2016-01.
• Results first posted 2016-01-27.
• 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

NCT01158924 is a completed Phase I/IIa, multicenter, open-label trial sponsored by DePuy Spine. It evaluated single administration of intradiscal rhGDF-5 in early lumbar disc degeneration, with groups receiving 1.0mg or 2.0mg. Enrollment was 40; the recorded study start was 2010-03 and primary completion was 2014-03.

The primary endpoint was the number of participants with clinically significant abnormal neurological assessment results at 12 months. Assessments were conducted on 13 subjects from the 1.0mg group and 25 subjects from the 2.0 mg group. Numerical primary and secondary outcome results are not reported in the registry record. The adverse-event information lists serious and other affected-participant counts by group, but does not establish causality. Randomization, masking and a control group are not described, and the record lists zero analyses.