A Study to Evaluate Two Formulations of Carisoprodol in Subjects With Musculoskeletal Spasm of the Lower Back: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study to Evaluate Two Formulations of Carisoprodol in Subjects With Musculoskeletal Spasm of the Lower Back (NCT00671502), a randomized phase 3 study. The primary outcome is Subject Rating of Pain on a 100-point Visual Analog Scale (VAS).

2. Clinical Question

The study asked whether either of two sustained-release carisoprodol formulations differed from placebo on a participant-rated measure of lower-back pain. The primary outcome was the least-squares mean rating on a 100-point visual analog scale, with ratings described as collected before treatment and during treatment at each visit. The registry lists the outcome timeframe as up to 14 days.

The registry’s primary question is framed around comparing the formulations with placebo. The posted outcome values are group-level estimates, not individual pain histories. The record does not report a direct between-group treatment contrast, its confidence interval, or a p-value for the primary outcome. It also does not specify in the posted results which visit or summary across visits corresponds to each reported estimate. Consequently, the group estimates can be described as posted, but they do not by themselves establish the size or precision of a treatment-versus-placebo difference.

3. Trial Design

This is a completed phase 3 study with randomized allocation and a parallel-group model. The registry lists quadruple masking, and the official title characterizes the study as randomized, double-blind, and double-dummy. Those descriptions indicate a controlled comparison designed to limit bias in treatment assignment and outcome assessment, although the registry record does not explain the masking procedures in detail.

The interventions were two sustained-release carisoprodol formulations and placebo. The arms are listed as Carisoprodol 500mg Tablets, Carisoprodol 700mg Tablets, and Placebo Tablets. The posted outcome entries list group sizes of 280, 281, and 279, respectively. Enrollment is recorded as 840. These values describe the registry entries and should not be treated as interchangeable: the enrollment field and the outcome-group counts refer to different record elements.

The study start is recorded as 2008-04, and primary completion as 2009-02. No further dates are needed to interpret the posted primary endpoint. The registry lists two secondary outcomes: Subject Functional Assessment Based on the Roland-Morris Disability Questionnaire and Adverse Event Assessment. The record contains three outcome measures, but it reports no analyses for the primary endpoint; a statistical analysis count is listed as 0. Results for the secondary outcomes are not reported in the registry record in the registry record for this account.

The primary-outcome description says efficacy analyses were based on the ITT population and that LOCF was used for missing data. It also includes planning statements about a targeted difference, alpha level, power, and planned group sizes. Those statements are not the same as a reported treatment-effect analysis. No protocol, detailed statistical analysis plan, or further explanation of the design choices is 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

Analysis population for the primary outcome, as defined in the registry: efficacy analyses based on ITT population. LOCF used to impute missing data. To detect a 14% difference between the carisoprodol and placebo treated subjects, 196 ITTsubjects per group (alpha level 0.025,power 80%).Assuming 15% dropout rate, 226 subjects per group were needed.A total of678 subjects were required to achieve 584 ITT subjects.

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 Subject Rating of Pain on a 100-point Visual Analog Scale (VAS), measured over up to 14 days.

The primary endpoint is Subject Rating of Pain on a 100-point Visual Analog Scale (VAS), reported in millimetres. The registry describes the scale as running from 0 to 100 mm, where 0 equaled no pain and 100 equaled maximum pain. Participants measured their pain before treatment and during treatment at each visit. The stated timeframe is up to 14 days.

A participant-rated pain scale captures the participant’s own assessment rather than relying only on an external observer’s judgment. In general, a continuous scale can retain gradations in reported experience instead of reducing responses to a small set of categories. The registry identifies the reported summary as a least-squares mean, a model-based group estimate, and gives a 95% confidence interval for each arm.

The posted least-squares means are 27.5 for Carisoprodol 500mg Tablets, 28.0 for Carisoprodol 700mg Tablets, and 28.6 for Placebo Tablets. Their posted 95% confidence intervals are -21.0 to 83.0, -19.0 to 89.0, and -36.0 to 82.0, respectively. The intervals are broad and include values outside the stated scale. The registry record does not explain this feature or provide the model specification used to calculate the estimates. It also does not identify a specific visit-level contrast in the outcome results.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a least-squares mean represent?

General statistical context: a least-squares mean is a model-based estimate of a group mean. Depending on the model, it can account for specified covariates or other features of the analysis, rather than being a simple arithmetic average of the observed values. The registry identifies the primary outcome parameter as a least-squares mean but does not report the model formula, covariates, or other estimation details. The estimates should therefore be described by the label used in the record, without assuming which adjustments were made.

The reported arm estimates are 27.5 for Carisoprodol 500mg Tablets, 28.0 for Carisoprodol 700mg Tablets, and 28.6 for Placebo Tablets. The outcome is measured on the 0 to 100 mm scale described in the record, with lower values defined as less pain and higher values as more pain. The registry does not specify the visit or model-based time summary represented by each least-squares mean. It also does not report baseline-adjusted changes, so the posted values should not be recast as changes from baseline.

How should the confidence intervals be read?

General statistical context: a confidence interval expresses the precision of an estimate under the statistical procedure used. A narrower interval indicates greater precision than a wider interval, all else equal. It does not describe the spread of individual participant responses, and a 95% confidence interval is not a guarantee that a particular interval contains the true value. Its interpretation relies on the assumptions of the method that generated it.

The registry gives 95% confidence intervals of -21.0 to 83.0 for the 500mg formulation, -19.0 to 89.0 for the 700mg formulation, and -36.0 to 82.0 for placebo. They are wide relative to the scale’s stated limits and extend outside those limits. The record does not describe the reason, the model’s behavior at the scale boundaries, or whether the limits were transformed back to the scale. This uncertainty should be preserved in interpretation rather than replaced with an explanation that is not documented.

Most importantly, these are arm-specific intervals. General statistical context: an interval for each group separately is not a substitute for an interval around the difference between groups. The precision of a contrast depends on the uncertainty in both groups and on the analysis structure. The registry does not report those contrasts or their confidence intervals. It also does not report primary-outcome p-values, so there is no posted significance test to interpret.

Why does over-dispersion matter in general?

General statistical context: over-dispersion describes variability greater than a model assumes. It can make standard errors too small if the model does not account for the extra variability, which can make confidence intervals too narrow and tests too optimistic. This is a general concern when choosing statistical models; it is not a finding about this trial. The registry record does not report a dispersion assessment or provide enough model detail to determine whether over-dispersion was relevant to the continuous pain endpoint.

What do randomized allocation and masking contribute?

General statistical context: random allocation can help balance participant characteristics across groups on average, while masking can reduce the influence of treatment knowledge on behavior, reporting, or assessment. These design features do not guarantee that groups are identical or eliminate all possible bias. In this study, the registry describes randomized allocation, a parallel model, and quadruple masking; the official title describes a double-blind, double-dummy trial. Detailed implementation and the identities of each masked party are not reported in the registry record.

What do the planning statements mean?

The primary-outcome description states that the design sought to detect a 14% difference between carisoprodol and placebo, with alpha level 0.025 and power 80%, and that 196 ITT subjects per group were needed. It further states that, assuming 15% dropout, 226 subjects per group were needed, and includes the statement “A total of678 subjects.” These are statements recorded in the outcome description, not observed treatment-effect results. The record does not explain the derivation of the targeted difference or reconcile those planning statements with the enrollment field of 840.

General statistical context: a sample-size calculation is based on assumptions about the effect to detect, variability, allocation, and testing procedure. Power is a design quantity under those assumptions; after a study is completed, it does not measure the probability that a finding is true. Any separate sample-size planning illustration based on an observed effect is also a planning exercise, not observed power. The registry record does not provide enough information to independently assess the design calculation.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists one primary outcome: Subject Rating of Pain on a 100-point Visual Analog Scale. It also lists two secondary outcomes, Subject Functional Assessment Based on the Roland-Morris Disability Questionnaire and Adverse Event Assessment. The record identifies three outcome measures but does not report results for the secondary outcomes in the material available for this account. It does not describe a multiplicity adjustment, a hierarchy among outcomes, or a strategy for controlling the chance of false-positive findings across multiple comparisons. Such a plan is not reported in the registry record.

The primary-outcome description says efficacy analyses were based on the ITT population and that LOCF was used to impute missing data. In general, ITT analysis aims to retain participants in the groups to which they were assigned, preserving the randomized comparison. The record does not clarify which randomized participants were included in the analysis, how the ITT population was operationalized, or whether any participants were excluded from the efficacy analysis.

LOCF carries an assumption that the last observed outcome can stand in for an outcome that is missing later. In general, this can fail to represent subsequent change if a participant’s condition would have changed after the last observation. The registry record does not report how much data were missing, the timing or reasons for missingness, or sensitivity analyses using alternative assumptions. It also does not say whether missingness differed among groups.

The registry lists no analyses and notes that values were missing or not estimable for a two-arm comparison of the continuous endpoint. It therefore does not provide the planned primary treatment comparisons needed to evaluate the stated question. A detailed statistical analysis plan, multiplicity procedures, and additional analysis-population definitions are not reported in the registry record.

11. 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 0.7% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: transient ischemic attack (0.4%).

The registry reports serious adverse events among 278 participants at risk in the Carisoprodol 700mg group, with 0 affected; among 280 at risk in the Carisoprodol 500mg Tablet group, with 1 affected; and among 275 at risk in the Placebo Tablet group, with 0 affected. The record’s top serious-event term is transient ischemic attack, listed as 0.4%. These figures describe the posted serious-adverse-event information; they do not establish why an event occurred or whether it was caused by study treatment.

General statistical context: a count of affected participants is not a complete description of safety. Interpretation also depends on event definitions, observation time, ascertainment, and the clinical context. The registry record does not provide detailed event narratives, timing, seriousness criteria, or a causal assessment for the reported serious event. The figures should not be read as proof that serious events did or did not occur beyond the counts recorded.

The registry also lists other adverse events for 78 of 278 at risk in the 700mg group, 65 of 280 at risk in the 500mg group, and 37 of 275 at risk in the placebo group. These are separate from the serious-event counts. Deaths are not reported in the registry record. The adverse-event entries alone do not provide a full comparison of safety between the groups.

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

The registry’s primary outcome gives a descriptive view of pain ratings in the three randomized groups. The reported least-squares means are 27.5 for Carisoprodol 500mg Tablets, 28.0 for Carisoprodol 700mg Tablets, and 28.6 for Placebo Tablets. Each estimate has a 95% confidence interval, and each interval is broad. Those estimates and intervals are the primary numerical results available in the record.

They do not, by themselves, answer whether either formulation differed from placebo. A treatment effect is ordinarily expressed as a contrast between groups, with uncertainty around that contrast. The registry does not report a primary-outcome contrast, confidence interval for a contrast, or p-value. It also does not report values for the individual groups at baseline or changes from baseline. Therefore, the arm-level estimates should not be interpreted as measured improvement, and they do not establish a treatment benefit or lack of benefit.

The study design includes randomized allocation, a parallel model, and masking described in the registry and official title. Those features are relevant to the reliability of a comparison, but they cannot replace the missing comparative results. Likewise, the primary-outcome description’s planning statements are not evidence of the observed effect and do not indicate whether the study met its target.

In general, absence of a reported significant difference is not the same as evidence that groups are equivalent. Equivalence or non-inferiority requires a defined margin and an analysis designed to evaluate it. The registry record does not report such a margin or analysis. The broad arm-specific intervals also should not be treated as evidence that all values within them are equally plausible or as a direct measure of the uncertainty in a treatment contrast.

The serious adverse-event entries record 0 affected in the 700mg group, 1 affected in the 500mg group, and 0 affected in placebo, with transient ischemic attack listed as a top serious-event term at 0.4%. These entries are useful as a limited account of reported safety events, but they do not establish causality or provide a full safety assessment. Overall, the posted record allows a careful description of the observed registry entries, while the comparative efficacy conclusions remain undetermined from the analyses reported.

13. Why This Trial Matters Statistically

This trial is statistically notable because its registry record pairs an explicit randomized, masked, placebo-controlled design with incomplete primary comparative results. Random allocation and masking are important design safeguards in general, especially for a participant-rated pain outcome, where expectations and assessment can influence reported ratings. However, the key inferential quantities for the stated comparison—the treatment contrasts and their uncertainty—are not reported.

The outcome is continuous and is presented as a least-squares mean with a 95% confidence interval. That format can communicate both a group estimate and its precision. Here, the intervals are broad and extend outside the stated scale limits, while the registry gives no explanation of the model or interval calculation. This makes it important to distinguish faithfully reported values from conclusions the record cannot support.

The record also illustrates why an endpoint description, a design calculation, and an efficacy result are different kinds of evidence. The primary-outcome description states a target difference and planning assumptions, but those statements do not substitute for results from the randomized comparison. Similarly, a group-level estimate is not a treatment effect unless it is compared with the relevant control through an appropriate analysis.

For clinical researchers and statisticians, the missing pieces are concrete: the analysis model, the exact summary represented by each least-squares mean, treatment contrasts, interval estimates for contrasts, p-values, missing-data details, and sensitivity analyses are not reported in the registry record. Without them, readers can identify what was measured and see the arm-level estimates, but cannot evaluate the primary comparative question using the registry results alone.

The safety entries likewise emphasize the difference between event counts and a complete safety analysis. Counts can describe what was recorded, but interpretation requires context about event definitions, follow-up, and assessment. The registry provides some counts and a serious-event term, but not that wider context.

14. 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 registry reports arm-level least-squares means and confidence intervals but not a direct comparison between either carisoprodol formulation and placebo. No primary-outcome p-values or analysis results are listed, and the record states that values were missing or not estimable for a two-arm continuous-endpoint comparison. As a result, the principal comparative question cannot be answered from the posted analyses.

The description identifies a 100-point pain scale and a timeframe of up to 14 days, but does not specify which visit, averaging procedure, or time summary is represented by each arm estimate. It does not provide the statistical model, covariates, standard errors, or explanation for confidence interval limits outside the stated scale. The record also does not show baseline values or changes from baseline.

The primary-outcome description says LOCF was used, but the extent and pattern of missing data are not reported. No sensitivity analyses are reported, and the registry does not give further details about the ITT population or analysis exclusions. These omissions limit assessment of how robust the estimates are to missing-data assumptions.

Planning information in the outcome description includes a target difference, alpha level, power, and planned group sizes, but the calculation’s assumptions and rationale are not fully documented. The record also does not reconcile the planning statement with the enrollment entry. No detailed protocol or statistical analysis plan is reported in the registry record.

Finally, secondary-outcome results are not reported in the record, and the safety information lacks event timing, detailed definitions, and causal assessment. The posted serious and other adverse-event counts should therefore be treated as limited registry entries rather than a comprehensive evaluation.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Study to Evaluate Two Formulations of Carisoprodol in Subjects With Musculoskeletal Spasm of the Lower Back — NCT00671502.
• Registry record last updated 2011-11-09; status last verified 2011-10.
• Results first posted 2011-11-09.
• 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.

18. Record Summary

NCT00671502 is a completed phase 3, randomized, parallel-group study sponsored by Meda Pharmaceuticals. The registry lists quadruple masking; the official title describes a double-blind, double-dummy trial. Enrollment is recorded as 840. The study start is 2008-04, and primary completion is 2009-02.

The study compared sustained-release carisoprodol 500mg and 700mg tablets with placebo in subjects with acute, painful musculoskeletal spasm of the lower back. The primary endpoint was a participant-rated pain score on a 0 to 100 mm visual analog scale over up to 14 days. The posted least-squares means were 27.5, 28.0, and 28.6, respectively, with broad 95% confidence intervals.

The primary-outcome description identifies an ITT efficacy population and LOCF imputation. The registry reports no analyses and does not provide treatment contrasts or primary-outcome p-values. It lists two secondary outcomes and adverse-event counts, including the serious-event entries. Detailed analysis methods, missing-data sensitivity analyses, and full comparative results are not reported in the registry record.