Orphenadrine and Methocarbamol for LBP: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Orphenadrine and Methocarbamol for LBP (NCT02665286), a randomized phase 4 study. The primary outcome is Functional Impairment as Measured on the Roland Morris Disability Questionnaire.

2. Clinical Question

This is a comparison of treatment regimens, not a comparison of either muscle relaxant used alone with placebo. The shared naproxen component matters when interpreting the question: the study sought to assess the additional contribution of the assigned drug when used alongside naproxen. The posted record does not establish what the result would be for other doses, longer treatment, other populations, or other care settings.

3. Trial Design

The registry identifies this as a randomized, parallel, three-arm, phase 4 study with quadruple masking. It is listed as completed. Montefiore Medical Center is named as sponsor. The enrollment field records 240 participants. The registry gives a start of 2016-03 and primary completion of 2017-04.

The three assigned regimens were naproxen with placebo, naproxen with orphenadrine, and naproxen with methocarbamol. The arm descriptions specify naproxen 500 mg twice per day for 10 days. Orphenadrine was described as 100 mg twice per day, and methocarbamol as 750 mg in 1 or 2 tablets thrice per day. Placebo dosing is described with alternative capsule schedules. Further details about how these alternatives were applied are not reported in the registry record.

Random assignment supports interpreting differences between assigned arms as comparisons of the study regimens, subject to the conduct and analysis of the trial. The registry does not describe the sequence-generation method, concealment procedures, or which roles were masked. The quadruple-masking label is present, but the identities of the masked groups are not reported in the registry record.

The listed primary outcome is change in Roland Morris Disability Questionnaire score between baseline and 1 week. Three secondary outcomes are also posted, each with a 1 week timeframe. The registry record has no reported analyses for these outcomes. The posted arm-level results therefore describe the recorded outcome values, while the displayed two-arm secondary comparisons are unadjusted recalculations from those summaries rather than sponsor-reported analyses. The primary two-arm continuous comparison is not estimable from the posted summary statistics.

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:

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 Functional Impairment as Measured on the Roland Morris Disability Questionnaire, measured over 1 week.

The primary endpoint is change in functional impairment from baseline to 1 week, measured with the Roland Morris Disability Questionnaire, or RMDQ. This is a 24-item questionnaire about functional limitations related to low back pain. The registry describes the scale as ranging from 0, indicating no functional impairment, to 24, indicating severe functional impairment; higher scores signify greater low back-related impairment.

Function is relevant to low back pain research because symptoms can affect ordinary activities as well as pain intensity. A change score is intended to represent how the measured impairment differs from a participant’s baseline over the stated assessment period. The registry identifies the outcome as a mean and reports arm-level values with 95% confidence intervals.

The record does not specify how to interpret the sign of the change values, including whether a positive value represents improvement or worsening. The values should therefore be read as the posted mean change estimates, rather than assigned an improvement direction. Nor does the record report an established threshold for a clinically important change. These omissions limit interpretation of the size and practical importance of the estimates.

The RMDQ provides a structured functional measure, but it is not the only possible account of recovery. Symptoms, medication use, and satisfaction are addressed through secondary outcomes. Their presence complements the primary measure, but does not replace a clearly specified analysis of the primary endpoint.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The following statistical explanations are general. The registry record does not report a detailed statistical analysis plan, so the methods used for the sponsor’s primary analysis cannot be reconstructed from the listed outcomes and arm summaries alone.

What does a mean change summarize?

A mean change condenses participants’ individual changes into an average for an arm. It can be useful for comparing groups when the outcome is measured on a numerical scale. But the arm means do not reveal the spread of individual changes, the shape of their distribution, or whether a few large changes strongly influence the average. The posted primary outcome gives confidence intervals but no standard deviations or other measure of participant-level variability.

For a treatment comparison, the central quantity is usually a contrast between arms, such as the difference in mean change. A direct contrast addresses whether the average changes differ, while separate arm estimates describe each group in isolation. The registry record says values were missing or not estimable for a two-arm comparison of this continuous endpoint. A difference should not be calculated from the arm-level means as though it were the trial’s reported analysis: that would not account for the design, uncertainty, or any analysis choices.

How should confidence intervals be read?

In general, a confidence interval conveys the precision of an estimate under a statistical procedure and its assumptions. A narrower interval indicates greater precision than a wider interval on the same scale. The interval does not describe the range of individual outcomes. Nor should it be interpreted as a probability statement about the particular fixed effect after the data have been observed.

For a comparison, the confidence interval is especially useful because it shows which effect sizes remain compatible with the data under the method. When an interval for a difference includes zero, the results are compatible with no difference as well as with effects in either direction. That does not demonstrate equivalence or rule out effects that could matter. An equivalence or non-inferiority conclusion requires a suitable design, a specified margin, and an appropriate analysis; these are not reported in the registry record.

What are the secondary risk differences?

The secondary outcomes are counts of participants meeting a stated outcome in each arm. A risk difference compares the proportion with the outcome in one arm against the proportion in the comparator arm. A negative risk difference indicates a lower observed proportion in the named active arm under the comparison’s coding; a positive value indicates a higher observed proportion. The confidence interval describes uncertainty around that contrast. The registry-posted recalculations are unadjusted and should not be treated as reported sponsor analyses.

Risk differences are expressed on an absolute scale and can be useful for understanding the size of a group contrast. They depend on the event frequency in the comparator group and do not by themselves establish causation. A relative risk or odds ratio answers a different question and can make the same data appear different in scale. Those relative measures are not needed to interpret the broad pattern of the posted secondary results.

Why does uncertainty matter?

All estimates from a trial are subject to sampling variation: results can differ across studies even if the underlying effects are similar. A p-value assesses how surprising data at least as extreme as those observed would be under a specified null model and its assumptions. It is not the probability that the null hypothesis is true, nor is it a measure of clinical importance. A large p-value does not establish no effect, especially when estimates are imprecise.

Precision depends on factors such as the amount of outcome information and its variability. For binary outcomes, the number of outcome events is relevant to how precisely a group contrast can be estimated. The posted counts and recalculated intervals show why a direction or apparent separation of arm counts should not be treated as definitive evidence. The registry does not report a protocol-based sample-size justification, so the enrollment figure cannot establish whether the study was designed to detect a particular primary effect.

How should planning illustrations be used?

Planning illustrations based on an observed effect are not observed power and do not show that the trial had a particular chance of detecting a true effect. Their values depend strongly on the effect chosen for planning. The stated calculation assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. Rows describing 100%, 75%, or 50% of the observed effect are hypothetical planning scenarios, not trial findings.

When an observed estimate is close to zero, planning around that estimate can produce very large sample-size illustrations. Such values should not be read as a recommendation or as evidence that a future study must use that size. A clinically meaningful target effect, design details, expected missingness, and an appropriate analysis plan would need to be specified independently. Those matters are not reported in the registry record.

Because the record does not provide the sponsor’s analysis methods, the registry-posted secondary recalculations should be kept distinct from any original trial analysis. The primary comparison is not estimable from the listed summary statistics, and the absence of reported analyses does not establish that no analyses were conducted outside the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists one primary outcome and three secondary outcomes, but does not report a statistical plan describing how these outcomes were prioritized or analyzed. It does not state whether there was a hierarchy among outcomes, whether comparisons were adjusted for multiplicity, or whether any interim analyses were planned or conducted. Those details are not reported in the registry record and should not be inferred from the posted results.

Multiplicity arises when researchers assess multiple outcomes or comparisons. Even when each test uses the same nominal threshold, considering many results can increase the chance that at least one appears noteworthy by chance. A prespecified strategy can address this, for example by identifying a primary comparison or controlling error across a defined family of tests. Without such information, the recalculated secondary p-values are unadjusted and should be interpreted cautiously.

The registry gives arm-level counts for the secondary outcomes, but does not describe missing outcome data, reasons for missingness, or methods used to handle missing observations. The denominators differ across some outcome listings, and the record does not explain why. The number randomized to each arm is not a substitute for an account of which participants contributed to each analysis.

Analysis populations are also not reported in enough detail to determine whether the outcomes were analyzed by intention to treat, per protocol, or another approach. The record does not describe adherence, crossover, exclusions after randomization, or sensitivity analyses. These details affect how an estimate should be interpreted, particularly if the population included in the analysis differs from the randomized population.

Consequently, the registry data do not establish whether missingness or analysis-population choices influenced the results. This is a reporting limitation: it is not evidence that data were missing, that analyses were biased, or that the trial did not follow an analysis plan. The record simply does not report enough information to assess these questions.

11. 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 non-serious adverse event terms

The adverse-event listing records zero serious adverse events affected in each of the three arms and zero deaths in each arm. The registry also records other adverse events affecting 9 participants in the placebo arm, 8 in the orphenadrine arm, and 14 in the methocarbamol arm. These are counts as posted, not a complete comparison of safety risks.

A zero count in a trial does not establish that a serious event cannot occur. Safety estimates are uncertain, and the ability to detect uncommon events depends on the amount and duration of observation. The registry record does not give further detail about event definitions, collection procedures, severity grading, or a comparative statistical analysis. It lists no top serious-event terms.

The counts of other adverse events should not be interpreted as proof that one regimen is safer or less safe than another. The listing does not describe event types or whether participants could contribute more than one event. It also does not report exposure-adjusted analyses or details about follow-up completeness. These figures are therefore descriptive registry counts, not a standalone assessment of comparative safety.

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

The registry record describes a randomized comparison of naproxen combined with orphenadrine or methocarbamol against naproxen with placebo. Its primary outcome is functional impairment at 1 week, measured as change on the RMDQ. The posted mean changes differ across arms, and the confidence intervals express uncertainty around each arm’s estimate. However, the record does not provide an estimable primary two-arm comparison. The arm-level values cannot establish whether either added medication changes functional outcomes relative to the comparator.

The secondary results give counts and unadjusted recalculated contrasts for symptoms, medication use, and satisfaction. Their intervals include zero, and the registry lists no sponsor-reported analyses. This leaves considerable uncertainty about the size and direction of the comparisons. Lack of a clear statistical distinction is not proof of identical effects, while differences in observed counts are not proof of a treatment effect.

The findings apply most directly to the study regimens, population, and 1 week assessment described in the registry. The record does not establish how the results would generalize to other groups, treatment schedules, durations, settings, or outcomes. The primary change-score direction is not specified, and no clinically important threshold is reported, which also limits judgments about practical importance.

These registry results should not be used as medical advice. They provide a limited statistical account of a trial and do not, on their own, settle the comparative benefits or harms of the regimens. A fuller interpretation would require the primary analysis, the protocol and statistical plan, and further details about missing data and analysis populations, none of which are reported in the registry record.

13. Why This Trial Matters Statistically

This study illustrates an important distinction between reporting group summaries and reporting a treatment comparison. Arm-level means can describe the observed outcomes within each group, but the scientific question asks how the assigned regimens compare. Without an estimable primary contrast, readers cannot assess the size and precision of the primary difference directly from the registry record.

It also demonstrates why an outcome’s measurement scale and direction should be explicit. The RMDQ gives a familiar functional measure, and the record explains that higher scores indicate greater impairment. Yet the interpretation of the posted change values depends on a sign convention that the record does not state. That missing detail makes the direction of change harder to explain, even though the arm estimates and intervals are available.

The secondary outcomes show another statistical lesson: multiple measures can provide complementary information, but unadjusted tests across multiple outcomes do not have the same evidential status as a prespecified primary analysis. The counts may be clinically interpretable as descriptions, while the recalculated comparisons remain exploratory in the absence of a reported analysis plan and multiplicity approach.

Finally, the planning illustrations emphasize the dependence of sample-size calculations on the assumed target effect. Calculations based on observed differences are especially unstable when estimates are uncertain or near zero. They are planning scenarios, not retrospective evidence of study power. Clear reporting of the intended effect, analysis, missing-data handling, and comparison estimates is central to assessing what a trial can establish.

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.

Several limitations specific to this record restrict interpretation. The primary outcome is reported by arm, but a two-arm comparison is not estimable from the posted summary statistics. The record does not provide a primary contrast, its confidence interval, or a sponsor-reported primary test. The sign convention for the change score is also not stated, and no threshold for a clinically important RMDQ change is reported.

The registry provides limited information about trial conduct and analysis. Eligibility criteria, the recruitment setting, masking roles, randomization procedures, and the detailed statistical plan are not reported in the registry record. Nor are analysis populations, missing-data methods, adherence information, or sensitivity analyses described. The difference in denominators across some outcomes is not explained.

Secondary comparisons are unadjusted recalculations from posted counts, and the registry reports no sponsor analyses for them. A multiplicity strategy is not reported, so isolated secondary p-values should not be given confirmatory weight. The adverse-event listing is also brief: event definitions and types, ascertainment methods, and comparative safety analyses are not reported.

The record identifies a 1 week assessment, but does not report longer-term outcomes in these results. Accordingly, the posted information does not establish persistence of any observed pattern or allow conclusions about outcomes beyond the specified assessment. These are limitations of what the registry record reports; they do not show that the underlying trial or other records lack further information.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Orphenadrine and Methocarbamol for LBP — NCT02665286.
• Registry record last updated 2018-06-26; status last verified 2018-05.
• Results first posted 2018-06-26.
• 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

NCT02665286 is a completed, randomized, parallel, phase 4 study with quadruple masking, sponsored by Montefiore Medical Center. The registry lists enrollment of 240 and a study start of 2016-03, with primary completion in 2017-04.

The three arms received naproxen with placebo, naproxen with orphenadrine, or naproxen with methocarbamol. The primary outcome was change in RMDQ functional impairment from baseline to 1 week. The posted primary results are arm-level mean estimates with 95% confidence intervals; a two-arm comparison is not estimable from the posted summaries.

Three secondary outcomes are listed at 1 week. Their posted counts permit unadjusted recalculations, but sponsor-reported analyses, multiplicity methods, and details of missing-data handling and analysis populations are not reported in the registry record. Serious adverse events affected zero participants in each listed arm, and deaths were zero in each arm.