Acute Low Back Pain. Topical Diclofenac and Oral Ibuprofen.: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Acute Low Back Pain. Topical Diclofenac and Oral Ibuprofen. (NCT04611529), a randomized phase 4 study. The primary outcome is Change in Pain Disability - Roland Morris Disability Questionnaire (RMDQ) Score.

2. Clinical Question

3. Trial Design

This is a completed, Phase 4, randomized parallel-group study sponsored by Montefiore Medical Center. The registry lists enrollment of 198 participants and a study period beginning 2021-03-02, with primary completion on 2023-06-30. The record describes three assignments: oral ibuprofen 400 mg with topical diclofenac 4 gm; oral ibuprofen 400 mg with topical placebo; and oral placebo with topical diclofenac 4 gm.

The design separates the two treatment routes across the three groups. The combined-treatment group receives both active treatments, while each of the other groups receives one active treatment and one placebo. The registry's primary-result display identifies oral ibuprofen plus topical placebo as the control. This setup allows arm-level results to be viewed across the three assignments, but the posted primary result does not include an estimable two-arm comparison.

The registry reports quadruple masking. Its brief summary describes the study as double-blind and placebo-controlled. These descriptions are both present in the record; the details of who was masked and how masking was implemented are not reported in the registry record.

Outcomes were scheduled for 48 hours and 7 days, according to the brief summary. The primary endpoint covers baseline to 48 hours, and the record lists secondary outcomes concerning pain, medication use, usual activities, healthcare visits, satisfaction, and disability. Details of randomization procedures, allocation concealment, the full protocol, and the planned statistical analysis 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.

Before assignment: In total, 3281 patients were screened for participation and 198 were randomized into the study. 1 patient was excluded post-randomization due to missing RMDQ data.

2-day Follow up

Reasons for not completing this period:

7-day Follow up

Analysis population for the primary outcome, as defined in the registry: 5 participants in the 'Oral ibuprofen + topical diclofenac' group; 6 participants in the 'Oral ibuprofen + topical placebo' group; and 3 participants in the 'Oral placebo + topical diclofenac' group were lost to follow-up (LTFU) prior to the 48 hour assessment timepoints.

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 Change in Pain Disability - Roland Morris Disability Questionnaire (RMDQ) Score, measured over Baseline to 48 hours.

The primary endpoint is change in Pain Disability measured with the Roland-Morris Disability Questionnaire (RMDQ), from baseline to 48 hours. The RMDQ is a 24-item self-report questionnaire about the effects of low-back pain on functional activities. Each item is scored yes or no and contributes one point; the instrument ranges from 0, indicating no disability, to 24, indicating severe disability.

The registry defines change as the baseline RMDQ score minus the score at the 2-day follow-up. Under this definition, a positive value indicates improvement, or less pain-related disability. The posted result is expressed as a mean change with a 95% confidence interval for each arm.

As a general measurement principle, a functional disability score can describe an aspect of a person's experience that is not captured by pain intensity alone. The RMDQ focuses on activity limitations associated with low-back pain. A change score summarizes how the measured score moved over the specified interval; its interpretation depends on the stated scoring direction and timing. Here, the registry supplies both, so positive changes should be read as improvement in disability score, not as a change in pain intensity itself.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The endpoint is continuous: each participant's change is represented by a numerical RMDQ score, and the posted group summaries report means. In general, a mean summarizes the center of a set of measurements. It is useful for describing average change within an arm, but it does not show how much individuals varied or whether a particular participant experienced the average change. The registry reports 95% confidence intervals alongside the means, but does not report a separate measure of participant-level spread.

The direction of the score matters. The registry defines change as baseline score minus the 48-hour score, so positive values represent reduced disability on the questionnaire. This is the reverse of a change definition that subtracts baseline from follow-up. Reading the sign against the registry's definition prevents an otherwise easy reversal of interpretation. The endpoint is a score change, not a direct measurement of pain intensity or a count of activities completed.

What do the confidence intervals show?

As a general statistical explanation, a confidence interval represents the uncertainty associated with an estimate under a specified statistical procedure. Here, each interval accompanies an arm-specific mean change. Narrower intervals generally indicate greater precision than wider intervals, all else equal. These intervals do not describe the full range of participant outcomes. The registry does not state which procedure produced them, so no claim about the exact assumptions or calculation method is warranted.

For a treatment comparison, the central quantity would ordinarily be a contrast between groups, accompanied by an uncertainty interval and potentially a test result. The posted material instead gives separate means and intervals for the three arms. Because the registry says values are missing or not estimable for a two-arm comparison, a comparison should not be reconstructed from the arm summaries. In particular, an apparent difference between two displayed means is not itself a reported inferential result.

What can be learned from the three-arm structure?

The assignments combine active and placebo treatments across oral and topical routes. The combined arm receives active ibuprofen and active diclofenac; the other two arms receive one active treatment and one placebo. This structure creates distinct groups for descriptive review. However, the registry record does not report a factorial analysis, a model that estimates separate route-specific effects, or a formal interaction analysis. The labels and arm-level summaries alone do not establish that such effects were estimated.

The record identifies the primary outcome and its timeframe, but does not report the model, covariates, analysis population, or standard-error method used for a comparative analysis. It also does not report a prespecified superiority or non-inferiority margin. Any description of these as features of the trial's analysis would therefore go beyond what the registry record states.

How should the planning illustration be read?

The sample-size section is a planning illustration based on the observed effect, not the trial's own design calculation. Its stated assumptions are a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect to detect defined as a stated fraction of the observed effect. For non-time-to-event settings, such illustrations are expressed as participants per arm for 80% or 90% power. These figures are hypothetical planning quantities, not observed power and not a report of the trial's actual enrollment target rationale. The sample-size justification used by the trial is not reported in the registry record.

General power calculations describe how often a planned statistical test would be expected to detect an effect of a specified size if the assumptions held. They do not tell whether a completed study's result is true, nor do they supply missing comparative results. Since the posted primary result has no estimable two-arm comparison, a planning illustration should not be presented as evidence that the trial did or did not detect a treatment difference.

Why does variation matter?

In general, greater variation among observations can make a mean less precise, while the amount of information also depends on the number of observed participants and the analysis method. The displayed confidence intervals summarize uncertainty around the means, but the registry does not provide a participant-level distribution or a separate spread estimate for this endpoint. If data were highly skewed or otherwise inconsistent with a method's assumptions, an analysis might need to address that; the record does not report distributional checks or alternative analyses. This is a general consideration, not a claim that such a problem occurred in this trial.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 14 outcome measures and 13 posted secondary outcomes. Those secondary outcomes cover worst low back pain, medication use, pain frequency, return to usual activities, visits to healthcare providers, treatment satisfaction, and RMDQ disability, among other listed measures. With multiple outcomes and timepoints, many statistical comparisons may be of interest. As a general principle, evaluating many hypotheses can increase the chance of finding an apparently noteworthy result by chance unless the analysis plan addresses multiplicity. The registry record does not report a multiplicity adjustment, a hierarchy of secondary outcomes, or a strategy for interpreting multiple tests.

The primary endpoint is identified as change in RMDQ from baseline to 48 hours. The detailed statistical analysis plan, including whether additional timepoints or subgroup analyses were prespecified, is not reported in the registry record. The brief summary mentions assessment at 48 hours and 7 days, but does not describe how results across those times were to be analyzed or prioritized.

For the 48-hour primary assessment, the record identifies participants lost to follow-up before measurement: 5 in the oral ibuprofen plus topical diclofenac group, 6 in the oral ibuprofen plus topical placebo group, and 3 in the oral placebo plus topical diclofenac group. The endpoint summaries use the posted group counts of 60, 60, and 63. The handling of missing observations, including any imputation, complete-case approach, or sensitivity analysis, is not reported in the registry record. The analysis population and any deviations from assigned treatment are also not reported. These omissions make it difficult to assess how missingness might affect interpretation of the arm-level estimates.

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 registry reports serious adverse events and deaths by study group. For the oral ibuprofen plus topical diclofenac group, 0 serious adverse events were reported among 60 participants at risk; for oral ibuprofen plus topical placebo, 0 among 60; and for oral placebo plus topical diclofenac, 0 among 63. Deaths are reported as 0 in each group. The serious adverse event terms list is empty.

Other, non-serious adverse events are listed for 4 participants in the oral ibuprofen plus topical diclofenac group, 3 in the oral ibuprofen plus topical placebo group, and 1 in the oral placebo plus topical diclofenac group. These are the posted counts, not evidence about the cause of each event. The registry record does not provide event descriptions here, and no serious event terms are listed.

As a general statistical point, observing no serious events in a group does not establish that the underlying risk is absent. Safety counts depend on the number observed, the duration and completeness of follow-up, and how events were collected and classified. The record does not report detailed ascertainment procedures or exposure time. These figures describe what was posted for this trial and should not be interpreted as a comprehensive safety assessment.

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

The posted data show positive mean change in RMDQ score from baseline to 48 hours in all three groups, under the registry's definition in which positive change indicates improvement in disability score. The group means and 95% confidence intervals describe the observed arm-level summaries. They do not establish that one assigned treatment produced more improvement than another, because the registry does not report an estimable two-arm comparison for this endpoint.

This distinction is important: within-group change and between-group treatment effect answer different questions. Participants may change over time for many reasons, and a mean change within an arm does not isolate the effect of its assigned treatment. A comparative estimate is needed to quantify how outcomes differ between assignments, with uncertainty around that contrast. The posted results do not supply such an estimate, so claims of superiority, equivalence, or no difference are not supported by the primary results.

The intervals around each mean indicate uncertainty in those group estimates, not the range of individual responses and not a prediction for a new participant. The numbers also refer only to the RMDQ endpoint over the baseline-to-48-hour interval. They do not establish what happened at 7 days, or what occurred for the listed secondary outcomes, even though the registry describes those measures.

Missing 48-hour assessments are noted in all three arms, and the registry does not report how those missing values were handled. As a result, readers cannot assess from this record whether the displayed estimates depend on a particular missing-data assumption. The sample-size section's planning illustrations, where shown, are hypothetical calculations based on stated assumptions; they are not observed power and cannot replace a comparative result.

The appropriate reading is therefore descriptive and bounded: the record presents arm-level mean RMDQ changes with confidence intervals and reports some adverse-event counts. It does not provide the information needed to make a formal comparative claim about the primary endpoint.

13. Why This Trial Matters Statistically

This trial is statistically notable for its three-arm arrangement of oral and topical treatments. The groups are not simply active treatment versus no treatment: one receives both active treatments, while the other two receive one active treatment alongside a placebo for the other route. That arrangement makes clear why a result needs to be interpreted in relation to the precise comparison being estimated. An arm-level average alone does not answer every possible question about the treatment components.

The study also illustrates the difference between a clinically meaningful endpoint and a complete comparative analysis. The RMDQ measures functional disability associated with low-back pain, and the registry clearly defines the direction of change and the assessment interval. Yet the posted primary results are means and confidence intervals by arm, without an estimable two-arm comparison. A well-defined endpoint is essential, but it does not substitute for a reported analysis that directly addresses the treatment contrast.

Multiplicity and missing observations are relevant context. The registry lists multiple secondary outcomes and notes losses to follow-up before the primary assessment. Without a reported multiplicity strategy or missing-data method, readers have limited information for judging how the full set of outcomes was handled. These are not merely technical details: they affect how confidently a set of estimates can be interpreted.

Finally, the record offers an opportunity to distinguish observed results from planning calculations. Sample-size illustrations based on an observed effect can help readers understand hypothetical design requirements, but they are not evidence that a trial was adequately powered or that it detected a treatment effect. Keeping those roles separate is central to sound interpretation of registry results.

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 most important limitation for interpreting the primary endpoint is that the registry posts arm-specific means and confidence intervals but no estimable two-arm comparison. A comparative treatment estimate and its uncertainty are therefore unavailable in the registry record. The displayed summaries support description of each arm, not a formal conclusion about differences between assignments.

The record notes losses to follow-up before the 48-hour assessment: 5 participants in the oral ibuprofen plus topical diclofenac group, 6 in the oral ibuprofen plus topical placebo group, and 3 in the oral placebo plus topical diclofenac group. It does not state how missing measurements were handled, whether sensitivity analyses were performed, or which analysis population was used. This limits assessment of possible missing-data effects.

The registry does not report the statistical model, the method used to construct confidence intervals, adjustment variables, or a detailed analysis plan. It also does not report a multiplicity strategy despite listing multiple outcomes. Protocol details, sample-size justification, interim analyses, and analysis of the 7-day assessment are not reported in the registry record.

The posted results are limited to the specified RMDQ change from baseline to 48 hours. Although the RMDQ has a defined score range and direction, the record does not provide participant-level values or a separate measure of outcome variability. The safety display provides counts but not event descriptions or detailed ascertainment information. These limitations concern what can be learned from the registry record; they do not establish that the trial did or did not collect further information elsewhere.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Acute Low Back Pain. Topical Diclofenac and Oral Ibuprofen. — NCT04611529.
• Registry record last updated 2026-06-11; status last verified 2026-05.
• Results first posted 2024-10-09.
• 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

The registry record describes a completed, randomized, Phase 4 parallel-group study of acute non-radicular low back pain, with enrollment of 198 and sponsor Montefiore Medical Center. It lists three groups: oral ibuprofen 400 mg plus topical diclofenac 4 gm; oral ibuprofen 400 mg plus topical placebo; and oral placebo plus topical diclofenac 4 gm.

The primary outcome is mean change in RMDQ disability score from baseline to 48 hours, with positive change defined as improvement. Posted arm means are 8.7, 10.1, and 6.4, with 95% confidence intervals and endpoint group counts displayed in the results. The registry does not report an estimable two-arm comparison for this continuous outcome. It notes losses to follow-up before the primary assessment and does not report the missing-data method.

The record lists multiple secondary outcomes and reports no serious adverse events or deaths in the displayed groups. The available information supports a descriptive account of the posted endpoint and safety counts, but not a formal comparative conclusion for the primary outcome.