This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for BOTOX® Efficacy and Safety in the Treatment of Knee Osteoarthritis (NCT02230956), a randomized phase 2 study. The primary outcome is Change From Baseline in the 7-Day Average Daily Pain Score Using an 11-Point Scale.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02230956 |
| Phase | Phase 2 |
| Condition | Osteoarthritis |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Triple |
| Enrollment | 176 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Allergan |
| Results posted | Yes |
2. Clinical Question
Population
Participants with knee osteoarthritis were enrolled in a study with a total enrollment of 176. The registry record does not report further eligibility details, such as disease severity or other characteristics defining who could take part.
Intervention
Participants received a single intra-articular injection of onabotulinumtoxinA into the study knee on Day 1. The two dose groups were 200 U and 400 U.
Comparator
The comparator was placebo, described as a Normal Saline injection into the intra-articular space of the study knee on Day 1.
Primary question
The primary outcome was change from baseline in the 7-day average daily pain score, measured on an 11-point scale, at Baseline and Week 8. The record defines a negative change as improvement. It does not report the numerical results needed to compare change between either onabotulinumtoxinA dose and placebo.
3. Trial Design
This was a Phase 2, randomized, triple-masked, parallel trial of onabotulinumtoxinA for knee osteoarthritis. The registry lists 176 participants enrolled and identifies Allergan as the sponsor. The study status is Completed. Its recorded start was 2014-10, and its primary completion was 2016-03.
The three treatment groups were onabotulinumtoxinA 400 U, onabotulinumtoxinA 200 U, and placebo. Each treatment description specifies a single injection into the intra-articular space of the study knee on Day 1. The placebo was Normal Saline. The record does not identify which parties were masked, so the meaning of triple masking in terms of specific roles is not reported in the registry record.
In general, random allocation is intended to make treatment groups comparable at the start of a trial, while masking can limit the influence of treatment knowledge on care or assessment. These are general purposes, not evidence that groups were balanced on every characteristic or that masking was maintained throughout this trial. The registry record does not report the allocation procedure or details about how masking was implemented.
The stated primary endpoint was a mean change in a continuous pain score, with standard deviation as the measure of dispersion. The listed secondary outcomes include WOMAC pain and physical function scores, Patient Global Impression of Change, and a 7-day average daily worst pain score. Although the record lists five outcome measures, it does not provide a numerical primary outcome comparison. The actual analyzed sample sizes for the primary endpoint 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
| Stage | OnabotulinumtoxinA 400 U | OnabotulinumtoxinA 200 U | Placebo |
|---|---|---|---|
| STARTED | 44 | 43 | 89 |
| COMPLETED | 39 | 37 | 82 |
| NOT COMPLETED | 5 | 6 | 7 |
Reasons for not completing this period:
| Reason | OnabotulinumtoxinA 400 U | OnabotulinumtoxinA 200 U | Placebo |
|---|---|---|---|
| Adverse Event | 1 | 1 | 0 |
| Lack of Efficacy | 1 | 1 | 1 |
| Lost to Follow-up | 1 | 1 | 2 |
| Personal Reasons | 2 | 1 | 1 |
| Protocol Violation | 0 | 1 | 1 |
| Other Miscellaneous Reason | 0 | 1 | 2 |
Analysis population for the primary outcome, as defined in the registry: Safety population consisted of all randomized participants who received the study treatment and were analyzed by treatment actually received.
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.
| Characteristic | Unit | OnabotulinumtoxinA 400 U | OnabotulinumtoxinA 200 U | Placebo | Total |
|---|---|---|---|---|---|
| Participants analysed | 44 | 43 | 89 | 176 | |
| Age, Continuous | years | 60.7 (SD 8.25) | 60.2 (SD 8.41) | 61.1 (SD 7.79) | 60.8 (SD 8.02) |
| Sex: Female, Male: Female | Participants | 30 | 26 | 51 | 107 |
| Sex: Female, Male: Male | Participants | 14 | 17 | 38 | 69 |
6. Primary Endpoint
The registry lists the primary outcome as Change From Baseline in the 7-Day Average Daily Pain Score Using an 11-Point Scale, measured over Baseline, Week 8.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Standard Deviation |
| Unit | score on a scale |
| Endpoint classification | Continuous Endpoint |
The primary endpoint measures change from baseline in the 7-day average daily pain score on an 11-point scale. Participants recorded their knee pain during the previous 24 hours in a daily diary, with 0 meaning no pain and 10 meaning the worst pain possible. The daily scores over 7-days were averaged. The registry specifies Baseline and Week 8 as the timeframe and states that a negative change from baseline indicates improvement.
Averaging daily reports is a way to represent pain across multiple days rather than relying on one diary entry. In general, a continuous score can capture differences in degree, not only whether an event occurred. The average describes the group’s central outcome, while the standard deviation describes how much individual scores vary around that average. Neither statistic by itself establishes whether treatment groups differ.
The registry identifies this measure as the primary outcome, but does not report group means, changes, a between-group contrast, or uncertainty estimates for the endpoint. Therefore the magnitude and precision of any treatment comparison cannot be described from the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record establishes the trial’s comparison: two single-dose intra-articular onabotulinumtoxinA groups versus a Normal Saline placebo group, with pain change assessed at Week 8. It also defines the direction of the endpoint: a negative change from baseline indicates improvement. These design and measurement details explain what the planned primary outcome represents, but they do not establish the observed treatment effects.
Numerical results for the primary endpoint are not reported in the registry record. In particular, the registry does not report the group-specific baseline or Week 8 scores, mean changes, treatment contrasts, confidence intervals, or p-values. Without those values, the size and direction of any difference between either dose and placebo cannot be assessed. The precision of a possible difference is also unknown. The result should not be inferred from the trial’s completion status, enrollment, or safety counts.
In general, an estimate of a treatment contrast describes how far apart the group outcomes are on the outcome scale. A confidence interval describes uncertainty around that estimate; a narrower interval generally indicates greater precision than a wider interval. A p-value addresses compatibility between data and a specified null hypothesis under an analysis model, but does not express the magnitude or clinical importance of a difference. These general interpretations cannot be applied to this trial’s primary effect because those statistics are not reported.
The record identifies the primary analysis population as the safety population: randomized participants who received study treatment and were analyzed by the treatment actually received. That description does not give the number included in each primary outcome analysis or explain how the analyzed population was applied to the Week 8 endpoint. Those details are not reported in the registry record.
The listed secondary outcomes broaden the range of measured experiences, but their numerical results are not included in the record. No conclusion about those measures can be drawn from their titles alone. Likewise, safety counts are distinct from evidence about the primary pain outcome and cannot substitute for an efficacy comparison. The statistical interpretation is therefore limited to the trial design, endpoint definition, and recorded adverse-event counts; the primary outcome’s observed effect remains unreported.
9. Statistical Methods Explained
What does the endpoint’s mean represent?
The primary outcome is identified as a mean, or average, of a continuous score. In general, a mean gives a summary of the observed scores in a group, while the standard deviation describes their spread. A mean change can describe the group’s average movement from its starting score, but a comparison of means between groups is needed to estimate a treatment contrast. The registry record does not report the group means or mean changes for the primary endpoint.
Why does the scale direction matter?
The pain diary uses an 11-point scale, with 0 meaning no pain and 10 meaning the worst pain possible. The record states that a negative change from baseline indicates improvement. This direction convention is important because the sign of a change is meaningful only when the scale and subtraction direction are understood. The actual changes are not reported in the registry record, so the direction of the observed result cannot be determined.
What can a confidence interval tell a reader?
In general, a confidence interval gives a range of values compatible with the data and the statistical procedure used. It communicates uncertainty around an estimate, rather than simply classifying a result as statistically significant or not. The interval’s width is relevant to precision, and its location relative to a null value is relevant to a test of no difference. No confidence interval or treatment contrast for the primary endpoint is reported in the registry record. There is therefore no trial-specific interval to interpret.
What does randomization contribute?
In general, randomized allocation is used to reduce systematic differences in treatment assignment and support a fair comparison of groups. It does not guarantee that every characteristic is balanced in a particular trial, especially in the realized groups. The record labels allocation as randomized but does not report the sequence-generation or allocation-concealment methods. It is not possible to describe those procedures in more detail.
What does triple masking mean statistically?
The record labels the trial triple-masked. In general, masking can reduce the influence of treatment expectations on participants, clinical care, and outcome assessment. However, the registry does not state which parties were masked or how masking was maintained. Those implementation details are not reported in the registry record; no specific claim about the masked roles can be made.
How should dispersion be understood?
The endpoint is described using standard deviation. In general, standard deviation summarizes the amount of variation among individual values around the group mean. It is not the same as the uncertainty around the mean, and it does not alone show whether groups differ. A complete interpretation of a mean comparison would also need the estimated between-group difference and an uncertainty measure. Those primary outcome statistics are not reported in the registry record.
Why can over-dispersion matter?
As a general statistical concept, over-dispersion occurs when observed variability is greater than a model assumes. If a model underestimates variability, its uncertainty estimates can be too small and inferential conclusions can be unreliable. The primary endpoint is a continuous mean score with standard deviation, and the record does not describe an over-dispersion model or report diagnostics. It would be inappropriate to assume that over-dispersion was assessed or relevant to the analysis.
What do the planning assumptions mean?
In general, a sample-size illustration based on a stated effect, significance level, allocation, and approximation describes a planning scenario under those assumptions. It is not observed power and does not show that the trial had a particular probability of detecting an effect after the data were collected. The registry record includes assumptions for a planning illustration based on the observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It does not report a trial-specific sample-size justification or the calculated planning values. Those values should not be treated as the trial’s own design rationale.
The record states that the effect in the illustration is a stated fraction of the observed effect. No resulting planning numbers are available in the registry record. Such illustrations depend on their assumptions and do not replace interpretation of the trial’s actual estimates and uncertainty.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists five outcome measures, including the primary pain endpoint and secondary measures of WOMAC pain, WOMAC physical function, Patient Global Impression of Change, and 7-day average daily worst pain. Assessing several outcomes can raise a multiplicity question: when many statistical comparisons are made, the chance of at least one apparently unusual result can increase. In general, study plans may address this by defining a primary comparison, using an adjustment, or interpreting secondary analyses as exploratory. The registry record does not report whether a multiplicity adjustment or other strategy was planned or used.
The primary outcome is described as having several categories or time points and is not reduced to one comparison in the registry. Consequently, a single primary contrast is not available for interpretation. The statistical analysis plan, the specific comparisons tested, and any interim analyses are not reported in the registry record.
Missing-data handling is also not reported in the registry record. The record does not explain how absent diary entries, incomplete follow-up, or missing Week 8 scores were treated, if any occurred. It does not report imputation methods, sensitivity analyses, or assumptions about missingness.
The stated safety population consisted of all randomized participants who received study treatment and were analyzed by treatment actually received. The record does not report how many participants contributed data to each primary or secondary outcome analysis, whether any participants were excluded from those analyses, or how analysis populations were defined beyond that safety-population description. These omissions limit assessment of attrition, analysis denominators, and the robustness of the outcome findings.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| OnabotulinumtoxinA 400 U | 6 | 44 | 13.6% |
| OnabotulinumtoxinA 200 U | 4 | 43 | 9.3% |
| Placebo | 6 | 89 | 6.7% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| OnabotulinumtoxinA 400 U | 9 of 44 |
| OnabotulinumtoxinA 200 U | 15 of 43 |
| Placebo | 26 of 89 |
Most frequent serious adverse event terms
| Event term | Organ system | OnabotulinumtoxinA 400 U | OnabotulinumtoxinA 200 U | Placebo |
|---|---|---|---|---|
| Osteoarthritis | Musculoskeletal and connective tissue disorders | 0 of 44 | 0 of 43 | 2 of 89 |
| Cerebrovascular accident | Nervous system disorders | 1 of 44 | 0 of 43 | 0 of 89 |
| Dizziness | Nervous system disorders | 1 of 44 | 0 of 43 | 0 of 89 |
| Basal ganglia infarction | Nervous system disorders | 0 of 44 | 1 of 43 | 0 of 89 |
| Incision site infection | Infections and infestations | 1 of 44 | 0 of 43 | 0 of 89 |
| Pneumonia | Infections and infestations | 1 of 44 | 0 of 43 | 0 of 89 |
| Chronic obstructive pulmonary disease | Respiratory, thoracic and mediastinal disorders | 1 of 44 | 0 of 43 | 0 of 89 |
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | 0 of 44 | 1 of 43 | 0 of 89 |
| Retinal detachment | Eye disorders | 1 of 44 | 0 of 43 | 0 of 89 |
| Constipation | Gastrointestinal disorders | 1 of 44 | 0 of 43 | 0 of 89 |
Most frequent non-serious adverse event terms
| Event term | Organ system | OnabotulinumtoxinA 400 U | OnabotulinumtoxinA 200 U | Placebo |
|---|---|---|---|---|
| Arthralgia | Musculoskeletal and connective tissue disorders | 4 of 44 | 9 of 43 | 9 of 89 |
| Nasopharyngitis | Infections and infestations | 3 of 44 | 2 of 43 | 8 of 89 |
| Joint swelling | Musculoskeletal and connective tissue disorders | 0 of 44 | 4 of 43 | 4 of 89 |
| Osteoarthritis | Musculoskeletal and connective tissue disorders | 1 of 44 | 2 of 43 | 5 of 89 |
| Hypertension | Vascular disorders | 1 of 44 | 3 of 43 | 2 of 89 |
Serious events with the highest arm-level rate: basal ganglia infarction (2.3%), pulmonary embolism (2.3%), atrial fibrillation (2.3%), muscle strain (2.3%), cerebrovascular accident (2.3%).
The adverse-event record lists the number at risk and the number affected for serious and other adverse events in each group. For onabotulinumtoxinA 400 U, the serious-adverse-event figures are 44 at risk and 6 affected; the other-adverse-event figures are 44 at risk and 9 affected. For onabotulinumtoxinA 200 U, the corresponding figures are 43 and 4 for serious events, and 43 and 15 for other events. For placebo, they are 89 and 6 for serious events, and 89 and 26 for other events.
These are registry counts, not a statistical comparison. The record does not provide adjusted comparisons, uncertainty intervals, or a definition of whether the affected counts represent people, events, or both. The groups also have different numbers at risk, so the counts alone should not be read as comparable rates. Death counts are not reported in the registry record.
The listed serious-event terms each have a recorded frequency of 2.3%: Basal ganglia infarction, Pulmonary embolism, Atrial fibrillation, Muscle strain, Cerebrovascular accident, and Dizziness. The record does not specify the group allocation for these terms in the available information. The listed terms and counts do not establish causation or determine an overall benefit-risk judgment.
12. What the Result Does, and Does Not, Mean
The record describes a randomized comparison of two onabotulinumtoxinA doses with placebo for knee osteoarthritis, using a diary-based average pain score as the primary endpoint. It defines the score scale, the follow-up timeframe, and the direction in which a change is interpreted. These registry entries establish what the trial set out to measure, but they do not reveal the primary outcome result.
The numerical primary endpoint results are not reported in the registry record. Therefore, the direction, magnitude, and precision of any difference between the treatment groups cannot be determined from the record. No claim that either dose did or did not change pain relative to placebo is supported by the posted information. A completed trial and a stated endpoint are not substitutes for outcome estimates.
The adverse-event counts offer descriptive safety information, but they do not establish whether an event was caused by treatment or whether groups differ statistically. Counts by themselves do not account for uncertainty or provide a complete comparison. The registry also does not report deaths, missing-data methods, or the actual outcome-analysis populations in sufficient detail for those questions.
In general, clinical interpretation of a trial result considers the estimated effect, its precision, the outcome’s meaning, the study design, and the completeness of reporting. That general framework cannot fill gaps in the numerical results. The record supports a description of trial structure and the reported adverse-event figures; it does not support a conclusion about the treatment effect on the primary pain endpoint.
13. Why This Trial Matters Statistically
This trial illustrates why endpoint definitions and result reporting must be read together. The registry specifies a diary-based measure, an 11-point scale, a 7-day average, and assessment at Baseline and Week 8. It also defines negative change as improvement. Those details make the intended measurement interpretable, but without the observed group results there is no estimate to interpret.
For statistical readers, the distinction between a within-group change and a between-group contrast is important. In general, a group may change over time for reasons that do not distinguish the assigned treatments. A treatment comparison requires an estimate of how outcomes differ between groups, along with information about its uncertainty. The registry does not report these primary endpoint estimates.
The record also highlights the importance of analysis transparency. The population is described as randomized participants who received study treatment and were analyzed by treatment actually received, while outcome-specific denominators and missing-data procedures are not reported. Such details help readers understand which observations inform an estimate and how incomplete data could affect it.
Finally, the trial lists multiple outcomes and three groups, but the record does not report a multiplicity strategy or a single reduced primary comparison. This leaves the analysis structure unclear. These are general statistical considerations, not evidence that a particular method was or was not used. The central statistical lesson is that a detailed endpoint description and safety counts cannot replace the effect estimates and analysis details needed to evaluate the primary question.
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 principal limitation of the registry information is that the numerical primary outcome results are not reported. Group means, changes from baseline, treatment contrasts, confidence intervals, and p-values are not available. As a result, the primary pain comparison cannot be quantitatively interpreted.
The primary outcome is described across categories or time points and is not reduced to one comparison in the record. The analysis plan, specific contrasts, and multiplicity handling are not reported. Outcome-specific sample sizes and methods for missing diary or Week 8 data are also not reported in the registry record. These gaps make it difficult to assess the analysis population and the effect of incomplete outcome data.
The record labels the study randomized and triple-masked but does not describe the randomization procedure, allocation concealment, or which parties were masked. It also does not report eligibility details beyond the knee osteoarthritis context, or the characteristics of the enrolled participants. These details should not be inferred from the trial title or design labels.
Safety information is limited to recorded counts and listed event terms. The registry does not provide uncertainty estimates, comparative analyses, attribution, or the group distribution for the listed serious-event terms. Death counts are not reported. The recorded counts therefore provide only a limited descriptive view and do not support a causal interpretation.
The registry includes assumptions for a planning illustration but not its calculated values or a trial-specific design justification. The illustration should not be mistaken for observed power or evidence about the primary result.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: BOTOX® Efficacy and Safety in the Treatment of Knee Osteoarthritis — NCT02230956.
- Registry record last updated 2017-05-31; status last verified 2017-05.
- Results first posted 2017-04-20.
- 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.
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18. Record Summary
NCT02230956 is a completed Phase 2 randomized, triple-masked, parallel trial sponsored by Allergan, with 176 participants enrolled. It compared single intra-articular injections of onabotulinumtoxinA 400 U and 200 U with Normal Saline placebo for knee osteoarthritis.
The primary outcome was change from baseline in the 7-day average daily pain score on an 11-point scale at Week 8; negative change was defined as improvement. The registry record describes the endpoint and safety counts but does not report numerical primary outcome results, a treatment contrast, or its precision. It also does not report the missing-data approach, multiplicity strategy, or outcome-specific analysis sample sizes. Safety counts are descriptive, and death counts are not reported in the registry record.