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 Efficacy and Safety of the Lidoderm Patch Applied to Patients With Osteoarthritis of the Knee (NCT00589979), a randomized phase 2 study. The primary outcome is Time-to-Exit From Current Study Treatment.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00589979 |
| Phase | Phase 2 |
| Condition | Osteoarthritis of the Knee |
| Allocation | Randomized |
| Design model | Crossover |
| Masking | Triple |
| Enrollment | 169 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Endo USA Inc., a Keenova Therapeutics Company |
| Results posted | Yes |
2. Clinical Question
Population
The trial concerned patients with osteoarthritis of the knee who had sub-optimal pain relief from their current analgesic regimen. The registry describes 169 participants enrolled. The primary outcome’s modified intent-to-treat population consisted of intent-to-treat participants randomized on or after January 22, 2008. The record does not report further eligibility details in the registry record for this analysis.
Intervention
The active treatment was Lidoderm, a lidocaine 5% patch. The arm description specifies patches measuring 10cm X 14cm on both the front and back of the index knee every 24 hours (q24h). The registry also lists a run-in period with Lidoderm. The duration and other operational details of that run-in are not reported in the registry record.
Comparator
The comparator was a placebo patch, also described as patches measuring 10cm X 14cm on the front and back of the index knee every 24 hours (q24h). The trial is recorded as randomized, triple-masked, and crossover. The treatment sequence, any washout procedures, and the details of masking are not reported in the registry record.
Primary question
The primary endpoint was time-to-exit from the current study treatment, measured in days. Exit occurred when a participant met a specified worsening criterion on the Pain Relief Scale for two consecutive days or discontinued from the study. The clinical question was therefore about the timing of treatment exit under the study conditions, rather than a single end-of-period pain score. Numerical primary outcome estimates and a direct treatment comparison are not reported in the registry record.
3. Trial Design
This was a Phase 2, randomized, triple-masked crossover trial, recorded as completed. Enrollment was 169. The registry gives a start date of 2007-03 and a primary completion date of 2008-06. Endo USA Inc., a Keenova Therapeutics Company, is listed as the sponsor. The trial studied patients with knee osteoarthritis who were experiencing sub-optimal pain relief from their current analgesic regimen.
The active intervention was Lidoderm (lidocaine 5% patch), compared with a placebo patch. Both arm descriptions specify patches applied to the front and back of the index knee every 24 hours (q24h). The primary outcome timeframe refers to baseline and treatment periods, each described as up to 4 weeks ±2 days, or premature discontinuation. The registry also identifies a run-in period with Lidoderm, a double-blind treatment period with Lidoderm, and a double-blind active treatment period with placebo in its adverse-event group descriptions.
In a crossover trial, participants receive more than one treatment during the study, so the treatment comparison may use information from the same participants under different treatment conditions. That is a general description of crossover designs, not a statement about the exact analysis used in this trial. The treatment sequence, period allocation details, washout procedures, and any approach to carryover effects are not reported in the registry record. The record identifies the design as crossover but does not provide enough detail to reconstruct its conduct or analysis.
The registry lists 16 outcome measures and 38 analyses. Named secondary outcomes include time-to-exit due to lack of efficacy, exit status, pain intensity, pain relief, pain quality, patient and investigator global impressions of change, and patient satisfaction. Their numerical results and the prespecified hierarchy among outcomes are not reported in the registry record. The trial’s primary outcome is described across multiple periods or categories, and no single numerical comparison is available in the registry record for this analysis.
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: During the active Run-in Period, eligible patients applied Lidoderm patches every 24 hours for 28 days. During the 12-week Double-blind Treatment Period, patients were randomized to apply Lidoderm patches or matching placebo patches every 24 hours for 4 weeks and then crossed over to the other treatment for the next two 4-week treatment periods.
Run-In Period
| Stage | Run-in Period: Lidoderm | Treatment Sequence: Lidoderm - Placebo - Placebo | Treatment Sequence: Placebo - Lidoderm - Lidoderm |
|---|---|---|---|
| STARTED | 169 | 0 | 0 |
| COMPLETED | 93 | 0 | 0 |
| NOT COMPLETED | 76 | 0 | 0 |
Reasons for not completing this period:
| Reason | Run-in Period: Lidoderm | Treatment Sequence: Lidoderm - Placebo - Placebo | Treatment Sequence: Placebo - Lidoderm - Lidoderm |
|---|---|---|---|
| Adverse Event | 5 | 0 | 0 |
| Protocol Violation | 3 | 0 | 0 |
| Did not qualify for randomization | 54 | 0 | 0 |
| Withdrawal by Subject | 10 | 0 | 0 |
| Informed Consent Withdrawn | 4 | 0 | 0 |
Double-Blind Treatment Period 1
| Stage | Run-in Period: Lidoderm | Treatment Sequence: Lidoderm - Placebo - Placebo | Treatment Sequence: Placebo - Lidoderm - Lidoderm |
|---|---|---|---|
| STARTED | 0 | 50 | 43 |
| COMPLETED | 0 | 48 | 41 |
| NOT COMPLETED | 0 | 2 | 2 |
Reasons for not completing this period:
| Reason | Run-in Period: Lidoderm | Treatment Sequence: Lidoderm - Placebo - Placebo | Treatment Sequence: Placebo - Lidoderm - Lidoderm |
|---|---|---|---|
| Adverse Event | 0 | 1 | 0 |
| Protocol Violation | 0 | 1 | 1 |
| Withdrawal by Subject | 0 | 0 | 1 |
Double-Blind Treatment Period 2
| Stage | Run-in Period: Lidoderm | Treatment Sequence: Lidoderm - Placebo - Placebo | Treatment Sequence: Placebo - Lidoderm - Lidoderm |
|---|---|---|---|
| STARTED | 0 | 48 | 41 |
| COMPLETED | 0 | 47 | 39 |
| NOT COMPLETED | 0 | 1 | 2 |
Reasons for not completing this period:
| Reason | Run-in Period: Lidoderm | Treatment Sequence: Lidoderm - Placebo - Placebo | Treatment Sequence: Placebo - Lidoderm - Lidoderm |
|---|---|---|---|
| Adverse Event | 0 | 1 | 0 |
| Withdrawal by Subject | 0 | 0 | 1 |
| Other | 0 | 0 | 1 |
Double-Blind Treatment Period 3
| Stage | Run-in Period: Lidoderm | Treatment Sequence: Lidoderm - Placebo - Placebo | Treatment Sequence: Placebo - Lidoderm - Lidoderm |
|---|---|---|---|
| STARTED | 0 | 47 | 39 |
| COMPLETED | 0 | 46 | 38 |
| NOT COMPLETED | 0 | 1 | 1 |
Reasons for not completing this period:
| Reason | Run-in Period: Lidoderm | Treatment Sequence: Lidoderm - Placebo - Placebo | Treatment Sequence: Placebo - Lidoderm - Lidoderm |
|---|---|---|---|
| Protocol Violation | 0 | 1 | 0 |
| Withdrawal by Subject | 0 | 0 | 1 |
Analysis population for the primary outcome, as defined in the registry: The modified intent-to treat (MITT) population consisted of all intent-to-treat (ITT) patients who were randomized on or after January 22, 2008. Note: Kaplan-Meier estimates for median time-to-exit from current study treatment could not be calculated for Period 2 or Period 3, because the survival distribution function did not fall below 0.5000.
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 | Sequence: Lidoderm - Placebo - Placebo | Sequence: Placebo - Lidoderm - Lidoderm | Total |
|---|---|---|---|---|
| Participants analysed | 50 | 43 | 93 | |
| Age, Continuous | years | 61.1 (SD 10.0) | 61.1 (SD 10.9) | 61.1 (SD 10.4) |
| Sex: Female, Male: Female | Participants | 32 | 28 | 60 |
| Sex: Female, Male: Male | Participants | 18 | 15 | 33 |
| Region of Enrollment: United States | participants | 50 | 43 | 93 |
6. Primary Endpoint
The registry lists the primary outcome as Time-to-Exit From Current Study Treatment, measured over Baseline, Period 1 (up to 4 weeks ±2 days), Period 2 (up to 4 weeks ±2 days), Period 3 (up to 4 weeks ±2 days), or Premature Discontinuation.
| Element | Registry entry |
|---|---|
| Result type | Median |
| Measure of spread | 95% Confidence Interval |
| Unit | Days |
| Endpoint classification | Time-to-Event Analysis |
The primary endpoint was time-to-exit from the current study treatment, measured in days. The registry defines time-to-exit as the time at which a participant either met the switching criterion or discontinued from the study. The switching criterion was a 2-category change in the Pain Relief Scale score in the worsening direction, for 2 consecutive days. Worsening could mean increasing pain or decreasing pain relief.
The Pain Relief Scale is described as a 9-point categorical scale assessing pain relief in the last 24 hours. Its endpoints are 0, completely worse, and 8, complete pain relief. Thus, the endpoint combines a defined worsening threshold with treatment discontinuation; it is not simply a measurement of pain intensity at one visit. It can summarize how long participants remained on the current treatment before meeting the study’s exit definition. As a general statistical concept, a time-to-event endpoint retains information about when an event occurs, rather than treating all events as if they happened at the same assessment.
The registry reports medians with 95% confidence intervals as the endpoint summary, but numerical estimates are not reported in the registry record. It also states that traditional survival models assuming event times are independent and homogeneous across patients were not suitable for this study. Kaplan-Meier estimates for median time-to-exit could not be calculated for Period 2 or Period 3; the full explanation is not reported in the registry record. The specific rationale for choosing this endpoint is also not reported.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The posted record identifies time-to-exit from the current study treatment as the primary outcome, but it does not include a numerical median, confidence interval, or treatment-effect estimate in the registry record for this analysis. Consequently, the magnitude and precision of the primary treatment comparison cannot be described from the registry information. The record’s endpoint definition clarifies what was counted as exit, but a definition alone does not establish the direction or size of a result.
The event was defined as meeting a worsening threshold on the Pain Relief Scale for two consecutive days or discontinuing from the study. This combined endpoint is important to keep in mind when interpreting any time-to-exit estimate: it is not limited to a worsening score, and it does not provide a separate account of the reasons for discontinuation. A difference in time-to-exit, if reported, would need to be interpreted in the context of the endpoint’s composite definition and the treatment periods used.
The registry states that conventional survival models treating event times as independent and homogeneous across patients were not suitable. It also states that Kaplan-Meier median estimates could not be calculated for Period 2 or Period 3. These notes limit what can be inferred about the analysis from the posted record. The reason the estimates could not be calculated is incomplete in the registry record, and numerical estimates for other periods are not reported in the registry record for this analysis.
The trial is described as randomized, triple-masked, and crossover. These features characterize the intended design, but do not substitute for the missing effect estimate or its uncertainty. In a crossover design, within-participant observations can be relevant to a comparison, but the analysis needs to account appropriately for treatment period and the structure of repeated observations. The registry entries needed to assess those aspects—including treatment sequence, carryover handling, and the specific model—are not reported in the registry record.
The listed secondary outcomes cover pain intensity, pain relief, pain quality, time-to-exit due to lack of efficacy, exit status, and global assessments by patients and investigators, as well as treatment satisfaction. Their presence indicates that the study recorded multiple aspects of treatment experience, but their results cannot be inferred from their names. Numerical values, confidence intervals, and inferential statistics for those measures are not reported in the registry record. Without the result values and the analysis plan, the overall pattern of evidence and its precision cannot be assessed.
Accordingly, the appropriate statistical reading is limited: the registry describes the endpoint and design, and reports adverse-event counts for the listed periods, but the primary efficacy comparison is not numerically available in this record. No conclusion about the size, direction, or statistical uncertainty of an efficacy difference can be drawn from endpoint definitions or design labels alone.
9. Statistical Methods Explained
What does a time-to-event endpoint represent?
Time-to-event analysis concerns the duration until a defined event occurs. In this trial, the event was treatment exit, defined as meeting the switching criterion or discontinuing from the study. The time unit was days. As a general statistical concept, this type of endpoint uses both whether an event occurred and when it occurred. A median time-to-event is the time by which half of the relevant population has experienced the event, if the data and method permit that estimate. A confidence interval describes uncertainty around an estimate under the assumptions of the method; it is not a range containing a fixed proportion of individual participants’ event times.
The registry identifies the reported summary as a median with a 95% confidence interval. Numerical medians and intervals are not reported in the registry record within the registry entries summarized for this analysis. The endpoint is specifically a time to treatment exit, not a time to disease progression or a direct measurement of pain severity. Its meaning depends on the operational exit rule and on how discontinuations were handled.
How was the event defined?
The switching component required a 2-category worsening on the Pain Relief Scale for 2 consecutive days. The scale assesses pain relief over the last 24 hours and ranges from 0, completely worse, to 8, complete pain relief. Worsening was described as increasing pain or decreasing pain relief. Discontinuation from the study also counted as an event. Combining these events can be useful when the study question concerns remaining on a treatment, but it also means that an estimate does not isolate one specific reason for leaving treatment.
As a general principle, the event definition should be read alongside the outcome estimate. If several kinds of events are combined, a single summary can conceal differences in the event types. Separate counts or analyses by reason can help clarify the pattern, but those details are not reported in the registry record for this primary outcome.
Why might standard survival methods be unsuitable?
The registry explicitly states that traditional survival models assuming event times are independent and homogeneous across patients were not suitable for this study. In general, independence means that one participant’s event-time information does not provide unmodeled dependence with another’s; homogeneity refers to assumptions that event-time patterns are sufficiently alike across participants for the chosen model. Repeated treatment periods and the crossover structure can create complexities for event-time analysis. This is general statistical context, not a reconstruction of the trial’s specific analysis.
The specific statistical method used for the primary endpoint is not reported in the registry record. The record also says Kaplan-Meier estimates for median time-to-exit could not be calculated for Period 2 or Period 3. It does not fully state why those estimates were unavailable. The absence of an estimable median for those periods should not be treated as evidence that no events occurred or that treatment groups were equivalent; it is a limitation on the reported summary.
What does crossover add to the analysis?
In general, a crossover design allows participants to receive more than one treatment over different periods. This can make within-participant comparisons possible, because each participant may contribute information under multiple conditions. Such data also require attention to period effects, order of treatment, and potential carryover from one period to another. The registry identifies this study as randomized and crossover, but its treatment sequence, washout details, and handling of period or carryover effects are not reported in the registry record. The design label alone does not establish which comparison model was used.
The registry describes a Lidoderm run-in and double-blind periods with Lidoderm and placebo in the adverse-event group labels. The exact relationship between these periods, the randomization sequence, and the primary endpoint analysis is not specified in the registry record. Therefore, the period descriptions should not be used to infer a particular analysis population or participant flow.
How should confidence intervals and significance be read?
As a general concept, a confidence interval expresses the statistical uncertainty around an estimate under a specified method and its assumptions. A narrower interval indicates greater precision than a wider interval, while both the estimate and interval are needed to understand the possible range of effects compatible with the analysis. A confidence interval does not remedy limitations in the outcome definition, design, or analysis.
No numerical primary estimate or confidence interval is reported in the registry record within the registry entries summarized for this analysis, and no p-value for the primary comparison is reported. It is therefore not possible to assess the estimate’s precision or statistical compatibility with a null value from these registry entries. The registry’s description of the planned endpoint summary does not provide the missing numerical result.
What do the planning assumptions mean?
The record describes sample-size illustrations based on a fraction of the observed effect, a two-sided significance level of 0.05, equal allocation, and a normal approximation. For time-to-event illustrations, the stated quantity is the total number of events using the Schoenfeld approach; other illustrations are expressed as participants per arm. These are planning illustrations, not observed power and not a report of the trial’s original design justification. The actual illustration values are not reported in the registry record for this analysis. The trial’s own sample-size justification is not reported in the registry record.
As a general concept, planning calculations ask how much information a future study might need under specified assumptions. They do not show that a completed study had a particular probability of detecting an effect, and they do not replace interpretation of the observed estimate and its uncertainty. The effect size used for a planning illustration may be uncertain, especially when based on an observed result. The registry’s full statistical plan, including any interim analyses or prespecified modeling choices, is not reported in the registry record.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 16 outcome measures and 38 analyses. The outcomes include time-to-exit and exit status, pain intensity and relief, pain quality, patient and investigator impressions of change, and treatment satisfaction. When a study evaluates many outcomes or analyses, the chance of at least one apparently notable result can increase if each is interpreted separately. As a general statistical principle, prespecified outcome hierarchies or multiplicity adjustments can address that concern. The registry record does not report whether such procedures were planned or used, nor does it report a testing hierarchy among the listed outcomes.
The primary outcome description defines a modified intent-to-treat population as intent-to-treat participants randomized on or after January 22, 2008. Further details about the intent-to-treat population, exclusions, and participant flow are not reported in the registry record. The record’s use of a modified population therefore cannot be evaluated fully in the registry record.
Rules for missing measurements, censoring, or handling participants who discontinued are not reported in the registry record. Discontinuation itself was part of the primary endpoint definition, but that does not explain how other incomplete observations were treated or how participants without a qualifying event were handled. The registry says Kaplan-Meier median estimates could not be calculated for Period 2 or Period 3; it does not provide a complete explanation in the registry record for this analysis. The specific analysis method, sensitivity analyses, and handling of repeated periods are also not reported.
These gaps matter because multiplicity, missingness, and the analysis population affect how confidently one can interpret a reported estimate. In this case, numerical primary outcome results are not reported in the registry record within the registry entries summarized for this analysis, so the effect and its uncertainty cannot be assessed independently of those methodological details.
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 |
|---|---|---|---|
| Run-In Period With Lidoderm (Lidocaine 5% Patch) | 1 | 169 | 0.6% |
| Double-Blind Treatment Period With Lidoderm | 1 | 91 | 1.1% |
| Double-Blind Active Treatment Period With Placebo | 1 | 91 | 1.1% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0.5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Run-In Period With Lidoderm (Lidocaine 5% Patch) | 51 of 169 |
| Double-Blind Treatment Period With Lidoderm | 24 of 91 |
| Double-Blind Active Treatment Period With Placebo | 23 of 91 |
Most frequent serious adverse event terms
| Event term | Organ system | Run-In Period With Lidoderm (Lidocaine 5% Patch) | Double-Blind Treatment Period With Lidoderm | Double-Blind Active Treatment Period With Placebo |
|---|---|---|---|---|
| Pneumonia | Infections and infestations | 1 of 169 | 0 of 91 | 1 of 91 |
| Supraventricular extrasystoles | Cardiac disorders | 0 of 169 | 1 of 91 | 0 of 91 |
| Respiratory failure | Respiratory, thoracic and mediastinal disorders | 0 of 169 | 0 of 91 | 1 of 91 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Run-In Period With Lidoderm (Lidocaine 5% Patch) | Double-Blind Treatment Period With Lidoderm | Double-Blind Active Treatment Period With Placebo |
|---|---|---|---|---|
| Nasopharyngitis | Infections and infestations | 3 of 169 | 2 of 91 | 3 of 91 |
| Sinusitis | Infections and infestations | 2 of 169 | 2 of 91 | 3 of 91 |
| Application site reaction | General disorders | 1 of 169 | 4 of 91 | 1 of 91 |
| Application site erythema | General disorders | 2 of 169 | 1 of 91 | 2 of 91 |
| Diarrhoea | Gastrointestinal disorders | 2 of 169 | 0 of 91 | 2 of 91 |
| Headache | Nervous system disorders | 3 of 169 | 1 of 91 | 0 of 91 |
| Oedema peripheral | General disorders | 2 of 169 | 1 of 91 | 0 of 91 |
| Upper respiratory tract infection | Infections and infestations | 1 of 169 | 2 of 91 | 0 of 91 |
| Constipation | Gastrointestinal disorders | 2 of 169 | 1 of 91 | 0 of 91 |
| Chest wall pain | Musculoskeletal and connective tissue disorders | 2 of 169 | 1 of 91 | 0 of 91 |
Serious events with the highest arm-level rate: pneumonia (1.1%), supraventricular extrasystoles (1.1%), respiratory failure (1.1%).
The registry lists adverse-event groups for a Lidoderm run-in period and double-blind periods with Lidoderm and placebo. The reported numbers at risk are 169 for the run-in group and 91 for each double-blind group. Serious adverse events affected 1 participant in each of the three groups. The other adverse-event counts are 51 in the run-in group, 24 in the Lidoderm double-blind group, and 23 in the placebo double-blind group.
The listed serious adverse-event terms are pneumonia, supraventricular extrasystoles, and respiratory failure, each reported as 1.1%. These terms and percentages should be read as registry-reported entries; they do not establish causation or a comparative risk. The group labels refer to different study periods, and participants may contribute to more than one period in a crossover study. The counts should not be added to infer a number of unique participants affected. The registry record does not report the deaths values in the registry record.
As a general statistical principle, adverse-event counts describe events or affected participants as defined in the record; interpretation also depends on exposure, observation time, event definitions, and completeness of reporting. Those additional details are not reported in the registry record. These figures describe the posted safety entries and do not, by themselves, establish a treatment effect on safety.
12. What the Result Does, and Does Not, Mean
The trial record describes a randomized, triple-masked crossover comparison of Lidoderm (lidocaine 5% patch) with a placebo patch in patients with knee osteoarthritis and sub-optimal pain relief from their current analgesic regimen. It defines a primary endpoint that combines time to a specified worsening threshold with discontinuation. These details establish what the study set out to evaluate and how the principal event was defined.
They do not establish the direction or magnitude of any treatment difference. Numerical primary endpoint results, including median estimates and confidence intervals, are not reported in the registry record within the registry entries summarized for this analysis. The results for the listed secondary outcomes are also not reported in the registry record. Without estimates and their uncertainty, the record cannot support a numerical account of the primary comparison or its precision.
The adverse-event entries provide counts for the named study periods and list three serious adverse-event terms at 1.1% each. These are descriptive entries, not a complete comparative safety analysis. The periods arise within a crossover design, and the counts should not be interpreted as unique people across the entire trial. Additional details needed to assess exposure, event timing, and causality are not reported in the registry record.
As a general principle, a completed trial is not interpreted solely from its design label or endpoint definition. Interpretation depends on the observed estimates, uncertainty, population analyzed, missing-data handling, and analysis methods. Several of those elements are not reported in the registry record. The evidence therefore supports a careful description of the design and outcome definitions, but not a conclusion about treatment efficacy or comparative safety.
Nor do the planning assumptions establish the trial’s observed power. The record describes planning illustrations based on a fraction of an observed effect, but the numerical illustrations are not reported in the registry record for this analysis, and they are not substitutes for the observed treatment effect. The trial’s own sample-size justification is not reported in the registry record.
13. Why This Trial Matters Statistically
This trial raises a useful statistical issue: a clinically meaningful endpoint can be a time until a prespecified treatment decision rather than a measurement at a single visit. Here, treatment exit was triggered by a defined worsening pattern on the Pain Relief Scale or by discontinuation. Such an endpoint captures timing, but its interpretation depends on both components and on how the study handles repeated treatment periods.
The crossover design adds another methodological layer. As a general matter, participants receiving multiple treatments can contribute within-participant information, but the analysis must account for the structure of treatment periods and sequence. The registry identifies the design but does not report the sequence, washout procedures, or model details needed to evaluate those issues. Its statement that traditional survival models were unsuitable underscores that a familiar analysis cannot simply be assumed to fit every time-to-event outcome.
The record also illustrates the difference between an endpoint definition and an endpoint result. It gives a detailed definition of time-to-exit and states that medians with 95% confidence intervals were the intended summaries, yet numerical primary estimates are not reported in the registry record for this analysis. A reader can understand what the outcome represents without being able to assess the treatment contrast or its precision.
Finally, the number of listed outcome measures and analyses makes multiplicity relevant as a general concern. The registry does not report a testing hierarchy or adjustment strategy. Without those details and the numerical results, a complete account of the statistical evidence is not possible. The trial is therefore informative for discussing endpoint construction, crossover analysis, and registry reporting, while its treatment-effect findings cannot be quantified from the registry record.
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 main limitation for interpreting this trial from the registry record is that numerical estimates for the primary endpoint are not reported in the registry record for this analysis. Although the outcome is described as a median time-to-exit with a 95% confidence interval, the estimates and intervals themselves are unavailable. Numerical results for the secondary outcomes are likewise not reported in the registry record within these registry entries. The direction, size, and precision of the treatment comparison therefore cannot be evaluated.
The endpoint combines meeting a worsening criterion with discontinuation. The registry defines the worsening threshold but does not report separate results by reason for exit. Thus, the record does not permit separation of exits associated with worsening pain relief from other discontinuations. The complete rationale for the endpoint is not reported in the registry record.
The registry says that traditional survival models assuming event-time independence and homogeneity were unsuitable, and that Kaplan-Meier estimates could not be calculated for Period 2 or Period 3. The reason for the latter is not fully reported in the registry record. The specific primary analysis method, treatment sequence, washout details, and handling of period or carryover effects are not reported in the registry record for this analysis.
The modified intent-to-treat population is defined by randomization on or after January 22, 2008, but participant flow and further analysis-population details are not reported in the registry record. Missing-data rules, multiplicity procedures, and sensitivity analyses are also not reported. These gaps limit assessment of the robustness of any result. The registry’s listed adverse-event counts are period-specific; the record does not provide the additional exposure and event details needed for a fuller comparative safety interpretation.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Efficacy and Safety of the Lidoderm Patch Applied to Patients With Osteoarthritis of the Knee — NCT00589979.
- Registry record last updated 2017-10-05; status last verified 2017-09.
- Results first posted 2010-09-22.
- 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
The registry record describes NCT00589979, a completed Phase 2, randomized, triple-masked crossover trial sponsored by Endo USA Inc., a Keenova Therapeutics Company. It enrolled 169 patients with osteoarthritis of the knee who had sub-optimal pain relief from their current analgesic regimen. The study began in 2007-03, with primary completion in 2008-06.
The active treatment was Lidoderm (lidocaine 5% patch), compared with a placebo patch. Both were described as applied to the front and back of the index knee every 24 hours (q24h). The primary endpoint was time-to-exit from the current study treatment, defined by a worsening criterion on the Pain Relief Scale or study discontinuation. The record lists multiple secondary outcomes addressing pain and treatment impressions.
Numerical primary outcome estimates and secondary outcome results are not reported in the registry record for this analysis. The registry states that conventional survival models were unsuitable and that Kaplan-Meier median estimates could not be calculated for Period 2 or Period 3. Adverse-event counts are reported for the listed periods, but further details needed for a complete comparative interpretation are not reported in the registry record.