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 Study to Determine the Safety and the Efficacy of Fasinumab Compared to Placebo and Nonsteroidal Anti-inflammatory Drugs (NSAIDs) for Treatment of Adults With Pain From Osteoarthritis of the Knee or Hip (NCT03304379), a randomized phase 3 study. The primary outcome is Change From Baseline in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Scores up to Week 24 in Participants Treated With Fasinumab Compared to Placebo.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT03304379 |
| Phase | Phase 3 |
| Condition | Osteoarthritis, Knee, Osteoarthritis, Hip |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Triple |
| Enrollment | 1650 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Regeneron Pharmaceuticals |
| Results posted | Yes |
2. Clinical Question
Population
Adults with pain due to osteoarthritis of the knee or hip. The registry record describes the primary outcome population as a modified full analysis set, including randomized participants in the full analysis set but excluding participants from four sites. The remainder of the population description is incomplete in the registry record.
Intervention
Fasinumab, with the primary outcome population description identifying the 1mg arm. The registry lists additional fasinumab regimens, including 3mg Q4W and 6mg Q8W. Detailed descriptions of all dosing regimens are not reported in the registry record.
Comparator
Matching placebo for the primary comparison. The trial also included NSAID comparisons, and the listed interventions include diclofenac and celecoxib. The registry record does not describe the allocation of those NSAIDs to specific arms in detail.
Primary question
How did the change from baseline in WOMAC pain score up to Week 24 differ between participants treated with fasinumab and placebo? The registry record identifies this as the primary endpoint but does not report its numerical estimates, confidence intervals, or p-values.
3. Trial Design
This was a phase 3, randomized, triple-masked, parallel-group study of fasinumab for pain due to osteoarthritis of the knee or hip. The registry lists an enrollment of 1650 and records the study as completed. The listed start date is 2017-10-26, and the primary completion date is 2019-12-13. These dates describe the registry record and do not, by themselves, explain the timing or conduct of individual analyses.
The primary objective was to evaluate fasinumab against placebo when administered for up to 24 weeks. Secondary objectives included comparisons with NSAIDs and assessments of safety and tolerability against placebo and NSAIDs. The intervention list names fasinumab, diclofenac, celecoxib, and matching placebo. Safety results are listed for placebo, NSAIDs, fasinumab 1mg Q4W, fasinumab 3mg Q4W, and fasinumab 6mg Q8W. The registry record does not give full descriptions of the four dosing-regimen arms, so their detailed treatment schedules and the mapping of all listed interventions to those regimens are not reported in the registry record.
Random allocation and masking can reduce some sources of bias in comparisons, but they do not establish that groups were balanced on every measured or unmeasured factor. The specific randomization procedure, allocation concealment details, and masking roles are not reported in the registry record. The record lists six analyses and 18 outcome measures. It does not report the statistical analysis plan in enough detail to establish which model or adjustment procedure generated the primary estimate, or how the different outcomes and comparisons were handled together.
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 May 2018, the sponsor implemented an urgent safety measure to stop dosing for participants randomized to Fasinumab (6 mg and 3 mg), to prevent further randomization to these regimens across the Fasinumab program based on review of unblinded data in an ongoing study R475-PN-1523 (NCT02683239). Participants from Fasinumab 3 mg and 6 mg group were moved directly into the 20-week follow-up period.
Overall Study
| Stage | Placebo | NSAIDs | Fasinumab 1 mg | Fasinumab 3 mg | Fasinumab 6 mg |
|---|---|---|---|---|---|
| STARTED | 308 | 612 | 612 | 59 | 59 |
| Full Analysis Set (FAS) | 308 | 612 | 612 | 0 | 0 |
| Safety Analysis Set (SAF) | 309 | 609 | 609 | 0 | 0 |
| Urgent Safety Measure Set (USMS) | 0 | 0 | 0 | 59 | 59 |
| Completed Treatment | 218 | 436 | 454 | 0 | 0 |
| COMPLETED | 238 | 471 | 463 | 42 | 42 |
| NOT COMPLETED | 70 | 141 | 149 | 17 | 17 |
Reasons for not completing this period:
| Reason | Placebo | NSAIDs | Fasinumab 1 mg | Fasinumab 3 mg | Fasinumab 6 mg |
|---|---|---|---|---|---|
| Protocol Violation | 8 | 10 | 5 | 0 | 2 |
| Adverse Event | 4 | 20 | 17 | 1 | 0 |
| Lack of Efficacy | 17 | 16 | 20 | 0 | 0 |
| Physician Decision | 6 | 10 | 6 | 9 | 10 |
| Withdrawal by Subject | 26 | 58 | 66 | 3 | 5 |
| Lost to Follow-up | 8 | 24 | 35 | 4 | 0 |
| Death | 1 | 2 | 0 | 0 | 0 |
| Other | 0 | 1 | 0 | 0 | 0 |
Analysis population for the primary outcome, as defined in the registry: This outcome measure examined only placebo vs. fasinumab 1mg arms. Here, "Number of Subjects Analysed" signifies those subjects who were evaluable for this endpoint. Modified full analysis set (mFAS) includes all randomized participants in FAS but excludes participants from 4 sites for which there were potential concerns regarding data quality, identified prior to database lock.
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 | Placebo | NSAIDs | Fasinumab 1 mg | Fasinumab 3 mg | Fasinumab 6 mg | Total |
|---|---|---|---|---|---|---|---|
| Participants analysed | 308 | 612 | 612 | 59 | 59 | 1650 | |
| Age, Continuous | Years | 62.0 (SD 9.30) | 62.3 (SD 9.41) | 62.1 (SD 9.13) | 62.8 (SD 9.38) | 61.5 (SD 9.55) | 62.2 (SD 9.28) |
| Sex: Female, Male: Female | Participants | 222 | 418 | 436 | 36 | 34 | 1146 |
| Sex: Female, Male: Male | Participants | 86 | 194 | 176 | 23 | 25 | 504 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 20 | 44 | 31 | 5 | 10 | 110 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 285 | 568 | 581 | 54 | 49 | 1537 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 3 | 0 | 0 | 0 | 0 | 3 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 0 | 2 | 0 | 0 | 2 |
| Race (NIH/OMB): Asian | Participants | 33 | 57 | 54 | 8 | 3 | 155 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 1 | 0 | 1 | 0 | 0 | 2 |
| Race (NIH/OMB): Black or African American | Participants | 60 | 134 | 132 | 12 | 16 | 354 |
| Race (NIH/OMB): White | Participants | 202 | 396 | 405 | 39 | 40 | 1082 |
| Race (NIH/OMB): More than one race | Participants | 11 | 24 | 18 | 0 | 0 | 53 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 1 | 1 | 0 | 0 | 0 | 2 |
| Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Score | Score on a scale | 6.42 (SD 1.394) | 6.38 (SD 1.344) | 6.46 (SD 1.321) | 6.43 (SD 1.401) | 6.54 (SD 1.279) | 6.42 (SD 1.344) |
| WOMAC Physical Function Subscale Scores | Score on a scale | 6.40 (SD 1.495) | 6.32 (SD 1.418) | 6.39 (SD 1.462) | 6.50 (SD 1.350) | 6.34 (SD 1.392) | 6.37 (SD 1.445) |
6. Primary Endpoint
The registry lists the primary outcome as Change From Baseline in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Scores up to Week 24 in Participants Treated With Fasinumab Compared to Placebo, measured over Baseline up to Week 24.
| Element | Registry entry |
|---|---|
| Result type | Least Squares Mean |
| Measure of spread | Standard Error |
| Unit | Score on a Scale |
| Endpoint classification | Continuous Endpoint |
The primary endpoint was change from baseline in the Western Ontario and McMaster Universities Osteoarthritis Index pain subscale up to Week 24, comparing fasinumab with placebo. The subscale uses five questions about pain due to osteoarthritis in the index knee or hip during the past 48 hours. Each question is scored on a numerical rating scale from 0, no pain, to 10, higher pain; the subscale score is the mean of the five question scores. Higher scores indicate more pain.
Change from baseline expresses how a participant’s score at follow-up differs from the starting score. In this endpoint, the treatment comparison is about the average change over the specified period, rather than a count of participants reaching a particular threshold. The registry identifies the reported summary measure as a least-squares mean and its dispersion as a standard error. A least-squares mean is generally a model-based average; the precise model and covariate adjustments used for this estimate are not reported in the registry record.
This measure is used to quantify pain on a common scale and to compare average score changes between randomized groups. Its interpretation depends on the estimated between-group contrast, its uncertainty, the analysis population, and how missing observations were handled. The primary endpoint’s numerical results are not reported in the registry record, so the direction, size, and precision of the observed contrast cannot be described from this record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record identifies a primary comparison of fasinumab 1mg with placebo for change from baseline in WOMAC pain score up to Week 24. It does not report the least-squares mean changes for either group, the estimated between-group difference, a confidence interval, or a p-value. As a result, the observed primary treatment contrast cannot be quantified or classified as favoring either group from the information in the registry record.
This distinction matters because naming an endpoint and its analysis population is not the same as reporting its result. Without the estimated contrast, readers cannot assess how large the average difference was. Without a confidence interval or other uncertainty measure for the contrast, readers cannot judge how compatible the data are with a range of possible effects. The endpoint’s standard error is identified as the dispersion measure, but the numerical standard errors are not reported in the registry record.
The record does list several secondary outcomes, including WOMAC pain and physical function comparisons with NSAIDs, patient global assessment, walking pain, and adjudicated arthropathy outcomes. It also states that the primary objective concerned placebo comparison and that NSAID comparisons were secondary objectives. However, numerical estimates for those outcomes are not reported in the registry record either. Their listing does not establish whether the outcomes were analyzed, what the estimates were, or how their uncertainty was assessed.
The overall enrollment was 1650, but that number should not be treated as the number analyzed for the primary endpoint. The record says the endpoint population was a modified full analysis set and indicates that participants from four sites were excluded; it also says the number analyzed refers to participants evaluable for the endpoint. The number analyzed in each primary comparison group is not reported in the registry record. The explanation for excluding those sites and the consequences for the analysis are not fully reported in the registry record.
Accordingly, the registry information supports a description of the question, design, outcome definition, and some safety counts, but not a conclusion about the magnitude or precision of the primary efficacy estimate. This is a limit of the reported information, not evidence that the comparison showed no difference. No numerical result should be inferred from the trial’s completion status, its enrollment, or the planned endpoint.
9. Statistical Methods Explained
The record describes the study as randomized, triple-masked, and parallel-group. In general, randomization assigns participants to groups using a chance-based process, helping make group comparisons less vulnerable to systematic differences at baseline. Masking is intended to limit the influence of treatment knowledge on participants, clinicians, or outcome assessment, depending on who is masked. The registry identifies triple masking but does not specify the roles covered by that description or the operational details of masking. These design features support fair comparisons in principle; they do not guarantee that missing data, protocol deviations, or other sources of bias were absent.
What does change from baseline represent?
For a continuous outcome such as a pain score, change from baseline compares a participant’s follow-up value with that participant’s starting value. The trial’s primary measure was based on the five-item WOMAC pain subscale, with higher scores indicating higher pain. A group-level mean change describes the average observed or model-estimated change among the participants included in the analysis. A contrast between group means describes how those average changes differ. Neither quantity is available numerically in the registry record for the primary comparison.
The stated summary measure is a least-squares mean. In general, least-squares means are model-based group averages, often adjusted for variables included in a statistical model. The particular model, included covariates, treatment of repeated measurements, and assumptions used to estimate the primary result are not reported in the registry record. It is therefore not possible to determine from this record whether the estimate was adjusted for baseline score or other factors, or how observations across follow-up visits contributed to it.
How should uncertainty be understood?
A standard error describes the estimated sampling variability of an estimate under the assumptions of its statistical model. It is not the same as the spread of individual participants’ scores. A confidence interval is generally used to convey a range of values compatible with the data and analysis at a stated confidence level. A narrow interval indicates greater precision than a wide interval, while an interval’s location relative to a null value can inform statistical interpretation. The primary numerical standard error, confidence interval, and p-value are not reported in the registry record, so these concepts cannot be applied to quantify the trial’s primary result.
Statistical significance and clinical importance are also different considerations. A p-value, when reported, addresses compatibility with a specified null hypothesis under the analysis assumptions; it does not measure the size or practical importance of an effect. An estimate can be interpreted fully only with its magnitude and uncertainty, alongside a relevant context for judging the outcome. Neither a numerical primary estimate nor a threshold for clinical importance is reported in the registry record.
Why can over-dispersion matter?
For count outcomes, a simple model may assume that the variability in counts follows a particular relationship to their average. Over-dispersion means the observed variability is greater than that model expects. If not handled appropriately, uncertainty estimates can be too small and statistical tests can appear more decisive than warranted. This is a general consideration for count data, not a description of a method used in this trial. The registry record does not report enough detail to determine whether over-dispersion was assessed or how count outcomes were modeled.
The primary endpoint is continuous, while several secondary and safety outcomes are counts or percentages. Their methods need not be the same as the primary continuous-outcome method. The statistical procedures used for each outcome, including any distributional assumptions, model diagnostics, or robust variance methods, are not reported in the registry record.
What do the planning illustrations mean?
Sample-size illustrations based on an observed effect are planning calculations, not evidence about the probability that the completed trial detected an effect. In general, such calculations ask how many participants per arm might be needed under stated assumptions to detect an effect of a specified size. The stated assumptions for the illustrations include a two-sided significance level of 0.05, equal allocation, a normal approximation, and an effect defined as a fraction of the observed effect. These are planning assumptions, not evidence that the trial itself used those assumptions.
The sample-size assumptions also distinguish participants per arm for continuous outcomes from total event counts for time-to-event outcomes. No numerical planning results are reported in the registry record. The trial’s enrollment of 1650 is an enrolled total, not a substitute for an analysis-specific sample size and not a measure of observed power. The trial’s own sample-size justification is not reported in the registry record.
Likewise, the registry record does not report whether interim analyses were planned or conducted, whether any stopping rules applied, or whether the final analysis differed from a prespecified plan. Such details can affect interpretation of estimates and error rates, but should not be inferred when they are absent.
10. Multiplicity, Missing Data and Analysis Populations
The study registered 18 outcome measures and lists six analyses. Multiple outcomes, treatment groups, time points, and pairwise comparisons can create a multiplicity issue: when many statistical tests are considered, the chance of at least one apparently unusual result can increase. Statistical plans may address this through a hierarchy, adjustment procedure, or prespecified distinction between confirmatory and exploratory comparisons. The registry record does not report whether such a strategy was used, which comparisons were included in any testing hierarchy, or how multiplicity was handled. The primary outcome’s several categories or time points are not reduced to a single comparison in the recorded analysis description.
Missing outcome data can also affect a group comparison. The record describes a modified full analysis set for the primary endpoint, states that it includes randomized participants in the full analysis set, and excludes participants from four sites. It further defines the number analyzed as those evaluable for the endpoint. The complete rationale for the site exclusions, the number of participants with missing Week 24 scores, and the methods used to address missing values are not reported in the registry record. The handling of discontinuations and other post-randomization events is not reported either.
These omissions make it difficult to assess whether the analyzed participants represent the randomized groups and how sensitive the primary estimate might be to missingness or exclusions. The detailed statistical analysis plan, including definitions of analysis populations and any sensitivity analyses, is not reported in the registry record. The absence of those details does not establish that the analyses were inappropriate; it limits what can be evaluated from the registry information.
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 |
|---|---|---|---|
| Placebo | 20 | 309 | 6.5% |
| NSAIDs | 45 | 609 | 7.4% |
| Fasinumab 1mg Q4W | 35 | 609 | 5.7% |
| Fasinumab 3mg Q4W | 5 | 58 | 8.6% |
| Fasinumab 6mg Q8W | 2 | 59 | 3.4% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Placebo | 1 of 309 |
| NSAIDs | 3 of 609 |
| Fasinumab 1mg Q4W | 1 of 609 |
| Fasinumab 3mg Q4W | 0 of 58 |
| Fasinumab 6mg Q8W | 0 of 59 |
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 |
|---|---|
| Placebo | 121 of 309 |
| NSAIDs | 263 of 609 |
| Fasinumab 1mg Q4W | 261 of 609 |
| Fasinumab 3mg Q4W | 17 of 58 |
| Fasinumab 6mg Q8W | 15 of 59 |
Most frequent serious adverse event terms
| Event term | Organ system | Placebo | NSAIDs | Fasinumab 1mg Q4W | Fasinumab 3mg Q4W | Fasinumab 6mg Q8W |
|---|---|---|---|---|---|---|
| Rapidly progressive osteoarthritis | Musculoskeletal and connective tissue disorders | 2 of 309 | 0 of 609 | 8 of 609 | 2 of 58 | 2 of 59 |
| Osteoarthritis | Musculoskeletal and connective tissue disorders | 3 of 309 | 6 of 609 | 1 of 609 | 1 of 58 | 0 of 59 |
| Knee arthroplasty | Surgical and medical procedures | 1 of 309 | 4 of 609 | 2 of 609 | 1 of 58 | 0 of 59 |
| Joint arthroplasty | Surgical and medical procedures | 1 of 309 | 3 of 609 | 1 of 609 | 0 of 58 | 0 of 59 |
| Hip arthroplasty | Surgical and medical procedures | 1 of 309 | 3 of 609 | 1 of 609 | 0 of 58 | 0 of 59 |
| Atrial fibrillation | Cardiac disorders | 1 of 309 | 2 of 609 | 0 of 609 | 0 of 58 | 0 of 59 |
| Prostate cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 0 of 309 | 2 of 609 | 1 of 609 | 0 of 58 | 0 of 59 |
| Gastrointestinal haemorrhage | Gastrointestinal disorders | 0 of 309 | 0 of 609 | 2 of 609 | 0 of 58 | 0 of 59 |
| Cellulitis | Infections and infestations | 0 of 309 | 2 of 609 | 0 of 609 | 0 of 58 | 0 of 59 |
| Femur fracture | Injury, poisoning and procedural complications | 1 of 309 | 0 of 609 | 1 of 609 | 0 of 58 | 0 of 59 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Placebo | NSAIDs | Fasinumab 1mg Q4W | Fasinumab 3mg Q4W | Fasinumab 6mg Q8W |
|---|---|---|---|---|---|---|
| Headache | Nervous system disorders | 48 of 309 | 107 of 609 | 95 of 609 | 2 of 58 | 2 of 59 |
| Arthralgia | Musculoskeletal and connective tissue disorders | 36 of 309 | 78 of 609 | 82 of 609 | 4 of 58 | 3 of 59 |
| Urinary tract infection | Infections and infestations | 25 of 309 | 35 of 609 | 50 of 609 | 1 of 58 | 2 of 59 |
| Back pain | Musculoskeletal and connective tissue disorders | 17 of 309 | 44 of 609 | 46 of 609 | 1 of 58 | 1 of 59 |
| Nasopharyngitis | Infections and infestations | 22 of 309 | 38 of 609 | 29 of 609 | 2 of 58 | 1 of 59 |
| Upper respiratory tract infection | Infections and infestations | 15 of 309 | 30 of 609 | 30 of 609 | 3 of 58 | 1 of 59 |
| Blood creatine phosphokinase increased | Investigations | 3 of 309 | 5 of 609 | 5 of 609 | 3 of 58 | 3 of 59 |
| Ligament sprain | Injury, poisoning and procedural complications | 2 of 309 | 4 of 609 | 5 of 609 | 0 of 58 | 3 of 59 |
| Muscle strain | Injury, poisoning and procedural complications | 0 of 309 | 4 of 609 | 6 of 609 | 3 of 58 | 1 of 59 |
Serious events with the highest arm-level rate: rapidly progressive osteoarthritis (3.4%), arthralgia (1.7%), osteoarthritis (1.7%), knee arthroplasty (1.7%), atrioventricular block complete (1.7%).
The registry lists serious adverse event counts alongside the number at risk for each group. The listed counts are 20 among 309 participants for placebo, 45 among 609 for NSAIDs, 35 among 609 for fasinumab 1mg Q4W, 5 among 58 for fasinumab 3mg Q4W, and 2 among 59 for fasinumab 6mg Q8W. Death counts are listed as 1, 3, 1, 0, and 0, respectively. These are descriptive counts; they do not by themselves establish whether an event was caused by treatment.
The registry also lists other adverse event counts: 121 among 309 for placebo, 263 among 609 for NSAIDs, 261 among 609 for fasinumab 1mg Q4W, 17 among 58 for fasinumab 3mg Q4W, and 15 among 59 for fasinumab 6mg Q8W. Differences in group size and exposure can affect the interpretation of raw counts. The record does not give exposure-adjusted rates or sufficient detail about event timing and duration to support those comparisons.
Among the listed serious-event terms, rapidly progressive osteoarthritis is shown as 3.4%; arthralgia, osteoarthritis, knee arthroplasty, complete atrioventricular block, and subchondral insufficiency fracture are each shown as 1.7%. The registry record does not provide enough context to establish the denominator or to attribute these events to a treatment. These figures should be read as reported event information, not as a causal comparison.
12. What the Result Does, and Does Not, Mean
The record establishes that a randomized, triple-masked phase 3 study was conducted to compare fasinumab with placebo and NSAIDs in adults with pain due to knee or hip osteoarthritis. It defines the primary endpoint as change in WOMAC pain score up to Week 24 and gives the score’s construction and direction. It also records enrollment, several secondary outcomes, and descriptive safety counts.
It does not report the primary endpoint’s group estimates or between-group contrast. There is therefore no basis in the registry record for describing how much the groups differed, which group had the more favorable mean change, or how precise the estimate was. The trial being completed and having an enrollment of 1650 do not answer those questions. Nor does the existence of a planned primary outcome establish what its result was.
Similarly, the listed safety counts do not by themselves determine comparative risk or causation. The groups differ in their listed numbers at risk, and the record does not provide all the information needed to interpret exposure, event timing, severity detail, or adjustment for group size. A count of events should not be read as proof that treatment caused an event, or that an event was unrelated to treatment.
In general, results from a randomized study apply most directly to the participants, treatments, outcome definitions, and follow-up represented in the analysis. The registry identifies adults with knee or hip osteoarthritis and a primary follow-up period up to Week 24, but it does not supply enough primary result and analysis detail to evaluate the observed effect or its generalizability. The detailed dosing regimens, complete analysis populations, and missing-data methods are also not fully reported in the registry record.
The appropriate statistical conclusion is therefore limited: the registry record documents the trial question and design, but not the numerical primary result needed to judge the efficacy comparison. This is not a finding of no effect. It is a statement that the primary estimate and its uncertainty are not reported in the registry record.
13. Why This Trial Matters Statistically
This trial is statistically notable as a randomized, triple-masked, parallel-group phase 3 study with placebo and NSAID comparisons. Its primary endpoint is a continuous pain score, while the registered secondary outcomes span pain response thresholds, patient global assessment, physical function, walking pain, and adjudicated joint events. The range of outcomes illustrates why statistical interpretation depends on more than identifying a single p-value: endpoint definitions, analysis populations, missing data, and multiplicity all matter.
The primary endpoint also demonstrates why an outcome’s measurement details are essential. The WOMAC pain subscale aggregates five questions about pain in the previous 48 hours, and higher values indicate greater pain. A mean change can summarize average group experience, but an estimate should be considered with its uncertainty and with information about who contributed data. The registry identifies the summary measure and an analysis population description, but does not report the numerical contrast or complete analysis details.
The safety information adds a separate statistical perspective. Raw counts are easy to read, but group sizes differ and counts alone do not express exposure-adjusted comparisons or establish causality. The posted serious adverse event and other adverse event counts can describe what was recorded, yet they cannot replace a full account of timing, follow-up, and comparative analysis.
Finally, the registry record shows the difference between trial completion and transparent result reporting. A completed study with a large enrollment still requires estimates, uncertainty measures, analysis details, and missing-data information for readers to assess its findings. Here, the design and outcome definitions are described, but the central efficacy estimate is not reported in the registry record. That gap limits statistical interpretation without implying any particular result.
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 consequential limitation for interpreting efficacy is that the registry record does not report numerical results for the primary endpoint. The least-squares means, their between-group contrast, standard errors, confidence intervals, and p-values are not reported in the registry record. The direction, magnitude, and precision of the primary comparison therefore cannot be assessed.
The primary analysis population description is incomplete. It identifies a modified full analysis set and exclusion of participants from four sites, but the reason for those exclusions and the remainder of the population description are not reported in the registry record. The numbers analyzed in each group are not reported either. The overall enrollment should not be treated as the endpoint-specific analysis size.
Detailed descriptions of the dosing-regimen arms are not reported in the registry record, despite the listing of four regimen labels. The relationship among all listed interventions, regimens, and analysis groups is not fully explained. The statistical model, covariate adjustment, missing-data approach, sensitivity analyses, and handling of protocol deviations are not reported in the registry record.
The record lists many outcome measures and analyses but does not state how multiplicity was addressed, whether interim analyses occurred, or what sample-size justification was used for the trial. Numerical results for secondary efficacy outcomes are also not reported in the registry record. Safety counts are available, but fuller exposure and event-timing information is not reported in the registry record. These limitations restrict evaluation of efficacy and safety comparisons; they do not establish that the study’s analyses or conduct were deficient.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Study to Determine the Safety and the Efficacy of Fasinumab Compared to Placebo and Nonsteroidal Anti-inflammatory Drugs (NSAIDs) for Treatment of Adults With Pain From Osteoarthritis of the Knee or Hip — NCT03304379.
- Registry record last updated 2023-02-24; status last verified 2023-01.
- Results first posted 2023-02-24.
- 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
NCT03304379 is a completed phase 3 randomized, triple-masked, parallel-group study of fasinumab in adults with pain due to osteoarthritis of the knee or hip. The registry lists enrollment of 1650, a start date of 2017-10-26, and a primary completion date of 2019-12-13. Its primary objective was comparison of fasinumab with placebo over up to 24 weeks; secondary objectives included NSAID comparisons and safety and tolerability assessments.
The primary endpoint was change from baseline in WOMAC pain score up to Week 24, analyzed as a least-squares mean with standard error identified as the dispersion measure. The score averages five pain questions, with higher scores indicating higher pain. The registry describes the primary population as a modified full analysis set, including an exclusion of participants from four sites.
Although the outcome definition and design are recorded, the primary numerical estimate and its uncertainty are not reported in the registry record. The record also lists secondary outcomes and descriptive adverse event counts, but does not provide sufficient statistical detail to fully assess multiplicity, missing data, or the analysis methods.