This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record.
1. Trial at a Glance
FACT OA1 was a randomized, parallel-group, triple-masked phase 3 study evaluating the safety and efficacy of fasinumab compared with placebo and naproxen in adults with pain from osteoarthritis of the knee or hip. The registry reports 3,307 participants and four registered primary endpoints, all assessed as changes in WOMAC pain or physical-function scores from baseline to Week 16.
| Feature | FACT OA1 |
|---|---|
| Trial name | FACT OA1 |
| NCT identifier | NCT03161093 |
| Phase | Phase 3 |
| Status | Completed |
| Therapeutic area | Immunology & Rheumatology |
| Conditions | Osteoarthritis, Knee; Osteoarthritis, Hip |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Triple |
| Primary purpose | Treatment |
| Enrollment | 3,307 |
| Lead sponsor | Regeneron Pharmaceuticals |
| Sponsor type | Industry |
| Primary endpoint type | Binary |
| Results posted | Yes |
| Statistical analyses posted | 4 |
2. Clinical Question
The central efficacy question was whether fasinumab produced greater improvement in osteoarthritis pain and physical function than placebo at Week 16. The registered primary endpoints separately evaluated the WOMAC Pain Subscale and WOMAC Physical Function Subscale for the fasinumab 1 mg Q4W and 1 mg Q8W regimens.
Population
Adults with pain from osteoarthritis of the knee or hip.
Intervention
Fasinumab, with registered regimens including 1 mg SC Q4W and 1 mg SC Q8W in the primary efficacy comparisons.
Comparator
Placebo. The study also included naproxen as a registered intervention.
Primary question
How did the change from baseline to Week 16 in WOMAC pain and physical-function scores compare between fasinumab and placebo?
3. Trial Design
Registered interventions
Fasinumab
- Registered as a drug intervention.
- Primary efficacy analyses included fasinumab 1 mg SC Q4W.
- Primary efficacy analyses also included fasinumab 1 mg SC Q8W.
Naproxen
- Registered as a drug intervention.
- The registry also lists fasinumab-matching placebo and naproxen-matching placebo.
4. Endpoints
The registry lists four primary endpoints. Each measures change in a WOMAC subscale from baseline to Week 16. Two endpoints evaluate fasinumab 1 mg Q4W versus placebo, and two evaluate fasinumab 1 mg Q8W versus placebo.
| Primary endpoint | Time frame | Comparison |
|---|---|---|
| Change in the WOMAC Pain Subscale Scores From Baseline to Week 16 in Participants Treated With Fasinumab 1mg SC Q4W Compared With That of Participants Treated With Placebo | Baseline to Week 16 | Placebo vs Fasinumab 1 mg SC Q4W |
| Change in the WOMAC Physical Function Subscale Scores From Baseline to Week 16 in Participants Treated With Fasinumab 1mg Q4W Compared With That of Participants Treated With Placebo | Baseline to Week 16 | Placebo vs Fasinumab 1 mg Q4W |
| Change in the WOMAC Pain Subscale Scores From Baseline to Week 16 in Participants Treated With Fasinumab 1mg SC Q8W Compared With That of Participants Treated With Placebo | Baseline to Week 16 | Placebo vs Fasinumab 1 mg SC Q8W |
| Change in the WOMAC Physical Function Subscale Scores From Baseline to Week 16 in Participants Treated With Fasinumab 1mg Q8W Compared With That of Participants Treated With Placebo | Baseline to Week 16 | Placebo vs Fasinumab 1 mg SC Q8W |
WOMAC measurement
The WOMAC index is comprised of 24 parameters grouped into three subscales: pain, physical function, and stiffness. The pain subscale contains five questions, the physical-function subscale contains 17 questions, and the stiffness subscale contains two questions. Each question uses a 0–10 grading scale.
The scores for each subscale are summed and divided by the number of questions, with each subscale reported using a Numerical Rating Scale score of 0–10. The total WOMAC score is the sum of normalized subscale scores divided by three and is also reported on a 0–10 scale. Higher scores indicate worse pain, stiffness, and functional limitations.
Because higher WOMAC scores indicate worse symptoms and limitations, a negative between-group difference in change favors the fasinumab group when the comparison is defined as fasinumab minus placebo. The posted estimates are negative for all four primary analyses.
5. Analysis Populations
The primary efficacy analyses used analysis populations specified in the registry for the relevant fasinumab dose groups. The analysis population matters because the treatment effect estimate applies to the participants included in that particular analysis rather than automatically to every person enrolled in the study.
| Primary analysis | Analysis population |
|---|---|
| Fasinumab 1 mg Q4W | Modified Full Analysis Set (mFAS). The mFAS excluded additional participants from the Full Analysis Set due to regional irregularities noted in some study sites and was the main analysis population for efficacy endpoints for the fasinumab 1 mg Q4W group. The registry defines “n” as the number of evaluable participants at the specified point in time. |
| Fasinumab 1 mg Q8W | mFAS Post Protocol Amendment 5 analysis set. For the analysis of the fasinumab 1 mg Q8W group compared with the control groups, only the subset of participants concurrently randomized after Protocol R475-OA-1611 Amendment 5 Global was implemented were included. |
The registry also identifies intention-to-treat analysis as a concept in the analysis text for the Q4W primary analyses. The exact posted estimates, however, are explicitly tied to the modified analysis populations described above.
6. Statistical Methodology
Mixed-effects model for repeated longitudinal measurements
The registry identifies a Mixed Models Analysis as the method for all four posted primary analyses and normalizes the method as a mixed-effects model within the longitudinal/mixed-model family. This is appropriate for an endpoint based on repeated measurements over time because the model can use information across the longitudinal outcome trajectory rather than reducing the analysis to a single observed value.
The registry does not provide enough information in the posted statistical-analysis fields to reproduce the full covariance specification or every model term. The important reported feature is that the primary analyses used a mixed-model framework and reported least-squares mean estimates.
Least-squares mean
The effect measure reported by the registry is the Least Squares Mean, with the effect measure identified as a mean difference. A least-squares mean is a model-adjusted mean: it represents the estimated mean outcome for a treatment group under the fitted model rather than simply the arithmetic average of observed values.
Superiority hypothesis
All four posted primary analyses are identified as superiority analyses. The objective is therefore to estimate whether the fasinumab group and placebo group differ in the direction specified by the endpoint, rather than to establish that two treatments are sufficiently similar within a predefined non-inferiority margin.
Confidence intervals
Each primary estimate is accompanied by a two-sided 95% confidence interval. The interval describes statistical uncertainty around the estimated between-group difference under the analysis model. It is not a prediction interval for individual patients and does not describe the amount of symptom change that every participant experienced.
P-values
The posted p-values quantify evidence against the relevant null hypothesis under the specified statistical framework. They do not measure the magnitude of the treatment effect. The magnitude is better described by the estimated mean difference and its confidence interval.
7. Results
The registry reports four formal statistical analyses corresponding exactly to the four registered primary endpoints. All four use a mixed-model analysis and report least-squares mean estimates with two-sided 95% confidence intervals.
7.1 WOMAC Pain — Fasinumab 1 mg SC Q4W vs Placebo
Least-squares mean difference
95% CI: −1.028 to −0.324 · P = 0.0002
Endpoint: change in WOMAC Pain Subscale score from baseline to Week 16.
| Element | Reported result |
|---|---|
| Comparison | Placebo vs Fasinumab 1 mg SC Q4W |
| Time frame | Baseline to Week 16 |
| Analysis method | Mixed Models Analysis |
| Analysis population | Modified Full Analysis Set |
| Effect measure | Least Squares Mean; normalized as mean difference |
| Estimate | −0.68 |
| 95% CI | −1.028 to −0.324 |
| P-value | 0.0002 |
| Hypothesis | Superiority |
The estimated difference in change was −0.68. Because higher WOMAC scores indicate worse pain, a negative treatment-versus-placebo difference represents greater improvement in the fasinumab group under the reported analysis.
The 95% confidence interval extends from −1.028 to −0.324. The interval remains below zero, so the range of model-based estimates represented by this confidence interval is consistently in the direction of greater improvement with fasinumab.
The P = 0.0002 result addresses evidence against the null hypothesis; it does not mean that the treatment effect is “0.02%” or otherwise quantify the size of benefit. The estimate and confidence interval are the appropriate quantities for describing magnitude and precision.
The result applies to the specified mFAS analysis population and Week 16 endpoint. It does not by itself establish how the effect changes beyond Week 16, how individual patients respond, or whether the magnitude is clinically important for every participant.
7.2 WOMAC Physical Function — Fasinumab 1 mg Q4W vs Placebo
Least-squares mean difference
95% CI: −1.046 to −0.346 · P < 0.0001
Endpoint: change in WOMAC Physical Function Subscale score from baseline to Week 16.
| Element | Reported result |
|---|---|
| Comparison | Placebo vs Fasinumab 1 mg Q4W |
| Time frame | Baseline to Week 16 |
| Analysis method | Mixed Models Analysis |
| Analysis population | Modified Full Analysis Set |
| Effect measure | Least Squares Mean; normalized as mean difference |
| Estimate | −0.70 |
| 95% CI | −1.046 to −0.346 |
| P-value | < 0.0001 |
| Hypothesis | Superiority |
The estimated between-group difference was −0.70. Given that higher WOMAC scores indicate worse functional limitations, the negative estimate indicates greater improvement in physical-function score with fasinumab under the reported model.
The 95% confidence interval, −1.046 to −0.346, is entirely below zero. This provides a measure of the precision of the estimated difference and indicates that the uncertainty interval remains on the same side of the null value.
The reported P < 0.0001 indicates strong statistical evidence against the null hypothesis within the stated analysis. It does not describe the size of the effect and should not be interpreted as a probability that the null hypothesis is true.
As with the pain endpoint, the estimate concerns the specified analysis population and Week 16 assessment. It should not be interpreted as a statement that every individual experienced the same degree of improvement.
7.3 WOMAC Pain — Fasinumab 1 mg SC Q8W vs Placebo
Least-squares mean difference
95% CI: −0.594 to 0.401 · P = 0.7036
Endpoint: change in WOMAC Pain Subscale score from baseline to Week 16.
| Element | Reported result |
|---|---|
| Comparison | Placebo vs Fasinumab 1 mg SC Q8W |
| Time frame | Baseline to Week 16 |
| Analysis method | Mixed Models Analysis |
| Analysis population | mFAS Post Protocol Amendment 5 analysis set |
| Analysis-set restriction | Only participants concurrently randomized after Protocol R475-OA-1611 Amendment 5 Global was implemented |
| Effect measure | Least Squares Mean; normalized as mean difference |
| Estimate | −0.10 |
| 95% CI | −0.594 to 0.401 |
| P-value | 0.7036 |
| Hypothesis | Superiority |
The estimated difference was −0.10, a relatively small model-based difference on the 0–10 WOMAC subscale. The negative direction is consistent with greater improvement under the fasinumab comparison, but the estimate alone does not establish that the observed difference is distinguishable from zero.
The 95% confidence interval spans −0.594 to 0.401. Because the interval crosses zero, the registry's estimate is compatible with both a modest benefit and a modest difference in the opposite direction within the uncertainty represented by the interval.
The reported P = 0.7036 indicates little statistical evidence against the null hypothesis in this analysis. It does not prove that fasinumab and placebo have identical effects, nor does it establish equivalence.
The Q8W analysis uses a distinct post-Amendment 5 analysis set restricted to participants who were concurrently randomized after the amendment was implemented. That population restriction is important when interpreting this estimate and comparing it with the Q4W result.
7.4 WOMAC Physical Function — Fasinumab 1 mg Q8W vs Placebo
Least-squares mean difference
95% CI: −0.657 to 0.297 · P = 0.4605
Endpoint: change in WOMAC Physical Function Subscale score from baseline to Week 16.
| Element | Reported result |
|---|---|
| Comparison | Placebo vs Fasinumab 1 mg SC Q8W |
| Time frame | Baseline to Week 16 |
| Analysis method | Mixed Models Analysis |
| Analysis population | mFAS Post Protocol Amendment 5 analysis set |
| Analysis-set restriction | Only participants concurrently randomized after Protocol R475-OA-1611 Amendment 5 Global was implemented |
| Effect measure | Least Squares Mean; normalized as mean difference |
| Estimate | −0.18 |
| 95% CI | −0.657 to 0.297 |
| P-value | 0.4605 |
| Hypothesis | Superiority |
The estimated difference in physical-function change was −0.18. The negative point estimate is in the direction of greater improvement with fasinumab, but the estimate is accompanied by substantial uncertainty relative to the magnitude of the point estimate.
The 95% confidence interval ranges from −0.657 to 0.297 and crosses zero. Thus, the reported interval includes values consistent with improvement as well as values in the opposite direction.
The P = 0.4605 result does not provide strong evidence against the null hypothesis in this analysis. It should not be interpreted as proof of no treatment effect, and it does not provide a test of equivalence.
The analysis-set restriction after Protocol Amendment 5 is again relevant. The Q8W estimate describes the concurrently randomized post-amendment population rather than automatically representing every participant enrolled in the trial.
8. Primary Results Side by Side
| Primary endpoint | Regimen | Estimate | 95% CI | P-value |
|---|---|---|---|---|
| WOMAC Pain | Fasinumab 1 mg SC Q4W vs placebo | −0.68 | −1.028 to −0.324 | 0.0002 |
| WOMAC Physical Function | Fasinumab 1 mg Q4W vs placebo | −0.70 | −1.046 to −0.346 | < 0.0001 |
| WOMAC Pain | Fasinumab 1 mg SC Q8W vs placebo | −0.10 | −0.594 to 0.401 | 0.7036 |
| WOMAC Physical Function | Fasinumab 1 mg Q8W vs placebo | −0.18 | −0.657 to 0.297 | 0.4605 |
The four results illustrate why an overall trial conclusion should not be reduced to a single p-value. The Q4W analyses have negative estimates whose 95% confidence intervals remain below zero, whereas both Q8W confidence intervals cross zero. The Q8W analyses also use a distinct post-Amendment 5 analysis set, so the numerical differences between regimens should be interpreted in the context of both the dosing schedule and the analysis population.
9. Statistical Methods Explained
Why was a mixed-effects model used?
The primary outcomes are changes in continuous WOMAC scores measured over time. A mixed-effects model is designed for longitudinal data because it can account for repeated observations within participants and estimate treatment effects while modeling the correlation created by those repeated measurements. The registry specifically reports “Mixed Models Analysis” for all four primary analyses.
What does a least-squares mean difference of −0.68 mean?
It represents the model-based difference between the compared treatment groups in the WOMAC Pain Subscale change from baseline to Week 16. Because higher WOMAC scores represent worse pain, a negative difference indicates greater improvement in the fasinumab group under the reported comparison. It is not the percentage of patients who improved and is not a relative risk.
Why is the confidence interval important?
The 95% confidence interval communicates the precision of the estimated treatment difference. For the Q4W pain endpoint, the interval is −1.028 to −0.324, whereas the Q8W pain interval is −0.594 to 0.401. The latter is wider relative to its point estimate and crosses zero, illustrating how uncertainty affects interpretation.
What does the p-value tell us?
The p-value describes the statistical evidence against a null hypothesis under the specified model and assumptions. A smaller p-value indicates stronger evidence against that null hypothesis. It does not tell us whether an effect is clinically important, and it does not quantify the magnitude of the effect.
Why does the Q8W analysis use a different analysis set?
The registry states that the Q8W analysis used an mFAS Post Protocol Amendment 5 analysis set and included only participants concurrently randomized after Protocol R475-OA-1611 Amendment 5 Global was implemented. Consequently, the Q8W estimates describe that defined subset of participants rather than the entire enrollment population.
Why should the Q4W and Q8W estimates not simply be compared by p-value?
A smaller p-value in one regimen and a larger p-value in another does not, by itself, establish that the underlying treatment effects are statistically different. A formal comparison of treatment effects would require an appropriate interaction or treatment-by-regimen analysis. The posted results provide separate treatment-versus-placebo estimates rather than such a formal between-regimen comparison.
What does a confidence interval crossing zero mean?
For a mean difference, zero is the value corresponding to no difference between groups. When a two-sided 95% confidence interval crosses zero, the estimate is statistically compatible with both a negative and positive difference at that confidence level. It does not prove that the treatments are equivalent.
10. Intention-to-Treat and Modified Analysis Sets
Randomization provides the foundation for causal comparison because treatment assignment is determined independently of subsequent participant characteristics. An intention-to-treat analysis generally preserves that randomized comparison by analyzing participants according to their assigned treatment.
The registry, however, explicitly identifies a modified Full Analysis Set for the Q4W efficacy analyses and a post-Protocol-Amendment-5 mFAS for the Q8W analyses. These distinctions are important because the estimand represented by a reported statistical result depends not only on the endpoint and model but also on who contributes observations to the analysis.
Q4W analysis set
The mFAS excluded additional participants from the FAS because of regional irregularities noted at some study sites.
Q8W analysis set
The post-Amendment-5 mFAS included only participants concurrently randomized after the specified protocol amendment was implemented.
Therefore, the enrollment total of 3,307 should not be substituted for the number of evaluable participants contributing to any individual primary analysis. The registry explicitly defines analysis “n” as the number of evaluable participants at the specified point in time.
11. Safety Results
The registry reports serious adverse events by treatment category as affected participants divided by participants at risk. These counts provide a treatment-group safety summary distinct from the efficacy analyses.
| Treatment category | Serious adverse events | At risk |
|---|---|---|
| Placebo | 49 | 352 |
| Naproxen | 103 | 1,056 |
| Fasinumab 1 mg Q8W | 81 | 554 |
| Fasinumab 1 mg Q4W | 175 | 1,052 |
| Fasinumab 3 mg Q4W | 7 | 145 |
| Fasinumab 6 mg Q8W | 6 | 139 |
These are counts of participants affected by serious adverse events, together with the corresponding numbers at risk. They should be interpreted as safety-event summaries rather than as efficacy comparisons. The registry reports these categories separately from the four posted primary efficacy analyses.
12. Trial Timeline
Study start
The registry records August 17, 2017 as the study start date.
Q8W analysis population defined around concurrent randomization
The registry identifies a post-Amendment-5 mFAS for the fasinumab 1 mg Q8W primary analyses, restricted to participants concurrently randomized after the global amendment was implemented.
Primary completion
The registry records September 9, 2019 as the primary completion date.
Primary statistical analyses available
The registry reports four posted statistical analyses corresponding to the four registered primary endpoints.
13. What the Mean Difference Does — and Does Not — Mean
A mean difference such as −0.68 describes the model-estimated difference in the change of the WOMAC Pain Subscale between the compared groups. Because the WOMAC scale runs from 0 to 10 and higher values indicate worse pain, the negative direction represents greater improvement with the fasinumab comparison.
The estimate is not a 68% reduction in pain. It is a difference on the WOMAC numerical scale. Converting it into a percentage would require additional information and a specific denominator that is not part of the reported estimate.
A group-level least-squares mean difference does not mean that each participant improved by exactly 0.68 points. Individual responses can vary substantially around a group-level treatment estimate.
The confidence interval adds information about uncertainty. The Q4W pain estimate of −0.68 has a 95% CI of −1.028 to −0.324, while the Q8W pain estimate of −0.10 has a 95% CI of −0.594 to 0.401. The difference between these intervals illustrates why point estimates should not be interpreted without their uncertainty.
14. Interpreting the Four Primary Analyses Together
The primary results form two pairs: pain and physical function for the 1 mg Q4W regimen, and the corresponding two outcomes for the 1 mg Q8W regimen. This structure matters statistically because the trial does not have a single efficacy estimate that summarizes every regimen and every endpoint.
| Question | Q4W findings | Q8W findings |
|---|---|---|
| WOMAC Pain | Estimate −0.68; 95% CI −1.028 to −0.324; P = 0.0002 | Estimate −0.10; 95% CI −0.594 to 0.401; P = 0.7036 |
| WOMAC Physical Function | Estimate −0.70; 95% CI −1.046 to −0.346; P < 0.0001 | Estimate −0.18; 95% CI −0.657 to 0.297; P = 0.4605 |
| Analysis framework | Mixed Models Analysis; mFAS | Mixed Models Analysis; post-Amendment-5 mFAS |
Within the reported Q4W analyses, both primary endpoints have negative estimates and confidence intervals entirely below zero. Within the reported Q8W analyses, both estimates are negative but their confidence intervals cross zero. These are descriptive interpretations of the posted estimates; a formal comparison of Q4W and Q8W treatment effects would require a separate statistical test.
15. Multiplicity and Multiple Primary Endpoints
The registry identifies four registered primary endpoints and four posted primary statistical analyses. Multiple primary endpoints create an important statistical-design issue because each formal hypothesis test contributes to the overall opportunity for a false-positive finding if considered independently.
The information available in the registry record identifies the endpoints, methods, estimates, confidence intervals, and p-values, but does not specify a multiplicity-adjustment strategy for these four posted analyses. Accordingly, the individual p-values should be interpreted as the p-values reported for their respective analyses rather than as evidence that a particular familywise error-control procedure was used.
16. Missing Data and Longitudinal Interpretation
Longitudinal mixed-effects models are often useful in clinical trials because they can incorporate repeated observations rather than relying only on a single complete-case measurement. However, the statistical properties of a mixed model depend on the assumptions governing the missing-data process and the specified covariance structure.
The registry identifies the primary method as a mixed-effects model but does not provide sufficient detail in the posted analysis fields to describe the complete missing-data strategy, covariance structure, or every model specification. Those details should therefore not be inferred from the reported treatment estimates.
A mixed-effects model does not make missing observations irrelevant. Its validity depends on whether the assumptions used to represent incomplete longitudinal data are reasonable for the study and endpoint.
17. Limitations
- Different analysis populations: the Q4W and Q8W primary analyses use different modified analysis sets, so their estimates should not be compared as though they necessarily arose from identical populations.
- Four primary endpoints: the registry reports four primary endpoints and four corresponding analyses. The complete multiplicity-control strategy is not specified in the posted statistical-analysis information.
- Endpoint direction: WOMAC scores are interpreted with higher values representing worse symptoms and limitations. The sign of the mean difference therefore depends on the direction used for the comparison.
- Clinical importance: statistical significance does not by itself establish whether the magnitude of a WOMAC difference is clinically meaningful for an individual participant.
- Model dependence: the reported least-squares means are model-based quantities. Their interpretation depends on the assumptions and specification of the mixed-effects model.
- Limited model specification: the registry identifies the mixed-model method but does not provide all covariance, missing-data, and model-specification details needed to independently reproduce the analysis from the posted statistical-analysis fields alone.
- Safety denominators differ: the serious adverse-event summaries are reported with treatment-specific numbers at risk and should not be interpreted as though every safety category had the same denominator.
- Week 16 focus: all four registered primary endpoints use the baseline-to-Week-16 time frame. These results therefore describe the specified primary assessment period rather than establishing the persistence of an effect beyond that time point.
18. Why This Trial Matters Statistically
FACT OA1 is a useful statistical teaching case because the trial combines randomized treatment assignment, triple masking, multiple continuous patient-reported outcome endpoints, longitudinal modeling, modified analysis populations, and treatment-regimen comparisons.
| Concept | How it appears in FACT OA1 |
|---|---|
| Randomization | The study uses randomized allocation in a parallel-group phase 3 design. |
| Blinding | The registry identifies the trial as triple masked. |
| Longitudinal analysis | Primary efficacy analyses use a mixed-model framework. |
| Model-based means | Primary effects are reported as least-squares mean estimates. |
| Confidence intervals | All four primary analyses report two-sided 95% confidence intervals. |
| P-values | Each primary analysis reports a p-value for its superiority hypothesis. |
| Multiple endpoints | Four primary endpoints are registered and all four have posted statistical analyses. |
| Analysis populations | Q4W and Q8W analyses use specifically defined modified analysis sets. |
| Patient-reported outcomes | Primary endpoints are based on changes in WOMAC pain and physical-function subscale scores. |
| Safety analysis | Serious adverse events are reported by treatment category with affected and at-risk counts. |
19. Statistical Methods Explained: A Deeper View
Why not simply compare Week 16 means?
The registered analysis uses a mixed-model approach rather than a simple unadjusted comparison of Week 16 arithmetic means. Longitudinal modeling can incorporate repeated information and estimate treatment effects within a prespecified model.
Why report least-squares means?
Least-squares means are model-derived estimates. They allow the treatment comparison to be expressed within the structure of the fitted longitudinal model rather than as a raw difference between simple observed averages.
Why does the sign matter?
WOMAC is coded so that higher scores indicate worse pain and functional limitations. Therefore, negative changes or negative between-group differences represent improvement when interpreted in the appropriate comparison direction.
Why is a non-significant p-value not equivalence?
The Q8W p-values of 0.7036 and 0.4605 do not establish that fasinumab and placebo have identical effects. Equivalence requires a prespecified equivalence margin and an analysis designed around that question.
20. Related Tutorials
Learn more about the methods used in this trial:
21. Related Statistical Calculators
22. Sources
- ClinicalTrials.gov: NCT03161093 — FACT OA1.
- PubMed: PMID 41545313.
- PubMed: PMID 39004211.
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23. Record Summary
FACT OA1 provides a useful example of how a randomized phase 3 trial can produce multiple model-based efficacy estimates from longitudinal patient-reported outcomes. The four registered primary endpoints all evaluated change in WOMAC pain or physical-function scores from baseline to Week 16, with formal mixed-model analyses reported for fasinumab 1 mg Q4W and 1 mg Q8W compared with placebo.
The Q4W analyses produced estimates of −0.68 for WOMAC pain and −0.70 for physical function, with 95% confidence intervals entirely below zero. The corresponding Q8W estimates were −0.10 and −0.18, with confidence intervals that crossed zero. The Q8W analyses also used a specifically defined post-Amendment-5 analysis population, which is an important part of their interpretation.
Statistically, the trial illustrates why treatment effects should be read as a combination of the effect estimate, confidence interval, p-value, analysis population, endpoint definition, and model specification. A p-value alone cannot describe the magnitude or clinical meaning of an observed difference, while a point estimate without its uncertainty can give an incomplete picture of the evidence.