A Study to Evaluate the Safety and Efficacy of Efalizumab in Adult Patients With Moderate to Severe Plaque Psoriasis With Involvement of the Scalp: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study to Evaluate the Safety and Efficacy of Efalizumab in Adult Patients With Moderate to Severe Plaque Psoriasis With Involvement of the Scalp (NCT00669214), a randomized phase 4 study. The primary outcome is Proportion of Patients Who Achieved a ≥ 75% Decrease in Psoriasis Scalp Severity Index (PSSI) Score at 12 Weeks.

2. Clinical Question

The primary question concerns a threshold response, rather than the average change in scalp severity. A patient either met the specified decrease in PSSI score or did not. This makes the endpoint a binary outcome, summarized as a proportion within each group. The key comparison is the difference between those proportions, interpreted alongside its confidence interval and the reported statistical test.

The study also listed other scalp and whole-body outcomes, including additional PSSI response thresholds, physician global assessment categories, scalp-related quality of life, and scalp itch. Those outcomes address related but distinct questions. The primary comparison is limited to the specified PSSI response at Week 12; results for the other outcomes should not be substituted for it.

3. Trial Design

This was a Phase IV randomized, double-blind, placebo-controlled, parallel-group study of subcutaneous efalizumab in adults with moderate to severe plaque psoriasis involving the scalp. The official title specifies a dose of 1.0 mg/kg. Participants were assigned to efalizumab or placebo for the double-blind comparison. The study description also identifies a screening period, an open-label treatment period, and an observation or follow-up period.

The registry lists an enrollment of 89. The study summary separately states that 100 patients were enrolled and that 11 were excluded from all analyses because of data issues. The primary outcome results give 27 participants in the placebo arm and 62 in the efalizumab arm. These enrollment and analysis descriptions should be kept distinct: the record reports both the overall enrollment statement and the arm sizes used for the posted primary outcome.

The primary endpoint was assessed at Week 12, also described as Day 84. It was the proportion of patients with at least a 75% reduction from baseline in PSSI score. The primary population is identified as intent-to-treat, with specified handling for some missing Day 84 PSSI values. The full protocol and complete analysis details are not reported in the registry record.

The record lists the trial as completed and identifies Genentech, Inc. as sponsor. It gives a start date of 2008-02 and a primary completion date of 2009-01. It also lists 12 outcome measures and 11 posted secondary outcomes. The registry record does not report the rationale for the chosen enrollment, the randomization procedure in further detail, or the durations of the treatment and follow-up periods.

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.

Double-Blind Treatment Period (Week 12)

Open-Label Treatment Period (Week 24)

Analysis population for the primary outcome, as defined in the registry: Intent-to-treat (ITT) population. If PSSI at Day 84 was missing for a patient who discontinued before the final scheduled dose, the patient was considered a treatment failure (nonresponder) for analysis. If PSSI at Day 84 was missing for a patient who completed treatment, the last available PSSI from the treatment period was used for analysis.

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

6. Primary Endpoint

The registry lists the primary outcome as Proportion of Patients Who Achieved a ≥ 75% Decrease in Psoriasis Scalp Severity Index (PSSI) Score at 12 Weeks, measured over Week 12.

The primary endpoint is the proportion of patients who achieved at least a 75% decrease in PSSI score at Week 12 relative to baseline. The PSSI combines the extent of scalp involvement with assessments of erythema, induration, and desquamation. The area involved is scored from 1 to 6, and each clinical sign is scored from 0 to 4. The three clinical-sign scores are added and multiplied by the involved-area score, producing a PSSI score ranging from 0 to 72.

A response threshold turns the score change into a binary outcome: each participant is classified as having reached or not reached the threshold. The reported group proportions therefore describe how common this defined response was in each arm. This approach is different from comparing average PSSI changes, because it focuses on the proportion crossing a prespecified level of improvement rather than the size of every participant’s change.

Using a defined threshold can make the clinical meaning of a response easier to communicate, but it also discards information about variation within the responder and nonresponder groups. Participants just below the threshold are classified differently from those just above it, even if their score changes are similar. The endpoint should therefore be read as a measure of reaching this particular PSSI threshold, not as a complete description of scalp disease or of every change in severity.

The registry record specifies the endpoint and assessment time, but the full rationale for choosing this threshold is not reported in the registry record. The endpoint’s interpretation is consequently tied to the stated score definition, threshold, and Week 12 assessment.

7. Results Posted in the Registry

• Efalizumab: 0.0% (0/62) versus 0.0% (0/27) on control; risk difference 0.0 percentage points (95% CI 0.0 to 0.0); unadjusted two-proportion z-test p = n/a.

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is binary: each participant either achieved at least a 75% decrease in PSSI score by Week 12 or did not. A proportion expresses the number meeting that outcome relative to the relevant group size. The posted proportions are 0.111 for placebo and 0.274 for efalizumab. Their comparison is reported as a difference in proportions, 0.163. A difference in proportions keeps the comparison on the original probability scale: zero corresponds to equal proportions, and positive values indicate a larger proportion in the efalizumab group under the reported group ordering.

What does the confidence interval describe?

General statistical explanation: a confidence interval is a range generated by a method designed to reflect sampling uncertainty in an estimate. A narrower interval indicates greater precision under that method, while a wider interval indicates less precision. The reported 95% confidence interval for the difference is -0.063 to 0.393. Because the interval includes zero, it does not exclude no difference. Its endpoints also convey that the estimate is uncertain about both the direction and the size of the group difference.

A confidence interval is not a guarantee that the true value lies inside its particular endpoints, and it is not a range of participant-level outcomes. It concerns uncertainty in the estimated group comparison under the statistical method. Interpretation also depends on the quality of the data, the appropriateness of the analysis, and whether the comparison was selected and reported according to a prespecified plan. The complete plan is not reported in the registry record.

Why is Fisher’s Exact test used?

The reported method is Fisher Exact. General statistical explanation: Fisher’s Exact test evaluates evidence about an association between two categorical variables using the observed allocation of outcome counts across groups. It is often used for binary outcomes, particularly when counts are limited, because its calculation does not rely on the same large-sample approximation as some alternative tests. Here, the categories are treatment group and whether the PSSI response threshold was reached.

The test produces a p-value under a null hypothesis of no association or difference, according to its formulation. The reported p-value is 0.105. A p-value does not measure the probability that the result occurred by chance in an unrestricted everyday sense, and it does not describe the size or practical importance of an effect. The estimated difference and confidence interval are needed to convey direction, magnitude, and precision.

What does a binary endpoint leave out?

General statistical explanation: converting a continuous score into a responder classification can make an outcome easier to interpret as a proportion, but it loses information about the amount of change among participants. The PSSI threshold distinguishes those meeting the at-least-75% reduction criterion from those who did not. The result does not reveal the distribution of individual score changes or how close nonresponders were to the threshold. The posted group proportions should therefore be understood as threshold-response estimates, not as average PSSI change.

The PSSI itself combines extent of scalp involvement with clinical signs. Its stated score range is 0-72. The endpoint uses the change relative to baseline, which means its classification depends on both the baseline score and the Week 12 score. The record gives a missing-data rule for some participants but does not give the complete details of how all records, protocol deviations, or other analysis issues were handled.

How should the planning illustrations be read?

General statistical explanation: sample-size calculations describe what a hypothetical study design might require under specified assumptions. They are not a measure of the probability that the completed trial detected an effect, and they do not change the uncertainty in the observed result. The planning assumptions associated with this trial use a two-sided significance level of 0.05, equal allocation, and a normal approximation. The effect to detect is defined as a stated fraction of the observed effect. For binary outcomes, the planning quantities are participants per arm.

Those are planning assumptions, not evidence that the original trial was designed with those exact assumptions. The trial’s own sample-size justification and design calculations are not reported in the registry record. A calculation based on the observed effect is also sensitive to that estimate, which is uncertain. It should be treated as an illustrative planning exercise, not as observed power or as proof that the trial was adequately or inadequately sized.

Finally, multiple outcomes are listed in the record. When several outcomes or comparisons are examined, the chance of at least one apparently unusual finding can be affected by how many tests are considered and by the analysis plan. Whether and how multiplicity was addressed is not reported in the registry record. The primary p-value should not be interpreted as though it automatically accounts for all other outcomes.

10. Confidence Intervals and Precision

The estimated difference in Week 12 response proportions is 0.163. Its 95% confidence interval extends from -0.063 to 0.393. The interval is wide enough to include zero, so the result does not precisely distinguish a positive difference from no difference or a difference in the opposite direction. The point estimate is only one value within a broader range of estimates compatible with the reported uncertainty.

For a binary outcome, precision depends in part on the number of participants and the frequency of the outcome in each group. The primary outcome results report 27 participants in the placebo arm and 62 in the efalizumab arm. Those group sizes are not equal, and the observed response proportions differ. The confidence interval reflects uncertainty in the estimated comparison; it should be considered rather than relying only on the direction of the point estimate.

General statistical explanation: a 95% confidence interval describes the behavior of an interval-generating procedure over repeated applications under its assumptions. It does not mean there is a 95% probability that the true effect is inside the specific interval after the data have been observed. Nor does it show the range of effects that are clinically important. The record does not report a threshold for a clinically important difference, so the interval cannot be classified against such a threshold using this information.

The lower endpoint is below zero and the upper endpoint is above zero. Thus the interval allows a range that includes a difference favoring placebo as well as a difference favoring efalizumab. This is a statement about statistical uncertainty, not a conclusion that the groups are equivalent. A formal equivalence or noninferiority conclusion would require an appropriate design and prespecified margin, neither of which is reported in the registry record.

The reported p-value, 0.105, is consistent with the interval’s failure to exclude zero in the ordinary two-sided comparison. The estimate should be read as imprecise rather than as evidence of a precisely established effect. The enrollment discrepancy and exclusions noted in the record are additional context when considering how representative the analyzed participants are of everyone enrolled.

11. Analyses Reported by the Sponsor

The sponsor-reported primary comparison uses Fisher Exact and reports a difference in proportions of 0.163. Its 95% confidence interval is -0.063 to 0.393, and its p-value is 0.105. These are the values to use when describing the registry-reported analysis. The point estimate indicates a higher observed response proportion in the efalizumab group, while the interval includes zero and the p-value does not provide strong evidence against a no-difference null under a conventional 0.05 reference threshold.

The registry also contains a comparison entry with zero values for the estimate, interval, and test quantities. That entry does not align with the separately reported Fisher Exact analysis. The substantive interpretation should therefore be based on the sponsor-reported analysis rather than treating the zero-valued entry as an alternative estimate. The registry record does not explain why that entry appears or give additional detail that would reconcile it.

No separate recalculated estimate is needed to replace the reported comparison. The reported proportions and the sponsor’s own analysis provide the primary numerical result. The uncertainty remains important: the point estimate alone should not be read as a definitive group difference, and the confidence interval does not establish equivalence.

12. Multiplicity, Missing Data and Analysis Populations

The registry lists 12 outcome measures and 11 posted secondary outcomes. The secondary outcomes include other PSSI response thresholds at Week 12 and Week 24, whole-body physician global assessment categories at Week 12 and Week 24, changes in Scalpdex score at both time points, and a scalp-itch visual analog scale change at Week 12. These are distinct outcomes and assessment times, not interchangeable versions of the primary endpoint.

When a study assesses multiple outcomes, the interpretation of individual p-values can depend on whether testing was planned as a family and whether any adjustment or hierarchy was prespecified. The registry record does not report a multiplicity strategy, a hierarchy among outcomes, or whether the primary endpoint was the sole confirmatory test. Accordingly, the reported p-value should be interpreted as the result for this comparison, not as an adjustment for the full set of listed outcomes.

The primary population is described as intent-to-treat. The record states that if Day 84 PSSI was missing for a patient who discontinued before the final scheduled dose, that patient was treated as a nonresponder. If the value was missing for a patient who completed treatment, the description says the last available PSSI was used. The description is truncated, so the complete missing-data procedure is not reported in the registry record.

The study summary says that 11 patients were excluded from all analyses because of data issues, while the registry lists enrollment of 89 and the primary outcome arms contain 27 and 62 participants. The record does not explain the data issues, identify the affected participants, or fully reconcile the enrollment statements. Exclusions from analyses can affect the relationship between an intended intent-to-treat analysis and the population actually analyzed. The available record does not support a fuller assessment of that issue.

The registry record also does not report the extent or pattern of missing primary outcome data, sensitivity analyses for missingness, or how other analysis deviations were handled. These omissions limit assessment of robustness. They do not by themselves show that the reported analysis is biased, but they leave readers without information needed to evaluate how sensitive the result may be to alternative assumptions.

13. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: atrial fibrillation (3.7%), abdominal pain (2.1%), injury (2.1%), back pain (1.8%), nephrolithiasis (1.6%).

The adverse-event record separates the double-blind, open-label, and follow-up periods and lists serious and other adverse events for each group and period. For the double-blind period, the serious-event figures are 1 of 27 for placebo and 1 of 62 for efalizumab. The record also lists other adverse events for 11 of 27 placebo participants and 32 of 55 efalizumab participants in that period. These are the posted counts and denominators; they should be read within their stated period and group rather than combined across periods.

During the open-label period, serious adverse events are listed for 0 of 22 in the placebo group and 1 of 55 in the efalizumab group. Other adverse events are listed for 11 of 22 and 22 of 55, respectively. During follow-up, serious events are listed for 0 of 18 and 2 of 48, while other adverse events are listed for 3 of 18 and 15 of 48. The treatment context changes across periods, so these groupings are not a single randomized comparison throughout.

Deaths are not reported in the registry record. The listed serious-event terms include atrial fibrillation, abdominal pain, injury, back pain, and nephrolithiasis, with percentages stated in the adverse-event record. The registry does not give enough detail to establish causality or to interpret those terms as treatment-related. Counts also do not by themselves account for event timing, severity, recurrence, or exposure duration.

These figures describe reported events in the recorded periods. They are not a complete comparative safety analysis, and the open-label and follow-up data should not be interpreted as if they preserve the original blinded comparison.

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

The result describes the proportion of analyzed participants meeting a specific scalp-response threshold at Week 12. The observed proportions were 0.274 for efalizumab and 0.111 for placebo. The reported difference was 0.163, with a 95% confidence interval from -0.063 to 0.393 and a Fisher Exact p-value of 0.105. Together, these statistics show a point estimate favoring a higher response proportion in the efalizumab group, alongside uncertainty that includes no difference.

The endpoint does not describe all changes in scalp disease. It classifies participants according to whether their PSSI score decreased by at least 75% relative to baseline. It does not show the average amount of score change, the distribution of individual changes, or the response of each participant. Nor does this single assessment establish the pattern of outcomes at other times.

The result does not establish that the treatments are equivalent. An interval that includes zero indicates that the comparison is not precise enough to exclude no difference under the reported method; equivalence requires a different inferential framework and a prespecified margin. The result also does not, on its own, establish the clinical importance of the point estimate, because the registry record does not report a minimum clinically important difference for this endpoint.

The trial’s design and reported outcome support a controlled comparison in the randomized, double-blind period, but the registry record does not provide a complete account of trial conduct, missing data, or analysis decisions. The reported exclusion of 11 patients from all analyses and the different enrollment statements are important context. The result applies most directly to the participants represented in the posted outcome analysis, not necessarily to all people with psoriasis or to every treatment setting.

Finally, the primary outcome is one among multiple outcomes recorded. Without a reported multiplicity strategy, secondary findings should be interpreted cautiously and separately. The primary comparison is informative as an estimate with uncertainty, but it is not a complete account of efficacy, safety, durability, or individual experience.

15. Why This Trial Matters Statistically

This trial illustrates why an estimated effect should be read together with its uncertainty. The difference in Week 12 response proportions is 0.163, but its 95% confidence interval ranges from -0.063 to 0.393. The point estimate alone suggests a direction; the interval shows that the direction and size are not tightly determined by these data. A p-value adds information about compatibility with a null hypothesis, but it cannot replace the estimate and interval.

It also illustrates the interpretive consequences of using a threshold endpoint. The PSSI combines extent of involvement and clinical signs, but the primary outcome reduces score change to whether a participant crossed the at-least-75% response threshold. This creates an accessible proportion while leaving out the scale and distribution of changes among individuals. Readers need to know what the threshold captures and what it omits.

The record’s enrollment statements make population definitions consequential. It lists enrollment of 89, while the summary states that 100 were enrolled and 11 were excluded from all analyses. The arm sizes in the primary outcome results are 27 and 62. Understanding which participants contributed to the primary result matters when interpreting an analysis identified as intent-to-treat.

Finally, the record lists multiple outcomes and periods, while the multiplicity approach and full missing-data procedure are not reported. This demonstrates why results are best interpreted with the analysis plan and participant accounting, not only with a single p-value. The statistical lesson is one of calibrated interpretation: distinguish the observed estimate, its precision, the endpoint’s definition, and what the registry record leaves unresolved.

16. 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.
• Participant counts were reconstructed from posted percentages and arm sizes, so small rounding differences are possible.

The enrollment information is not internally reconciled in the registry record. The registry lists 89 participants, while the study summary reports 100 enrolled and says 11 were excluded from all analyses because of data issues. The primary outcome results report 27 participants in the placebo arm and 62 in the efalizumab arm. The record does not identify the affected participants or explain the data issues, limiting assessment of the analyzed population.

Although the primary population is called intent-to-treat, the stated exclusions and missing-data rules complicate interpretation of that label. The available description says that some missing Day 84 values were classified as nonresponse and that last available PSSI was used for some participants who completed treatment. The full procedure is not reported in the registry record, nor are the amount and pattern of missingness or sensitivity analyses.

The primary comparison is imprecise: its confidence interval includes zero and spans differences in either direction. This limits conclusions about the direction and size of the group difference. The registry record does not report a clinically important difference threshold, so the point estimate cannot be judged against such a threshold using the posted information alone.

The record lists multiple primary and secondary outcome measures, but does not report how multiplicity was handled or whether the primary analysis was part of a prespecified testing hierarchy. It also does not report the trial’s sample-size justification, interim analyses, or complete statistical plan. These gaps make it difficult to assess the intended inferential framework and the robustness of the reported analysis.

Finally, the adverse-event information is separated by study period, and later periods include open-label treatment and follow-up. The record does not report deaths, and the adverse-event figures alone do not establish causality or provide a complete comparative safety assessment. These limitations are specific to the information available in the registry record and should temper interpretation of both the efficacy comparison and the safety summaries.

17. Related Tutorials

18. Related Statistical Calculators

19. Sources

• ClinicalTrials.gov: A Study to Evaluate the Safety and Efficacy of Efalizumab in Adult Patients With Moderate to Severe Plaque Psoriasis With Involvement of the Scalp — NCT00669214.
• Registry record last updated 2017-06-06; status last verified 2017-05.
• Results first posted 2011-02-14.
• 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.

20. Record Summary

NCT00669214 is a completed Phase IV randomized, double-blind, placebo-controlled, parallel-group study sponsored by Genentech, Inc. It assessed subcutaneous efalizumab, identified in the official title as 1.0 mg/kg, in adults with moderate to severe plaque psoriasis involving the scalp. The registry lists enrollment of 89; the study summary separately reports 100 enrolled and 11 excluded from all analyses because of data issues.

The primary outcome was the proportion achieving at least a 75% decrease in PSSI score at Week 12. The posted proportions were 0.111 for placebo and 0.274 for efalizumab. The reported difference was 0.163, with a 95% confidence interval of -0.063 to 0.393 and a Fisher Exact p-value of 0.105. The interval includes zero, so the estimate is uncertain about the direction and size of the group difference.

The registry also lists secondary outcomes and adverse-event information across the double-blind, open-label, and follow-up periods. The complete multiplicity approach, sample-size justification, and missing-data details are not reported in the registry record.