A Study of the Safety and Efficacy of Ustekinumab (CNTO 1275) in Patients With Moderate to Severe Psoriasis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of the Safety and Efficacy of Ustekinumab (CNTO 1275) in Patients With Moderate to Severe Psoriasis (NCT00307437), a randomized phase 3 study. The primary outcome is Number of Participants With Psoriasis Area and Severity Index (PASI) Score of 75 Percent or Above at Week 12.

2. Clinical Question

The study record describes a phase 3 trial evaluating the efficacy and safety of ustekinumab for moderate to severe plaque-type psoriasis. Its primary outcome is a response threshold rather than a direct comparison of average PASI scores: participants either met the stated improvement criterion at Week 12 or did not. The record also lists physician global assessment, dermatology-related quality of life, and PASI response over a later follow-up period as secondary outcomes.

The randomized comparison can describe differences between assigned groups under the trial’s analysis definitions. It does not, by itself, establish how the findings apply to people outside the studied population, or answer questions about outcomes not recorded in the registry results.

3. Trial Design

The registry describes a phase 3, multicenter, randomized, triple-masked, parallel-group, placebo-controlled trial. It lists enrollment of 1230 and a completed status. The recorded study start is 2005-05, and primary completion is recorded as 2006-12. The sponsor is Centocor Research & Development, Inc.

Participants were assigned to placebo, ustekinumab 45 mg, or ustekinumab 90 mg. The primary endpoint compared each active-dose group with placebo. The primary outcome is recorded over Week 0 to Week 12, with the main response assessed at Week 12. The posted group counts for this endpoint are 410.0 for placebo, 409.0 for 45 mg, and 411.0 for 90 mg. These are endpoint denominators; the registry record does not describe any further adjustment to them.

The analysis population is described as intent to treat. The record says randomized participants were analyzed according to their assigned treatment groups. It also says participants were considered non-responders if they used pre-specified prohibited medications, discontinued due to lack of efficacy, or had missing data at Week 1. That wording is recorded as written; the registry does not clarify the reference to Week 1 for an endpoint assessed at Week 12.

The record does not report the original sample-size justification, the planned allocation ratio, detailed masking procedures, or the statistical analysis plan. Although enrollment and the numbers analyzed for the primary endpoint are reported, they do not reveal the study’s original design assumptions. The record also does not describe whether there were interim analyses or how treatment assignment was generated.

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: 2 participants from placebo group (in controlled period \[CP\]) after completing the CP did not crossover to the Placebo -\> Ustekinumab 90 mg (after CP) treatment group and they are not included in this group (after CP). Thus, 1199 participants completed the 1st period (CP); however, only 1197 participants started the 2nd period (after CP).

Only the first 6 of 7 groups are shown.

Controlled Period

Reasons for not completing this period:

After Controlled Period

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Intent to treat. All participants randomized were included in the analysis according to the assigned treatment groups. Participant is considered a non- responder if the participant has used any pre-specified prohibited medications or discontinued due to lack of efficacy or had missing data at Week 12.

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 Number of Participants With Psoriasis Area and Severity Index (PASI) Score of 75 Percent or Above at Week 12, measured over Week 0 to Week 12.

The primary endpoint counts participants who achieved at least 75 percent improvement in PASI at Week 12. PASI is a measure of psoriasis severity that combines redness, scaling, and thickness with the extent of body involvement. The registry describes its scale as ranging from 0, best, to 72, worst. The endpoint therefore classifies a participant according to whether the specified improvement threshold was reached, rather than reporting the size of each participant’s change as a continuous score.

A threshold response is useful because it gives a clinically interpretable summary of how many participants crossed a prespecified level of improvement. It also makes the outcome suitable for comparing response counts between assigned groups. However, reducing a continuous severity measure to a yes-or-no outcome discards information: people just below and just above the threshold can have similar changes, while those who meet it may differ in the amount of improvement.

The endpoint description specifies an intent-to-treat analysis and a non-responder classification for certain events, including prohibited medication use, discontinuation due to lack of efficacy, or missing data at Week 1. The registry record does not provide additional detail about the handling of other missing observations or deviations from the stated rules. Results should therefore be interpreted as counts under the registry’s stated response definition, not as a complete account of every participant’s PASI trajectory.

7. Results Posted in the Registry

• Group II: Ustekinumab 45 mg: 66.7% (273/409) versus 3.7% (15/410) on control; risk difference 63.1 percentage points (95% CI 58.2 to 68.0), risk ratio 18.24 (11.05–30.12); unadjusted two-proportion z-test p = <0.001.
• Group III: Ustekinumab 90 mg: 75.7% (311/411) versus 3.7% (15/410) on control; risk difference 72.0 percentage points (95% CI 67.5 to 76.5), risk ratio 20.68 (12.55–34.09); unadjusted two-proportion z-test p = <0.001.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Number of Participants With Physician Global Assessment (PGA) of Cleared or Minimal at Week 12

• Endpoint type: Binary: the number of participants with the event, compared as proportions.
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Group II: Ustekinumab 45 mg: 67.7% (277/409) versus 4.4% (18/410) on control; risk difference 63.3 percentage points (95% CI 58.4 to 68.3), risk ratio 15.43 (9.77–24.35); unadjusted two-proportion z-test p = <0.001.
  • Group III: Ustekinumab 90 mg: 73.0% (300/411) versus 4.4% (18/410) on control; risk difference 68.6 percentage points (95% CI 63.9 to 73.3), risk ratio 16.63 (10.54–26.22); unadjusted two-proportion z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the proportion with the event is statistically higher for Group II: Ustekinumab 45 mg than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.
  • The 95% confidence interval excludes no difference, so the proportion with the event is statistically higher for Group III: Ustekinumab 90 mg than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

The registry lists secondary outcomes covering physician global assessment at Week 12, dermatology-related quality of life at Week 12, and PASI response over Week 40 through Week 52. Detailed numerical results are posted for the physician global assessment outcome. The registry record does not report detailed results for the listed DLQI change or the later PASI outcome.

For the reported physician global assessment endpoint, the observed counts show more participants rated cleared or minimal in each ustekinumab group than in placebo. The sponsor-reported tests for both active-dose comparisons have p <0.001, and the simple recalculations also show positive contrasts with intervals above zero. This is directionally consistent with the primary PASI response finding: both outcomes distinguish the active-dose groups from placebo at Week 12 in the posted results.

This agreement across the two reported Week 12 outcomes adds context, but it does not replace the primary endpoint or establish results for the secondary outcomes without posted numerical data. The secondary outcomes address different aspects of disease assessment and follow-up, so they should not be treated as interchangeable measures of the same response.

Unadjusted secondary results carry less confirmatory weight when multiple outcomes or comparisons are examined. If a multiplicity plan was used, its details are not reported in the registry record. Without that information, an isolated secondary p-value can be more vulnerable to chance findings across a set of tests. The primary outcome remains the clearest prespecified focus in the registry description; the secondary outcomes are best read as supportive or exploratory evidence unless their place in a prespecified testing hierarchy is documented.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Number of Participants With Physician Global Assessment (PGA) of Cleared or Minimal at Week 12
• Change in Dermatology Life Quality Index (DLQI) at Week 12
• Number of Participants Visits With Psoriasis Area and Severity Index (PASI) 75 From Week 40 Through Week 52

9. Statistical Interpretation

10. Statistical Methods Explained

What does the response count represent?

The endpoint is binary at the participant level: a participant either met the PASI response threshold at Week 12 or did not, according to the registry’s rules. The posted arm values are counts, with an analyzed denominator for each assigned group. The count is not an average PASI score and does not describe the distribution of individual changes. Comparing counts without their denominators can be misleading, so the reported comparisons use the arm sizes as well as the number meeting the criterion.

What is a risk difference?

General explanation: a risk difference compares the proportion with an outcome in one group with the proportion in another group. It is expressed on an absolute scale, which makes it interpretable as a difference in the frequency of the outcome between groups. The recalculated values are unadjusted comparisons of the posted summary data. The confidence interval describes a range of effect estimates compatible with the data under the method’s assumptions; it is not a range containing a fixed percentage of individual participant outcomes.

For both active-dose comparisons, the recalculated risk difference is positive and its interval is entirely above zero. This indicates that the estimated response frequency was higher in the active group than in placebo under this calculation. The registry record does not report adjusted risk-difference estimates from the sponsor. The separate ratios in the posted comparisons are alternative effect scales; they are not needed to understand the absolute risk-difference contrast.

What does the sponsor’s test do?

The sponsor reports a Cochran-Mantel-Haenszel chi-square test for each active group versus placebo. General explanation: this family of tests assesses association between assigned group and a categorical outcome, and can account for stratification when strata are part of the analysis. The registry names the method but does not report the stratification variables, a test statistic, or an effect estimate from that analysis. Its reported p-value for each comparison is <0.001.

A p-value is calculated under a statistical model in which there is no group difference for the tested outcome. A small value indicates that data at least as incompatible with that model would be unusual if its assumptions held. It is not the probability that the null hypothesis is true, and it does not measure clinical importance. The sponsor’s test and the unadjusted recalculation need not produce identical quantities because they use different methods and report different statistics.

Why use a confidence interval as well as a test?

General explanation: a test gives a summary of evidence against a specified null hypothesis, while a confidence interval communicates both the estimated direction and the uncertainty around an effect estimate. For the recalculated risk differences, the intervals exclude zero, consistent with the small unadjusted p-values. The width of an interval is also informative: narrower intervals indicate greater precision under the model, while wider intervals indicate more uncertainty. The registry does not post confidence intervals for the sponsor’s CMH analyses.

All confidence intervals depend on assumptions about the sampling process and the calculation method. These intervals do not automatically address missing-data bias, deviations from the analysis rules, multiplicity across outcomes, or limitations in generalizing to other populations. Such concerns require design and analysis information beyond the interval itself.

Why do the analysis rules matter?

The primary analysis is described as intent to treat, with participants analyzed according to randomized assignment. The record also defines specified circumstances as non-response, including prohibited medication use, discontinuation for lack of efficacy, and missing data at Week 1. Such rules affect the endpoint classification and therefore the response counts. The record does not explain how every possible missing observation was handled, whether any sensitivity analyses were performed, or whether deviations from the stated rules occurred.

General explanation: missing outcome data can affect an estimate when the chance of missingness is related to treatment or outcome. Treating missing values as non-response is one possible rule, but the consequences depend on how missingness arose and how consistently the rule was applied. The registry’s summary alone cannot establish whether missingness changed the comparison.

The record lists secondary outcomes in addition to the primary endpoint. Testing multiple outcomes or comparisons can increase the chance of at least one apparently unusual result if no multiplicity strategy is used. Whether a prespecified adjustment or hierarchy was used is not reported in the registry record. Consequently, individual secondary p-values, where available, should not automatically be read with the same confirmatory weight as a prespecified primary comparison.

The simple recalculations are unadjusted and use the posted group summaries. They provide a transparent descriptive comparison, but do not reproduce any unreported adjustment, stratification, or covariate model. The discrepancy indicator is false, so no discrepancy between the recalculation and the sponsor’s reported analysis is flagged in the record. The sponsor’s own analysis remains the trial’s reported inferential analysis.

11. Confidence Intervals and Precision

The recalculated risk differences for both ustekinumab doses are positive, and their confidence intervals lie entirely above zero. This supports a direction of contrast favoring a higher observed PASI response frequency in each active-dose group than in placebo, while still allowing a range of plausible magnitudes under the unadjusted calculation. The interval is more informative than a single estimate because it displays sampling uncertainty as well as direction.

The registry does not report confidence intervals or effect estimates for the sponsor’s CMH tests; it reports p-values of <0.001 for both comparisons. The confidence intervals belong to the simple unadjusted recalculations, not to the sponsor’s analysis. They should not be attributed to the reported CMH tests.

General explanation: a confidence interval reflects uncertainty under a statistical method and its assumptions. It does not account automatically for bias from missing data, selective reporting, multiplicity, or differences between the trial population and another population. Nor does excluding zero prove that the estimated effect is exact or that every participant has the same response. For this binary outcome, the interval concerns the group-level risk difference, not individual PASI changes.

The posted group sizes are substantial, but precision cannot be judged from size alone; event frequency, the effect scale, and the analysis method also matter. The record does not report a sponsor-derived confidence interval for the primary contrast or enough analysis-plan detail to assess all sources of uncertainty. The recalculated intervals should therefore be read as uncertainty summaries for the stated unadjusted comparisons, not as a complete measure of the study’s limitations.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The planning figures are participants per arm for 80% power and participants per arm for 90% power. They are not total event counts. The calculation uses a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. It uses a stated fraction of the observed effect as the effect to detect. The original trial’s own design assumptions are not reported in the registry record.

For the comparison with ustekinumab 45 mg, planning for 100% of the observed effect gives 8 participants per arm for 80% power and 10 participants per arm for 90% power. Planning for 75% of the observed effect gives 13 and 17 participants per arm, respectively. Planning for 50% of the observed effect gives 24 and 31 participants per arm, respectively.

For the comparison with ustekinumab 90 mg, planning for 100% of the observed effect gives 6 participants per arm for 80% power and 8 participants per arm for 90% power. Planning for 75% of the observed effect gives 11 and 14 participants per arm, respectively. Planning for 50% of the observed effect gives 20 and 26 participants per arm, respectively.

In plain terms, the 80% and 90% columns describe the planned chance of detecting the specified effect under the calculation assumptions if that effect were present. The higher power target generally requires more participants for the same assumed effect. Smaller effects also require more participants to detect than larger effects. These are planning illustrations based on observed effects, not observed power and not a reconstruction of the trial’s original sample-size calculation.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, p₀ and p₁ are the control and treatment proportions, and p̄ is their average.

Worked calculation for this trial

1. Control proportion p₀ = 0.037; treatment proportion p₁ = 0.667; average p̄ = 0.352.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.6754 = 1.3238.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.5071 = 0.4268.
4. n = (1.3238 + 0.4268)² / (0.6309)² = 7.7, rounded up to 8 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
p0 <- 0.0365853658536585                          # control proportion
p1 <- 0.667481662591687                          # treatment proportion
n_per_arm <- function(power, frac = 1) {
  q1 <- p0 + (p1 - p0) * frac               # smaller effect = fraction of the observed difference
  pbar <- (p0 + q1) / 2
  z_b <- qnorm(power)
  ceiling(round((z_a * sqrt(2 * pbar * (1 - pbar)) + z_b * sqrt(p0 * (1 - p0) + q1 * (1 - q1)))^2 / (q1 - p0)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (unrounded n per arm)
cat("power.prop.test:", round(power.prop.test(p1 = p0, p2 = p1, power = 0.80)$n, 1), "\n")

# Simulation: how often does the z-test reject at the 80%-power sample size?
set.seed(307437)
n    <- n_per_arm(0.80)
reps <- 20000
x0 <- rbinom(reps, n, p0); x1 <- rbinom(reps, n, p1)
ph <- (x0 + x1) / (2 * n)
z  <- ((x1 - x0) / n) / sqrt(ph * (1 - ph) * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(z) > z_a, na.rm = TRUE), reps))

Output from running the code

100% of observed effect: n per arm = 8 (80% power), 10 (90% power)
 75% of observed effect: n per arm = 13 (80% power), 17 (90% power)
 50% of observed effect: n per arm = 24 (80% power), 31 (90% power)
power.prop.test: 7.7 
Simulated power at n = 8 per arm: 0.857 (20000 replicates)

The simulation draws many pairs of event counts at the planned sample size and counts how often the two-proportion z-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

14. Analyses Reported by the Sponsor

The sponsor’s reported primary analyses compare placebo separately with ustekinumab 45 mg and ustekinumab 90 mg using Cochran-Mantel-Haenszel chi-square tests. Each comparison has a reported p-value of <0.001. The registry does not give the sponsor’s effect estimates or confidence intervals for these tests.

The recalculated comparisons use the posted counts and denominators to estimate unadjusted risk differences and confidence intervals. They also show positive contrasts, with intervals excluding zero. These recalculations are not a reproduction of the sponsor’s CMH analysis: they are simple unadjusted calculations from the posted summary statistics and answer the comparison on a different reported scale.

The record does not flag a discrepancy between the posted results and the recalculations. The sponsor’s own analysis is the trial’s reported analysis and takes precedence as the sponsor’s inferential result. The recalculation is useful as a complementary, transparent description of the absolute group contrast, but it cannot supply details omitted from the registry, such as any stratification or adjustment used in the sponsor’s method.

15. Multiplicity, Missing Data and Analysis Populations

The registry identifies a primary endpoint and lists secondary outcomes, but the statistical plan for controlling multiplicity is not reported in the registry record. In particular, the record does not say whether the sponsor used a family-wise error strategy, a hierarchical testing sequence, or another approach for the multiple endpoints and active-dose comparisons.

General explanation: when several hypotheses are tested, the chance of obtaining at least one small p-value by chance can increase if each test is interpreted independently. Prespecifying which comparisons are primary and how later tests depend on earlier results can help control that risk. Because the registry does not describe such a plan, the reported p-values should be interpreted as the results of their stated tests, not assumed to have a multiplicity adjustment.

The primary analysis population is described as intent to treat, with randomized participants analyzed according to their assigned groups. The record specifies that prohibited medication use, discontinuation due to lack of efficacy, and missing data at Week 1 were treated as non-response. It does not provide a complete account of missing observations, the extent of missingness, sensitivity analyses, or departures from these rules. The Week 1 wording is retained in the registry description, although the primary endpoint is assessed at Week 12.

These omissions limit assessment of robustness. General explanation: a stated analysis population defines who is intended to contribute to a comparison, while missing-data rules determine how absent outcomes enter that comparison. If missingness is related to outcome or assignment, the resulting estimate may depend on the assumptions used to classify or handle missing values. The registry summaries do not permit an independent evaluation of those assumptions.

The record also does not report the original sample-size justification, interim analyses, or a detailed statistical analysis plan. Their absence does not establish that a particular procedure was or was not used; it means those methods are not reported in the registry record.

16. 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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: chest pain (1.7%), myocardial infarction (1.5%), diverticulitis (1.5%), nephrolithiasis (1.5%), coronary artery disease (1.5%).

The registry reports serious adverse event counts during the period labeled CP. There were 8 affected participants among 410 at risk in the placebo group, 8 among 409 at risk in the ustekinumab 45 mg group, and 5 among 411 at risk in the ustekinumab 90 mg group. These are counts of participants affected, not counts of all serious events, and the registry does not provide a comparative statistical analysis for them.

The record also lists serious event terms with percentages, including chest pain at 1.7%, myocardial infarction at 1.5%, diverticulitis at 1.5%, nephrolithiasis at 1.5%, coronary artery disease at 1.5%, and angina unstable at 1.0%. These terms provide context about reported serious events, but the listed percentages alone do not establish a treatment-related cause or a difference between groups.

Additional adverse event groups are labeled “After CP,” including participants who moved from placebo to an ustekinumab dose. Those counts concern a different labeled period and should not be combined with or directly compared as if they represented the same exposure period as the CP groups. Death counts are not reported in the registry record. These summaries do not by themselves characterize all safety outcomes or determine the balance of risks and benefits.

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

The posted primary results show that the number of participants meeting the PASI response threshold at Week 12 was much higher in each ustekinumab group than in placebo. The recalculated risk-difference intervals are positive and exclude zero, and the sponsor reports p <0.001 for each active-dose comparison with placebo. Together, these results describe a clear statistical separation for this defined outcome and time point.

That finding is specific to the trial’s enrolled population, the assigned doses, the response definition, and the Week 12 assessment. It is not a direct comparison of the two active doses, because the registry reports each dose against placebo rather than a test between the doses. A comparison of the observed counts across active groups alone cannot establish a dose difference.

The result also does not mean that every participant responded, that all participants experienced the same degree of change, or that the PASI threshold captures every outcome important to participants. The endpoint classifies response at a cutoff; it does not show the full distribution of PASI changes. The registry lists quality-of-life and later PASI outcomes, but detailed results for those listed outcomes are not reported in the registry record.

Statistical evidence is not equivalent to proof of a causal mechanism, a guarantee of an individual outcome, or a complete assessment of safety. The trial’s randomization supports comparison of assigned groups, but interpretation also depends on the analysis rules, missing-data handling, and methods for multiple outcomes. Some of those details are not reported in the registry record. The serious adverse event counts should be read as descriptive safety information, not as a complete safety comparison.

Accordingly, the most defensible conclusion is narrow: in the posted Week 12 results, each active-dose group had a higher observed PASI response frequency than placebo, with sponsor-reported tests and unadjusted recalculations both indicating statistical separation. Broader claims require outcome, population, and analysis information beyond these registry results.

18. Why This Trial Matters Statistically

This trial illustrates why outcome definitions should be read before interpreting a treatment comparison. The primary endpoint is not a general statement that psoriasis improved; it is a count of participants crossing a specified PASI improvement threshold at Week 12. That distinction makes the result interpretable while also identifying what the analysis leaves out, including the size and distribution of individual score changes.

It also demonstrates the value of presenting an effect estimate with uncertainty rather than relying on a p-value alone. The unadjusted risk-difference recalculations convey the direction and precision of the group contrast, while the sponsor’s CMH tests provide the trial’s reported inferential results. The methods are related but not interchangeable, and the registry does not report enough detail to reconstruct all aspects of the sponsor’s analysis.

The endpoint’s non-responder rules and the lack of complete missing-data details matter because response classification depends on how participants with specified events or absent data are handled. Likewise, a trial with primary and secondary outcomes raises questions about multiplicity; the registry does not report a strategy for addressing it.

Finally, the safety counts and the efficacy outcome answer different questions. A strong separation on the primary response measure does not substitute for a comprehensive safety analysis, and descriptive serious adverse event counts do not establish comparative risk. Reading the record statistically means keeping the estimand, analysis method, uncertainty, safety information, and unreported details distinct.

19. 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 registry’s outcome description contains a specific missing-data rule referring to missing data at Week 1, while the primary endpoint is assessed at Week 12. The record does not explain this wording or detail how other missing outcome observations were handled. It also does not report the amount or pattern of missing data, or sensitivity analyses that might show whether conclusions depend on the stated non-responder classification.

The sponsor’s reported tests are identified as CMH chi-square analyses, but the registry does not report their effect estimates, confidence intervals, test statistics, or any stratification details. The posted recalculations are unadjusted and therefore cannot verify any adjustment used in the sponsor’s analysis. The discrepancy indicator is false, but that does not fill in the methodological details absent from the record.

The registry does not report the original sample-size assumptions, interim-analysis procedures, a complete statistical analysis plan, or a multiplicity strategy. These omissions limit assessment of whether all analyses followed a prespecified plan and how the secondary findings should be weighted. Detailed numerical results are also not reported for the listed DLQI and later PASI outcomes, limiting assessment of consistency across those domains.

The primary outcome is a threshold-based response and does not preserve all information in the underlying PASI score. The study summary also does not provide detailed information about participant characteristics, treatment adherence, or follow-up completeness. These limitations do not negate the posted group contrast, but they constrain conclusions about robustness, generalizability, dose comparisons, longer-term outcomes, and the full safety profile.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: A Study of the Safety and Efficacy of Ustekinumab (CNTO 1275) in Patients With Moderate to Severe Psoriasis — NCT00307437.
• Registry record last updated 2013-01-24; status last verified 2013-01.
• Results first posted 2012-11-02.
• 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.

23. Record Summary

The registry describes a completed, randomized, triple-masked, parallel-group, placebo-controlled phase 3 trial of ustekinumab in moderate to severe plaque-type psoriasis. Enrollment is listed as 1230, with study start recorded as 2005-05 and primary completion as 2006-12.

The primary endpoint was the number of participants reaching at least 75 percent PASI improvement at Week 12. The posted response counts were 15.0 for placebo, 273.0 for ustekinumab 45 mg, and 311.0 for ustekinumab 90 mg. Sponsor-reported CMH tests give p <0.001 for each active-dose comparison with placebo. Unadjusted recalculations also show positive risk differences with confidence intervals excluding zero.

The registry lists physician global assessment, DLQI, and later PASI outcomes as secondary outcomes; detailed numerical results are not reported for all of them. Serious adverse event counts are posted for the labeled CP and After CP periods, but deaths are not reported. Details of multiplicity control, full missing-data handling, the original design assumptions, and the complete statistical analysis plan are not reported in the registry record.