This page separates reported trial results from statistical interpretation. Numerical results are restricted to the ClinicalTrials.gov record for NCT04256421. ClinicalTrials.gov provides the official trial registry record.
1. Trial at a Glance
SKYSCRAPER-02 was a randomized, parallel-group, triple-masked phase 3 trial evaluating whether adding tiragolumab to atezolizumab, carboplatin, and etoposide improved time-to-event and response outcomes compared with placebo plus atezolizumab, carboplatin, and etoposide in patients with untreated small cell lung cancer.
| Feature | SKYSCRAPER-02 |
|---|---|
| Phase | Phase 3 |
| Condition | Small Cell Lung Cancer |
| Brief title | A Study of Atezolizumab Plus Carboplatin and Etoposide With or Without Tiragolumab in Patients With Untreated Extensive-Stage Small Cell Lung Cancer |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Triple |
| Primary purpose | Treatment |
| Enrollment | 490 |
| Primary endpoints | 2; both time-to-event endpoints |
| Results posted | Yes |
| Outcome measures posted | 25 |
| Statistical analyses posted | 14 |
| Lead sponsor | Hoffmann-La Roche |
| Sponsor type | Industry |
2. Clinical Question
The primary statistical question was whether adding tiragolumab to atezolizumab plus carboplatin and etoposide produced a superior time-to-event outcome compared with placebo plus atezolizumab plus carboplatin and etoposide in patients with untreated extensive-stage small cell lung cancer.
Population
Patients with untreated extensive-stage small cell lung cancer, as described by the study's brief title and registered population definitions.
Intervention
Tiragolumab plus atezolizumab, carboplatin, and etoposide.
Comparator
Placebo plus atezolizumab, carboplatin, and etoposide.
Primary question
Does the tiragolumab-containing regimen improve investigator-assessed PFS and OS relative to the placebo-containing regimen?
3. Trial Design
Control regimen
- Placebo
- Atezolizumab
- Carboplatin
- Etoposide
Investigational regimen
- Tiragolumab
- Atezolizumab
- Carboplatin
- Etoposide
4. Randomization, Stratification, and Analysis Populations
The posted primary and secondary time-to-event analyses were performed using stratified methods. The registry identifies lactate dehydrogenase (LDH) and Eastern Cooperative Oncology Group (ECOG) status as the stratification factors used in the reported primary analyses.
| Population | Registry definition / role |
|---|---|
| Primary Analysis Set (PAS) | All randomized participants without presence or history of brain metastases at baseline. |
| Full Analysis Set (FAS) | All randomized participants, whether or not the participant received the assigned treatment. |
| PAS for OS rates | All randomized participants without presence or history of brain metastases at baseline; for the posted rate analysis, the overall number analyzed is the number of participants with data available for analysis. |
| FAS for OS rates | All randomized participants, whether or not the participant received the assigned treatment; the posted analysis uses participants with data available for analysis. |
This distinction is statistically important. The PAS excludes participants with the presence or history of brain metastases at baseline, whereas the FAS includes all randomized participants regardless of whether assigned treatment was received. The choice of population therefore changes the estimand being summarized.
5. Primary Endpoints
| Endpoint | Registered definition and time frame | Primary analysis |
|---|---|---|
| Investigator-assessed Progression-free Survival (PFS) in the PAS | From randomization to the first occurrence of PD or death from any cause, whichever occurred first (up to approximately 24 months)). PFS was defined as the time from randomization to the first documented PD as determined by the investigator with the use of RECIST v1.1 or death from any cause, whichever occurred first. | Stratified log-rank comparison; hazard ratio reported. |
| Overall Survival (OS) in the PAS | From randomization to death from any cause (up to approximately 24 months). | Stratified log-rank comparison; hazard ratio reported. |
6. Statistical Methodology
Time-to-event analysis
Both primary endpoints are time-to-event outcomes. PFS measures the time from randomization until the first occurrence of progression or death, whichever comes first. OS measures the time from randomization until death from any cause.
These endpoints differ from simple binary outcomes because not every participant necessarily experiences the event during the observation period. Participants without an observed event contribute information up to their censoring time. This makes methods such as Kaplan-Meier estimation and the log-rank test natural tools for analyzing randomized survival data.
Stratified log-rank test
The registry reports the log-rank test for both primary endpoints and identifies stratified analysis as an additional concept. The reported stratification factors were LDH (> ULN vs. ≤ ULN) and ECOG (0 vs. 1).
Stratification allows the comparison of treatment groups to account for prespecified categorical factors when evaluating time-to-event outcomes. Conceptually, instead of treating every participant as belonging to a single undifferentiated risk set, the analysis respects the prespecified strata and combines information across them.
The log-rank test evaluates evidence against equality of the survival experience between the randomized groups. The hazard ratio provides a separate measure of the relative event rate.
Hazard ratio
The primary PFS analysis produced an HR of 1.11, while the primary OS analysis produced an HR of 1.14, with Arm A listed first in both comparisons: placebo + atezolizumab versus tiragolumab + atezolizumab.
Because the registry lists Arm A first and Arm B second, an HR above 1 corresponds to a higher estimated instantaneous event rate in the placebo + atezolizumab arm relative to the tiragolumab + atezolizumab arm. The confidence interval and p-value determine how precisely and convincingly that estimate distinguishes the groups.
Wald / z-test
The registry reports a Wald / z-test for the secondary OS-rate analyses at months 12 and 24. This is a different statistical framework from the log-rank comparison of the entire time-to-event experience. A fixed-time survival rate comparison asks about the event-free proportion at a specified month rather than comparing the full time-to-event distributions.
Cochran-Mantel-Haenszel test
Confirmed objective response rate was analyzed with a Cochran-Mantel-Haenszel test. This is appropriate for comparing a binary response outcome while accounting for prespecified strata. The registry identifies LDH and ECOG as the stratification factors in these analyses.
7. Primary Results: Progression-Free Survival
The posted primary PFS analysis compared investigator-assessed PFS in the PAS between placebo + atezolizumab and tiragolumab + atezolizumab. The analysis used a log-rank test with stratification by LDH and ECOG.
Investigator-assessed PFS
95% CI: 0.89–1.38 · P = 0.3504
PAS: all randomized participants without presence or history of brain metastases at baseline.
| Feature | Reported result |
|---|---|
| Comparison | Arm A: Placebo + Atezolizumab vs Arm B: Tiragolumab + Atezolizumab |
| Endpoint | Investigator-assessed Progression-free Survival (PFS) in the PAS |
| Analysis | Log-rank test |
| Effect measure | Hazard ratio |
| Estimate | 1.11 |
| 95% CI | 0.89–1.38 |
| P-value | 0.3504 |
| Stratification | LDH (> ULN vs. ≤ ULN) and ECOG (0 vs. 1) |
The reported HR of 1.11 means that, with Arm A as the numerator in the comparison, the estimated instantaneous rate of progression or death was 1.11 times the corresponding rate in Arm B under the reported time-to-event analysis. Put another way, the point estimate is above 1 rather than below 1.
It does not mean that 11% more participants progressed, that the absolute probability of progression was 11% higher, or that every individual experienced an 11% difference in risk. A hazard ratio is a relative, model-based time-to-event measure.
The 95% CI of 0.89–1.38 indicates substantial uncertainty around the point estimate. It includes 1, so the reported interval is compatible with both a lower and a higher instantaneous event rate for Arm A relative to Arm B.
The p-value of 0.3504 is evidence about compatibility with the null hypothesis under the specified statistical test; it is not a measure of the size or clinical importance of the effect. The p-value should therefore be interpreted alongside the HR and its confidence interval.
Because PFS is a censored time-to-event endpoint, interpretation also depends on the censoring rules and on the assumptions underlying the survival analysis. A single hazard ratio is most straightforward to interpret when the relative hazards are reasonably stable over time; the ClinicalTrials.gov record does not provide a separate assessment of the proportional-hazards assumption.
8. Primary Results: Overall Survival
The primary OS analysis evaluated time from randomization to death from any cause in the PAS. As with PFS, the registry reports a stratified log-rank analysis using LDH and ECOG as stratification factors.
Overall Survival
95% CI: 0.90–1.44 · P = 0.2859
Time frame: from randomization to death from any cause, up to approximately 24 months.
| Feature | Reported result |
|---|---|
| Comparison | Arm A: Placebo + Atezolizumab vs Arm B: Tiragolumab + Atezolizumab |
| Endpoint | Overall Survival (OS) in the PAS |
| Analysis | Log-rank test |
| Effect measure | Hazard ratio |
| Estimate | 1.14 |
| 95% CI | 0.90–1.44 |
| P-value | 0.2859 |
| Time frame | From randomization to death from any cause (up to approximately 24 months) |
| Stratification | LDH (> ULN vs. ≤ ULN) and ECOG (0 vs. 1) |
The OS HR of 1.14 indicates that the estimated instantaneous rate of death in Arm A was 1.14 times the corresponding rate in Arm B in the reported analysis. The direction of the point estimate therefore corresponds to a higher estimated hazard in Arm A, but the estimate alone should not be interpreted as an absolute increase in mortality.
The 95% CI of 0.90–1.44 crosses 1.00. This means the confidence interval includes values corresponding to a lower event rate in Arm A as well as values corresponding to a higher event rate. The interval is therefore important for understanding the uncertainty that accompanies the point estimate.
The p-value of 0.2859 is not an effect-size measure. A larger or smaller p-value does not tell us directly how clinically large the treatment difference is. Effect magnitude and statistical uncertainty are better assessed by considering the HR together with its confidence interval and the endpoint definition.
The OS analysis is also subject to ordinary time-to-event considerations, including censoring and the interpretation of a hazard ratio over time. The ClinicalTrials.gov record does not report a separate proportional-hazards diagnostic, so no conclusion about that assumption should be inferred from the HR alone.
9. Secondary Time-to-Event Results
The registry contains additional formal analyses of PFS, OS, and time to confirmed deterioration. These analyses are useful for understanding how the statistical conclusions behave across different analysis populations and patient-reported outcome endpoints.
| Endpoint | Population | HR | 95% CI | P-value |
|---|---|---|---|---|
| PFS | FAS | 1.08 | 0.89–1.31 | 0.4440 |
| OS | FAS | 1.09 | 0.88–1.35 | 0.4205 |
| TTCD of EORTC QLQ-C30 Physical Functioning | PAS | 1.00 | 0.68–1.48 | 0.9819 |
| TTCD of EORTC QLQ-C30 Physical Functioning | FAS | 1.12 | 0.81–1.55 | 0.5122 |
| TTCD of EORTC QLQ-C30 GHS/QoL | PAS | 1.20 | 0.81–1.79 | 0.3614 |
| TTCD of EORTC QLQ-C30 GHS/QoL | FAS | 1.29 | 0.90–1.84 | 0.1681 |
All six analyses used the log-rank test and incorporated the same reported LDH and ECOG stratification factors. The direction of the HRs varies numerically, but the confidence intervals for all six analyses include 1.
10. Objective Response Rate
Confirmed investigator-assessed objective response rate was analyzed as a binary endpoint. The registry reports a Cochran-Mantel-Haenszel analysis with the effect measure expressed as the difference in overall response rates.
| Population | Estimate | 95% CI | P-value | Method |
|---|---|---|---|---|
| PAS | 6.80 | -2.57 to 15.99 | 0.1418 | Cochran-Mantel-Haenszel test |
| FAS | 5.19 | -3.33 to 13.61 | 0.2191 | Cochran-Mantel-Haenszel test |
The PAS analysis defines the population as all randomized participants without presence or history of brain metastases at baseline. The FAS analysis includes all randomized participants, whether or not the participant received the assigned treatment.
The reported difference is presented by the registry as the difference in overall response rates. The exact direction should be interpreted in the context of the listed treatment ordering: Arm A is placebo + atezolizumab and Arm B is tiragolumab + atezolizumab.
The PAS estimate of 6.80 has a 95% CI from -2.57 to 15.99. Because the interval crosses zero, the analysis is compatible with a range of possible differences in either direction.
The FAS estimate of 5.19 has a 95% CI from -3.33 to 13.61, again spanning zero. The p-values of 0.1418 and 0.2191 should be interpreted as hypothesis-test results, not as measures of how large or clinically meaningful the response-rate difference is.
11. Overall Survival Rates at 12 and 24 Months
The registry also reports fixed-time OS-rate comparisons at month 12 and month 24. These analyses use a Wald / z-test and express the treatment effect as a difference in event-free rate.
| Population | Time point | Difference in event-free rate | 95% CI | P-value |
|---|---|---|---|---|
| PAS | Month 12 | -3.74 | -13.60 to 6.13 | 0.4580 |
| PAS | Month 24 | -8.12 | -17.80 to 1.55 | 0.0999 |
| FAS | Month 12 | -3.02 | -11.92 to 5.88 | 0.5059 |
| FAS | Month 24 | -5.29 | -14.23 to 3.65 | 0.2458 |
These fixed-time analyses answer a different question from the log-rank test. Instead of comparing the complete survival experience over follow-up, they focus on a specified time point. The confidence intervals for all four posted comparisons include zero.
12. Statistical Methods Explained
Why was a log-rank test used for PFS and OS?
PFS and OS are time-to-event endpoints. Participants can have different follow-up durations, and some participants may not have experienced the event by the time they are censored. The log-rank test is designed to compare survival distributions while using information from the timing of events and accounting for censoring.
What does an HR of 1.11 mean in the PFS analysis?
Because the reported comparison lists placebo + atezolizumab first and tiragolumab + atezolizumab second, an HR of 1.11 means the estimated instantaneous rate of progression or death in the first arm was 1.11 times the corresponding rate in the second arm under the fitted time-to-event analysis. It does not mean that 11% more participants necessarily progressed.
Why is the confidence interval more informative than the point estimate alone?
A point estimate such as 1.11 is only one estimate of the treatment contrast. The 95% CI of 0.89–1.38 shows how uncertain that estimate is within the stated statistical framework. Since the interval includes 1, the data are compatible with effects in either direction around the null value.
Why does the p-value not measure effect size?
A p-value describes how compatible the observed data are with a specified null hypothesis under the statistical model and test. It does not quantify the magnitude of treatment benefit or harm. Two studies can have similar effect estimates but different p-values because of differences in sample size, event information, variability, or other features of the data.
Why use both PAS and FAS?
The PAS and FAS define different analysis populations. The PAS excludes participants with the presence or history of brain metastases at baseline, whereas the FAS includes all randomized participants whether or not they received assigned treatment. Comparing analyses across these populations can show whether the reported treatment contrast is sensitive to the population definition.
Why was the Cochran-Mantel-Haenszel test used for objective response?
Objective response is a binary outcome rather than a time-to-event outcome. A Cochran-Mantel-Haenszel analysis can compare treatment groups while accounting for the trial's stratification factors. This is conceptually different from the log-rank test, which is designed for censored time-to-event data.
Why are fixed-time OS rates different from an OS hazard ratio?
A fixed-time OS rate asks what proportion remains alive at a particular month. A hazard ratio summarizes a relative event-rate contrast over the analyzed time-to-event experience. The two measures therefore provide different perspectives and should not be treated as interchangeable.
13. Safety
The ClinicalTrials.gov record reports serious adverse events by randomized arm. These figures are presented as affected participants divided by the number at risk for the corresponding arm.
| Arm | Serious adverse events, affected / at risk |
|---|---|
| Arm A: Placebo + Atezolizumab | 108 / 246 |
| Arm B: Tiragolumab + Atezolizumab | 109 / 239 |
The ClinicalTrials.gov record does not provide a complete adverse-event table, grade-specific event frequencies, treatment-related event counts, or detailed safety definitions. Accordingly, no additional safety conclusions are drawn here.
14. Blinding and Randomization
The trial is registered as randomized and triple masked. Randomization is central to the causal interpretation of the treatment comparison because, in expectation, it balances measured and unmeasured prognostic factors between treatment groups at assignment.
Masking serves a different purpose. By keeping specified participants or study personnel unaware of treatment assignment, it can reduce the opportunity for treatment knowledge to influence assessment or behavior. The registry's designation of triple masking identifies the design feature, but the ClinicalTrials.gov record does not specify the individual parties included in the masking designation.
Randomization
Creates the foundation for a randomized comparison by assigning participants to the two treatment arms according to the trial's allocation mechanism.
Masking
Triple masking is recorded in the registry. The ClinicalTrials.gov record does not identify each masked role separately.
Stratification
The reported primary analyses account for LDH and ECOG strata.
Analysis population
PAS and FAS analyses answer related but not identical statistical questions because their inclusion criteria differ.
15. Multiplicity and Interpretation of Multiple Analyses
SKYSCRAPER-02 has two primary endpoints and multiple posted secondary analyses. The registry reports superiority as the hypothesis type for the formal analyses reported here, but the ClinicalTrials.gov record does not provide a complete multiplicity-control hierarchy or alpha allocation across all endpoints.
| Analysis family | Reported method | Interpretive issue |
|---|---|---|
| Primary PFS | Log-rank test | Primary time-to-event comparison |
| Primary OS | Log-rank test | Primary time-to-event comparison |
| PFS and OS in FAS | Log-rank test | Secondary analyses in a broader randomized population |
| Confirmed ORR | Cochran-Mantel-Haenszel test | Binary response comparison |
| OS rates at months 12 and 24 | Wald / z-test | Fixed-time comparisons rather than full survival-curve comparisons |
| TTCD endpoints | Log-rank test | Multiple patient-reported time-to-deterioration analyses |
When many hypotheses are examined, the probability of observing at least one apparently unusual result can increase. Formal confirmatory interpretation therefore depends not only on individual p-values but also on the prespecified multiplicity strategy. Because the ClinicalTrials.gov record does not specify that strategy, this page does not assign a confirmatory status beyond the registry's designation of the endpoints as primary or secondary.
16. Crossover, Interim Analysis, and Missing Data
Crossover
The ClinicalTrials.gov record does not report a crossover policy or crossover rate. No crossover effect on OS is therefore inferred.
Interim analysis
The ClinicalTrials.gov record does not report an interim-analysis schedule, stopping boundary, or alpha-spending method.
Missing-data imputation
The ClinicalTrials.gov record does not report a missing-data or imputation strategy for the posted efficacy analyses.
Bayesian methods
No Bayesian method is reported among the registry-reported normalized statistical methods.
These omissions are important because the statistical properties of a clinical trial can depend on how interim monitoring, missing observations, and treatment switching are handled. Where the ClinicalTrials.gov record does not describe those features, the analysis does not attempt to reconstruct them.
17. Understanding the Primary PFS Result
The primary PFS HR was 1.11. With the comparison defined as placebo + atezolizumab versus tiragolumab + atezolizumab, the point estimate corresponds to a higher estimated instantaneous rate of progression or death in the first-listed arm.
The 95% CI was 0.89–1.38. The interval crosses 1, so the data are compatible with a range of relative hazards around the null value. The interval is therefore essential for understanding the uncertainty in the point estimate.
The p-value was 0.3504. It does not quantify the magnitude of the observed HR and should not be translated into a probability that one treatment is effective or ineffective.
PFS is defined using the first occurrence of progression or death. Participants without an observed event may be censored, so the analysis uses partial follow-up information. A hazard ratio also summarizes an event-rate relationship rather than providing an absolute probability for an individual participant.
18. Understanding the Primary OS Result
The primary OS HR was 1.14. With Arm A listed first, the point estimate corresponds to a higher estimated instantaneous death rate in Arm A relative to Arm B under the reported analysis.
The 95% CI was 0.90–1.44. The interval includes 1 and therefore does not isolate one direction of the treatment contrast with high precision.
The p-value was 0.2859. As with PFS, this is a hypothesis-test quantity rather than a direct measure of effect size or clinical importance.
The registered OS time frame was from randomization to death from any cause, up to approximately 24 months) 24 months. This makes OS a time-to-event outcome rather than a simple proportion of participants who died during an unspecified observation period.
19. Why This Trial Matters Statistically
SKYSCRAPER-02 is a useful teaching case because it illustrates how the same randomized comparison can be examined through several complementary statistical lenses. The trial combines randomized allocation, masking, stratified survival analysis, binary response analysis, fixed-time survival-rate comparisons, multiple analysis populations, and patient-reported time-to-deterioration endpoints.
| Concept | How it appears in SKYSCRAPER-02 |
|---|---|
| Randomization | Randomized allocation to two parallel treatment arms. |
| Blinding | Triple masking is recorded in the trial design. |
| Time-to-event endpoints | PFS and OS are both primary endpoints. |
| Log-rank test | Used for primary and secondary time-to-event analyses. |
| Hazard ratio | Used as the effect measure for PFS, OS, and time-to-deterioration analyses. |
| Confidence intervals | Reported as two-sided 95% intervals for the posted formal analyses. |
| Stratified analysis | LDH and ECOG are identified as stratification factors. |
| Cochran-Mantel-Haenszel test | Used for confirmed objective response rate. |
| Wald / z-test | Used for OS rates at months 12 and 24. |
| Analysis populations | PAS and FAS provide distinct efficacy populations. |
| Patient-reported outcomes | Time to confirmed deterioration was analyzed for physical functioning and GHS/QoL. |
20. Limitations
- Registry-level detail: the ClinicalTrials.gov record provides formal estimates and methods for 14 analyses, but they do not provide the complete statistical analysis plan.
- No median PFS or OS: median survival estimates are not included in the ClinicalTrials.gov record and are therefore not reported here.
- No Kaplan-Meier estimates: the ClinicalTrials.gov record does not contain survival probabilities or numbers at risk sufficient to reproduce a Kaplan-Meier curve.
- No baseline table: baseline demographic and disease characteristics are not included in the ClinicalTrials.gov record.
- No subgroup results: the ClinicalTrials.gov record identifies the stratification factors but do not provide subgroup-specific treatment estimates.
- No complete safety profile: only serious adverse-event counts by arm are reported. Grade-specific and event-specific safety results are not added.
- Multiplicity information is incomplete: the ClinicalTrials.gov record does not specify a complete hierarchy or alpha allocation across all primary and secondary analyses.
- Interim monitoring is not described: the ClinicalTrials.gov record does not specify whether an interim efficacy analysis was performed or what stopping boundaries were used.
- Missing-data strategy is not reported: no imputation or censoring-sensitivity framework is reported in the provided dataset.
- Proportional-hazards assessment is not reported: the hazard ratios should not be interpreted as proof that the proportional-hazards assumption holds.
21. What the Hazard Ratio Does — and Does Not — Mean
The HR describes a relative event-rate contrast in the time-to-event analysis. It is not an absolute risk difference and does not describe the experience of every individual participant.
An HR of 1.14 means the estimated instantaneous event rate in the first-listed arm was 1.14 times that in the second-listed arm under the reported model. It does not mean that 14% more participants died.
This distinction is fundamental in survival analysis. A hazard is an instantaneous event-rate concept conditional on remaining event-free up to a given time. A probability, by contrast, describes the proportion experiencing an event by a specified time. Confusing these quantities can lead to substantially different interpretations of the same trial result.
22. Confidence Intervals and Statistical Uncertainty
The primary PFS and OS estimates were accompanied by two-sided 95% confidence intervals. For PFS, the interval was 0.89–1.38; for OS, it was 0.90–1.44.
PFS precision
The PFS interval spans 1 and extends from 0.89 to 1.38, showing that the point estimate of 1.11 should not be treated as a precise measurement.
OS precision
The OS interval spans 1 and extends from 0.90 to 1.44, again showing uncertainty around the point estimate of 1.14.
What the CI is not
A confidence interval is not the range of effects that individual participants experienced. It describes statistical uncertainty around the estimated treatment contrast.
Why the null matters
For a hazard ratio, 1 represents equal hazards. For a difference, 0 represents no difference. The appropriate null value depends on the effect measure.
23. Secondary Endpoint Interpretation
The secondary analyses reinforce the importance of matching the statistical interpretation to the endpoint type.
| Endpoint type | Statistical question | Reported method | Effect measure |
|---|---|---|---|
| Time-to-event | Do the event-time distributions differ? | Log-rank test | Hazard ratio |
| Binary response | Do response rates differ? | Cochran-Mantel-Haenszel test | Difference in overall response rates |
| Fixed-time OS rate | Do event-free rates differ at a specified month? | Wald / z-test | Difference in event-free rate |
Using a single statistical concept for all three endpoint types would obscure important differences. A hazard ratio cannot be substituted directly for a response-rate difference, and a fixed-time survival-rate comparison does not summarize the complete time-to-event distribution.
24. Trial Timeline
Trial start
The registered trial start date was 2020-02-04.
Primary completion
The registered primary completion date was 2022-09-06.
Registry status
The trial is recorded as completed.
25. Trial Results: A Statistical Synthesis
The two primary time-to-event analyses produced HR estimates above 1 when expressed as placebo + atezolizumab versus tiragolumab + atezolizumab: 1.11 for PFS and 1.14 for OS. Both 95% confidence intervals included 1, and the corresponding p-values were 0.3504 and 0.2859.
The secondary analyses were directionally heterogeneous in magnitude but similarly characterized by confidence intervals that included their respective null values. The FAS PFS HR was 1.08 (95% CI 0.89–1.31; P = 0.4440), and the FAS OS HR was 1.09 (95% CI 0.88–1.35; P = 0.4205). Confirmed ORR analyses produced differences of 6.80 and 5.19 in the PAS and FAS, respectively, with both confidence intervals spanning zero.
The patient-reported time-to-deterioration analyses likewise produced HRs ranging from 1.00 to 1.29, with all reported 95% confidence intervals including 1. Taken together, these results illustrate why a trial should be read through its full set of effect estimates, uncertainty intervals, analysis populations, and endpoint definitions rather than through any single p-value.
26. Related Tutorials
Learn more about the methods used in this trial:
27. Related Statistical Calculators
28. Sources
- ClinicalTrials.gov: NCT04256421 — SKYSCRAPER-02. Trial design, endpoint definitions, analysis populations, statistical methods, reported estimates, confidence intervals, p-values, and safety counts used on this page.
- Linked publication: PubMed PMID 37976444.
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29. Record Summary
SKYSCRAPER-02 provides a useful example of how a phase 3 randomized trial can generate several complementary statistical analyses from the same treatment comparison. The primary endpoints were investigator-assessed PFS and OS in the PAS, both analyzed with stratified log-rank methods and reported as hazard ratios. The primary PFS estimate was 1.11 (95% CI 0.89–1.38; P = 0.3504), while the primary OS estimate was 1.14 (95% CI 0.90–1.44; P = 0.2859), with Arm A defined as placebo + atezolizumab and Arm B as tiragolumab + atezolizumab.
The secondary results demonstrate why endpoint-specific methods matter. PFS and OS in the FAS used log-rank testing, confirmed ORR used the Cochran-Mantel-Haenszel test, fixed-time OS rates used a Wald / z-test, and time to confirmed deterioration used log-rank testing. Across these analyses, the appropriate interpretation requires attention to the analysis population, effect measure, confidence interval, p-value, stratification, and endpoint definition.
The ClinicalTrials.gov record does not provide median survival times, Kaplan-Meier estimates, baseline characteristics, subgroup estimates, crossover information, interim-analysis rules, missing-data methods, or a complete multiplicity strategy. Those elements are therefore not reconstructed here. Keeping those distinctions explicit is essential to an independent statistical analysis: the goal is to explain what the reported data support without adding results that are not contained in the source record.