This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Randomized, Double-blind Study Comparing Tremelimumab to Placebo in Subjects With Unresectable Malignant Mesothelioma (NCT01843374), a randomized phase 2 study. The primary outcome is Overall Survival (OS).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01843374 |
| Phase | Phase 2 |
| Condition | Unresectable Pleural or Peritoneal Malignant Mesothelioma |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Quadruple |
| Enrollment | 571 |
| Arms in the primary outcome | n/a |
| Lead sponsor | MedImmune LLC |
| Results posted | Yes |
2. Clinical Question
Population
Subjects with unresectable pleural or peritoneal malignant mesothelioma receiving second- or third-line treatment. The primary outcome is specified for the ITT population.
Intervention
Tremelimumab, a study drug assigned in the randomized comparison.
Comparator
Placebo, assigned alongside tremelimumab in a parallel-group design.
Primary question
How does overall survival compare by treatment arm over the stated 3 years? The registry lists overall survival as the primary outcome, but the primary outcome results are not reported in the registry record.
The study was designed to compare assigned treatment groups in a population with unresectable pleural or peritoneal malignant mesothelioma. Its official title specifies second- or third-line treatment. The brief summary describes randomization in a 2:1 ratio to tremelimumab or placebo. Random assignment is intended to support a fair comparison of groups, although the registry record does not report the detailed allocation procedure or how the assignment sequence was generated.
The main statistical question concerns overall survival, with the outcome described as the number of participants and a timeframe of 3 years. The record identifies the ITT population for this endpoint. It does not report the number of participants alive at a specified time, a survival estimate, a treatment-effect estimate, a confidence interval, or a primary-outcome significance test. Thus, the clinical question can be identified, but its answer cannot be read from the posted primary-outcome information.
3. Trial Design
This is a Phase 2b, randomized, double-blind, parallel-group study of tremelimumab compared with placebo. The condition listed is unresectable pleural or peritoneal malignant mesothelioma, and the official title specifies second- or third-line treatment. The registry lists quadruple masking. It does not explain which groups of people were masked or how masking was maintained.
The brief summary describes a planned 2:1 randomization ratio and approximately 564 subjects to be enrolled at study centers in multiple countries. The recorded enrollment is 571. These are different descriptions of planned and recorded enrollment; the registry does not explain the difference. The reported enrollment alone does not establish how many participants were assigned to each arm or included in each outcome analysis.
The stated study periods include screening, treatment, a 90-day safety follow-up, and long-term survival follow-up. The listed primary-outcome timeframe is 3 years. The study start is recorded as 2013-05-17, and primary completion as 2016-01-24. Its status is active, not recruiting. These registry entries describe the study record; they do not establish the timing or completeness of every participant’s follow-up.
The interventions are tremelimumab and placebo. The registry lists secondary outcomes that include overall-survival rate at 18 months, progression-free survival, response and disease-control outcomes, and adverse-event counts. It lists 10 outcome measures and 3 analyses, but does not explain the analyses or identify how those analyses relate to particular outcomes. The exact dosing, visit schedule, randomization procedure, and operational details are not reported in the registry record.
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: A total of 658 patients were screened, 87 patients were excluded from randomisation and 571 patients were randomised: Of the 78 excluded, 66 did not meet inclusion/exclusion criteria; 19 withdrew consent and 2 were excluded for other reasons.
Overall Study
| Stage | PLACEBO | TREMELIMUMAB |
|---|---|---|
| STARTED | 189 | 382 |
| RANDOMIZED | 189 | 382 |
| COMPLETED | 0 | 3 |
| NOT COMPLETED | 189 | 379 |
Reasons for not completing this period:
| Reason | PLACEBO | TREMELIMUMAB |
|---|---|---|
| Death | 155 | 313 |
| Withdrawal by Subject | 14 | 20 |
| Withdrawing due to Other reason | 20 | 46 |
Analysis population for the primary outcome, as defined in the registry: ITT population
5. Baseline Characteristics
The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.
| Characteristic | Unit | TREMELIMUMAB | PLACEBO | Total |
|---|---|---|---|---|
| Participants analysed | 382 | 189 | 571 | |
| Age, Continuous | Years | 65.2 (SD 9.24) | 66.3 (SD 8.8) | 65.6 (SD 9.10) |
| Age, Customized: < 65 years | Participants | 162 | 75 | 237 |
| Age, Customized: >= 65 years | Participants | 220 | 114 | 334 |
| Sex: Female, Male: Female | Participants | 99 | 38 | 137 |
| Sex: Female, Male: Male | Participants | 283 | 151 | 434 |
6. Primary Endpoint
The registry lists the primary outcome as Overall Survival (OS), measured over 3 years..
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | Number of Participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is overall survival, described in the registry as the number of participants by treatment arm, in the ITT population, with a timeframe of 3 years. Overall survival is used in clinical trials to describe survival over time. In general, it is an important endpoint because it concerns whether participants are alive rather than relying only on a measure of tumor response or disease progression. That general explanation does not establish how this trial defined or analyzed survival at the participant level.
The registry wording gives a timeframe and outcome category, but does not specify the precise event definition, the timing of assessment, or whether the reported measure was a fixed-time count, a survival proportion, or another summary. It also does not provide the number of participants analyzed, arm-specific results, an estimate of the contrast between arms, or a confidence interval. The primary endpoint results are not reported in the registry record.
Survival data are often analyzed with methods that account for different follow-up lengths and participants whose eventual outcome is not known by the end of observation. That is a general feature of time-to-event analysis, not a description of the analysis used in this study. The registry record does not report whether such methods were used, how censoring was handled, or whether the primary analysis used a particular survival model. Consequently, the endpoint’s stated purpose is clear, while its operational definition and numerical result remain unavailable in the record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry identifies overall survival as the primary outcome and names the ITT population and a 3 years timeframe. It does not report the primary outcome result. In particular, there are no arm-specific survival counts or estimates, no estimate of the treatment contrast, no confidence interval, and no primary-outcome p-value in the registry record. The primary outcome therefore cannot be interpreted as showing either a difference or no difference between the assigned groups.
The posted safety information gives serious adverse-event counts among 189 participants at risk in the placebo group, with 85 affected, and among 380 participants at risk in the tremelimumab group, with 218 affected. Separate other-event counts are 159 of 189 for placebo and 338 of 380 for tremelimumab. These are counts, not a complete account of safety: the record excerpt does not specify the definitions attached to the separate other-event category, event severity beyond the serious category, timing, or whether events were considered related to treatment. The groups also differ in the numbers at risk, so the raw counts alone do not convey a treatment comparison adjusted for exposure or follow-up.
The registry lists serious-event terms including Diarrhoea, Dyspnoea, Colitis, Vomiting, Pericardial effusion, and Ascites, with corresponding percentages of 18.2%, 12.7%, 6.3%, 3.7%, 3.2%, and 3.2%. The record does not make clear in this information which arm or denominator applies to each listed percentage. These values should therefore be read as registry-listed term percentages, not as arm-specific risks or a comparison between treatments.
Deaths are listed as 160 in the placebo group and 318 in the tremelimumab group. These counts are part of the posted safety information and should not be substituted for the primary overall-survival result. The record does not specify their timing, analysis population, follow-up completeness, or relationship to the survival endpoint. No conclusion about comparative survival or treatment effect can be drawn from these death counts alone.
In general, a confidence interval communicates the range of effect values compatible with the data and analysis, while a p-value addresses compatibility with a specified null hypothesis under an analysis model. Neither can be interpreted in this case because primary-outcome estimates and inferential statistics are not reported in the registry record. The displayed safety counts likewise do not supply a causal estimate. They describe recorded event counts, with important details of measurement and comparison not available.
9. Statistical Methods Explained
The registry gives limited information about the statistical methods used to analyze the outcomes. It identifies the primary endpoint as overall survival in the ITT population, but does not report the primary analysis method, the effect measure, the handling of follow-up, or inferential results. The explanations below distinguish general statistical concepts from methods documented for this trial.
What does randomization contribute?
In general, randomization assigns participants to treatment groups by chance. If implemented as intended, it helps make the groups comparable with respect to measured and unmeasured characteristics at the time of assignment. It does not guarantee that every characteristic will be balanced, especially in a particular realized trial. The registry describes a randomized study and a 2:1 planned assignment ratio. The method for generating or concealing assignments is not reported in the registry record.
The study is also described as double-blind and as having quadruple masking. In general, masking is intended to limit the influence of treatment knowledge on participant behavior, clinical care, outcome assessment, or analysis. The record does not identify which people were masked, the procedures used, or whether masking was maintained. These details therefore cannot be evaluated from the registry information.
What does the ITT population mean?
In general, an intention-to-treat analysis includes participants according to their randomized group, regardless of whether they completed treatment as planned. This approach aims to preserve the comparison created by randomization. The registry identifies the ITT population for the primary overall-survival outcome, but does not define the analysis set in detail, state how participants with missing outcome information were handled, or report the number analyzed in each arm. The exact implementation should not be assumed from the label alone.
How should survival analysis be understood?
In general, time-to-event data record how long it takes for an event to occur. Some participants may not experience the event during their observed follow-up, or their follow-up may end before their eventual status is known. Survival methods can account for this incomplete observation through censoring, provided the relevant assumptions and procedures are suitable. A survival curve can describe the probability of remaining event-free over time, while other methods can estimate a contrast between groups. These are general concepts; the registry does not state which survival methods, model, or effect measure were used for this trial.
The primary endpoint is described as overall survival by treatment arm, with the number of participants as its unit and a timeframe of 3 years. That wording does not reveal whether the primary analysis used a fixed-time count, a survival curve, or another summary. The registry also does not report the number of deaths included in the primary analysis or the duration of follow-up used for each participant. The death counts in the safety information do not resolve those questions.
What do counts and uncertainty convey?
The posted serious adverse-event information reports how many participants were at risk and how many were affected in each treatment group. Counts can be useful descriptions, but do not by themselves express uncertainty or account for differences in follow-up. In general, a confidence interval provides a range of values compatible with the data under the chosen statistical model. Its width reflects precision, and its interpretation depends on the analysis assumptions. No confidence interval for the primary outcome or safety comparisons is reported in the registry record.
In general, over-dispersion is a concern when observed variation in count outcomes is greater than a statistical model expects. A model that fails to accommodate that extra variation can understate uncertainty. The registry classifies the outcome kind as participants with an event, reported as counts, but does not report a model for the primary analysis, an over-dispersion assessment, or a variance adjustment. It is therefore not possible to say whether over-dispersion was relevant or how it was addressed.
What do the planning illustrations represent?
The planning illustrations are described as calculations based on the observed effect, rather than the trial’s own design justification. Their stated assumptions are a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation; the effect to detect is a stated fraction of the observed effect. For time-to-event outcomes, the illustrations give a total number of events using the Schoenfeld approach, while other outcomes give participants per arm. These are planning illustrations, not observed power and not evidence that the trial used those assumptions.
The equal-allocation assumption in those illustrations differs from the 2:1 ratio described for trial randomization. The registry does not report the sponsor’s sample-size justification, the effect size targeted in the original design, or whether the illustration assumptions match the trial’s protocol. Nor does it report the detailed statistical analysis plan. The numerical planning outputs cannot be reconstructed from the information in the registry record and are not presented as trial results.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists multiple outcomes, including overall survival at 18 months, progression-free survival, overall response, duration of response, disease control, durable disease control, and adverse-event counts. It identifies overall survival as the primary outcome and lists 10 outcome measures and 3 analyses. However, the registry does not explain how the analyses map to the listed outcomes, which comparisons were prespecified, or how the analysis handled the possibility of multiple statistical tests.
In general, when several outcomes or comparisons are tested, the chance of obtaining at least one apparently unusual result can increase. Statistical plans may address this through a prespecified hierarchy, adjusted significance thresholds, or other procedures. Those are general options, not methods documented for this study. A multiplicity adjustment or testing strategy is not reported in the registry record. Since the primary results and secondary test results are also not reported in the registry record, no conclusion about their statistical significance or the control of false-positive findings can be made.
The record names the ITT population for the primary endpoint, but does not describe missing outcome data, losses to follow-up, censoring rules, or sensitivity analyses. In general, missingness can affect interpretation when the chance that an outcome is unavailable is related to participants’ health or outcomes. Appropriate handling depends on the outcome and the reasons for missingness. No specific missing-data method is reported in the registry record, so it would be inappropriate to infer how missing information was managed.
The registry lists a primary-outcome timeframe of 3 years and a long-term survival follow-up period, but does not provide follow-up completeness or a detailed analysis population for each outcome. It also does not explain whether participants were analyzed in groups as randomized for every secondary endpoint. These omissions limit assessment of outcome-specific denominators and the robustness of the reported comparisons.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| PLACEBO | 85 | 189 | 45.0% |
| TREMELIMUMAB | 218 | 380 | 57.4% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| PLACEBO | 160 of 189 |
| TREMELIMUMAB | 318 of 382 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| PLACEBO | 159 of 189 |
| TREMELIMUMAB | 338 of 380 |
Most frequent serious adverse event terms
| Event term | Organ system | PLACEBO | TREMELIMUMAB |
|---|---|---|---|
| Diarrhoea | Gastrointestinal disorders | 1 of 189 | 69 of 380 |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | 24 of 189 | 29 of 380 |
| Colitis | Gastrointestinal disorders | 0 of 189 | 24 of 380 |
| Vomiting | Gastrointestinal disorders | 7 of 189 | 12 of 380 |
| Pneumonia | Infections and infestations | 6 of 189 | 11 of 380 |
| Pericardial effusion | Cardiac disorders | 6 of 189 | 9 of 380 |
| General physical health deterioration | General disorders | 4 of 189 | 9 of 380 |
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | 6 of 189 | 6 of 380 |
| Abdominal pain | Gastrointestinal disorders | 4 of 189 | 7 of 380 |
| Pyrexia | General disorders | 0 of 189 | 11 of 380 |
Most frequent non-serious adverse event terms
| Event term | Organ system | PLACEBO | TREMELIMUMAB |
|---|---|---|---|
| Diarrhoea | Gastrointestinal disorders | 35 of 189 | 168 of 380 |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | 60 of 189 | 103 of 380 |
| Decreased appetite | Metabolism and nutrition disorders | 45 of 189 | 110 of 380 |
| Fatigue | General disorders | 60 of 189 | 91 of 380 |
| Nausea | Gastrointestinal disorders | 38 of 189 | 103 of 380 |
| Constipation | Gastrointestinal disorders | 53 of 189 | 65 of 380 |
| Pruritus | Skin and subcutaneous tissue disorders | 15 of 189 | 103 of 380 |
| Cough | Respiratory, thoracic and mediastinal disorders | 29 of 189 | 66 of 380 |
| Rash | Skin and subcutaneous tissue disorders | 14 of 189 | 76 of 380 |
| Vomiting | Gastrointestinal disorders | 16 of 189 | 71 of 380 |
Serious events with the highest arm-level rate: diarrhoea (18.2%), dyspnoea (12.7%), colitis (6.3%), vomiting (3.7%), pericardial effusion (3.2%).
The serious adverse-event counts are reported by treatment group. In the placebo group, 189 participants were at risk and 85 were affected; in the tremelimumab group, 380 were at risk and 218 were affected. The record separately gives other-event counts of 159 among 189 at risk for placebo and 338 among 380 at risk for tremelimumab. These are participant counts. The registry information does not define the separate other-event category in enough detail to characterize it further.
The listed serious-event terms are Diarrhoea at 18.2%, Dyspnoea at 12.7%, Colitis at 6.3%, Vomiting at 3.7%, Pericardial effusion at 3.2%, and Ascites at 3.2%. The information does not identify the arm or denominator for those percentages. They should not be interpreted as percentages within each treatment group unless that denominator is established elsewhere in the registry record.
In general, an adverse-event count does not establish that the treatment caused the event. A comparison also depends on participant exposure, follow-up duration, event definitions, and whether repeated events or participants are counted. Those details are not reported in the registry record. The listed deaths, 160 in placebo and 318 in tremelimumab, should be kept distinct from the primary overall-survival analysis: the record does not specify that the counts are the analyzed primary endpoint results.
12. What the Result Does, and Does Not, Mean
The record establishes that a randomized, double-blind, parallel-group Phase 2b study compared tremelimumab with placebo in subjects with unresectable pleural or peritoneal malignant mesothelioma. It identifies overall survival as the primary outcome, specifies the ITT population, and gives a timeframe of 3 years. These details define the intended comparison and outcome, but do not provide the primary result.
Without arm-specific primary-outcome estimates, an effect estimate, a confidence interval, or an inferential test, the registry information does not show whether the survival outcomes differed between assigned groups or how precisely any difference was estimated. The absence of those results is not evidence that the groups had identical outcomes. It means the comparative primary outcome cannot be assessed from the registry record.
The safety information documents participant counts affected by serious adverse events, other events, and deaths, as well as several listed serious-event terms and percentages. Those data describe what the registry reports, but lack details needed for a full comparative safety interpretation, including the denominator for the listed term percentages and relevant exposure and follow-up information. Counts alone cannot establish whether an event was caused by treatment or whether one group had a higher event rate.
In general, randomized comparisons can support causal interpretation when allocation, follow-up, outcome measurement, and analysis are appropriate. That general principle does not remove the need to examine the actual estimates and methods. The registry does not report enough information to assess the trial’s primary statistical analysis, missing-data handling, or multiplicity procedures. The record therefore supports a description of study design and selected safety counts, but not a conclusion about comparative efficacy or a complete evaluation of comparative harms.
The planning illustrations are not results from the trial and are not observed power. Their stated assumptions describe a planning calculation based on an observed effect; they do not replace a reported treatment-effect estimate or uncertainty interval. The sponsor’s original design justification is not reported in the registry record.
13. Why This Trial Matters Statistically
This trial is statistically notable in the way its design and posted outcome information need to be kept separate. Randomization and masking describe how the study sought to structure a treatment comparison. The primary outcome is identified as overall survival, but the numerical result and analysis details are not reported in the registry record. Design labels alone cannot answer the treatment comparison.
The study describes a planned 2:1 allocation, while the planning illustrations use equal allocation. That distinction matters because planning assumptions are not automatically the same as the actual trial design. The illustrations are explicitly based on an observed effect and are not the trial’s own design justification. They should be understood as planning calculations, not as a statement about the study’s probability of finding a result.
The record also demonstrates why counts need context. Serious-event counts are available for both groups, but counts alone do not supply uncertainty, exposure-adjusted comparisons, or causal attribution. The term percentages are listed without a clear denominator or arm assignment in the record information. Likewise, death counts in a safety display cannot substitute for a defined analysis of overall survival.
In general, sound interpretation requires the outcome definition, analysis population, effect estimate, uncertainty, and handling of follow-up and missing data. Here, the ITT population and timeframe are stated, but important analysis details and primary results are absent. Recognizing that boundary is statistically important: it avoids treating the existence of an endpoint, a planning illustration, or an event count as if it were a reported estimate of treatment effect.
14. Limitations
- The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
- Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.
The most important limitation of the available registry information is that it does not report the primary overall-survival results. The record supplies no arm-specific survival estimates, primary effect estimate, confidence interval, or significance test. Although it identifies the ITT population and a timeframe of 3 years, it does not explain the exact endpoint definition or analysis method.
The record does not describe the randomization sequence, allocation concealment, details of masking, or the populations included in each outcome analysis. It lists quadruple masking but does not identify the masked groups. The planned enrollment of approximately 564 and recorded enrollment of 571 are both stated, but the record does not explain the difference or provide complete arm-specific outcome denominators.
Important follow-up and missing-data details are not reported in the registry record. These include follow-up completeness, censoring procedures, loss to follow-up, missing-outcome handling, and sensitivity analyses. The record also does not report the multiplicity strategy for the listed outcomes, the prespecified analysis plan, or the sponsor’s sample-size justification. These omissions prevent a full evaluation of statistical robustness.
Safety interpretation is limited by the lack of detail on the other-event category, event timing, exposure, and the denominator and treatment-group attribution for the listed serious-event percentages. The posted counts cannot independently establish event rates or causation. The deaths listed in the safety information are not accompanied by details showing how they relate to the primary survival analysis.
Finally, the planning illustrations are not the original design justification and use equal allocation, whereas the described study assignment ratio is 2:1. The illustrations should not be used as a substitute for primary results or interpreted as observed power. The limitations above concern what the registry record reports; they do not establish that the study protocol or other records lack these details.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Randomized, Double-blind Study Comparing Tremelimumab to Placebo in Subjects With Unresectable Malignant Mesothelioma — NCT01843374.
- Registry record last updated 2026-07-27; status last verified 2026-06.
- Results first posted 2017-08-17.
- Data retrieved from ClinicalTrials.gov on 2026-11-09.
- Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.
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18. Record Summary
The registry record describes NCT01843374, a Phase 2b randomized, double-blind, parallel-group comparison of tremelimumab and placebo in subjects with unresectable pleural or peritoneal malignant mesothelioma. The official title specifies second- or third-line treatment. Planned assignment is described as 2:1, with approximately 564 subjects expected; recorded enrollment is 571. The status is active, not recruiting.
Overall survival is the primary outcome, with the ITT population and a 3 years timeframe specified. The primary results and statistical analysis details are not reported in the registry record. Safety information includes serious-event counts of 85 among 189 at risk for placebo and 218 among 380 at risk for tremelimumab, along with separate other-event counts and deaths. The listed serious-event percentages lack a stated arm or denominator in the available information.
The record lists 10 outcome measures and 3 analyses, but does not describe multiplicity handling, missing-data methods, or the sponsor’s design justification. Planning illustrations use stated assumptions and are not trial results or observed power.