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 A Study of SHR-1210 in Combination With Apatinib in Advanced Non-Small Cell Lung Cancer(NSCLC) (NCT03083041), a randomized phase 2 study. The primary outcome is Incidence and Grade of Adverse Events (AEs) and Serious Adverse Events (SAEs).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT03083041 |
| Phase | Phase 2 |
| Condition | Carcinoma, Non-Small-Cell Lung |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 210 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Jiangsu HengRui Medicine Co., Ltd. |
| Results posted | Yes |
2. Clinical Question
Population
People with locally advanced or metastatic non-small cell lung cancer were eligible for the study. The registry says tumor samples were screened at baseline for EGFR mutations, EML4-ALK translocation, and PD-L1 expression; positive PD-L1 expression was not required for enrollment.
Intervention
The study examined intravenous SHR-1210, 200mg every two weeks, in combination with oral apatinib. The arm descriptions list apatinib doses of 250mg/d, 375mg/d, and 500mg/d.
Comparator
The brief description says Part 2 randomized participants between apatinib 250mg/d and 500mg/d, with SHR-1210 in both groups. The posted adverse-event results instead list apatinib 250 mg and 375 mg groups. The relationship between these descriptions is not reported in the registry record.
Primary question
The stated primary outcome is the incidence and grade of adverse events and serious adverse events. The record gives participant counts for adverse events and serious adverse events, but does not give a dose-comparison analysis of the primary outcome or a grade breakdown.
This is a Phase II study with a randomized, parallel-group description and no masking. The registry reports enrollment of 210. The stated safety follow-up extends from signing informed consent to safety follow-up, over 61 months. That long interval describes the outcome timeframe; it does not by itself establish how consistently events were captured, how follow-up differed among participants, or whether every participant completed follow-up.
The question is therefore principally one of safety across dose combinations, as represented by recorded adverse events. The record also describes a first part focused on safety, tolerability, and pharmacokinetics, followed by a randomized comparison in Part 2. It does not report enough detail to determine which participants or study part underlie each adverse-event group. Nor does the posted outcome summary establish a comparison of tumor response or survival.
3. Trial Design
The registry describes a multicenter, open-label, Phase II study. Its overall model is parallel group, and its allocation is listed as randomized. The brief description separates the study into two parts: an initial assessment of safety, tolerability, and pharmacokinetics, then a randomized comparison of apatinib doses combined with SHR-1210. This structure matters when reading the safety counts, because the record does not explain how participants in the first part relate to the groups listed in the posted outcome results.
SHR-1210 is described as 200mg intravenously every two weeks. The arm descriptions list apatinib at 250mg/d, 375mg/d, or 500mg/d, taken orally once daily. However, the brief description of the randomized comparison names 250mg/d and 500mg/d, while the adverse-event results list only a 250 mg group and a 375 mg group. The record does not reconcile this difference. The 500mg/d arm appears in the intervention descriptions, but corresponding adverse-event figures are not listed in the result summary.
The registry reports enrollment of 210 and status as completed. The study start date is 2017-03-13 and primary completion date is 2022-04-22. Those record dates describe the study timeline, not the timing of individual outcomes. The primary outcome timeframe is given as from signing informed consent to safety follow-up, 61 months.
No masking means treatment assignment was not concealed from participants and study personnel as described by the registry. The record does not report further details about randomization procedures, allocation concealment, stratification, adherence, treatment changes, or the handling of participants who discontinued treatment. These omissions limit the ability to assess how the actual conduct aligned with the summarized design.
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.
Overall Study
| Stage | Driver Gene Negative Population | Driver Gene Positive Population | Cohort 4 | Apatinib 375 mg Group |
|---|---|---|---|---|
| STARTED | 130 | 43 | 25 | 12 |
| Treated | 130 | 43 | 25 | 12 |
| COMPLETED | 75 | 25 | 13 | 1 |
| NOT COMPLETED | 55 | 18 | 12 | 11 |
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 | Driver Gene Negative Population | Driver Gene Positive Population | Cohort 4 | Apatinib 375 mg Group | Total |
|---|---|---|---|---|---|---|
| Participants analysed | 130 | 43 | 25 | 12 | 210 | |
| Age, Continuous | years | 59.0 (35 to 70) | 55.0 (33 to 69) | 61.0 (47 to 69) | 55.5 (43 to 68) | 59 (33 to 70) |
| Sex: Female, Male: Female | Participants | 28 | 18 | 6 | 2 | 54 |
| Sex: Female, Male: Male | Participants | 102 | 25 | 19 | 10 | 156 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Asian | Participants | 130 | 43 | 25 | 12 | 210 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): White | Participants | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): More than one race | Participants | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 | 0 | 0 |
| Region of Enrollment: China | participants | 130 | 43 | 25 | 12 | 210 |
6. Primary Endpoint
The registry lists the primary outcome as Incidence and Grade of Adverse Events (AEs) and Serious Adverse Events (SAEs), measured over from signing the informed consent form to safety follow-up, 61 months.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | participants |
| Endpoint classification | Binary Endpoint |
The stated primary outcome is the incidence and grade of adverse events and serious adverse events. It is measured as the number of participants experiencing these events, with the timeframe running from signing the informed consent form to safety follow-up, 61 months. The registry’s brief outcome description refers to the number of participants with adverse events and serious adverse events.
Safety outcomes are used to describe the types and frequency of unwanted medical events observed during a study. Counts of affected participants can communicate how many people experienced an event, while grades can distinguish levels of severity. Serious adverse events are a separately identified safety category; “serious” is not interchangeable with a severity grade. The registry record does not give the grading criteria or a breakdown of primary-outcome results by grade.
The posted safety figures give counts at risk and counts with serious adverse events and other adverse events for the Apatinib 250 mg and Apatinib 375 mg groups. They do not provide a complete, explicit breakdown of the primary outcome by grade, nor an inferential comparison of the groups. The record also does not explain whether the “other” adverse-event counts are mutually exclusive from the serious adverse-event counts. Therefore, the counts should be read as separately reported categories, not combined into a total.
Safety monitoring is relevant to a study of combinations and dose levels because the outcome concerns events observed during exposure and follow-up. These descriptive counts alone do not establish that treatment caused an event or that the groups differ reliably.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry reports 112 participants with serious adverse events among 198 at risk in the Apatinib 250 mg group, and 7 among 12 at risk in the Apatinib 375 mg group. For other adverse events, it reports 197 among 198 at risk in the 250 mg group and 12 among 12 at risk in the 375 mg group. The death counts are 48 and 3, respectively. These are descriptive counts as posted; the registry record does not report a statistical comparison of these outcomes.
The result groups need cautious interpretation. Although the study description says the randomized comparison involved 250mg/d and 500mg/d, the adverse-event results name a 250 mg group and a 375 mg group. The record does not explain why the reported dose groups differ from the brief description, whether the listed results include both study parts, or how participants were assigned to the displayed groups. Consequently, the figures cannot be treated as a clearly documented randomized comparison of the two doses named in the study description.
The counts at risk differ substantially between the two displayed groups. This makes direct comparison of raw counts particularly uninformative: a larger count can reflect a larger group as well as a different event frequency. Even when denominators are available, interpreting a difference requires clarity about the populations, follow-up, outcome definitions, and analysis method. The registry does not provide an adjusted estimate, confidence interval, or hypothesis test for these event outcomes. No analyses are listed.
The serious-event terms most frequently listed include neoplasm progression and immune-mediated hepatitis, each at 16.7%. Immune-mediated lung disease, pneumothorax, gastrointestinal haemorrhage, and venous thrombosis limb are each listed at 8.3%. The denominator and method used to calculate these percentages are not reported in the registry record. These term percentages should not be interpreted as percentages of all participants without that information, nor as comparative risks by dose.
The death counts are not accompanied by a definition, cause-of-death information, timing, or an analysis relating deaths to treatment. They therefore cannot establish treatment attribution or explain the deaths. Similarly, the outcome summary does not provide efficacy results. Overall, the record supplies descriptive safety information, but it does not resolve a dose-specific safety comparison or establish causal effects.
9. Statistical Methods Explained
The registry identifies a binary outcome format, described as participants with an event (counts). A count is a descriptive summary: it records how many participants in a group met an outcome definition. When the number at risk is also reported, the count can be interpreted in relation to the group assessed, but the meaning of that denominator still depends on the analysis population and follow-up rules. Those details are not reported in the registry record.
What can a confidence interval tell a reader?
General explanation: a confidence interval expresses the uncertainty around an estimated effect under a statistical model. It is useful because an estimate from a study is not the only plausible value consistent with its data. A narrow interval indicates more precision than a wide interval, while an interval spanning values compatible with materially different effects can leave the comparison uncertain. The registry record does not report confidence intervals for the adverse-event outcomes.
Why do raw counts not settle a group comparison?
General explanation: counts depend both on how often an event occurs and on how many people are observed. Comparing counts without accounting for group size can mislead. Even a comparison based on proportions can be difficult to interpret if follow-up duration, eligibility, missing outcomes, or event definitions differ. In this record, counts at risk are reported for the displayed groups, but the underlying analysis populations and exposure or follow-up distributions are not reported. There is also a mismatch between the doses described for the randomized comparison and the dose groups shown in the safety results.
For a binary event outcome, statistical methods may estimate a difference in event proportions, a relative measure, or an adjusted effect. Each addresses a different question and relies on assumptions about the data and study design. The registry lists no analyses for the posted outcomes, so no such comparative estimate can be attributed to the record. No new comparative effect should be inferred from the counts alone.
What does randomization contribute?
General explanation: random assignment can help balance prognostic factors between treatment groups on average, making a valid group comparison more interpretable. It does not guarantee balance in a particular study, and it cannot compensate for unclear group definitions, missing outcome information, or an analysis that does not preserve the randomized comparison. The registry says allocation was randomized, but does not report the randomization method, concealment, stratification, or the connection between the stated randomized doses and the displayed safety groups.
How should the planning illustration be read?
The registry includes planning assumptions based on an observed effect, with a two-sided significance level of 0.05, equal allocation, and a normal approximation. Those assumptions describe a planning illustration, not a reported design justification or an observed-power calculation. The registry record does not report that these assumptions formed the original trial’s statistical plan. Equal allocation in a planning illustration also does not describe the displayed safety counts, which have different numbers at risk. Any planning estimate based on an observed effect is sensitive to uncertainty in that effect; it should not be read as proof that a future study will have a particular probability of detecting an effect.
General explanation: when event counts are sparse or group sizes are very different, approximate methods may perform poorly, and exact or model-based methods may be considered depending on the question. Over-dispersion is a concern when variation in event counts exceeds what a chosen model assumes; an inadequately specified model can then understate uncertainty. These are general statistical considerations, not methods reported for this trial. The registry does not specify a test, model, adjustment set, or approach to over-dispersion.
What is missing for interpretation?
The posted results do not report confidence intervals, p-values, a dose-comparison estimate, or a statistical analysis plan. They also do not state how multiple outcomes or event categories were handled statistically. Without these elements, the event counts support description but not a quantified claim about the precision or statistical compatibility of a between-group effect. The percentages attached to selected serious-event terms lack a stated denominator in the registry record, so their exact interpretation remains uncertain.
10. Multiplicity, Missing Data and Analysis Populations
The record names a primary safety outcome covering incidence and grade of adverse events and serious adverse events, and reports two outcome measures overall. It does not describe a multiplicity procedure, such as a prespecified hierarchy or adjustment for testing several outcomes or categories. The selected serious-event terms are presented as descriptive percentages, but the record does not say whether they were prespecified or how many terms were assessed. Their presence alone does not establish formal statistical testing.
Missing-data methods are not reported in the registry record. The record does not say how participants with incomplete follow-up, missing event assessments, or withdrawal were handled. It also does not explain whether the at-risk denominators change over the outcome timeframe or whether all participants had comparable opportunities for event observation. These omissions matter for interpreting safety counts across groups.
The analysis populations are not reported. In particular, the registry does not identify whether the counts represent all randomized participants, participants who received treatment, or another population. It also does not clarify which study part contributed the displayed results. That uncertainty is important because the study description includes both an initial part and a randomized comparison, while the reported doses do not align with the doses named for the randomized comparison.
No inferential analyses are listed. The record therefore does not provide a documented statistical approach to missing observations, multiplicity, or population definitions. The absence of such reporting does not show that these issues were mishandled; it means their handling cannot be evaluated from the registry record.
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 |
|---|---|---|---|
| Apatinib 250 mg Group | 112 | 198 | 56.6% |
| Apatinib 375 mg Group | 7 | 12 | 58.3% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Apatinib 250 mg Group | 48 of 198 |
| Apatinib 375 mg Group | 3 of 12 |
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 |
|---|---|
| Apatinib 250 mg Group | 197 of 198 |
| Apatinib 375 mg Group | 12 of 12 |
Most frequent serious adverse event terms
| Event term | Organ system | Apatinib 250 mg Group | Apatinib 375 mg Group |
|---|---|---|---|
| Neoplasm progression | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 19 of 198 | 2 of 12 |
| Hepatic function abnormal | Hepatobiliary disorders | 11 of 198 | 0 of 12 |
| Death | General disorders | 10 of 198 | 0 of 12 |
| Immune-mediated lung disease | Respiratory, thoracic and mediastinal disorders | 8 of 198 | 1 of 12 |
| Pneumonia | Infections and infestations | 8 of 198 | 0 of 12 |
| Pneumonitis | Respiratory, thoracic and mediastinal disorders | 5 of 198 | 0 of 12 |
| Respiratory failure | Respiratory, thoracic and mediastinal disorders | 5 of 198 | 0 of 12 |
| Haemoptysis | Respiratory, thoracic and mediastinal disorders | 5 of 198 | 0 of 12 |
| Interstitial lung disease | Respiratory, thoracic and mediastinal disorders | 4 of 198 | 0 of 12 |
| Malignant neoplasm progression | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 4 of 198 | 0 of 12 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Apatinib 250 mg Group | Apatinib 375 mg Group |
|---|---|---|---|
| Hypertension | Vascular disorders | 126 of 198 | 10 of 12 |
| Proteinuria | Renal and urinary disorders | 125 of 198 | 9 of 12 |
| Aspartate aminotransferase increased | Investigations | 106 of 198 | 8 of 12 |
| Alanine aminotransferase increased | Investigations | 89 of 198 | 7 of 12 |
| Palmar-plantar erythrodysaesthesia syndrome | Skin and subcutaneous tissue disorders | 84 of 198 | 6 of 12 |
| Anaemia | Blood and lymphatic system disorders | 78 of 198 | 4 of 12 |
| Asthenia | General disorders | 70 of 198 | 7 of 12 |
| Rash | Skin and subcutaneous tissue disorders | 66 of 198 | 11 of 12 |
| Decreased appetite | Metabolism and nutrition disorders | 66 of 198 | 9 of 12 |
| Cough | Respiratory, thoracic and mediastinal disorders | 63 of 198 | 6 of 12 |
Serious events with the highest arm-level rate: neoplasm progression (16.7%), immune-mediated hepatitis (16.7%), immune-mediated lung disease (8.3%), pneumothorax (8.3%), gastrointestinal haemorrhage (8.3%).
The adverse-event summary reports serious adverse events for the Apatinib 250 mg group as 112 participants among 198 at risk, and for the Apatinib 375 mg group as 7 among 12 at risk. Other adverse events are reported as 197 among 198 at risk and 12 among 12 at risk, respectively. Death counts are 48 for the 250 mg group and 3 for the 375 mg group. These are separate reported figures; the registry does not explain whether the other-event category excludes serious events, so the counts should not be added together.
The listed serious-event terms have percentages, but their denominator and calculation method are not reported in the registry record. They should be read as percentages attached to the terms as recorded, not automatically as proportions of all participants or as dose-specific rates. The record does not give a grade breakdown, timing for individual events, event duration, or causal attribution. Death counts likewise lack information about cause and relation to study treatment.
Most importantly, the safety results name 250 mg and 375 mg groups, whereas the randomized comparison is described as 250mg/d versus 500mg/d. Until the record clarifies this discrepancy and the populations represented, these figures cannot establish a reliable comparison between the doses named in the trial description.
12. What the Result Does, and Does Not, Mean
The posted data show that adverse events were recorded in the listed groups, with counts for serious adverse events, other adverse events, and deaths. They also identify several serious-event terms with associated percentages. This is useful descriptive information about what the registry reports during the safety follow-up timeframe. It is not, on its own, a complete statistical comparison of the study groups.
The record does not provide an effect estimate with a confidence interval or a hypothesis test for the adverse-event outcomes. As a result, it does not quantify the precision of a difference between groups or show how compatible the data are with different possible effects. The unequal numbers at risk further mean that raw counts alone cannot serve as a direct measure of comparative risk. The denominators are reported, but details about analysis populations and follow-up are not.
The record also does not establish that an event was caused by treatment. A safety report records events observed in participants; attribution requires information and methods that are not described. The death counts have no accompanying cause-of-death or treatment-relatedness information. The serious-event term percentages lack a stated denominator, limiting their interpretation.
The discrepancy between the dose comparison described in the study summary and the dose groups in the results is material. The registry record does not explain whether the results represent the randomized comparison, another part of the study, or a different grouping. Without clarification, a reader should not use these data to draw a dose-specific comparative conclusion. No tumor-response or survival result is included in the posted outcome summary, so the safety figures do not answer an efficacy question.
Accordingly, the record supports a cautious description of reported safety counts, while leaving comparative precision, causal attribution, and the relationship between reported dose groups unresolved.
13. Why This Trial Matters Statistically
This study is statistically notable because its registry description combines a two-part design with a randomized dose comparison, while the posted safety groups do not match the doses named for that comparison. Clear alignment between design, treatment groups, outcomes, and analysis populations is essential for interpreting a randomized study. Here, the record does not explain how the 250 mg and 375 mg safety groups relate to the stated 250mg/d and 500mg/d comparison.
The safety outcome is also broader than a single event count: it refers to incidence and grade of adverse events and serious adverse events over an extended follow-up timeframe. The posted summary gives counts, but no grade breakdown or inferential comparison. This illustrates the difference between having outcome data and having enough information to estimate a comparative effect with stated precision.
The reported group sizes differ, so raw counts are not directly comparable. Even where at-risk denominators appear, interpretation depends on who was included and how follow-up was handled. The record does not provide those details or an analysis plan. Nor does it provide confidence intervals or tests that would characterize uncertainty in a group comparison.
These limitations are not merely technical. They determine whether a reader can distinguish a descriptive report from evidence about a difference between doses. The registry contains useful safety counts and lists specific serious-event terms, but its internal dose-description discrepancy and missing analysis details prevent a confident reconstruction of the intended randomized comparison. The case underscores why transparent reporting of group definitions, denominators, follow-up, grades, and analysis methods is part of sound clinical-trial interpretation.
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 trial-specific limitation in the registry record is the inconsistency between the randomized comparison described in the study summary and the adverse-event groups reported. The summary names 250mg/d and 500mg/d, while the safety results list 250 mg and 375 mg groups. The 500mg/d arm appears in the arm descriptions, but no corresponding adverse-event figures are included in the posted summary. The record does not explain these differences.
The study has two parts, but the safety results do not identify which part or participants contributed to each group. Although the study is described as randomized, the record does not connect the reported group counts to the randomization or specify the analysis population. The at-risk denominators differ between displayed groups, and no explanation of follow-up duration by group is given.
The primary outcome includes event grade, but no grade-specific results or grading definitions are reported. The serious-event term percentages have no stated denominator or calculation method. Death counts are not accompanied by causes, timing, or treatment-relatedness assessments. The record also does not report missing-data methods, outcome adjudication, or how event overlap between serious and other adverse events was handled.
No inferential analyses are listed for the outcomes. The registry does not report a comparative estimate, confidence interval, p-value, or a statistical analysis plan. The study’s registry status is completed, but completion does not resolve these reporting gaps. These limitations constrain interpretation of the safety description; they do not establish that the study itself lacked procedures that are not reported in the registry record.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: A Study of SHR-1210 in Combination With Apatinib in Advanced Non-Small Cell Lung Cancer(NSCLC) — NCT03083041.
- Registry record last updated 2026-03-03; status last verified 2022-06.
- Results first posted 2026-03-03.
- 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 describes a completed, multicenter, open-label, randomized Phase II study of SHR-1210 with apatinib in locally advanced or metastatic non-small cell lung cancer. The study description includes an initial safety, tolerability, and pharmacokinetic part, followed by a randomized dose comparison. Enrollment is reported as 210.
The primary outcome concerns the incidence and grade of adverse events and serious adverse events, with follow-up described from informed consent through safety follow-up, 61 months. The posted safety summary lists counts for the Apatinib 250 mg and 375 mg groups, plus selected serious-event terms and death counts. The record does not list inferential analyses.
The randomized doses named in the summary do not match the doses named in the posted safety groups. The registry record does not explain the discrepancy, define the analysis populations, or report grade-specific results, confidence intervals, or a statistical comparison. The available figures are therefore descriptive and should be interpreted cautiously.