Second Line Erlotinib (Tarceva) Plus Digoxin in Non-Small Cell Lung Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Second Line Erlotinib (Tarceva) Plus Digoxin in Non-Small Cell Lung Cancer (NCT00281021), a na phase 2 study. The primary outcome is Therapeutic Response, Evaluated by Computed Tomography (CT) Scans of Chest & Abdomen..

2. Clinical Question

The central question is descriptive: what response was observed in the single group receiving the combination? A treatment effect, in the comparative sense, requires an estimate of what would have happened under a different treatment or under no addition of digoxin. This design has no concurrent control group to provide that comparison. As a result, even a reported response count would describe outcomes in the treated group, not isolate the contribution of digoxin.

The study is described as Phase 2 and as second-line treatment for non-small cell lung cancer. The registry’s brief description frames the purpose as determining the potential benefit of adding digoxin to erlotinib. However, the endpoint result and any analysis are not reported in the registry record. The record therefore does not answer whether a particular response rate was reached, how uncertain any estimate would be, or whether the combination differed from another treatment.

The primary endpoint is a participant count based on therapeutic response assessed with CT imaging of the chest and abdomen. Imaging was scheduled every 6 weeks after baseline until disease progression, with an average timeframe of 3 months. The registry record does not specify response criteria or provide the endpoint’s observed count. Interpretation must therefore stay with the study question and design rather than infer efficacy from the treatment’s stated purpose.

3. Trial Design

This is a Phase 2, single-group study of erlotinib plus digoxin in patients with non-small cell lung cancer. The intervention is described as a drug combination, and the study title places it in a second-line setting. The record lists enrollment as 26 and identifies the status as terminated. Study start is recorded as 2006-02 and primary completion as 2010-12. The reason for termination is not reported in the registry record.

Allocation is recorded as not applicable, masking is listed as none, and the model is single-group. These features mean the record does not describe a randomized comparison or a blinded control group. Participants in the listed arm received erlotinib and digoxin. There is no separate arm against which to estimate a relative response or separate the effects of the two drugs.

The sole listed primary outcome is therapeutic response assessed by CT scans of the chest and abdomen. The assessment timeframe is every 6 weeks after baseline until disease progression, with an average duration of 3 months. The registry record lists one outcome measure and no analyses. It does not report results for the primary endpoint, an analysis population, or details of how participants with missing assessments were handled.

Enrollment and the safety denominator are not the same reported figure: enrollment is 26, while the adverse-event group lists 24 participants at risk. The registry record does not explain the relationship between these figures. That difference should not be resolved by assumption; the relevant denominators should remain attached to the measures for which they are reported.

The record’s planning assumptions refer to a two-arm calculation with equal allocation, although the trial itself is single-group and has no comparison arm. Such planning assumptions are not a description of the actual trial design. No trial-specific sample-size justification, analysis plan, or explanation of the relationship between the planning illustration and this design is 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.

Overall Study

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 Therapeutic Response, Evaluated by Computed Tomography (CT) Scans of Chest & Abdomen., measured over Measured every 6 weeks after baseline until disease progression, an average of 3 months.

The primary endpoint is the number of participants with a therapeutic response, assessed using computed tomography scans of the chest and abdomen. Imaging was scheduled every 6 weeks after baseline until disease progression; the listed average timeframe is 3 months. The measure is expressed as a count of participants rather than as a continuous measurement or a time-to-event outcome.

In general, imaging-based response endpoints are used to describe whether a tumor’s appearance meets a defined response classification during treatment. A count can communicate how many participants met the endpoint, but its meaning depends on the response definition, the assessment schedule, the denominator, and how unevaluable or missing scans are handled. Those details are not reported in the registry record, so the endpoint’s precise classification rules cannot be evaluated.

The endpoint result itself is not reported in the registry record. There is no response count, estimate of uncertainty, or analysis result to interpret. The registry record also does not state the criteria used to distinguish response categories. Consequently, the listed endpoint identifies what was intended to be assessed, but does not establish what response was observed or how consistently it was assessed.

In a single-group study, a response count can describe outcomes among participants receiving the combination. It cannot, by itself, establish how those outcomes compare with another treatment or determine the contribution of digoxin. That distinction is especially important when the study’s stated purpose concerns the potential benefit of adding one drug to another.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The statistical interpretation begins with the study structure. This is a single-group study, not a randomized comparison. The record lists one intervention group receiving erlotinib and digoxin, with allocation marked not applicable and masking listed as none. A single-group design can describe outcomes among people receiving the intervention, but it does not directly estimate the contrast between that intervention and an alternative. General statistical explanation should not be mistaken for a trial-specific analysis: the registry record reports no analyses.

What does a count endpoint represent?

The primary endpoint is a number of participants with a therapeutic response assessed by CT. In general, a count for a binary outcome records how many participants meet a defined event condition and how many do not. To interpret such a count, the event definition and the population used as its denominator must be clear. Here, the record gives the endpoint description and schedule but does not report an endpoint count, denominator, response criteria, or analysis population. A response proportion or other derived estimate therefore cannot be interpreted from the registry record.

The imaging schedule is every 6 weeks after baseline until disease progression, with an average timeframe of 3 months. Repeated assessment can make the timing and availability of scans relevant: participants may have different numbers of assessments, and the endpoint may depend on which assessment is used. In general, a protocol specifies how such timing is summarized and what happens when assessments are missed or cannot be evaluated. Those rules are not reported in the registry record, so no assumptions about them are warranted.

Why does the lack of a control group matter?

A comparative treatment effect is based on contrasting outcomes under different interventions. Random allocation, when used, supports a fair comparison by reducing systematic differences between groups at the point of assignment. This study has no separate control arm and no randomized allocation. A result in the treated group would therefore be descriptive and would not, on its own, show what outcomes would have been under a different treatment. Differences from an external expectation, if any, could reflect differences in participants, care, measurement, or time as well as treatment.

Masking is listed as none. In general, awareness of treatment or study status can affect subjective decisions, care processes, or assessment. CT images may have objective features, but interpretation can still depend on defined criteria and assessment procedures. The registry record does not describe blinded image review, response rules, or other safeguards, so no claim about their use is justified.

How should uncertainty be understood?

In general, estimates from a sample are uncertain because they describe observed participants rather than all possible participants in the target population. A confidence interval gives a range of values compatible with the data under specified assumptions; its width reflects both the amount of information and variability. A point estimate without an interval can hide substantial uncertainty. Here, the registry record reports no primary outcome estimate or interval, so the precision of the therapeutic-response result cannot be assessed.

For a binary outcome, methods commonly estimate a response probability or compare probabilities between groups. The choice of method depends on the design, the number of events, and the analysis plan. In a single-group setting, an interval could describe the response probability, but it would not create a randomized comparison. No estimate, interval, model, test, or covariate adjustment is reported in this record. It would be inappropriate to infer one.

What do the planning assumptions mean?

The record describes a planning illustration using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It says the effect to detect is a stated fraction of the observed effect. In general, a sample-size calculation asks how much information a planned study might need under chosen assumptions. Such calculations depend on the target effect, outcome variability or event frequency, allocation, significance threshold, and desired power. A planning illustration is not an observed result and is not evidence that a study achieved a particular power.

Those assumptions do not match the recorded single-group design: equal allocation between two arms is not the actual allocation described for this trial. The registry record does not report a trial-specific sample-size justification or explain how the two-arm planning assumptions relate to the study. It also does not provide a primary endpoint result from which a posted-effect illustration could be interpreted. No calculated planning values are reported in the registry record.

Why can over-dispersion matter?

In general, over-dispersion arises when observed variation is greater than a statistical model expects. It can make standard errors too small if the model assumes less variability than the data contain, producing confidence intervals that are too narrow and tests that appear more decisive than warranted. This concept is not a reported feature of this study’s binary response endpoint, and the registry record gives no model or data with which to assess it. It is relevant as a general consideration in statistical modeling, not as a claim about the trial.

Finally, the registry record lists no analyses. That means there is no reported statistical procedure to reproduce or evaluate, and no basis for assessing model fit, missing-data assumptions, or multiplicity handling. Methodological concepts help clarify what would matter in an analysis; they do not fill in the analysis details absent from the record.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists one primary outcome measure and no analyses. A single listed endpoint does not establish that the protocol contained only one planned analysis, nor does it show whether any secondary outcomes or interim looks were planned. The presence or absence of a multiplicity strategy is not reported in the registry record. Multiplicity matters in general when many outcomes, time points, subgroups, or repeated tests are examined, because the chance of at least one apparently notable result can increase as the number of opportunities for testing grows. No such testing history is available to assess.

The record does not report a primary outcome result, a statistical analysis plan, or an analysis population. It therefore does not identify whether all enrolled participants, treated participants, or participants with evaluable scans were intended for the efficacy analysis. These populations can differ, and the choice can affect interpretation. The enrollment figure and the safety denominator should not be assumed to define the primary endpoint population.

Missing-data methods are not reported in the registry record. In general, missing scans or incomplete follow-up can matter if the chance of being assessed is related to disease status or treatment experience. A complete-case analysis, an assumption that missing outcomes indicate no response, or a model-based approach can lead to different interpretations. None can be attributed to this trial from the available record. The imaging schedule and disease-progression stopping point make the handling of incomplete assessments an important methodological detail, but the record does not specify that handling.

The record also does not report interim analyses, stopping rules, or prespecified subgroup analyses. Their presence or absence should not be inferred from the terminated status. Without an analysis plan and outcome results, statistical significance, robustness, and the scope of the reported evidence cannot be assessed.

11. Safety Results

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

Other (non-serious) adverse events

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

Most frequent non-serious adverse event terms

The adverse-event record lists the erlotinib-and-digoxin group with 24 participants at risk. It reports 0 participants with serious adverse events and 20 participants with other adverse events. These counts should be read in their respective categories and with that denominator. No percentages or comparisons are needed to understand the reported counts.

In general, serious adverse events are a defined category distinct from other adverse events; the two labels should not be treated as interchangeable measures of severity. The registry record does not provide the specific event terms, so the clinical nature of the reported events cannot be characterized. It also does not state whether individuals could appear in both categories, how events were collected, or how attribution to treatment was assessed.

Deaths are not reported in the registry record. The serious-event count of 0 should not be read as proof that no safety concerns occurred, and the count of 20 for other adverse events does not by itself establish causation or severity. These are descriptive registry figures, not a comparison with another regimen. The record’s enrollment figure is 26, while the safety group’s at-risk figure is 24; the reason for the different reported figures is not reported in the registry record.

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

The record establishes that a Phase 2, single-group study examined erlotinib plus digoxin in a second-line non-small cell lung cancer setting. It identifies CT-assessed therapeutic response as the primary endpoint and describes imaging every 6 weeks after baseline until disease progression, with an average timeframe of 3 months. These details state the clinical question and intended measurement, but the endpoint result is not reported in the registry record.

Accordingly, the posted information does not establish how many participants had a therapeutic response, how precise that result was, or whether the response met a prespecified criterion. The registry record contains no analyses. There is no reported effect estimate, confidence interval, or test result to interpret. The absence of such results is not evidence that the intervention had no effect; it means the record does not provide an efficacy result that can be evaluated.

Even if a response count were available, the single-group design would limit causal interpretation. It would describe outcomes among participants who received the combination, without a concurrent group receiving another treatment. It could not isolate the contribution of digoxin from erlotinib or distinguish treatment effects from other explanations. No claim that the combination works or does not work follows from the design description alone.

The safety record reports 0 serious adverse events among 24 at risk and 20 other adverse events among 24 at risk. Those figures provide limited descriptive information; event terms, deaths, timing, and attribution are not reported in the registry record. The record also identifies the trial as terminated, without reporting why. Termination should not be interpreted as evidence for or against benefit or harm without a stated reason and the corresponding outcome data.

The most defensible interpretation is therefore about what the registry record documents: the study design, intervention, imaging endpoint, and certain safety counts. It does not provide the efficacy result or comparative evidence needed to quantify a treatment effect. Statistical precision and clinical meaning of the intended response measure cannot be evaluated from the endpoint listing alone.

13. Why This Trial Matters Statistically

This trial is statistically informative as an example of the distinction between an endpoint and an endpoint result. A registry can define what investigators planned to measure without reporting the observations or analyses needed to estimate an effect. Here, therapeutic response is identified as the primary measure, but no response result or analysis is reported. Readers should keep those two types of information separate.

The single-group design also makes the estimand—the quantity a study can answer—especially important. The study can, in principle, describe outcomes among participants receiving erlotinib plus digoxin. It cannot directly estimate how those outcomes differ from a control treatment, because there is no control group. That design limitation is not repaired by a sample-size calculation or by a count of responses. A precise descriptive estimate would still not be a randomized comparative effect.

The record’s planning assumptions illustrate another statistical distinction. The assumptions describe a two-arm calculation with equal allocation, while the recorded trial is single-group. Planning illustrations are contingent on their assumptions and should not be mistaken for the study’s actual design, observed power, or outcome evidence. The registry record does not explain the relationship between those assumptions and this trial.

Finally, the record contains safety counts but no efficacy analyses, no analysis population, and no details on missing assessments. These gaps show why denominators, outcome definitions, and analysis procedures belong alongside numerical results. In general, statistical interpretation depends not just on a count, but also on who was counted, how the event was defined, and how incomplete observations were handled. Those issues are particularly relevant when the endpoint depends on repeated imaging.

The statistical lesson is not a judgment about the combination. It is that design, measurement, reporting, and inference are separate parts of evidence. The record allows a careful description of some of them, while leaving the treatment-response estimate and its uncertainty unreported.

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 main trial-specific limitation is the absence of a reported primary endpoint result. The registry record names CT-assessed therapeutic response but supplies no count, estimate, or analysis. As a result, neither the magnitude nor precision of response can be evaluated. The response criteria are also not reported, limiting interpretation of what would qualify as a response.

The single-group design has no concurrent comparator. This limits causal inference and prevents a direct estimate of the difference between the combination and an alternative treatment. The lack of masking is recorded, but the record does not describe image-reading procedures or other safeguards that might inform assessment reliability. No assumptions about those procedures can be made.

The study is marked terminated, but the reason for termination is not reported in the registry record. The record also does not explain the relationship between enrollment of 26 and the safety denominator of 24 participants at risk. These figures should be retained as reported for their respective contexts rather than reconciled by inference.

The imaging schedule is described, but response classifications, analysis timing, handling of progression, missing scans, and the efficacy analysis population are not reported. Such details can affect which observations contribute to an endpoint and how a count should be interpreted. No statistical analysis plan, multiplicity approach, or interim analysis information is reported either.

Safety reporting is limited to counts for serious and other adverse events. Event terms and deaths are not reported in the registry record, and the record does not explain event attribution or whether categories can overlap. These omissions prevent a detailed description of the safety profile. Together, the design and reporting limitations mean that the available record supports a narrow account of the study rather than a conclusion about efficacy or comparative safety.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Second Line Erlotinib (Tarceva) Plus Digoxin in Non-Small Cell Lung Cancer — NCT00281021.
• Registry record last updated 2018-03-29; status last verified 2018-03.
• Results first posted 2014-11-10.
• 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.

18. Record Summary

The registry record describes a Phase 2, single-group study of erlotinib plus digoxin for second-line non-small cell lung cancer. Enrollment is listed as 26; the study is marked terminated, with start recorded as 2006-02 and primary completion as 2010-12. The reason for termination is not reported in the registry record.

The primary outcome is therapeutic response assessed by CT scans of the chest and abdomen, scheduled every 6 weeks after baseline until disease progression, with an average timeframe of 3 months. The primary endpoint result and any statistical analysis are not reported in the registry record.

For safety, the listed group has 24 participants at risk, with 0 serious adverse events and 20 other adverse events. Deaths and specific event terms are not reported in the registry record. Because there is no separate control group, the record does not provide a randomized comparative estimate of treatment effect.