Pemetrexed Disodium in Treating Patients With Stage IV Non-small Cell Lung Cancer and ECOG Performance Status 3: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Pemetrexed Disodium in Treating Patients With Stage IV Non-small Cell Lung Cancer and ECOG Performance Status 3 (NCT02426658), a na phase 2 study. The primary outcome is Change in Quality of Life (QOL), Assessed by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (QLQ-C30) and QLQ-Lung Cancer 13-item (LC13).

2. Clinical Question

This design addresses change over time among participants receiving pemetrexed; it does not estimate a treatment effect against usual care, another drug, or no treatment. Without a concurrent control group, changes cannot be separated from the course of illness, other care, or influences on questionnaire completion. The registry lists hematologic toxicity, overall survival, and response rate among the secondary outcomes, but their numerical results are not reported in the registry record. The main interpretive focus is therefore the endpoint definition and design, not a conclusion about the magnitude or cause of any clinical change.

3. Trial Design

This was a completed phase II pilot study sponsored by Wake Forest University Health Sciences. The registry lists an enrollment of 16 and describes a single-group model, with allocation not applicable and masking absent. The study began in 2015-05, and primary completion was recorded as 2018-04-19. Its focus was pemetrexed disodium in patients with stage IV non-small cell lung cancer and ECOG performance status 3; the official title further identifies non-squamous disease.

Participants in the treatment group were to receive pemetrexed disodium intravenously over 10 minutes on day 1. Courses were planned to repeat every 21 days in the absence of disease progression or unacceptable toxicity. Quality-of-life assessment and laboratory biomarker analysis were also included. The registry lists five outcome measures and describes the primary endpoint as quality-of-life change from baseline to 12 weeks, with assessments at each treatment time, described as every three weeks.

The registry names hematologic toxicity, overall survival, and response rate as secondary outcomes. Those outcomes could provide context on safety and disease course, but numerical results are not reported in the registry record. The record also does not report a comparator arm, randomization, or masking; the design should therefore be read as an evaluation of a treated group over time, not a randomized head-to-head comparison. The registry status is completed. Completion indicates the study’s recorded status, not that every planned measure has a reported result.

Details such as eligibility criteria beyond the stated disease and performance status, treatment discontinuation rules beyond the stated progression and toxicity conditions, and the intended analysis populations are not reported in the registry record. The protocol’s rationale for the enrollment target and any sample-size justification are also 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.

Overall Study

Reasons for not completing this period:

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 Change in Quality of Life (QOL), Assessed by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (QLQ-C30) and QLQ-Lung Cancer 13-item (LC13), measured over Baseline to 12 weeks.

The primary endpoint is change in quality of life from baseline to 12 weeks, assessed with the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 and the QLQ-Lung Cancer 13-item questionnaire. The registry says quality of life would be assessed at each treatment time, described as every three weeks. The measure is a score on a scale, summarized as a mean with standard error.

The registry describes the score range as 0–100 and states that a higher score represents greater change in quality of life for the worse. That stated interpretation is important when reading any estimate: the direction should be understood according to the registry’s description, rather than assuming a conventional direction from the questionnaire name alone. The registry does not report the numerical baseline and follow-up scores or the resulting mean change.

Quality of life is used to capture patients’ reported experience during treatment, an outcome that is distinct from tumor response, survival, or recorded toxicity. Repeated assessments can describe how scores evolve over the treatment course. They do not, by themselves, establish that treatment caused a change, particularly in a single-group study without a concurrent comparator. The questionnaires, scoring details, and planned follow-up define what the endpoint is intended to measure; the absence of a numerical result in the registry record prevents assessment of the observed direction, size, or precision of change.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does the longitudinal mixed model address?

The registry says quality of life was to be assessed at each treatment time, described as every three weeks, and that longitudinal mixed models would examine scores over the time course. In general, a longitudinal model uses repeated observations from the same participant while accounting for the fact that measurements within a participant are related. This can help estimate an average pattern over time without treating every measurement as if it came from a different person.

The registry does not identify the model’s specific terms, covariance structure, estimation method, assumptions, or handling of incomplete measurements. Those details affect how the model uses the available observations and how its uncertainty is calculated. They are not reported in the registry record, so the planned model cannot be independently reconstructed from the description alone.

What does the paired t-test address?

A paired t-test evaluates the average difference between linked measurements, such as a participant’s baseline score and a later score. In general, pairing is useful because the comparison is within the same person, rather than between unrelated groups. The registry says this test would assess whether average change is more than 0, described as worsening, and also refers to a two-sided alternative that the difference is 0 or better. That wording does not fully clarify the hypothesis and direction of testing. The test result and its estimate are not reported in the registry record.

The paired t-test and longitudinal model answer related but distinct questions. A paired test focuses on a specified pair of assessments. A longitudinal model can use repeated measurements across the treatment course to describe a trajectory. The registry does not state how these analyses would be reconciled if they differed, whether one was designated primary for inference, or whether any adjustment for multiple analyses was planned.

How should standard error and confidence intervals be read?

The endpoint is described as a mean with standard error. In general, a standard error reflects the statistical precision of an estimated mean under the analysis assumptions; it is not a description of how much individual participants’ scores vary. A confidence interval combines an estimate with its uncertainty to communicate a range of values consistent with the data and model. The registry record does not report the mean change, standard error, or confidence interval, so it is not possible to judge the precision of the endpoint estimate.

The quality-of-life measure is described as a score on a scale from 0–100. The registry states that a higher score represents greater change in quality of life for the worse. That definition should be retained when discussing direction. The record does not report which questionnaire scales were combined, whether results were analyzed separately for the two questionnaires, or how any scale-level scores were handled in the primary analysis.

What do the planning calculations mean?

The registry’s sample-size assumptions describe planning illustrations based on the observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The effect to detect is defined as a stated fraction of the observed effect. For time-to-event calculations, the assumptions specify a total number of events; other calculations are expressed as participants per arm.

In general, such calculations describe hypothetical future study designs under stated assumptions. They are not observed power for this pilot, and they do not demonstrate that the study had a particular probability of detecting an effect. A planning result depends on the effect chosen, the statistical model, the significance threshold, and allocation assumptions. Equal allocation between two arms is an illustration assumption, not a feature of this single-group study. The registry does not report the observed primary quality-of-life effect needed to evaluate those calculations from this record.

Power is a design quantity, not a post-study measure of how convincing an observed result is. The relevant evidence for this endpoint would include the estimated change and its uncertainty, together with a prespecified interpretation of meaningful change. Neither the endpoint estimate nor a threshold for clinical importance is reported in the registry record. The planning assumptions should therefore be kept separate from findings about participants’ outcomes.

What does the study design allow?

Because the registry describes a single group without a comparator, analyses can characterize within-group change but cannot estimate a randomized between-group treatment contrast. In general, observations over time may be affected by the disease course, supportive care, measurement variation, and selective availability of follow-up data. A model can address some features of repeated measurements, but it cannot create a control group or remove all sources of bias. The registry does not report enough detail about missing observations, model assumptions, or analysis populations to determine how these issues were addressed.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary quality-of-life endpoint and names secondary outcomes of hematologic toxicity, overall survival, and response rate. The primary endpoint description includes both a longitudinal mixed-model analysis and a paired t-test. The record does not report whether one method was designated as the definitive primary analysis, how multiple questionnaire scales or time points were handled, or whether the secondary outcomes were confirmatory or descriptive. A multiplicity adjustment or testing hierarchy is not reported in the registry record.

Multiplicity matters in general when several outcomes, scales, time points, or statistical tests are examined: the chance of at least one apparently unusual result can increase as the number of tests grows. Whether and how that concern applies depends on the prespecified analysis plan. Since the plan is not described in enough detail, it is not possible to determine the intended control of false-positive findings or to interpret any unreported tests as confirmatory.

The record does not report how missing quality-of-life questionnaires were handled, whether participants who stopped treatment continued assessments, or how incomplete follow-up affected the analysis. It also does not identify the analysis population for the primary endpoint. In general, missing data can matter if the likelihood of providing a measurement is related to a participant’s health or score. A longitudinal model does not automatically remove potential bias from missingness; its interpretation depends on assumptions and implementation, which are not reported in the registry record.

There is no reported account of exclusions from the primary analysis, the number of participants contributing at each assessment, or sensitivity analyses for missing data. These omissions limit assessment of how representative the analyzed observations would be of those enrolled. The enrollment listed in the record should not be mistaken for the number with complete endpoint data.

11. Safety Results

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

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: death, nos (30.8%), sepsis (23.1%), anemia (15.4%), lymphocyte count decreased (15.4%), dysphagia (7.7%).

The registry’s treatment-group safety record lists 13 participants at risk and 12 affected for both serious and other adverse-event categories, and lists 4 deaths. These are the registry’s reported counts; the record does not provide enough detail in this summary to determine the relationship between each event and treatment. A listed death should not automatically be interpreted as a death caused by pemetrexed.

The serious adverse-event terms include Death, NOS at 30.8%, Sepsis at 23.1%, Anemia at 15.4%, Lymphocyte count decreased at 15.4%, Dysphagia at 7.7%, and Hypoalbuminemia at 7.7%. These percentages are reported by the registry. Event terms may describe overlapping events or participants, so their percentages should not be added to obtain a total. The record does not give the event-level timing, severity details beyond the serious-event listing, or attribution to study treatment.

These figures are descriptive safety information from a single treatment group, not a comparison of risk against another treatment. The registry separately lists hematologic toxicity as a secondary outcome, but its numerical outcome results are not reported in the registry record. The safety counts should therefore be read as recorded events in this study, without inferring a comparative rate, cause, or overall safety conclusion.

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

The record identifies a pilot study asking whether quality-of-life scores changed during treatment with pemetrexed among patients with stage IV non-small cell lung cancer and ECOG performance status 3. It specifies the questionnaires, the baseline-to-12-week primary time frame, repeated assessment during treatment, and planned statistical methods. It also reports a single-group design and an enrollment of 16.

Those details describe the research question and study structure, but they do not establish the direction or magnitude of the primary outcome. The registry record does not report a numerical quality-of-life change, standard error, confidence interval, or p-value. It therefore cannot show how precisely the average change was estimated or whether the observed data were consistent with improvement, worsening, or little change. The registry’s stated score direction should be used if an estimate is interpreted: higher scores represent greater change in quality of life for the worse.

Even if within-group change were available, it would not alone demonstrate that pemetrexed caused that change. Without a concurrent comparator, the analysis cannot distinguish treatment-associated change from the disease course, other care, measurement variation, or changes in who completed follow-up. Nor can the record establish a comparative effect against another treatment.

The listed serious adverse events provide descriptive safety counts and terms. They do not establish that the treatment caused the events, and they are not comparative evidence. Numerical results for the listed secondary outcomes are not reported in the registry record. The study’s completion status also does not mean that each planned endpoint has a posted result.

Accordingly, the record is informative about a clinical question and an exploratory design in a population identified by disease stage and performance status. It is not sufficient to quantify a treatment effect, judge the precision or clinical importance of quality-of-life change, or draw comparative conclusions. Those limits reflect what is reported and the single-group design, rather than a judgment about what individual patients should do.

13. Why This Trial Matters Statistically

This study is statistically notable because it focuses on quality of life in a population described as having stage IV disease and ECOG performance status 3, rather than framing its primary endpoint only around tumor response or survival. Patient-reported outcomes can describe an aspect of experience that is not captured by laboratory measures or disease-response categories. Repeated assessment also makes the time course of scores relevant to the analysis, rather than reducing the question to a single measurement.

The design illustrates the distinction between describing change and estimating a causal treatment effect. A single-group longitudinal study can examine how outcomes vary over time among participants receiving the intervention. Without a concurrent control group, it cannot separate treatment effects from other explanations for change. This distinction is particularly important when interpreting within-person analyses: pairing can account for stable differences between participants, but it does not provide the missing counterfactual course without treatment.

The registry also describes both a longitudinal mixed model and a paired t-test. These methods can summarize different features of repeated measurements, but the analysis plan needs to make their roles clear, especially when several scales or time points may be involved. In this record, the full testing strategy and multiplicity approach are not reported. The absence of a numerical endpoint result further means that no conclusion about the size or precision of change can be drawn.

Finally, the planning assumptions distinguish prospective sample-size illustrations from observed evidence. A calculation based on an observed effect can inform a hypothetical future design, but it is not observed power and cannot replace reported estimates and uncertainty. The case therefore highlights why transparent outcome reporting, analysis details, and clear separation of exploratory description from comparative inference matter in clinical research.

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 limitation for interpreting outcomes is that the registry record does not report numerical results for the primary quality-of-life endpoint. It gives no mean change, standard error, confidence interval, or p-value. The secondary outcomes of hematologic toxicity, overall survival, and response rate also lack numerical results in the registry record. Without those results, the magnitude and precision of outcomes cannot be assessed.

The study is described as single-group, with allocation not applicable and no masking. There is no concurrent control group to distinguish within-group change during treatment from change that might have occurred for other reasons. This design limits causal and comparative interpretation. It is not possible to use the enrollment listed in the record as a substitute for the number contributing usable observations at each assessment, since follow-up completeness is not reported.

Important analysis details are absent. The registry does not report the exact mixed-model specification, how the two questionnaires or their scales were handled, the analysis population, or the method for dealing with missing quality-of-life assessments. The relationship between the longitudinal model and paired t-test is not fully defined, and the wording of the test direction is unclear. A multiplicity strategy is not reported.

The record does not report a threshold for clinically important quality-of-life change or the protocol’s sample-size justification. The reported serious adverse-event figures are descriptive; event attribution, timing, and comparative safety information are not reported. These limitations mean that the registry can describe the intended question and design, but cannot support a complete assessment of efficacy, precision, clinical importance, or comparative safety.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Pemetrexed Disodium in Treating Patients With Stage IV Non-small Cell Lung Cancer and ECOG Performance Status 3 — NCT02426658.
• Registry record last updated 2023-10-12; status last verified 2023-08.
• Results first posted 2020-03-18.
• 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 describes a completed phase II pilot study of pemetrexed disodium in patients with stage IV non-small cell lung cancer and ECOG performance status 3. The official title specifies non-squamous disease. The study used a single-group model, with allocation not applicable and no masking, and lists an enrollment of 16.

Pemetrexed was planned as an intravenous infusion over 10 minutes on day 1, with courses repeating every 21 days in the absence of progression or unacceptable toxicity. The primary endpoint was change in quality of life from baseline to 12 weeks using the EORTC QLQ-C30 and QLQ-LC13. The registry describes repeated assessment and plans for longitudinal mixed models and a paired t-test.

Numerical primary and secondary outcome results are not reported in the registry record. The study design and endpoint can be described, but treatment effects, outcome precision, and comparative conclusions cannot be evaluated from the record.