A Study for Patients With Non-Squamous Non-Small Cell Lung Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study for Patients With Non-Squamous Non-Small Cell Lung Cancer (NCT00609518), a randomized phase 2 study. The primary outcome is Safety: Number of Participants With Drug-Related Grade 3 or 4 Toxicity.

2. Clinical Question

The trial addressed whether folic acid and steroid supplementation around pemetrexed could use a simpler schedule without increasing toxicity. The comparison was between two schedules used alongside the same named chemotherapy, rather than between pemetrexed and a different chemotherapy or no treatment. The registry record identifies the study as phase 2, randomized, open-label, and parallel-group.

The primary outcome focused on severe or life-threatening toxicity as defined by the registry: Grade 3 was severe, and Grade 4 was life-threatening or disabling. The analysis reports participants with at least one drug-related Grade 3 or 4 toxicity, not the total number of separate toxicity events. Overall survival and progression-free survival were also posted as secondary outcomes. The clinical question is comparative: the observed data describe how these outcomes differed between the two assigned schedules, while their uncertainty limits how confidently small or moderate differences can be distinguished.

3. Trial Design

This was a randomized, open-label, parallel-group phase 2 study sponsored by Eli Lilly and Company. The registry record lists enrollment of 111 and a completed status. The listed condition was non-small cell lung cancer, and the official title identifies the treatment setting as second-line chemotherapy for patients with non-squamous non-small cell lung cancer.

Both groups received pemetrexed with folic acid, vitamin B12, and dexamethasone supplementation. The standard schedule used a minimum of 5 daily folic acid doses before the first pemetrexed dose, with dexamethasone on the day before, day of, and day after treatment. The simplified schedule used 2 daily folic acid doses before the first pemetrexed dose and dexamethasone on the treatment day only. The record does not describe a masking procedure; masking is listed as none.

The primary endpoint was the number of participants with drug-related Grade 3 or 4 toxicity in the Q-ITT population. Its observation window ran from the first dose of treatment to the last dose plus 30 days. The posted primary groups included 51 participants in the standard-schedule arm and 47 in the simplified-schedule arm. The adverse-event summaries use different at-risk group counts, so those safety summaries should be read using their own denominators rather than substituting the primary-analysis group sizes.

Overall survival and progression-free survival were reported as secondary endpoints, with follow-up described from randomization, within 4 weeks of the baseline visit, to 12 months after randomization. The registry record also lists best overall tumor response among the secondary outcomes, but its result is not reported in the registry record. Details of the original sample-size justification, interim analyses, and the full statistical analysis plan 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: Completed is defined as:The patient has completed follow-up visits until 12 months after the randomization date. Qualified Intent-to-Treat (Q-ITT) is defined as: Include all randomized patients, with nonsquamous histology, who comply with their pretreatment folic acid and steroid supplementation schedule and take at least one dose of pemetrexed.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Qualified Intention to Treat (Q-ITT)

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 Safety: Number of Participants With Drug-Related Grade 3 or 4 Toxicity, measured over From first dose of treatment to last dose of treatment plus 30 days.

The primary endpoint counts participants who experienced drug-related Grade 3 or 4 toxicity during the specified treatment safety window. The registry defines Grade 3 as severe and Grade 4 as life-threatening or disabling; Grade 0 is no adverse event, Grade 1 mild, Grade 2 moderate, and Grade 5 death related to an adverse event. The outcome is a participant count for each arm, rather than a count of every event or a measure of how long toxicity lasted.

This type of endpoint is useful for comparing the frequency of serious treatment-related harm between schedules. A simpler supplement schedule would be of interest only if its safety profile could be assessed alongside its reduced schedule burden; the endpoint directly focuses on severe toxicity rather than on minor symptoms alone. It does not capture every aspect of tolerability, convenience, or treatment experience.

The registry reports 15 participants with the primary outcome among 51 in the standard-schedule arm and 18 among 47 in the simplified-schedule arm. The posted rates are 0.294 and 0.383, respectively. These are observed proportions within the Q-ITT analysis, and the comparison is an estimate from a limited trial population. The endpoint definition and observation window matter: these figures concern drug-related Grade 3 or 4 toxicity from the first dose through the last dose plus 30 days, not all adverse events over an unlimited period.

7. Results Posted in the Registry

• Simplified Vitamin and Steroid Schedule + Pemetrexed: 38.3% (18/47) versus 29.4% (15/51) on control; risk difference 8.9 percentage points (95% CI -9.8 to 27.6), risk ratio 1.30 (0.74–2.28); unadjusted two-proportion z-test p = 0.352.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Overall Survival

• Endpoint type: Time to event: compared as a hazard ratio.
• Test: Hazard ratio as reported by the sponsor (Regression, Cox); it was not recalculated.
• Result:
  • Standard Vitamin and Steroid Schedule + Pemetrexed vs Simplified Vitamin and Steroid Schedule + Pemetrexed: hazard ratio 0.90 (95% CI 0.54–1.49) (as reported in the registry).
• Interpretation:
  • The 95% confidence interval includes no difference (a ratio of 1), so these data do not show a statistically significant difference between Standard Vitamin and Steroid Schedule + Pemetrexed vs Simplified Vitamin and Steroid Schedule + Pemetrexed and the control. The interval gives the range of effects that remain compatible with the data.

Progression-free Survival (PFS)

• Endpoint type: Time to event: compared as a hazard ratio.
• Test: Hazard ratio as reported by the sponsor (Regression, Cox); it was not recalculated.
• Result:
  • Standard Vitamin and Steroid Schedule + Pemetrexed vs Simplified Vitamin and Steroid Schedule + Pemetrexed: hazard ratio 0.89 (95% CI 0.57–1.38) (as reported in the registry).
• Interpretation:
  • The 95% confidence interval includes no difference (a ratio of 1), so these data do not show a statistically significant difference between Standard Vitamin and Steroid Schedule + Pemetrexed vs Simplified Vitamin and Steroid Schedule + Pemetrexed and the control. The interval gives the range of effects that remain compatible with the data.

Across the posted secondary time-to-event outcomes, the estimates are broadly compatible with uncertainty about the differences between schedules: both hazard-ratio confidence intervals include 1, and both log-rank p-values are above conventional thresholds. The secondary results therefore do not provide a precise, consistent basis for claiming a difference in survival outcomes, nor do they establish that the schedules have equivalent effects. They offer contextual evidence alongside, rather than a replacement for, the primary toxicity comparison.

The secondary endpoints address different questions from the primary endpoint. Overall survival concerns time to death, while progression-free survival concerns time to progression or death as defined for that endpoint. They cannot be used as direct substitutes for the primary measure of drug-related severe toxicity. The registry lists best overall tumor response as another secondary outcome, but its result is not reported in the registry record.

Multiple outcomes and analyses create a multiplicity concern: when many hypotheses are examined, the chance of at least one apparently notable result can rise. General explanation: an adjustment or an explicitly hierarchical testing strategy can address this issue, but the registry record does not report a multiplicity adjustment or testing hierarchy. Consequently, secondary findings should be interpreted cautiously and given less weight than a single prespecified primary result, especially when their estimates are imprecise. The record lists four outcome measures and six analyses; those counts alone do not reveal the full testing strategy or whether all analyses were planned in advance.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Proportion of Participants With Best Overall Tumor Response (Response Rate)
• Overall Survival
• Progression-free Survival (PFS)

9. Statistical Interpretation

10. Statistical Methods Explained

What does the primary comparison estimate?

The primary outcome is binary at the participant level: a participant either had a drug-related Grade 3 or 4 toxicity in the specified window or did not. A risk is the proportion experiencing the outcome in an arm. The unadjusted recalculation compares the simplified schedule with the standard schedule by subtracting the standard-arm risk from the simplified-arm risk. The posted risk difference is 0.089. A positive value means the observed proportion was higher in the simplified-schedule arm; it is an estimate, not proof of a causal difference of that exact size.

The registry's reported analysis uses a linear probability model and gives a risk difference of 0.09. This is a direct, additive comparison on the risk scale. The registry also reports a 95% confidence interval from -0.10 to 0.28. The recalculated interval is -0.098 to 0.276. Their close agreement reflects the similar point estimates and uncertainty limits in the posted analysis and the simple unadjusted recalculation.

How should a confidence interval be understood?

General explanation: a confidence interval describes the uncertainty around an estimate under the statistical method used. It is not a range that guarantees the true effect lies within its endpoints, and it does not assign a probability to a particular treatment effect after the data have been observed. For a risk difference, zero represents no difference in the two risks. The primary interval spans zero, so the results do not distinguish clearly between no difference and effects in either direction. Its width also indicates that the data are compatible with a range of possible differences.

The recalculated p-value is unadjusted and equals 0.352. General explanation: a p-value measures how unusual data at least as inconsistent with a specified null model would be if that model and the test assumptions held. It is not the probability that the null hypothesis is true, and it does not measure the importance of the observed difference. A p-value above a conventional threshold does not demonstrate equivalence or exclude potentially important effects.

Why are relative measures also listed?

The recalculated relative measures are a risk ratio of 1.302, with a 95% confidence interval from 0.745 to 2.277, and an odds ratio of 1.49, with a 95% confidence interval from 0.642 to 3.457. General explanation: a risk ratio compares risks as a ratio, while an odds ratio compares odds. A value of 1 represents no relative difference for either measure. These measures describe the same binary outcome on different scales; they do not replace the risk difference or remove the uncertainty. Their intervals include 1 and are wide.

What do the survival methods estimate?

Overall survival and progression-free survival are time-to-event outcomes. Their reported median values describe the time by which half of the relevant group has experienced the event, subject to the survival analysis. The registry reports medians with 95% confidence intervals for each arm. A Cox regression hazard ratio compares event rates over follow-up under the model; a value of 1 represents no relative difference in the modeled hazards. General explanation: the hazard ratio is not a ratio of median survival times and is not itself a percentage change in survival.

The reported overall-survival hazard ratio is 0.90, with a 95% confidence interval from 0.54 to 1.49, and the log-rank p-value is 0.679. For progression-free survival, the hazard ratio is 0.89, with a 95% confidence interval from 0.57 to 1.38, and the log-rank p-value is 0.587. Both hazard-ratio intervals cross 1. The registry names Cox regression for the hazard-ratio estimates and the log-rank method for the separate tests. Details of additional model specifications are not reported in the registry record.

Why can binary outcomes be statistically challenging?

General explanation: binary event counts contain less information than a measurement that can take many values, especially when event numbers are limited. Estimates can consequently be imprecise, and confidence intervals can remain broad even when the observed proportions differ. Over-dispersion, in general, means observed variability exceeds what a simple statistical model expects; when present, it can make standard errors too small if not addressed. The registry record does not report an over-dispersion adjustment for the primary analysis, so no claim about such an adjustment can be made.

Randomization supports a between-group comparison by assigning participants to schedules, but the open-label design means masking was not used. General explanation: lack of masking can matter for outcomes influenced by assessment or reporting. The primary endpoint is a count of participants with toxicity, and the record defines the grades and drug-related nature of the outcome; it does not report details about adjudication or blinded assessment. These design features are considerations when interpreting estimates, not grounds to presume a particular direction of bias.

11. Confidence Intervals and Precision

The primary risk-difference estimate is 0.089 for simplified minus standard supplementation. Its 95% confidence interval runs from -0.098 to 0.276. Because zero lies within the interval, the data are compatible with no difference in the underlying risks as well as with a lower or higher risk under the simplified schedule. The estimate is not precise enough to settle the direction or size of the difference.

The registry's own risk-difference analysis gives 0.09, with a 95% confidence interval from -0.10 to 0.28. The recalculated and reported intervals are similar. The endpoints are wide relative to the point estimate, so the observed data do not tightly pin down the safety difference. The unadjusted p-value of 0.352 is consistent with substantial uncertainty; it should not be read as evidence that the two schedules are equivalent.

The relative estimates have similar limitations. The risk ratio is 1.302 with a 95% confidence interval from 0.745 to 2.277, and the odds ratio is 1.49 with a 95% confidence interval from 0.642 to 3.457. Both intervals include the no-difference value of 1 and permit a broad range of relative effects.

Precision is also limited for the survival comparisons. The overall-survival hazard ratio is 0.90, with a 95% confidence interval from 0.54 to 1.49. The progression-free-survival hazard ratio is 0.89, with a 95% confidence interval from 0.57 to 1.38. These intervals include 1 and leave room for differing effects in either direction. Confidence intervals describe uncertainty under the analysis methods; they do not establish clinical importance or equivalence.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The primary binary-outcome planning figures are participants per arm. They are illustrations based on the observed effect, not the original trial's design justification. For 80% power, the listed requirements are 444 participants per arm for planning at 100% of the observed effect, 778 for 75%, and 1,719 for 50%. For 90% power, the corresponding figures are 594, 1,040, and 2,301 participants per arm.

For the time-to-event outcomes, the planning figures are total events, not participants per arm. The overall-survival illustration lists 2,829 total events for 80% power and 3,787 for 90% power at 100% of the observed effect; at 75%, the figures are 5,028 and 6,731; at 50%, 11,313 and 15,145. The progression-free-survival illustration lists 2,312 and 3,095 total events at 100%, 4,110 and 5,503 at 75%, and 9,248 and 12,380 at 50%, for 80% and 90% power respectively.

General explanation: power is the probability that a planned analysis will detect an effect of a specified size under its assumptions, if that effect is present. The 80% and 90% columns describe different planned chances of detecting the specified effect, not different observed results. The listed assumptions are a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation; the effect to detect is the stated fraction of the observed effect. The time-to-event calculations use the Schoenfeld method and count total events. Smaller effects require more participants or events to detect. These figures are planning illustrations, not observed power.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, p₀ and p₁ are the control and treatment proportions, and p̄ is their average.

Worked calculation for this trial

1. Control proportion p₀ = 0.294; treatment proportion p₁ = 0.383; average p̄ = 0.339.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.6692 = 1.3117.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.6663 = 0.5607.
4. n = (1.3117 + 0.5607)² / (0.0889)² = 444.0, rounded up to 444 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
p0 <- 0.294117647058824                          # control proportion
p1 <- 0.382978723404255                          # treatment proportion
n_per_arm <- function(power, frac = 1) {
  q1 <- p0 + (p1 - p0) * frac               # smaller effect = fraction of the observed difference
  pbar <- (p0 + q1) / 2
  z_b <- qnorm(power)
  ceiling(round((z_a * sqrt(2 * pbar * (1 - pbar)) + z_b * sqrt(p0 * (1 - p0) + q1 * (1 - q1)))^2 / (q1 - p0)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (unrounded n per arm)
cat("power.prop.test:", round(power.prop.test(p1 = p0, p2 = p1, power = 0.80)$n, 1), "\n")

# Simulation: how often does the z-test reject at the 80%-power sample size?
set.seed(609518)
n    <- n_per_arm(0.80)
reps <- 20000
x0 <- rbinom(reps, n, p0); x1 <- rbinom(reps, n, p1)
ph <- (x0 + x1) / (2 * n)
z  <- ((x1 - x0) / n) / sqrt(ph * (1 - ph) * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(z) > z_a, na.rm = TRUE), reps))

Output from running the code

100% of observed effect: n per arm = 444 (80% power), 594 (90% power)
 75% of observed effect: n per arm = 778 (80% power), 1,040 (90% power)
 50% of observed effect: n per arm = 1,719 (80% power), 2,301 (90% power)
power.prop.test: 444 
Simulated power at n = 444 per arm: 0.799 (20000 replicates)

The simulation draws many pairs of event counts at the planned sample size and counts how often the two-proportion z-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

14. Analyses Reported by the Sponsor

The registry's reported primary comparison uses a linear probability model and estimates the risk difference as 0.09, with a 95% confidence interval from -0.10 to 0.28. The unadjusted recalculation estimates the simplified-minus-standard risk difference as 0.089, with a 95% confidence interval from -0.098 to 0.276 and p = 0.352. The estimates and interval limits are close, and the registry record does not flag a discrepancy.

The reported analysis is the trial's own analysis as recorded in the registry; the recalculation is a simple unadjusted comparison from the posted group counts. These approaches need not match exactly in every trial, because the sponsor's model or analysis choices may differ from a direct calculation. When a discrepancy is flagged, the sponsor's own analysis takes precedence. In this case, no discrepancy is flagged, and both summaries convey a similar point estimate and substantial uncertainty.

The reported risk-difference interval crosses zero. The recalculated p-value is unadjusted and should not be treated as a substitute for a fuller prespecified analysis plan. Details of the original analysis plan, any adjustment beyond the named linear probability model, and the handling of missing observations are not reported in the registry record.

15. Multiplicity, Missing Data and Analysis Populations

The registry record identifies a primary safety endpoint and lists overall survival, progression-free survival, and best overall tumor response among the secondary outcomes. It reports analyses for the primary endpoint and survival outcomes, but a tumor-response result is not reported in the registry record. The record lists four outcome measures and six analyses. It does not report whether secondary hypotheses were tested under a multiplicity adjustment, a hierarchical procedure, or another prespecified strategy. Without that information, the secondary p-values should be treated as exploratory or contextual rather than as stand-alone confirmatory evidence.

The primary analysis population is named Qualified Intention to Treat (Q-ITT). The registry does not report a definition of the qualification criteria in the available record, nor does it explain how participants were handled if they had missing outcome data or did not follow the assigned schedule. The primary group counts are 51 and 47, while the adverse-event summaries use at-risk groups of 54 and 57. These are distinct analysis summaries with their own stated denominators; the record does not explain the population differences.

Missing-data methods, imputation procedures, and sensitivity analyses are not reported in the registry record. The original sample-size justification and trial-specific design assumptions are also not reported; the posted planning illustrations are based on the observed effect and are not evidence about the original design. Interim analyses and stopping rules are not reported in the registry record. These gaps limit assessment of whether the analyses were fully prespecified and how robust the findings are to different assumptions about missing outcomes or repeated testing.

16. 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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: dyspnoea (5.6%), anaemia (3.7%), pneumonia (3.7%), hydropneumothorax (3.7%), pleural effusion (3.7%).

The primary safety outcome counts participants with drug-related Grade 3 or 4 toxicity in the Q-ITT analysis: 15 of 51 in the standard-schedule arm and 18 of 47 in the simplified-schedule arm. This is a different summary from the adverse-event listing, which reports participants at risk and participants affected in the adverse-event groups. For serious adverse events, the registry lists 18 affected among 54 at risk in the standard group and 18 among 57 at risk in the simplified group. For other adverse events, it lists 47 affected among 54 at risk and 54 among 57 at risk, respectively.

These affected-participant figures are not counts of all separate adverse-event episodes, and they should not be directly substituted for the primary drug-related Grade 3 or 4 outcome. The registry lists serious-event terms including Dyspnoea at 5.6%, Anaemia at 3.7%, Pneumonia at 3.7%, Hydropneumothorax at 3.7%, Pleural effusion at 3.7%, and Febrile neutropenia at 3.5%. The listed terms do not by themselves establish a comparative treatment effect for each event. Death counts by group are not reported in the registry record.

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

The posted primary results show that drug-related Grade 3 or 4 toxicity was observed in both schedule groups. The point estimate for the simplified-minus-standard risk difference is positive, but its confidence interval includes zero and extends in both directions. The data therefore do not clearly establish whether the simplified schedule has a higher or lower risk, and they do not demonstrate equivalence. A non-significant result is not proof that a difference is absent.

The survival estimates also have considerable uncertainty. Their confidence intervals include the no-difference value, and the log-rank tests do not provide clear evidence of a difference. These secondary outcomes should not be interpreted as confirmation of the primary safety finding, because they measure different outcomes and the registry record does not report a multiplicity plan. The best overall tumor-response outcome is listed, but its result is not reported in the registry record.

The trial compares two supplementation schedules given with pemetrexed in a phase 2, open-label, randomized study. It does not compare pemetrexed with another chemotherapy or with no chemotherapy. The primary endpoint covers drug-related Grade 3 or 4 toxicity from the first treatment dose through the last dose plus 30 days; it does not represent every possible adverse effect or every aspect of treatment burden. The findings also do not establish how the schedules compare outside the population and follow-up described in the registry.

Statistically, the main message is uncertainty around the size and direction of the safety difference. The estimates are useful descriptions of the posted trial data, but broad intervals, limited analysis counts, and unreported details about missing data and the original statistical plan constrain stronger conclusions. They should be read as estimates with uncertainty, not as a definitive demonstration that one schedule is safer or that the schedules have identical safety.

18. Why This Trial Matters Statistically

This trial is statistically informative because it makes a direct randomized comparison of two supplementation schedules alongside the same named chemotherapy, with severe toxicity as the primary outcome. The question is not only whether the observed group proportions differ, but how precisely the trial estimates that difference. Reporting a risk difference and its confidence interval makes the absolute scale of the comparison visible and shows how much uncertainty remains.

The results illustrate why a point estimate alone can mislead. The simplified-schedule group had a higher observed proportion for the primary endpoint, but the confidence interval spans zero and a wide range of possible differences. The data do not demonstrate no difference, and they do not provide a precise estimate of a difference. That distinction is central when interpreting a study whose practical question involves whether a simpler schedule can be used without an increase in toxicity.

The record also highlights how endpoint definitions and analysis populations shape interpretation. The primary outcome is specifically drug-related Grade 3 or 4 toxicity in the Q-ITT population and within a defined window. The separate adverse-event summaries use different at-risk counts. Keeping these denominators and outcome definitions distinct prevents a common statistical error: treating different safety summaries as if they were interchangeable.

Finally, the secondary time-to-event findings and planning illustrations demonstrate the importance of precision and design assumptions. The survival estimates have broad confidence intervals, while the planning illustrations indicate that smaller effects require more events or participants under their stated assumptions. The registry record does not report the trial's own design assumptions or multiplicity plan, so the available evidence supports careful description rather than expansive claims.

19. 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 primary comparison is based on the Q-ITT population, but the registry record does not explain the criteria used to define that population. It also does not report missing-data handling, sensitivity analyses, or how participants who did not follow the assigned schedule were treated. The primary analysis group counts differ from the at-risk counts in the adverse-event summaries, and the record does not explain that difference.

The trial was open-label, with no masking listed. The primary endpoint includes a drug-relatedness judgment, but assessment procedures or blinded adjudication are not reported in the registry record. The record also does not provide the original sample-size justification, interim-analysis plan, stopping rules, or the full statistical analysis plan. The observed-effect planning illustrations should not be mistaken for the study's original design calculations.

Several secondary outcomes were listed, but a tumor-response result is not reported in the registry record. A multiplicity adjustment or testing hierarchy is not reported. The survival estimates are imprecise, and the primary confidence interval also includes effects in either direction. The registry's summary does not establish whether the trial was designed to test equivalence or non-inferiority; that design information is not reported in the registry record.

The study is described as phase 2 and has limited posted group counts for the primary comparison. Its results concern the stated population, schedules, outcome definitions, and observation periods. The registry record does not support extending these estimates to other populations, treatment schedules, or follow-up periods.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: A Study for Patients With Non-Squamous Non-Small Cell Lung Cancer — NCT00609518.
• Registry record last updated 2010-12-28; status last verified 2010-12.
• Results first posted 2010-11-15.
• 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.

23. Record Summary

The registry record describes a completed, randomized, open-label, parallel-group phase 2 trial of pemetrexed with standard versus simplified folic acid and dexamethasone supplementation in non-squamous non-small cell lung cancer. The primary outcome was the number of Q-ITT participants with drug-related Grade 3 or 4 toxicity through 30 days after the last treatment dose.

The observed primary proportions were 0.294 with the standard schedule and 0.383 with the simplified schedule. The recalculated risk difference was 0.089, with a 95% confidence interval from -0.098 to 0.276 and p = 0.352. The registry-reported analysis was similar. Secondary survival estimates were also uncertain. The record does not report the original design assumptions, missing-data methods, or a multiplicity plan.