A Study to Evaluate the Efficacy and Safety of Anamorelin HCl for the Treatment of Malignancy Associated Weight Loss and Anorexia in Adult Patients With Advanced Non-Small Cell Lung Cancer (NSCLC) - 2: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study to Evaluate the Efficacy and Safety of Anamorelin HCl for the Treatment of Malignancy Associated Weight Loss and Anorexia in Adult Patients With Advanced Non-Small Cell Lung Cancer (NSCLC) - 2 (NCT03743064), a randomized phase 3 study. The primary outcome is Mean Change From Baseline in Body Weight Over 12 Weeks.

2. Clinical Question

3. Trial Design

This was a randomized, parallel-group phase 3 study comparing 100 mg anamorelin HCl with placebo in adults with advanced non-small cell lung cancer and cachexia. The registry lists the allocation as randomized and the model as parallel. Its masking field says quadruple masking, while the official title calls the study double-blind; the registry record does not explain this difference or identify which roles were masked.

The registry lists enrollment as 318. The brief summary says approximately 316 patients were to be enrolled and that an equal number were to be assigned to each group. These are different descriptions of the planned and recorded enrollment; the record does not provide a participant-flow account explaining the difference. The primary analysis population was the Intent-to-Treat Set, defined as all randomized patients analyzed according to planned treatment.

Both assigned treatments were oral tablets taken once daily for 24 weeks in a fasted condition. During treatment, participants were scheduled for study-site visits every 3 weeks for health and study-related assessments. The brief summary describes a follow-up phone call 2 weeks after the last treatment. The recorded primary outcome concerns mean body-weight change over 12 weeks, rather than the full treatment period.

The study status is completed. The registry lists a start date of 2019-05-06 and a primary completion date of 2022-12-27. The sponsor is Helsinn Healthcare SA. The record describes the study as evaluating efficacy and safety; the reported results include body-weight outcomes, duration-of-benefit outcomes, and adverse-event counts.

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: The protocol had pre-defined criteria regarding health and medication requirements to begin study drug administration, and if the patient's status for these requirements changed between screening and Study Day 1, treatment could not be initiated.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The Intent-to-Treat (ITT) Set included all randomized patients and was analyzed as per planned treatment.

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.

Population: The Intent-to-Treat (ITT) Set included all randomized patients and was analyzed as per planned treatment.

6. Primary Endpoint

The registry lists the primary outcome as Mean Change From Baseline in Body Weight Over 12 Weeks, measured over Mean change from baseline over 12 weeks..

The primary endpoint is mean change from baseline in body weight, measured in kilograms, over 12 weeks. It compares the anamorelin HCl group with the placebo group. The registry describes the measure as a least-squares mean and reports standard errors for the group estimates.

The endpoint definition uses changes from baseline up to each participant’s last assessment within the stated period, either at week 12 or earlier in the case of death. It then averages the observed or imputed assessments from baseline through that last assessment. This definition matters: the measure is not simply a comparison of a single final weight reading at week 12. The registry does not describe the imputation procedure in enough detail to identify how missing assessments were filled in.

Body weight is a continuous measure, so a mean change gives a group-level summary of the direction and size of change. Comparing the groups addresses whether average weight change differed between assigned treatments. The endpoint was selected in the registry as a co-primary efficacy outcome for a study addressing malignancy-associated weight loss and anorexia. The record’s broader question also mentions anorexia symptoms, but the posted primary result concerns body weight; it should not be taken as a direct summary of every symptom or aspect of the condition.

7. Results Posted in the Registry

• 100 mg Anamorelin HCl: mean 1.82 versus 0.54 on control; difference 1.28 (95% CI 0.57 to 2.00), standardized effect d = 0.40; z-test p = <0.001.

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.

Duration in Treatment Benefit (Weeks) From Baseline Over 12 Weeks in Body Weight (≥0 kg)

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard errors.
• Result:
  • 100 mg Anamorelin HCl: mean 8.86 versus 6.78 on control; difference 2.08 (95% CI 0.67 to 3.50), standardized effect d = 0.32; z-test p = 0.004.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically higher for 100 mg Anamorelin HCl than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Duration in Treatment Benefit (Weeks) From Baseline Over 12 Weeks in Body Weight (≥1.5 kg)

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard errors.
• Result:
  • 100 mg Anamorelin HCl: mean 5.49 versus 3.09 on control; difference 2.40 (95% CI 1.24 to 3.57), standardized effect d = 0.45; z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically higher for 100 mg Anamorelin HCl than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Duration of Treatment Benefit (Weeks) From Baseline Over 12 Weeks in 5-IASS (≥0 Points)

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard errors.
• Result:
  • 100 mg Anamorelin HCl: mean 9.47 versus 8.84 on control; difference 0.63 (95% CI -0.43 to 1.68), standardized effect d = 0.13; z-test p = 0.244.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between 100 mg Anamorelin HCl and the control. The interval gives the range of effects that remain compatible with the data.

The secondary outcomes cover duration of treatment benefit for body-weight thresholds and for 5-IASS thresholds over the stated period. Across these outcomes, the posted pattern is more favorable to anamorelin HCl for the body-weight duration measures, while the 5-IASS duration analysis does not show clear evidence of a between-group difference. These outcomes add information about how long specified levels of benefit were maintained, rather than simply repeating the primary mean-change measure.

The secondary outcomes relate to the primary result because they address weight-related benefit over time, while the 5-IASS measure concerns a separate symptom scale. A consistent direction across related measures can provide context, but related outcomes are not independent confirmations: they may reflect overlapping aspects of participants’ experience and may be affected by the same trial limitations. The absence of a clear difference for the 5-IASS duration result also means the secondary pattern is not uniform across all outcome types.

These analyses carry less weight than a prespecified primary analysis when the registry does not describe how multiple comparisons were handled. Testing several outcomes creates more opportunities for chance findings. The registry record does not report an adjustment for multiplicity, nor does it explain a hierarchy for interpreting the secondary tests. Their p-values should therefore be treated as unadjusted evidence for their specific comparisons, not as a single confirmatory conclusion across the whole outcome set.

The registry identifies the primary endpoint as a co-primary efficacy endpoint, but the record does not describe the full co-primary testing strategy. That missing context further limits how secondary results can be combined with the primary finding to make a broad claim about efficacy. The safest statistical reading is to distinguish the primary body-weight estimate from the additional outcome-specific findings and retain the uncertainty attached to each.

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

• Duration in Treatment Benefit (Weeks) From Baseline Over 12 Weeks in Body Weight (≥0 kg)
• Duration in Treatment Benefit (Weeks) From Baseline Over 12 Weeks in Body Weight (≥1.5 kg)
• Duration of Treatment Benefit (Weeks) From Baseline Over 12 Weeks in 5-IASS (≥0 Points)
• Duration of Treatment Benefit (Weeks) From Baseline Over 12 Weeks in 5-IASS (≥3 Points)

9. Statistical Interpretation

10. Statistical Methods Explained

The primary outcome is continuous, and the registry reports a mean change for each treatment group. A mean is a summary of the group’s observed or imputed measurements under the endpoint definition. It is useful for describing average change, but it can conceal variation among participants: the same group mean can arise when individual outcomes differ considerably. The group estimates are reported as least-squares means, with standard errors. The registry does not provide enough detail to reconstruct the full model used to produce those means.

What does the reported ANOVA analysis tell us?

The sponsor’s reported analysis is identified as ANOVA and as a mean difference in final values. ANOVA is a general method for comparing group means while accounting for variation in the outcome. The registry reports the estimated mean difference, a 95% confidence interval, a p-value, and a superiority classification. The record does not describe the model terms, any covariate adjustment, or other implementation details, so those should not be guessed. The reported result is the sponsor’s analysis as recorded, rather than a model that can be independently reconstructed from the group summaries alone.

The p-value describes how compatible the observed data are with a specified null hypothesis under the analysis assumptions. It is not the probability that the null hypothesis is true, nor does it measure the size or clinical importance of a difference. The confidence interval complements it by expressing uncertainty about the estimated difference on the outcome scale. Neither measure gives a complete picture without attention to the endpoint definition, analysis population, missing data, and any multiplicity from testing several outcomes.

What is the role of the recalculation?

The recalculated comparison is a simple unadjusted re-calculation from the posted summary statistics. It uses the arm-level estimates and their standard errors to derive a comparison, with an approximate pooled standard deviation also used for the standardized effect. The registry record marks that standard deviation as approximate. This re-calculation is useful as a check on the broad scale and direction of the posted group difference, but it is not a substitute for the sponsor’s ANOVA. It does not reproduce unreported model details or adjustments, and it cannot resolve how the sponsor handled data beyond what the registry states.

For the primary outcome, the recalculated mean difference is 1.284 kg, with a 95% confidence interval from 0.573 to 1.995 and p < 0.001. The sponsor’s reported mean difference is also 1.284 kg, but its 95% confidence interval is 0.718 to 1.851 and its p-value is < 0.001. The matching point estimates and differing uncertainty summaries illustrate why the two analyses should be labelled separately. The registry record does not report a discrepancy flag for this comparison.

Why does over-dispersion matter?

In general, over-dispersion means that measurements vary more than a statistical model expects. When a method assumes less variation than is actually present, standard errors can be too small and confidence intervals too narrow, making evidence appear more precise than it is. A suitable model should reflect the outcome’s variability. This is a general statistical consideration, not a claim that over-dispersion occurred in this trial. The registry does not report an over-dispersion assessment for the continuous primary outcome.

How should the analysis population be understood?

The registry states that the Intent-to-Treat Set included all randomized patients and was analyzed as per planned treatment. In general, an intention-to-treat approach retains participants in the groups to which they were assigned, regardless of treatment actually received. This preserves the randomized comparison in the analysis population as defined by the record. The registry does not report detailed participant flow, exclusions, adherence, or the number contributing observations at each assessment, so the extent of missing outcome data cannot be established from the stated population definition alone.

The primary endpoint description says that assessments were observed or imputed through the last assessment, which could be week 12 or an earlier assessment in case of death. That tells readers that imputed values could contribute, but not which imputation method was used, how many observations were imputed, or whether sensitivity analyses were performed. Those details are not reported in the registry record. The endpoint definition and the analysis population are therefore important context, but they do not provide a complete account of missing-data handling.

What limits interpretation of the p-values?

The record lists multiple outcomes and analyses, including the primary outcome and secondary duration outcomes. Testing several outcomes can increase the chance of finding at least one apparently notable result by chance. In general, multiplicity procedures address this issue by adjusting the testing strategy or interpretation. The registry record does not report whether a multiplicity plan was used, how the co-primary designation was handled statistically, or whether interim analyses occurred. A single reported p-value should therefore be read as belonging to its particular posted analysis, not as evidence that all possible testing considerations have been resolved.

The record describes the primary analysis as a co-primary efficacy endpoint, but the posted information does not explain whether another co-primary endpoint was analyzed, how success across co-primary endpoints was defined, or how family-wise error was controlled. These missing details restrict interpretation of the overall confirmatory testing strategy. They do not change the numerical result that the registry reports, but they matter when assessing how that result fits into a broader statistical plan.

11. Confidence Intervals and Precision

The sponsor’s primary estimate is a mean difference of 1.284 kg, with a 95% confidence interval from 0.718 to 1.851. The simple unadjusted re-calculation gives the same point estimate, 1.284 kg, but a 95% confidence interval from 0.573 to 1.995. Both intervals are above zero, while their widths differ. The distinction reflects that the sponsor’s reported analysis and the summary-statistic re-calculation are not identical procedures; the registry does not provide enough model detail to reconcile their uncertainty estimates.

In general, a confidence interval communicates both the estimated effect and its precision. A narrower interval indicates less uncertainty under the method’s assumptions, while a wider interval indicates more. The interval does not describe the range of individual participant outcomes, and it is not a guarantee about where the true effect lies. Its interpretation depends on the statistical method and assumptions used to construct it.

The group standard errors are 0.263 kg for anamorelin HCl and 0.25 kg for placebo. A standard error describes uncertainty in an estimated group mean, not the spread of individual weights. The registry does not report standard deviations for the primary outcome; the re-calculation uses an approximate pooled standard deviation derived from the reported standard errors. Consequently, the recalculated interval is best read as a transparent, unadjusted summary-statistic comparison rather than a replacement for the sponsor’s model-based result.

The reported p-value for the sponsor’s primary analysis is < 0.001; the unadjusted recalculated p-value is < 0.001. Both are reported with their original precision and thresholds. A small p-value does not quantify clinical importance, and it does not eliminate uncertainty about the estimate or unreported analysis details.

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 planning figures are participants per arm, not total events. They are illustrations calculated from the observed effect, not the trial’s original design assumptions. The listed assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation; each planning scenario targets the stated fraction of the observed effect. The trial’s own original sample-size assumptions and justification are not reported in the registry record.

The 80% power column gives the illustrative number of participants per arm needed, under those planning assumptions, for a specified chance of detecting the target effect if that effect were present. The 90% power column uses a higher target chance of detection. These are planning concepts, not guarantees about a future study’s result. They depend on assumptions about the effect, variability, analysis, and other design features.

The rows for 100%, 75%, and 50% of the observed effect represent progressively smaller target effects relative to the trial’s observed estimate. Smaller effects are harder to distinguish from random variation, so they require more participants per arm under otherwise unchanged assumptions. This relationship helps explain why planning based only on an observed effect can be optimistic when that estimate is uncertain.

These figures are not observed power. Observed power is not a useful substitute for interpreting the estimates and their confidence intervals after a study has been completed. The planning values are hypothetical illustrations based on the posted effect and stated assumptions; they do not describe the probability that this completed trial detected its result.

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, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = 1.284; pooled standard deviation σ = 3.232.
2. n = 2 × (1.96 + 0.842)² × 3.232² / 1.284² = 99.4, rounded up to 100 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
delta <- 1.284                      # observed difference in means
sigma <- 3.23181865659476                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^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 (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(3743064)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 100 (80% power), 134 (90% power)
 75% of observed effect: n per arm = 177 (80% power), 237 (90% power)
 50% of observed effect: n per arm = 398 (80% power), 533 (90% power)
power.t.test: 100.4 
Simulated power at n = 100 per arm: 0.801 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-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 reports the sponsor’s primary analysis as an ANOVA mean difference of 1.284 kg, with a 95% confidence interval from 0.718 to 1.851 and p < 0.001. The simple unadjusted re-calculation from the posted group summaries also estimates a mean difference of 1.284 kg, but gives a 95% confidence interval from 0.573 to 1.995 and p < 0.001. Thus, the estimates agree while the uncertainty summaries differ.

The re-calculation is a check based on posted summary statistics; it does not recreate the sponsor’s full analysis. The record identifies the sponsor’s method as ANOVA but does not report enough model details to reproduce it independently. The sponsor’s result should therefore be read as the registry’s reported analysis, and the recalculated result as a separate unadjusted comparison. The registry record does not flag a discrepancy between them, so there is no reported discrepancy requiring the sponsor analysis to take precedence under that criterion.

For the secondary outcomes, the same distinction applies: reported ANOVA estimates are separate from unadjusted summary-statistic re-calculations. Small differences in displayed estimates or intervals can reflect differences in the analysis procedure and rounding. They should not be conflated into a single analysis or used to infer unreported model specifications.

15. Multiplicity, Missing Data and Analysis Populations

The registry record lists a primary co-primary efficacy endpoint and several secondary outcomes, but it does not report a multiplicity adjustment or a testing hierarchy. Multiplicity matters because conducting tests across several outcomes can raise the chance of at least one result appearing notable by chance. In general, investigators can address this through prespecified procedures that control the overall error rate, or by treating secondary analyses as exploratory. The registry record does not state which approach was used.

The designation co-primary also leaves important statistical questions unanswered. The record does not explain how the co-primary outcomes were combined to define study success, whether every co-primary outcome had to meet a criterion, or whether any adjustment was applied across them. The posted primary body-weight result can be described on its own, but these missing details prevent a complete assessment of the study-wide confirmatory strategy.

The primary outcome description says that the mean was calculated using observed or imputed assessments through the last assessment, defined as week 12 or earlier in case of death. The record does not identify the imputation method, the amount of missing data, reasons for missingness, or sensitivity analyses. It also does not report detailed participant flow or the number with available measurements at each assessment. These omissions matter because conclusions may depend on how missing measurements are handled, especially when the endpoint definition permits imputation.

The stated Intent-to-Treat Set included all randomized patients and was analyzed according to planned treatment. That gives the intended analysis population in broad terms, but it does not by itself describe the implementation of the analysis or resolve missing-data questions. The registry record also does not report whether interim analyses were conducted or provide the original sample-size justification. These features should be treated as unreported rather than inferred from the trial’s completed status or the posted p-values.

16. 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 2% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: non-small cell lung cancer (11.7%), anaemia (2.6%), corona virus infection (1.9%), pneumonia (1.9%), malignant neoplasm progression (1.3%).

The registry reports serious adverse events in 44 of 154 participants in the 100 mg anamorelin HCl group and 46 of 164 participants in the placebo group. Other adverse events were reported for 114 of 154 participants and 127 of 164 participants, respectively. The record also lists 25 deaths in the anamorelin HCl group and 28 in the placebo group. These are recorded counts, not estimates of treatment effect or proof of causation.

The registry’s selected serious-event terms include non-small cell lung cancer at 11.7%, anaemia at 2.6%, corona virus infection at 1.9%, pneumonia at 1.9%, malignant neoplasm progression at 1.3%, and cardiac disorder at 1.3%. The listed terms and percentages describe entries in the registry record; they should not be interpreted as a complete account of every event or as evidence that study treatment caused them.

Safety comparisons require context about event definitions, follow-up, exposure, severity, timing, and relatedness. The registry record does not provide those details in the registry record. Counts alone do not establish that the groups had equivalent safety, and they do not show whether an event was judged related to treatment. The figures should be read descriptively alongside the study’s efficacy results, not as a standalone causal analysis.

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

The primary result describes an average difference in body-weight change between randomized treatment groups over 12 weeks. It does not predict the change for a particular participant, show how many participants gained weight, or describe the full range of individual responses. A group mean can coexist with substantial differences between individuals, and the registry does not provide the distribution of individual outcomes in the information.

The result concerns the endpoint as defined in the record: an average based on observed or imputed assessments through the last assessment, which could be week 12 or earlier in case of death. It should not be interpreted as a direct measure of every dimension of cachexia, overall health, or anorexia symptoms. Although the broader study question mentions anorexia symptoms, the primary result is body-weight change; the 5-IASS duration outcome is a separate secondary measure.

The randomized comparison provides a basis for comparing assigned groups, but the registry’s outcome definition, analysis details, and missing-data methods remain relevant. The record does not give enough information to assess all model assumptions, imputation choices, or multiplicity procedures. The reported estimate and interval therefore communicate the result of the posted analysis under its methods, not certainty that every possible source of bias or uncertainty has been eliminated.

Nor do the posted results alone establish an individual treatment recommendation or a general conclusion for every population with cancer-related weight loss. The trial record concerns adults with advanced non-small cell lung cancer and cachexia under the stated study conditions. Applicability outside that population and regimen is not established by these registry entries. The safety counts likewise describe recorded events and cannot be interpreted as proof of causation or as a complete comparative safety assessment.

In general, statistical evidence and clinical importance are different questions. A p-value addresses compatibility with a null hypothesis under a specified analysis; it does not state whether the size of a difference is meaningful to patients. The registry record does not provide a clinical-importance threshold for the body-weight difference. Interpretation should therefore keep the estimated magnitude, its uncertainty, the endpoint definition, and the limits of the record in view.

18. Why This Trial Matters Statistically

This trial illustrates why a reported treatment comparison should be read together with its endpoint definition and analysis method. The primary measure is not a single end-of-study weight: it averages changes from baseline across assessments through a participant’s last assessment within the stated period. That detail affects what the group mean represents and makes the registry’s description of observed and imputed assessments important to interpretation.

The posted primary mean difference is the same in the sponsor’s ANOVA analysis and the simple unadjusted re-calculation, while the confidence intervals differ. This is a useful distinction for readers: agreement on a point estimate does not imply that two analytical procedures have identical uncertainty estimates. The sponsor’s model-based result and the transparent summary-statistic comparison answer related but not identical computational questions.

The secondary outcomes also show why a collection of findings needs a multiplicity context. Several related measures can help characterize the result, but tests across multiple outcomes do not automatically represent independent confirmations. The registry record does not report the adjustment or hierarchy used, which limits the strength of broad conclusions drawn from the secondary analyses.

Finally, the record provides an example of the difference between efficacy statistics and a complete account of a trial. It reports randomized allocation, an ITT population definition, outcome estimates, and adverse-event counts, yet leaves the original sample-size justification, detailed missing-data methods, and some analysis-plan details unreported. Recognizing those boundaries is part of sound interpretation, not a reason to discard the reported estimates.

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.

Several trial-specific details needed for a fuller appraisal are not reported in the registry record. The primary outcome description permits observed or imputed assessments, but the imputation method, amount of missing data, reasons for missingness, and sensitivity analyses are not stated. The record defines an Intent-to-Treat Set but does not provide detailed participant flow or assessment availability over time.

The original sample-size justification and the trial’s own planning assumptions are not reported. The planning illustrations based on the observed effect do not reveal how the completed trial was originally designed. The registry also does not report whether interim analyses were performed, the full statistical model specification, or the covariates, if any, used in the sponsor’s ANOVA.

The registry identifies the endpoint as co-primary but does not describe how co-primary success was defined or how multiplicity across primary and secondary outcomes was handled. These omissions limit interpretation of the overall testing strategy. The masking field says quadruple masking, while the official title says double-blind; the record does not clarify this difference or identify the masked roles.

For safety, the record gives event counts and selected serious-event terms but does not provide the event definitions, exposure-adjusted summaries, timing, relatedness assessments, or complete event listings in the registry record. Those limitations mean the counts should not be treated as a full comparative safety analysis. The registry’s enrollment figure and its brief summary’s approximate planned enrollment also differ, and the record does not explain the difference through a participant-flow account.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: A Study to Evaluate the Efficacy and Safety of Anamorelin HCl for the Treatment of Malignancy Associated Weight Loss and Anorexia in Adult Patients With Advanced Non-Small Cell Lung Cancer (NSCLC) - 2 — NCT03743064.
• Registry record last updated 2026-10-06; status last verified 2024-06.
• Results first posted 2024-06-26.
• 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, parallel-group phase 3 study of 100 mg anamorelin HCl versus placebo in adults with advanced non-small cell lung cancer and cachexia. Treatment was oral and once daily for 24 weeks. The primary outcome was mean body-weight change over 12 weeks in the Intent-to-Treat Set.

The sponsor’s reported ANOVA estimated a primary mean difference of 1.284 kg, with a 95% confidence interval from 0.718 to 1.851 and p < 0.001. A simple unadjusted re-calculation gave the same estimate with a different confidence interval. The record also reports secondary duration-of-benefit outcomes and adverse-event counts.

Important analysis details, including the original sample-size justification, multiplicity procedures, and specific missing-data methods, are not reported in the registry record. The posted results are therefore best understood alongside those limits.