A Study Evaluating the Impact of Venetoclax on the Quality of Life for Subjects With Relapsed (Your Cancer Has Come Back) or Refractory (no Response to Previous Cancer Treatments) Chronic Lymphocytic Leukemia (CLL) While Receiving Venetoclax Monotherapy (a Single Agent).: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study Evaluating the Impact of Venetoclax on the Quality of Life for Subjects With Relapsed (Your Cancer Has Come Back) or Refractory (no Response to Previous Cancer Treatments) Chronic Lymphocytic Leukemia (CLL) While Receiving Venetoclax Monotherapy (a Single Agent). (NCT02980731), a na phase 3 study. The primary outcome is Mean Change From Baseline to Week 48 in Global Health Status/Quality of Life (GHS/QoL) Subscale of the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ-C30).

2. Clinical Question

The study asked how participants’ self-reported global health status and quality of life changed from baseline to Week 48 while they received venetoclax for relapsed or refractory chronic lymphocytic leukemia (CLL). It enrolled participants who received at least one dose and had available data for the primary endpoint. The study also included participants with or without 17p deletion or TP53 mutation, including those whose status was unknown, and participants previously treated with B-cell receptor inhibitor therapy.

This is a within-group question about change over time, not a randomized comparison of venetoclax with another treatment or with no treatment. The registry record does not report the mean change, its standard deviation, or a confidence interval for the primary endpoint. It therefore does not establish from the posted results whether the average score changed, how large any change was, or how precisely it was estimated.

3. Trial Design

This was a Phase 3b, open-label, single-arm, multicenter study of venetoclax in participants with relapsed or refractory CLL. The registry lists an enrollment of 210. Because there was one treatment group and no masking, participants and study personnel knew that venetoclax was being administered. Allocation to treatment groups was not applicable; there were no parallel groups to allocate participants between.

Venetoclax was taken orally once daily. The starting dose was 20 mg daily, with a gradual increase over 5 weeks to 400 mg daily. Treatment was planned for up to 2 years or until disease progression. The median time on treatment was 127 weeks. The study description also notes that participants could continue into a 2-year follow-up period after treatment.

The primary endpoint was the mean change from baseline to Week 48 in the EORTC QLQ-C30 global health status/quality-of-life subscale. The endpoint population was participants who received at least one dose and had available data. Other listed outcomes included change from baseline in the questionnaire’s physical, role, emotional, cognitive, and social functioning subscales, as well as fatigue and nausea/vomiting. The registry lists 30 outcome measures and one analysis.

The study started on 2016-12-13, had a primary completion date of 2021-12-29, and is recorded as completed. The registry record does not report a sample-size justification, a prespecified statistical analysis plan, or details of interim analyses. Without a concurrent control group, changes over time cannot by themselves separate treatment-associated change from other influences, such as the course of illness, expectations, or changes in participants’ circumstances.

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: All enrolled participants who received at least one dose of venetoclax

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: All enrolled participants who received at least one dose of venetoclax with available data

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: All enrolled participants who received at least one dose of venetoclax

6. Primary Endpoint

The registry lists the primary outcome as Mean Change From Baseline to Week 48 in Global Health Status/Quality of Life (GHS/QoL) Subscale of the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ-C30), measured over Baseline, Week 48.

The primary endpoint was the mean change from baseline to Week 48 in the global health status/quality-of-life subscale of the EORTC QLQ-C30. This is a participant self-report measure within a 30-item questionnaire that includes multi-item and single scales. The global health status/quality-of-life score ranges from 0 to 100. A higher score indicates a better level of functioning, and a positive change from baseline indicates improvement in the score.

Quality of life is relevant to a study focused on how participants experience their health during treatment. A score change can describe the average direction and magnitude of change in this measured aspect of health; it does not directly identify why the change occurred. The registry description characterizes a change of 5 - 10 points as small and a change of 10 - 20 points as moderate. These are interpretive guides stated in the registry, not observed results from this study.

The mean summarizes the average change among participants contributing endpoint data. It does not show whether every participant changed in the same direction, nor does it describe the full spread of individual experiences. The registry record does not report the primary mean change or its standard deviation. It also does not report a confidence interval for that change. Consequently, the posted information does not permit an assessment of the observed average, its precision, or whether it met the registry’s stated change thresholds.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is continuous: it is a score on a scale, and the registry specifies a mean change as the summary measure. Statistical interpretation of such an outcome depends on both the estimated average change and the variability of individual changes. The registry record gives the measurement definition and score interpretation, but does not report the observed mean change or standard deviation.

What does a mean change describe?

In general, a mean change is calculated by determining each participant’s follow-up score relative to that participant’s baseline score, then averaging those changes among participants included in the analysis. It gives a compact description of average direction and magnitude. It does not imply that all participants had the same experience. Some participants may have improved, some may have worsened, and some may have changed little, even when the mean is positive or negative.

For this endpoint, positive changes are described as improvement in the global health status/quality-of-life score. The score runs from 0 to 100, with higher scores indicating a better level of functioning. The registry states that a change of 5 - 10 points is small and a change of 10 - 20 points is moderate. Those interpretive descriptions can help contextualize a reported estimate, but the registry record does not state the study’s observed mean change.

Why does variability matter?

In general, the standard deviation describes how spread out individual observations are around their mean. When analyzing participant-level change, a standard deviation of the changes describes how much those changes differ across participants. A relatively consistent set of changes and a highly varied set can produce the same mean, while representing different patterns of individual experience. The registry identifies standard deviation as the measure of dispersion for the primary outcome but does not report its value.

A standard error and a confidence interval describe uncertainty in an estimated mean, rather than the spread of individual participant scores. In general, a confidence interval gives a range of values compatible with the data and the method used to calculate it. A narrower interval indicates greater precision under that method; a wider interval indicates less precision. It is not a guarantee that the true value lies within the interval. The registry record does not report a confidence interval for the primary mean change, so the precision of the estimate cannot be judged.

What can a one-group analysis establish?

In general, a single-arm study can describe outcomes observed in a treated group, including change from baseline. It cannot directly estimate a between-group treatment contrast because there is no concurrent comparator. Baseline measurements provide a reference for within-participant change, but they do not recreate the counterfactual outcome: what would have happened to the same participants over the same period under a different treatment or without the study treatment. Changes may reflect treatment, disease progression or fluctuation, other care, measurement variation, or other events during follow-up.

The open-label design also means the treatment was not masked from participants or study personnel. For a self-reported quality-of-life measure, awareness of treatment can be relevant to how participants interpret and report their experience. This is a general methodological consideration; it does not establish that responses in this study were affected by expectations.

How should missing measurements be considered?

In general, missing outcome data matter because the observed participants may differ from those without measurements. If missingness is related to a participant’s health, treatment experience, or score, an average among those with observed data may not represent all enrolled participants. Different statistical approaches make different assumptions about missingness and use of available measurements. The registry record does not report the number of participants with Week 48 data, the extent or reasons for missingness, or the method used to address missing data. It is therefore not possible to determine how missing observations influenced the primary estimate.

What is multiplicity?

In general, multiplicity arises when several outcomes, time points, or statistical tests are assessed. The more tests considered, the greater the chance that at least one result appears noteworthy by chance if no adjustment or prespecified testing strategy is used. The registry lists the primary endpoint and multiple secondary quality-of-life outcomes, and reports 30 outcome measures overall. However, the record does not describe a multiplicity adjustment, a testing hierarchy, or which outcomes were included in any confirmatory strategy. No claims about such a strategy can be made from the registry record.

How should planning illustrations be read?

In general, sample-size calculations use assumptions about the outcome, variability, target effect, significance level, allocation, and statistical method. Planning illustrations are hypothetical: they indicate the sample size associated with stated assumptions. They do not describe the study’s observed result or show the probability that the completed trial detected an effect. The registry notes that its illustrations use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the target effect set as a stated fraction of the observed effect. For time-to-event outcomes, the illustrations use total events; for other outcomes, they use participants per arm. These are planning conventions and do not turn this single-arm study into a two-arm comparison. The registry record does not report the trial’s own sample-size justification.

The registry lists one analysis for this record, but it does not provide a detailed statistical analysis plan. The precise model, handling of repeated measurements, treatment of missing data, inferential testing procedure, and any adjustments cannot be established from the information reported. These details matter when evaluating how an estimate was produced, but should not be inferred from the endpoint label alone.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("Venetoclax")
n   <- c(157)
m   <- c(9.3)
sp  <- c(20.11)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  Venetoclax  157  9.300  20.110  6.130  12.470

11. Multiplicity, Missing Data and Analysis Populations

The study assessed a primary quality-of-life endpoint and listed numerous secondary quality-of-life measures. The registry record also lists 30 outcome measures. When multiple outcomes or tests are examined, multiplicity can increase the chance of at least one result appearing notable by chance. In general, investigators may address this through a prespecified hierarchy, adjustment of significance levels, or another stated strategy. The registry record does not report whether any multiplicity strategy was used, so the interpretation of tests across outcomes cannot be fully assessed.

The primary analysis population is described as participants who received at least one dose of venetoclax and had available data. The registry does not report the number with primary endpoint data at Week 48 or the number missing that assessment. Reasons for missing data, the analysis approach to missing values, and any sensitivity analyses are also not reported in the registry record. The number enrolled, 210, does not by itself show how many participants contributed to the primary endpoint analysis.

In general, missingness can affect an estimated mean if participants without measurements have different outcomes from those whose data are observed. A complete-case average can be informative about measured participants, but its representativeness depends on why measurements are unavailable. Without missing-data details, the direction or size of any potential influence cannot be determined. The registry record does not report a detailed analysis population definition beyond the stated receipt of at least one dose and availability of data, nor does it report a statistical analysis plan sufficient to clarify these issues.

12. 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: pneumonia (10.0%), pyrexia (4.8%), febrile neutropenia (3.3%), thrombocytopenia (2.9%), anaemia (2.4%).

The registry records 210 participants at risk for the serious adverse event summary, with 106 affected, and 210 at risk for the other adverse event summary, with 179 affected. It also records 65 deaths. These are counts from the venetoclax group. They describe events recorded during the study; they do not, on their own, establish that venetoclax caused an event or death. The registry record does not provide a comparison group for contextualizing these counts.

The listed serious adverse event terms include pneumonia (10.0%), pyrexia (4.8%), febrile neutropenia (3.3%), thrombocytopenia (2.9%), anaemia (2.4%), and hyperphosphataemia (2.4%). These percentages are reported as registry values and should be read as event-term figures, not as comparative effects. The record does not give further details about event timing, duration, severity categories beyond the serious-event listing, or individual attribution.

Deaths are recorded separately from the list of serious adverse event terms. The count alone does not indicate cause, timing, or whether a death was considered related to treatment. Such details are not reported in the registry record. Safety counts should therefore be interpreted as descriptive observations in the enrolled group, not as evidence of a treatment effect compared with another option.

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

The trial’s primary question concerns average change in participants’ self-reported global health status/quality of life between baseline and Week 48 during venetoclax treatment. The registry describes the instrument, its score range, the direction of improvement, and the population intended for analysis. However, it does not report the primary mean change, its standard deviation, or a confidence interval. The posted results therefore do not establish the direction, size, or precision of the primary quality-of-life change.

Even a reported within-group change would answer a descriptive question rather than establish what would have happened under another treatment. The study had one open-label treatment group and no concurrent comparator. Without a control group, an observed change cannot be attributed solely to venetoclax: other influences over time cannot be separated from treatment-related change by this design alone.

The endpoint is a participant-reported measure, which captures an important aspect of experience but is not a direct measure of every health outcome. The registry’s scale guidance describes a change of 5 - 10 points as small and a change of 10 - 20 points as moderate. These categories provide context only; they cannot be applied without a reported estimate. The average would also not describe the full range of individual outcomes.

The registry reports the enrolled group, treatment schedule, duration information, and adverse-event counts. Those data support a description of who was studied, how venetoclax was administered, and which safety events were recorded. They do not fill the gap in the primary endpoint result or provide a comparative estimate of safety or quality of life.

Accordingly, the record supports no numerical conclusion about whether the average quality-of-life score improved, worsened, or remained similar at Week 48. It also does not support a causal comparison with another treatment or a conclusion about the experience of participants who lacked endpoint data. The distinction between a study question, a design, and a reported result is essential: describing the intended endpoint is not the same as reporting its observed value.

14. Why This Trial Matters Statistically

Quality of life is a patient-reported outcome, and a study focused on change in that outcome addresses a different question from one focused only on clinical events. The EORTC QLQ-C30 global health status/quality-of-life scale provides a structured way to summarize participants’ ratings over time. Its 0 to 100 scale, direction of improvement, and stated change categories help readers understand what a numerical estimate would mean.

Statistically, the study also illustrates the limits of interpreting a single-group change. A baseline measurement allows the study to describe how scores changed within the observed group, but without a comparator it cannot distinguish treatment-associated change from other changes over time. This matters particularly when the endpoint is self-reported and the study is open-label, because participant awareness and experiences during follow-up may shape responses. These are design considerations, not proof that any particular bias occurred.

The registry lists a substantial set of quality-of-life outcomes, including global health status, functioning domains, fatigue, and nausea/vomiting. Multiple outcomes can offer a broader view of participant-reported experience, while also making prespecification and multiplicity handling important for interpretation. The registry record does not report how multiplicity was addressed.

Finally, this record demonstrates why outcome definitions and numerical results must be distinguished. The primary endpoint is carefully defined, and the study’s population and treatment schedule are described, but the primary estimate and its uncertainty are not reported in the registry record. Without those values, neither clinical magnitude nor statistical precision can be judged. The study is therefore statistically informative as an example of a patient-reported outcome evaluated in a single-arm design, while the posted primary results remain insufficient for quantifying change.

15. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The most direct limitation for interpretation is that the registry record does not report the primary endpoint estimate. The mean change from baseline to Week 48, its standard deviation, and a confidence interval are absent. Therefore, the principal quality-of-life result cannot be evaluated for direction, magnitude, precision, or relation to the registry’s stated change categories.

The single-arm, open-label design has no concurrent control group. It can describe change among participants with observed data, but cannot estimate a comparative treatment effect or distinguish treatment-related change from other influences over time. Because the endpoint is self-reported, lack of masking is also relevant as a possible source of influence on responses; the record does not establish whether such influence occurred.

The endpoint population includes those who received at least one dose and had available data, but the number with Week 48 measurements and the extent and reasons for missing data are not reported in the registry record. The method for handling missing measurements and any sensitivity analyses are likewise not reported. This leaves uncertainty about how representative the analyzed participants were of the enrolled group.

The registry lists multiple secondary quality-of-life outcomes and 30 outcome measures overall, but it does not report a multiplicity strategy or a detailed statistical analysis plan. The method used to analyze repeated measurements, any inferential testing procedure, and any adjustment for multiplicity are not reported in the registry record. The record also does not state the original sample-size justification or interim-analysis plan.

Finally, the listed adverse-event figures are descriptive counts from a single treatment group. The registry does not provide a concurrent comparator in this study for interpreting those counts comparatively. These limitations do not negate the study’s stated purpose, but they constrain what can be concluded from the registry record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study Evaluating the Impact of Venetoclax on the Quality of Life for Subjects With Relapsed (Your Cancer Has Come Back) or Refractory (no Response to Previous Cancer Treatments) Chronic Lymphocytic Leukemia (CLL) While Receiving Venetoclax Monotherapy (a Single Agent). — NCT02980731.
• Registry record last updated 2023-02-22; status last verified 2023-01.
• Results first posted 2023-02-22.
• 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.

19. Record Summary

This completed Phase 3b study evaluated venetoclax in participants with relapsed or refractory CLL. It was open-label, multicenter, and single-arm, with 210 enrolled participants. Venetoclax was administered orally once daily, beginning at 20 mg and increasing over 5 weeks to 400 mg. Treatment was planned for up to 2 years or until disease progression; median time on treatment was 127 weeks.

The primary endpoint was mean change from baseline to Week 48 in the EORTC QLQ-C30 global health status/quality-of-life subscale among participants who received at least one dose and had available data. The registry describes the score and its interpretation, but does not report the primary numerical result or its precision. It also does not report missing-data handling, multiplicity methods, or a detailed statistical analysis plan.

The registry records 106 participants affected by serious adverse events, 179 affected by other adverse events, and 65 deaths. These are descriptive observations without a comparator in this study. The record does not support a quantitative conclusion about primary quality-of-life change or a comparative treatment effect.