Phase 2 Study of Atorvastatin Safety and Antitumor Effects in Non-Hodgkin's Lymphoma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Phase 2 Study of Atorvastatin Safety and Antitumor Effects in Non-Hodgkin's Lymphoma (NCT00185731), a na phase 2 study. The primary outcome is Tumor Apoptosis.

2. Clinical Question

The registry's brief summary frames the study as an exploration of targeting oncogene expression as a way to affect cancer cells while potentially reducing toxicity to the host. That statement describes a rationale, not a result established by the endpoint. The listed secondary outcomes are the correlation of tumor apoptosis to clinical response and atorvastatin toxicity. The registry record does not report results for those questions either.

3. Trial Design

This was a Phase 2, single-group study of atorvastatin in patients with low-grade or refractory non-Hodgkin's lymphoma. The registry lists enrollment as 25 and the study status as completed. Its dates are recorded as 2005-04 for study start and 2012-11 for primary completion. These are registry dates; they do not by themselves describe how long each participant was followed.

The intervention description specifies an 80 mg atorvastatin tablet taken orally each day, beginning on study day 1. Masking is listed as none, and allocation is listed as NA. The registry explicitly notes that this is not a randomized comparison and that its arms are not a like-for-like control comparison. The single-group model means that the primary question concerns observations during treatment, rather than a randomized contrast with a control group.

The primary endpoint is tumor apoptosis, expressed as the number of participants whose tumor cells showed an increase in apoptosis during atorvastatin treatment. Its stated timeframe is 1 year. The endpoint description says that 24 participants had tumors sampled for the primary endpoint as per protocol. It further says that 1 withdrew and that only 22 of the remaining participants had adequate tumor samples for analysis of apoptosis at baseline and at subsequent time points.

The registry record lists 3 outcome measures and 0 analyses. It names correlation of tumor apoptosis to clinical response and atorvastatin toxicity as secondary outcomes. Detailed eligibility criteria, the statistical analysis plan, and the rationale for the enrollment target are not reported in the registry record. The record's completion status does not fill in those details or establish what analyses were performed.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: 24 participants had tumors sampled for primary endpoint as per protocol. However, 1 withdrew, and only 22 of remaining participants had adequate tumor samples for analysis of apoptosis at baseline and at subsequent time points.

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 Tumor Apoptosis, measured over 1 year.

The primary endpoint counts participants whose tumor cells showed an increase in apoptosis during atorvastatin treatment. Apoptosis is a process of cell death; in this study, the endpoint is based on whether tumor samples showed an increase, rather than on a reported continuous measure of the amount of apoptosis. It is therefore a participant count for a binary outcome: each participant with suitable measurements could be classified according to whether the specified increase was observed.

Tumor apoptosis was selected to capture a biological change in tumor cells during treatment. Such a measure can address whether a biological response was observed, but it is not itself the same as a clinical response, disease control, or a comparison of patient outcomes between treatment groups. The registry lists correlation of tumor apoptosis to clinical response as a secondary outcome, signaling that the relationship between the tissue measure and clinical response was a separate question.

The timeframe is 1 year. The registry says 24 participants had tumors sampled for the endpoint as per protocol; 1 withdrew, and 22 of the remaining participants had adequate samples at baseline and subsequent time points for apoptosis analysis. The analyzed number with an increase in apoptosis is not reported in the registry record. Nor does the record give a confidence interval, a test result, or a treatment-effect estimate for this endpoint. Without those results, the definition and sampling information alone cannot establish the frequency of increased apoptosis.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The methods can be understood by separating the endpoint definition, the study design, and the analysis information that is actually available. The primary endpoint is a count of participants whose tumor cells showed an increase in apoptosis during treatment. Although the endpoint is expressed as a count, the underlying participant-level outcome is binary: a participant either meets the stated increase criterion or does not. The registry does not report the count meeting that criterion.

What does a participant count convey?

In general, a count records how many observed participants meet a specified definition. A count alone is not a measure of uncertainty and does not show how stable an estimate might be in another group of participants. Researchers commonly interpret a count alongside its denominator and, when an analysis is reported, an interval estimate that expresses uncertainty. The registry gives sample-availability information but does not report a primary endpoint count, an interval estimate, or a model for that endpoint. No rate or percentage should be inferred from the information in the record.

The endpoint requires tumor-sample measurements at baseline and subsequent time points. The record says 24 participants had tumors sampled as per protocol, 1 withdrew, and only 22 of the remaining participants had adequate samples for apoptosis analysis. These details distinguish enrollment from availability of endpoint data. Enrollment is listed as 25, but an enrolled participant is not automatically an evaluable participant for a tissue-based endpoint. The registry record does not specify a missing-data method or explain how a withdrawal or inadequate sample was treated in the analysis.

Why does the single-group design matter?

In general, a randomized comparison uses groups assigned to different conditions to estimate a contrast while reducing some sources of systematic differences. A single-group study instead describes outcomes within one group. The registry lists a single-group model, allocation NA, and no masking, and explicitly says there is no randomized comparison. Thus, the endpoint can describe the observed pattern in participants receiving atorvastatin if results are reported, but it cannot by itself estimate a randomized difference from a control condition. Changes over time can have explanations other than the intervention, and this design does not provide a concurrent control group to help distinguish them.

The registry lists the intervention as atorvastatin, with an 80 mg tablet taken orally each day from study day 1. The study timeframe for the primary outcome is 1 year. These details define the intended treatment and the outcome window in the record. They do not establish adherence, actual exposure for each participant, or duration of follow-up for each individual; those details are not reported in the registry record.

How should precision and significance be read?

In general, a confidence interval gives a range of values compatible with an estimate under the assumptions of the analysis. A narrower interval indicates greater statistical precision, while a wider interval indicates more uncertainty. A p-value, when reported, describes how compatible the data are with a specified statistical null model; it does not measure the probability that a treatment works or establish causation. The registry record reports no primary endpoint estimate, confidence interval, or p-value, so those concepts cannot be applied to a numerical result for this endpoint.

The registry's planning assumptions refer to a two-sided significance level of 0.05 and a normal approximation. They also describe equal allocation between two arms and an effect to detect defined as a stated fraction of the observed effect. These assumptions characterize planning illustrations. They do not describe the study's single-group design, and they do not establish that an analysis at that significance level was performed. The registry record does not report the trial's own sample-size justification, a statistical analysis plan, or the observed effect underlying the planning illustrations. Any sample-size values derived from observed effects are planning illustrations, not observed power.

What does over-dispersion mean in general?

In general, over-dispersion occurs when observed variability is greater than a statistical model assumes. It can make standard errors and confidence intervals too small if the model does not account for the extra variability. This concept is most relevant for particular count-data models; it should not be invoked as an explanation for this trial's results without knowing the model and the data. The registry describes the primary endpoint as a participant count and gives no dispersion measure or analysis model. It therefore does not report whether over-dispersion was assessed or relevant.

Finally, the registry lists 3 outcome measures and 0 analyses. The primary outcome is named, and two secondary outcomes are listed: correlation of tumor apoptosis to clinical response and atorvastatin toxicity. The names alone do not provide estimates or clarify how outcomes were analyzed. Without reported analysis methods and results, the record permits description of the intended measurement, but not evaluation of statistical significance, precision, model fit, or robustness.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Atorvastatin")
n      <- c(22)
events <- c(7)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Atorvastatin  22  7  31.8  13.9  54.9  16.4  52.7  16.4  52.9

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 3 outcome measures, including tumor apoptosis as the primary outcome and correlation of tumor apoptosis to clinical response and atorvastatin toxicity as secondary outcomes. The registry record does not report a multiplicity adjustment, a hierarchy for testing outcomes, or a plan for controlling the chance of false-positive findings across multiple analyses. It lists 0 analyses, so there are no reported endpoint-specific tests to interpret in light of multiplicity.

Missing endpoint information is especially relevant because the primary outcome requires tumor samples at baseline and later time points. The record says 24 participants had tumors sampled as per protocol; 1 withdrew; and 22 of the remaining participants had adequate samples for apoptosis analysis. The endpoint result among those participants is not reported in the registry record. The method used to handle the withdrawal, inadequate samples, or any other missing observations is also not reported.

The record does not define an analysis population, such as a population based on enrollment, treatment received, or availability of endpoint samples. It therefore does not establish whether all enrolled participants, all participants with samples, or another group was intended for the primary analysis. Nor does it describe sensitivity analyses for missing data. These omissions limit assessment of whether the analyzed population could differ from the intended study population.

The registry's sample-size assumptions describe planning illustrations, but do not supply the trial's own sample-size justification or a statistical analysis plan. The rationale for enrollment, planned handling of missing data, and any planned interim analyses are not reported in the registry record. These gaps mean that the reported endpoint definition and sample flow cannot be used to reconstruct a prespecified analysis or assess whether the final analysis followed one.

12. Safety Results

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

Other (non-serious) adverse events

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

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: diarrhoea (4.2%), cholecystitis (4.2%), mood alteration - anxiety (4.2%), pain - abdominal nos (4.2%).

The registry reports a serious adverse event group titled Atorvastatin. It lists 24 participants at risk and 4 affected. These are counts in the registry's safety reporting; they do not establish that atorvastatin caused the events. With no randomized control group reported, these figures cannot be compared with a like-for-like alternative-treatment or untreated group.

The listed serious-event terms are Diarrhoea, Cholecystitis, Mood alteration - Anxiety, and Pain - Abdominal NOS, each reported as 4.2%. These term-specific figures should be read as the registry's reported frequencies, not as evidence about causality or comparative risk. The registry record does not provide additional detail in the registry record about event timing, severity beyond the serious-event classification, or whether a participant had more than one event.

The death count is not reported in the registry record. The safety figures also should not be conflated with the primary tumor-apoptosis endpoint: they answer different questions and have different outcome definitions. The registry separately lists atorvastatin toxicity as a secondary outcome, but a detailed analysis of that outcome is not reported.

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

The study record identifies a focused biological question: whether tumor cells showed increased apoptosis during atorvastatin treatment. It gives the intervention, the primary endpoint definition, its 1 year timeframe, and information about tumor-sample availability. These details help clarify what the study set out to assess, but they are not a numerical result. The number of participants meeting the primary endpoint is not reported in the registry record.

The record also does not report an inferential analysis, confidence interval, or treatment-effect estimate. It lists 0 analyses. As a result, the available information cannot establish how often increased apoptosis was observed, how precise that estimate would be, or whether any observed change would be statistically distinguishable from chance under a specified model. No conclusion about the clinical effectiveness of atorvastatin follows from an endpoint definition or a completed study status.

The study's single-group design sets a further boundary on interpretation. Even if an outcome count were available, an observation during treatment would not be a randomized comparison against a control condition. The registry explicitly notes that the study is not a randomized comparison. This limits causal interpretation and prevents a like-for-like comparison of treatment outcomes.

The safety counts add descriptive information about serious adverse events in the atorvastatin group. They do not establish causation or comparative safety. The registry lists 4 affected among 24 at risk and four serious-event terms with frequencies of 4.2% each; a death count is not reported in the registry record. These details should be interpreted within the limits of the recorded safety data.

In short, the registry record supports a description of the study's question and design, but not a conclusion that atorvastatin did or did not produce a tumor-apoptosis response or a particular clinical benefit. The missing endpoint analysis and the lack of a randomized comparator are central to that distinction.

14. Why This Trial Matters Statistically

This study illustrates the difference between a biologically meaningful endpoint and an interpretable treatment-effect estimate. Tumor apoptosis can be used to ask whether a measurable change occurred in tumor cells during treatment. But a clearly stated biological endpoint does not, by itself, establish a clinical effect. The registry separately lists the correlation of tumor apoptosis to clinical response, underscoring that a tissue-level change and a clinical outcome are related but distinct questions.

It also shows why participant flow and outcome availability matter. Enrollment is listed as 25, while the endpoint description reports tumor sampling for 24 participants, a withdrawal, and adequate paired samples for 22 of the remaining participants. A tissue endpoint depends on usable samples, so the number enrolled and the number with endpoint data need not be interchangeable. Without an analysis result and a missing-data account, readers cannot assess how the available samples shaped the endpoint estimate.

The single-group design demonstrates another core statistical distinction: describing outcomes in a treated group is not the same as estimating a treatment effect against a comparator. The registry specifically notes that there was no randomized comparison. That restriction applies regardless of the biological rationale and regardless of whether the study reached completed status.

Finally, the record makes clear that registration details and analytical evidence are not the same. It identifies a primary endpoint, secondary outcomes, and safety counts, but lists 0 analyses. The absence of an endpoint estimate, uncertainty interval, and analysis plan leaves important questions unanswered. Statistically, careful interpretation depends not only on what was intended to be measured, but also on who contributed data, how missing observations were handled, and what analysis was actually performed.

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.

Several limitations are specific to the information recorded for this study. First, the primary endpoint is described, but its analyzed result is not reported in the registry record. The record lists 0 analyses, so the count of participants with increased tumor apoptosis, its precision, and any statistical test result are unavailable.

Second, the endpoint depends on tumor samples at baseline and subsequent time points. The record reports 24 participants sampled per protocol, 1 withdrawal, and adequate samples for 22 of the remaining participants. It does not explain how participants without adequate endpoint samples were handled analytically, or whether missingness could be related to outcome or treatment experience.

Third, the design is single group, with allocation listed as NA and masking as none. The registry explicitly states that this is not a randomized comparison. Without a concurrent control group, the design cannot provide a like-for-like estimate of how outcomes would differ under another condition.

Fourth, the registry lists secondary outcomes but does not report their analyses. It also does not report a multiplicity strategy, a statistical analysis plan, or a sample-size justification for the trial. The planning assumptions recorded for illustrations are not a substitute for those trial-specific details.

Finally, the safety record is limited to the reported counts and event terms. A death count is not reported in the registry record, and the posted details do not give further context for the event timing or attribution. These limits constrain interpretation of both efficacy-related and safety-related findings.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Phase 2 Study of Atorvastatin Safety and Antitumor Effects in Non-Hodgkin's Lymphoma — NCT00185731.
• Registry record last updated 2017-12-02; status last verified 2017-10.
• Results first posted 2017-12-02.
• 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

NCT00185731 is a completed Phase 2, single-group study of atorvastatin in patients described as having low-grade or refractory non-Hodgkin's lymphoma. The intervention was an 80 mg oral tablet taken daily beginning on study day 1. Enrollment is listed as 25, and the primary endpoint was the count of participants whose tumor cells showed increased apoptosis during treatment over a 1 year timeframe.

The registry reports tumor sampling for 24 participants, 1 withdrawal, and adequate baseline and subsequent samples for 22 of the remaining participants. It lists 3 outcome measures and 0 analyses. The primary endpoint result, its uncertainty, and the statistical analysis plan are not reported in the registry record. Serious adverse events are reported for 4 of 24 at risk; the listed serious-event terms each have a frequency of 4.2%. A death count is not reported.