Intravenous Chemotherapy or Oral Chemotherapy in Treating Patients With Previously Untreated Stage III-IV HIV-Associated Non-Hodgkin Lymphoma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Intravenous Chemotherapy or Oral Chemotherapy in Treating Patients With Previously Untreated Stage III-IV HIV-Associated Non-Hodgkin Lymphoma (NCT01775475), a randomized phase 2 study. The primary outcome is Overall Survival.

2. Clinical Question

The randomized comparison asks whether outcomes differed between two chemotherapy strategies in this population. One strategy combined intravenous drugs with oral prednisone; the other used oral drugs on specified days within each course. Both arms were studied alongside concomitant antiretroviral therapy, as stated in the official title. The registry does not report further details about the antiretroviral regimens.

The clinical question is bounded by the registered population, the two regimens, and the specified survival outcome. It is not a comparison of chemotherapy with no chemotherapy, nor does the posted primary endpoint describe response, disease control, or quality of life. The registry lists adverse-event measures separately, but those do not replace the primary survival question.

3. Trial Design

The record describes a randomized, phase II, open-label, parallel-group trial. Randomization means treatment assignment was allocated at random, but the allocation ratio and the method used to generate or conceal assignments are not reported in the registry record. Open-label means masking was not used; the record does not describe additional measures to limit bias in outcome assessment.

The trial enrolled 7 participants. The registry lists Arm I as CHOP and Arm II as oral chemotherapy. The posted primary outcome includes 3.0 participants in each arm. The registry record does not explain the relationship between overall enrollment and the number included in the primary outcome population, or why the adverse-event population counts differ from those primary outcome counts.

Arm I participants received cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and prednisone. The first three were administered intravenously on day 1 and prednisone was taken orally on days 1-5. Courses were scheduled every 3 weeks, for up to 6 courses, subject to disease progression or unacceptable toxicity.

Arm II participants received oral lomustine on day 1 of courses 1 and 3, oral etoposide on days 1-3, and oral cyclophosphamide and procarbazine hydrochloride on days 22-26. Courses were scheduled every 6 weeks, for up to 3 courses, subject to disease progression or unacceptable toxicity. These schedules describe the registered regimens; the record does not report how many participants completed each course or received each drug.

The trial status is completed. Its start date is 2016-09-15, and its primary completion date is 2021-04-01. The sponsor is the AIDS Malignancy Consortium. Although the official title refers to sub-Saharan Africa, the registry entries do not identify study sites or report country-specific results.

The posted design supports a descriptive comparison of outcomes by randomized arm. With the small enrolled population and no posted inferential analyses, the record does not provide a precise estimate of a comparative treatment effect. It also does not report a protocol-based sample-size justification or a planned analysis strategy beyond the registered endpoint description.

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: Study participants whose survival status was known at two years.

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 Overall Survival, measured over Up to 24 months.

The primary endpoint is overall survival, expressed as the proportion of participants who survived 2 years. The stated timeframe is up to 24 months. The analysis population is described as study participants whose survival status was known at two years, so the endpoint concerns survival status at that time rather than a reported time-to-event estimate over the full follow-up period.

Survival is a direct clinical outcome: it records whether a participant was alive at the specified assessment point. A proportion can communicate the observed share meeting that outcome in each arm. In general, a fixed-time survival proportion is easier to interpret as a status at a defined time than as a description of when deaths occurred. It does not, by itself, show the timing of events or account for differences in follow-up unless those methods are specified.

The registry reports a proportion of 0.0 for Arm I and 0.0 for Arm II. For both arms, it reports a 95% confidence interval from 0.0 to 0.0. The posted record does not provide an explanation of the interval calculation or additional details on follow-up completeness. Because the stated population includes only participants with known status at two years, the endpoint should not be read as an outcome for every enrolled participant unless the analysis population is shown to include them.

Overall survival is relevant to a comparison of cancer-treatment strategies because it captures a consequential outcome without requiring an interpretation of tumor response categories. However, the posted primary result alone does not explain the causes or timing of deaths, the burden of treatment, or other benefits and harms. Those questions require additional reported outcomes and methods.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The results are proportions: the endpoint records whether a participant survived 2 years, and each arm’s value expresses the share meeting that condition. A proportion is a summary of observed outcomes in an analysis group. It does not describe when deaths occurred, and it does not automatically incorporate incomplete follow-up or differences in observation time.

What does the confidence interval represent?

In general, a confidence interval describes statistical uncertainty around an estimate under a specified method and its assumptions. A narrower interval is usually read as greater precision, while a wider interval indicates that a broader range of values is compatible with the data and method. The registry reports 95% confidence intervals of 0.0 to 0.0 for both arms. Those limits coincide with the estimates, but the registry record does not identify the calculation method or explain the reported limits. They should therefore be quoted as posted, not treated as proof of certainty.

Methods for proportions can behave differently when event counts are very small or when an estimate is at a boundary such as zero. Some methods can produce boundary limits; others may give a wider interval. This is a general statistical issue, not a claim about which method was used in this trial. Since the calculation is not reported, no alternative interval should be substituted for the registry result.

Why does the analysis population matter?

The endpoint description specifies participants whose survival status was known at two years. This is a defined outcome population, and its size may differ from enrollment if some participants lack known status or are excluded for another reason. The registry does not state why the primary outcome lists 3.0 participants per arm while overall enrollment is 7. It also does not report the number with unknown status or the handling of missing status. Without those details, the completeness and potential selection of the primary analysis cannot be assessed.

In general, excluding participants with missing outcomes can bias a comparison if missingness is related to prognosis or treatment. This does not establish that such bias occurred. It explains why the number and reasons for missing observations, along with the planned handling method, are important to interpretation.

What can randomization support?

Randomization is intended to make treatment groups comparable on average with respect to measured and unmeasured characteristics at assignment. In a small trial, chance differences between arms can still occur, and the realized groups may not be balanced. The record identifies the trial as randomized but does not report the sequence-generation method, allocation concealment, stratification factors, or baseline characteristics. Consequently, readers cannot assess these features from the posted details.

The trial is open-label, meaning masking was not used. In general, knowledge of assigned treatment can influence care, reporting, or assessment of outcomes that involve judgment. Overall survival is a relatively objective endpoint, but open-label conduct can still affect aspects of follow-up and event recording. The registry does not report whether any independent outcome adjudication was used.

How should the planning calculations be read?

The sample-size assumptions describe a planning illustration based on the observed effect, not the trial’s own design. The stated assumptions are a two-sided significance level of 0.05, equal allocation between arms, a normal approximation, and an effect to detect expressed as a fraction of the observed effect. Such calculations can illustrate what a future study might require under those assumptions; they are not observed power and do not show the probability that this completed trial detected an effect. The registry record does not report its own sample-size justification. No planning sample-size result should be treated as an observed study outcome.

Sample-size calculations based on an observed effect also depend on that effect being a useful planning value. In general, effects estimated from small studies may be imprecise. A planning exercise can therefore be informative as an illustration while still being sensitive to assumptions about the target effect, the outcome, and the analysis method. The registry does not report further details needed to evaluate such sensitivity.

Why are no comparative tests available?

The record lists no analyses. It supplies arm-specific endpoint values and intervals, but no test statistic, p-value, or model-based comparison. A test of a difference between proportions would require a specified method and assumptions. With very small groups and observed values at zero, method choice can matter. Without a reported analysis, no significance claim or recalculated test is warranted.

Over-dispersion is a general concern when observed variation is greater than a model assumes, particularly in clustered or repeated observations. It is not possible to assess over-dispersion from the posted fixed-time binary summaries, and the record does not report a model that would require such an assessment. No adjustment for clustering or repeated measurements is reported.

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("Arm I (CHOP)", "Arm II (Oral Chemotherapy)")
n      <- c(3, 3)
events <- c(0, 0)
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  Arm I (CHOP)  3  0  0.0  0.0  70.8  0.0  56.1  0.6  60.2
ARM  Arm II (Oral Chemotherapy)  3  0  0.0  0.0  70.8  0.0  56.1  0.6  60.2

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 8 outcome measures, but it reports no secondary outcomes posted and no analyses. The primary endpoint is overall survival at 2 years. Because no additional outcome results or inferential analyses are posted, the record does not show whether multiple outcomes were tested, whether any testing hierarchy was specified, or whether an adjustment for multiplicity was planned or applied. These details are not reported in the registry record.

In general, testing many outcomes can increase the chance of at least one apparently notable result when each is assessed separately. Statistical plans sometimes control this by specifying a primary outcome, an ordered testing strategy, or an adjustment. The registry information available does not establish which, if any, approach was used. The count of registered outcome measures alone is not evidence that all were analyzed or tested.

For missing data, the primary population is described as participants whose survival status was known at two years. The arm-specific primary outcome counts are 3.0 and 3.0, while total enrollment is 7. The registry record does not report the reasons that the primary analysis population differs from enrollment, how many participants had unknown survival status, or whether any imputation or sensitivity analysis was conducted.

The adverse-event groups have their own reported at-risk counts, which also differ from the primary outcome population counts. The record does not explain whether the distinction reflects different eligibility rules, availability of observations, or another process. Those possibilities should not be assumed. Without a flow of participants through randomization, treatment, follow-up, and analysis, readers cannot determine how missingness or exclusions might influence the results.

The record does not report whether analyses followed randomized assignment, whether participants were analyzed according to treatment received, or whether another analysis population was used. It also does not report interim analyses or stopping rules. These omissions limit assessment of the planned statistical approach; they do not establish that any particular method was or was not used outside the registry information.

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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: neoplasms, other (66.7%), headache (50.0%), fever (33.3%), death cause unknown (33.3%), fatigue (25.0%).

The registry lists serious adverse-event groups separately from the primary survival analysis. For Arm I, the serious-event group lists 4 participants at risk and 4 affected. For Arm II, it lists 3 participants at risk and 3 affected. These are the registry counts; they should not be combined with the primary endpoint populations, which have different listed counts. The record does not explain the difference.

The posted serious-event terms include “Neoplasms, other” at 66.7%, “Headache” at 50.0%, “Fever” at 33.3%, “Death cause unknown” at 33.3%, “Fatigue” at 25.0%, and “Encephalitis infection” at 25.0%. The registry does not specify the denominator or whether these term percentages refer to participants, events, or another basis. The percentages therefore should be quoted as recorded rather than converted into counts or treated as risks for either arm.

The adverse-event data do not establish that chemotherapy caused a reported event. Nor do the listed terms provide a complete description of event timing, severity grading, duration, or relationship to treatment. The record lists 3 deaths in each arm, but does not provide a complete account of causes in the information. “Death cause unknown” is an adverse-event term and cannot be assumed to describe every death.

These safety figures are descriptive registry entries, not a comparative safety analysis. The differing at-risk counts and absence of a stated denominator for the term percentages make direct comparisons especially limited.

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

The result means that the registry reports a two-year survival proportion of 0.0 for each treatment arm, among the participants whose survival status was known at two years. Both arm-specific 95% confidence intervals are also reported as 0.0 to 0.0. These values describe the posted outcome; they do not, on their own, establish a comparative treatment effect.

The result does not show that the regimens are equivalent. A conclusion of equivalence would require a defined margin and an analysis designed for that purpose, neither of which is reported. The matching point estimates also do not prove that the treatments have identical effects in other patients or settings. With small primary analysis groups and no posted comparative test, uncertainty about the broader treatment difference remains substantial, even though the registry intervals are zero-width as reported.

The result does not tell readers when deaths occurred, what caused them, or how outcomes developed during follow-up. It is a fixed-time survival proportion, not a survival curve or a reported hazard ratio. The registry record does not report a time-to-event analysis, a breakdown of follow-up, or an explanation of the difference between overall enrollment and the primary outcome population.

Nor does the primary endpoint capture all aspects of treatment. The record contains adverse-event counts and terms, but the available safety information does not supply a full comparative assessment of event severity, attribution, timing, or duration. It also does not provide posted results for secondary outcomes. The primary result therefore cannot answer questions about response, disease control, tolerability, or quality of life.

The scope of inference is limited to the registered population and treatment schedules. The record does not provide enough information to assess how well participants represent other people with HIV-associated lymphoma, how treatment was delivered in practice, or whether follow-up was complete. The appropriate reading is descriptive: the registry reports the same two-year survival proportion in the two small primary outcome groups, while leaving important questions about precision, analysis populations, and comparative effects unresolved.

14. Why This Trial Matters Statistically

This trial is statistically informative as an example of how randomized design and sparse outcome data can coexist. Randomization can support a fair comparison in principle, but it cannot compensate for very limited information in the observed groups. Here, the record lists 3.0 participants per arm for the primary endpoint, with a survival proportion of 0.0 in both arms. The resulting equal estimates are descriptive and do not settle whether the regimens differ.

The confidence intervals also illustrate why interval methods and reporting details matter. The registry gives 0.0 to 0.0 for both arms, yet does not report the calculation method. A reader cannot determine from the record whether the limits reflect a particular boundary method, a reporting convention, or another calculation. Statistical interpretation depends not only on the point estimate but on how uncertainty was assessed and communicated.

The difference between total enrollment, the primary outcome counts, and the adverse-event at-risk counts highlights another key issue: analysis populations must be transparent. Without participant flow and reasons for missing status or differing denominators, it is difficult to judge whether outcome summaries cover the randomized groups as intended. This is relevant even for an apparently straightforward endpoint such as survival at a specified time.

The posted record also demonstrates the distinction between a planning illustration and a trial’s original design. A sample-size calculation based on an observed effect can help frame a future planning scenario, but it does not establish observed power or explain the basis for the completed trial’s enrollment. The registry does not report a sample-size justification or a comparative analysis.

Together, these features make the record useful for statistical reading: design labels, point estimates, uncertainty statements, analysis populations, and missing analysis details each contribute different information. None should be interpreted in isolation.

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 trial-specific limitations constrain interpretation. Enrollment was 7, and the primary outcome lists 3.0 participants in each arm. The registry does not explain why these counts do not account for all enrollment, identify the participants with unknown survival status, or describe their outcomes. This leaves uncertainty about the completeness of the two-year endpoint assessment.

The adverse-event group counts are not the same as the primary endpoint counts. Arm I lists 4 participants at risk for serious adverse events, compared with 3.0 in the primary outcome; Arm II lists 3 in each. The record does not explain the populations used for these summaries, so readers cannot determine whether the difference reflects data availability or distinct analysis rules.

The reported confidence intervals are 0.0 to 0.0 in both arms. The registry does not identify the method used to calculate them, and no alternative interval estimates or inferential comparison are posted. This prevents assessment of the uncertainty using the record alone. No secondary outcome results or analyses are reported, limiting the breadth of evidence available for judging the regimens.

The registry identifies the study as randomized and open-label but does not report the allocation procedure, concealment, baseline characteristics, or independent outcome assessment. It also does not report treatment adherence, course completion, detailed follow-up, or a participant flow diagram in the information available. These omissions make it harder to assess comparability, implementation, and the influence of missing outcomes.

Finally, the registered population and schedules define a specific comparison. The record does not give site-level details or results by lymphoma type, stage, or other participant characteristics. The posted results therefore cannot establish whether outcomes differed across such subgroups or how applicable they are beyond the trial population.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Intravenous Chemotherapy or Oral Chemotherapy in Treating Patients With Previously Untreated Stage III-IV HIV-Associated Non-Hodgkin Lymphoma — NCT01775475.
• Registry record last updated 2022-10-10; status last verified 2022-09.
• Results first posted 2022-10-10.
• 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

NCT01775475 is a completed randomized phase II, open-label, parallel-group trial comparing CHOP chemotherapy with oral chemotherapy for previously untreated stage III-IV HIV-associated non-Hodgkin lymphoma. The official title describes concomitant antiretroviral therapy. The sponsor is the AIDS Malignancy Consortium.

The registry reports enrollment of 7, a start date of 2016-09-15, and a primary completion date of 2021-04-01. The primary endpoint is the proportion surviving 2 years, assessed up to 24 months, among participants whose survival status was known at two years.

The primary result lists 3.0 participants in each arm and a survival proportion of 0.0 for both, with 95% confidence intervals of 0.0 to 0.0. No analyses are listed, and no secondary outcomes are posted. The record includes serious adverse-event counts and terms, but does not explain the differing analysis populations or specify the denominator for the reported term percentages.